QUO VADIS? SLOVENIA AT THE CROSSROADS OF CONSCIOUSNESS LEGALISATION

The Defendant was saddened to learn from his lawyers that the Slovenian judiciary has no interest in the health benefits of cannabis or psychedelics. The ZPPPD refers obliquely to health consequences, as though every result of any type of research into them - for a long time banned or impossibly expensive anyway - could be decided in advance by the law, in the style of Pope Urban VIII's appointee on astronomy Fr Vincenzo Maculano. As with geocentricism, all heretical findings about "drugs" will be unfavourable.

But the Slovenian law's diffident legal non-interest is itself interesting. If the law is about cannabis and psychedelics (hereinafter CaPs) being illegal for health reasons, but not for any specified health reason, what can the real reasons be? Are there any?

The answer is racism, prejudice, stigma and bias. The ZPPPD discriminates against people who use CaPs. Slovenia did not invent these ideas by itself. It is merely mimicking a format. The Defence exposes the poisonous roots of CaPs' international prohibition.

The translator was telling me her daughter recently visited London, where she was shocked to find hardly any white people. This was terrible, but it was not explained why.

It was not our first interaction where it seemed the translator was dog whistling in a familiar Ptuj fashion. She doesn't toss in the N-word, and is far from the worst example.

Many in Ptuj, observing for some reason that the Caucasian Defendant is "one of us", assume automatically that he will share their disgust or dismay with the world's unwhites.

But to the Defendant personally the Arabs, known for their contributions to mathematics, astronomy, and scientific method, do not seem more primitive or dangerous than the average psychopath patrolling the village bars.

The Defendant despairs at the religiosity of all country folk equally, regardless of their skin tone, and does not feel that its melanin content offers a reliable generalization of its owners' personality or intentions.

Racists are not concerned with such nuances. The Defendant is also an "alien" in the Slovenians' world view, but in Ptuj excused from the more vicious generalizations due to a superficially acceptable phenotype, and vague associations among the Ptujčani with various positive British cliches. He is one of us (white, from the north) - among us...but not one of us.

But this foreigner has no need of popularity with racists, however respectable they may think they have become. They pop up everywhere, from utility companies to the benefits office.

But most of all in bars, where the locals' constant disappointment with his reaction to this important bonding behaviour of shared hatreds makes socializing a risky venture.

To Ptuj's dismay the Englishman is not "one of us", but "one of them". And it is as a black man that the Defendant takes responsibility for the drug choice of 354,845 innocent Slovenian men, the pro-recreational cannabis activists - the 2024 referendum voters.

Racism in Ptuj is simply majority normal, a belief as reliably inherited as the geocentric rotation of the celestial spheres was to Father Maculano. This case is also about belief.

The translator is at the "what if it rubs off?" stage of racism, which the Defendant recalls from the 1960s, when British bigotry was first successfully satirised by Johnny Speight's TV comedy series Till Death Us Do Part. This appeared contemporaneously with enactment of the Race Relations Act 1965 - making them the first sitcom and legislation in the United Kingdom to address racial discrimination - and with the creation of the Race Relations Board in 1966. Has Slovenia had a comedy satirising myopic nationalism?

Is skin tone a reliable guide to character? One would hope a criminal court translator of all people would not think so. As her white picket fence appeared, coloured folks, the Defendant explained, are just people, some good, some bad. But when some kind of clarification was sought as to what the translator's problem with black people is exactly, nothing specific issued forth. It was clear non-white foreigners just make her...shudder.

Now possibly in her career the translator has met a large proportion of foreigners in trouble, or in conflict with the Slovenian authorities. In scientific terms, her clientele is a suspiciously skewed sample.

If she set out to analyse their personalities statistically, it would likely not occur to her that to compare anything she would need a control sample, of foreigners who don't need translator-interpreters, and of white people who don't, and who do. And who may not live in someone else's idea of a nationalist environment.

Her actual beliefs must be conflicted: foreigner trouble means income for her, but also confirms the idea that foreigners are trouble.

And it is the same for CaPs users and the courts.

Underlying her wordless disgust at her daughter's surroundings in London is of course the fear of miscegnation. What if her daughter runs off with a black man? Will she be carried off to live enslaved, in a tent in the desert? Or in a tent in Peckham? He will always be poor! Why? Because racists have made the economy work that way. And that's why her daughter found herself in a multicultural community, instead of surrounded by cheery Cockneys eating cucumber sandwiches and playing cricket on the village green.

The Defendant's favourite memory of this topic in discussions in Ptuj is of calling out an N-word user - who unblinkingly declared that he was not a racist. He just "doesn't like things that come from black people", he explained. The translator and CaPs prohibitors, including Ptuj Court, are expected by the Defendant to share similarly unwoke world views.

The idea of flexible dogmatic beliefs may seem like an oxymoron, but Slovenia has many: catholic atheists, atheist catholics, people who are anti the safer drugs that they use, but support alcohol cancer and violence as the only respectable social glue.

Slovenia has had people who were nazis and communists on different days, depending on who's marching through the village. Slovenia is a nation of Benedict Arnolds.

Pragmatism and survival are believed to be factors in these muddy flip-flops of the Slovenian psyche. Slovenia's politics are similarly elastic and opportunist, and if a generous black millionaire arrives you can be sure the N-word will vanish...for a while.

From social forays into a society that has never seen or heard of Blazing Saddles and wouldn't get it anyway, the Defendant has concluded outright racism and its wide penumbra, prejudices of the "not-racist-but" variety, are endemic in Slovenia. Its racists are as indistinguishable as pines in a forest. Its racism is not always self-aware: it has no one unusual at hand with whom to compare itself. Racism is normalized and traditional.

But not in the law, surely! Slovenia is supposed to be trying to make it look to outsiders as if it is not a racist country. But momentarily putting aside worries about crass generalizations, it is. If - as the evidence shows - racism and political prejudice are among the reasons for the international prohibition of CaPs it is important that the Defendant obtains the services of a translator with solid anti-racist credentials.

Not just someone who doesn't think they are a racist, but doesn't like things that come from black people. Or Chinese, Mexican, British or other unusual types in the village.

Though immigrants will receive no warning signs, Slovenia has institutionalised its racism with the ZJRS, which demands business uses a language it has no intention of teaching whatsoever - especially to people who are not Slovenian enough. [1559]

Given that the nuance of anti-racist evidence in English may be transmogrified into pro-racist Slovene by a xenophobic choice of words, or dumbed down due to concepts unavailable to the Slovene vocabulary or to casual racism, the Defendant worries that evidence about racism in the ban on CaPs will be subtly altered to the detriment of its communication to the Court.

In common with asylum seekers [1126, p5], Slovene has already been used as a weapon against the Defendant. Interpretations of history - hardly easy to present as evidence in a criminal trial to begin with - are easily tinged with loaded language, so there is no particular reason to trust the interpreter corps as a single, universally ethical entity when it comes to explaining the racist origin of cannabis's legal journey to a reluctant Slovenian audience. The Defendant knows this translator does not much care for technical language. Racism is a kind of superstition. The evidence will show the state's ideas about CaPs are superstitions too. This may not be the right gig for this translator.

The Court will recall that this objection to the Indictment cannot be late, as the expiry of the deadline for the former preceded the provision of a translation of the latter (letter to the Court 2 October 2024), with a very lackadaisical approach to this right. As a reminder of the Republic's melancholy situation, the Defendant was very interested in learning Slovene from the age of 47, but was totally thwarted in his attempts by all of Slovenia. Which, it turns out, is far more enthusiastic about criticising foreigners for not speaking Slovene than encouraging them or teaching them, by a ratio of thousands to one.

Typically, translations from English into Slovene are dumbed down and biased against any criticism of Slovenia, which helps with the racists' missions immensely. Slovenian translations frequently stray into the area of what the translator thinks it is proper and right to say, as opposed to what the client actually originally wanted said.

This tendency, along with the fear of miscegnation, could easily colour the transmission of evidence about the cultural atmosphere in which the antecessors of the ZPPPD were brewed. Ptuj's racism ranges from the most unspeakably moronic stereotyping to some of the politest racism you have ever heard. It's these polite racists who are the bigger problem: they run things.

In translation work, unreliable pseudoscience of the 1920s may just seem normal to a normal Ptuj racist, in a trial initiated on a racially-grounded law, in a racist town, run by polite racists, with their own ideas about how things about racism should be said.

The translation could become anodyne and chilly towards anti-discriminatory ideas being expressed, or warmer than necessary towards the obviously discriminatory.

In any meaning depending on a choice between Slovenia or the foreigner triumphing, Slovene grammar simply cannot handle the latter. Experience shows the translation will seek to dilute any unflattering descriptions down to homeopathic levels.

Drug stigmas can replace or supplement some racism, as they fulfil similar functions.

Nowadays, in mixed cultures like the UK, drug stigma has been teased out as a separate daily hate, a type of discrimination supposedly not racist, but scientific. Discrimination against self-adjustment of ECS tone or 5-HT2A is no better than colour or gender discrimination. The Court will recall that laws against these are dogmatic too.

So, against every stereotype, it is possible to be a Slovenian paramilitary boy scout group marching into Slovenska Bistrica police station with a fat joint on the go. But it is also possible to be a black left-wing intellectual shouldering the burden of the exploited workers and be completely ignorant of, and therefore opposed to, the benefits of CaPs - hereinafter "the Benedictions".

For if religion is the opiate of the people, LSD must be worse - because it wakes them up.

As the whole edifice of Slovenia's language and law unites to defend drunkenness and Slovenianness against foreignness and health, whether in linguistic or pharmacological formats, all a racist has to do is sit on his or her hands and watch the show.

For instance the Defendant has invited his lawyer to begin a case against Slovenia for discrimination, by the ZJRS. The Defendant's evidence is presented clearly enough [1559]. But for reasons unclear, the fight against Slovenian racism is stuck on the starting blocks.

Ptuj will have to find legal reasons to ignore the obvious role of its own creation: the second/third-class citizenship of the stalno or začasno prebivališče is the office child of the kind of thinking which gave us the Erased. And in [1559] as in this case, it is the legal order of the Republic of Slovenia, not the Defendant, which needs to mitigate its damaging racist actions. Hence the delay.

Racist or merely national? The Defence will show that nationalism is merely a racism of convenience, and that Slovenians belong to the human species Homo sapiens.

For Slovenia's prosecutions based on a century-old racist politic to appear non-racist, for its jails to be half full of people who are not Slovenian enough, and for its prosecution targets as drug suppliers to a putative 354,845 pro-cannabis referendum voters to be more non-Slovenian than is typically represented in the population, there must be compelling reasons why courts and translators can refuse to hear evidence demonstrating the ZPPPD is racist, or that CaPs are a good thing, in the right situation.

Slovenia's lack of interest in this skewing must be because foreigners really are the bad actors, explaining their over-representation in jail, and employing a lot of translators.

Why would this be? The Defendant, for his part, is not surprised at all to learn that racists trying to be "not-racist-but" have drafted the ZPPPD in such a way. Some drugs can of course cause serious or severe health consequences.

To do that, a drug must be physically poisonous. A person cannot be poisoned by a moral complaint or sinful thought, any more than being black or female can make you ill. Does the Court believe in a "curse" mechanism of illness? How did such an idea make its way into the regulation of human behaviour? How did it become a law, the ZPPPD?

Some like to climb mountains. Many avoid them completely. A subgroup, however, likes to hear about mountains being climbed, discuss issues around mountain climbing, attend conferences on theories about why people climb, make speeches and write papers about mountain climbing, but never climb mountains.

Suppose laws about mountain climbing were enacted...by guess who...What would these laws aim to do? These two groups - the mountaineers and the mountain regulators - are not the same.

Climbing mountains is definitely risky. An outright ban clearly delivers the safest result and greatest good for the greatest number if 100% successful, but would probably be quite expensive to police and so very unlikely to happen or work in practice.

But knowing Slovenia, its mountain experts would probably decide to be strict and invent a law anyway, knowing full well that they would be disregarding reality.

Their calculations would not try to put a value on the positives of alpinism, because a law has didactically proclaimed there are officially none. And that is that.

For defiant rogue mountaineers, the situation is considerably worsened, as there are now no mountain rescue services, as no one is supposed to be up there. Yet the man hours spent policing the mountains will produce a few accidents of their own. Unsurprisingly, there is a crossover between mountain cops and mountaineers. Some have been taking bribes to turn a blind eye. Quo vadis?

Has the anti-mountaineering law produced a desirable result? Clearly the mountaineers will be unhappy. Could they argue with the theoretical rationality of this law? Where are their statistics, perhaps showing that mountaineering is safer than the same time spent flying in a helicopter, and would the law then simply dogmatically refuse to hear these?

Cash value aside, they may assert getting high is for them a profound religious experience, healthy or fun, and point to their Constitutional rights. But ground-based mountain management experts would issue a press release pointing to hypoxia, and exceptions for public safety reasons under section 2 of the Zakon Proti Gorništvu.

The media can always fill space with mountain tales. Not about their beauty, challenge or isolation, but only shock stories about risks, like freezing and falling to your death, and calling for public vigilance against a dangerous climb-wave. Obviously nobody gets asked on TV to be interviewed about what a spiritual time they had clinging to some cliff.

This little analogy helps us see that CaPs users have different priorities from racists, bureaucrats, and media lapdogs. And it must be hard not being racist, when you are a pine in the forest, working in the legal bureaucracy, when the law you are trying to enforce was invented by racists, as an expression of their whiteness and fear of miscegnation, when the evidence has been stacked up to make it look like a foreigner problem, and when all the witnesses have to do is point at one and they will be ok.

So the exclusion of witnesses does not advantage the Defendant in his battle with the discriminatory ZPPPD. Rather the homeys are being allowed to flee the scene.

The fact is, we don't stigmatise or punish anyone for climbing mountains, and if we did, not everyone would stop anyway. But the mountaineers' woes are those of the CaPs user.

How does looking through a legal lens affect the legal practitioner's perception of cannabis? The legal team estimated from anecdotal evidence that it is ever-so-slightly less harmful than alcohol, ~0.8 times as harmful. The translator thought maybe five times more harmful than alcohol.

An astonishing effect is revealed by comparison with [852] in which Lachenmeier and Rehm, using the MOE approach, find the deadly plant to be 114 times less dangerous than alcohol - now pretty much the universal standard for drug toxicity as it routinely comes out top. Which the Court cannot consider in evidence. In some motivated denial of reality, a shared interest in getting high might result in miscegnation.

Among the realities being the fact that in the non-users' perception of CaPs, the supposed dangers are wildly exaggerated by their legal status.

Even some users seem to believe it!

And lawyers adjust their performance accordingly.

What are we to make of the fact that someone is willing to risk something 114 times more dangerous and rub five minutes off their life with every drink, having administered the processing and punishment of those willing to replace it with something 0.0088 times as dangerous?

Even if it was 0.9999 times as dangerous it would still be better! In physiological and behavioural analyses, alcoholism is significantly ameliorated by CaPs. Could they be a teeny bit jealous?

At least one thing is clear - no decent individual who took psychedelics could continue working in such an inauthentic way. Perhaps these really are enemies of the state.

The other thing to know about this rumoured rule prohibiting facts about drugs in drug trials is that the traditional buck-pass to the Executive leads nowhere. No politician wants to be seen contradicting the story all these people fell for. Even after 354,845 of them have declared that prohibition's dogma has had its day.

The electorate is only allowed to choose from pro-alcohol, anti-health policies, and in the referendum 333,555 voted against cannabis, which was conflated by the religious right with euthanasia, as though a commie was lurking around every corner with a hypodermic full of THC to take you out. The scientific quality of their beliefs may be inferred from such circuses.

Of the etiology of individual cases of cancer, for instance, we cannot ever speak with much certainty. It is revealed only in mass epidemiology. However, as witnesses in RS v Jašar some victims, perhaps of Slovenia's pro-alcohol, anti-health policies, perhaps of environmental circumstance, and perhaps of their own ovine lifestyle choices(!) - were indeed allowed to parade their health histories in Maribor's court, and bear witness to the relief cannabis belatedly brought them, as defence evidence of pro-health activities.

This contradicts the advice of the present Defendant's law firm that the benefits of cannabis or psychedelics are irrelevant.

However there are laws about causing death and sickness, and about negligence, which on good days even apply to the Government and its unexplained prohibitions.

These may be ignored by the Police, lawyers, NIJZ, and jurists, as a matter of religious observance. The problem with common knowledge is that it's just that: common.

It was suggested by the legal team that this exception to the rule against facts about drugs in drugs trials was permitted because Jašar had gifted, not sold the medicament. So? We see no legal pro-health treatments being gifted; rather, Slovenia is addicted to profiteering wherever possible from healthcare to the fullest extent. When it comes to supplying pro-health commodities, does the Court agree evil is price-dependent?

Drug laws like the ZPPPD are not meant to make sense. The Defence will show the alleged distinction between free CaPs and expensive pharmaceuticals is based on jealousy and destructiveness, rather than the intrinsic efficacy and consequent value of the Benedictions. Slovenia's two favourite hobbies do not generate honesty or health.

And it is indeed simply a fact that raw materials, be they chemicals to make pills and potions, or metal for pharmaceutical machinery and medical devices, and the real estate where they are made, are trapped in the same market economy realpolitik as pollution, factory farming, the junk food industry, and CaPs.

So this dogma about the "bad" rivals - these unprofitable drugs which work and do not require further expensive drugs to deal with the side-effects - further evidences the racial and political bias which has required the ZPPPD to rely on a circularly-defined "inappropriateness" and its accompanying narrowness of view.

CaPs have assisted human evolution - the vast majority of it without medical supervision or bureaucracy - and continue to do so.

This is why we, who know of that of which we are talking, are so curious about the reason for our prosecution, and advise the Court that although the Defendant understands the "nature" of the accusation, it is also a right under ECHR 6(3)(a) to know its "cause". The Defence will show the cause was nothing but woo woo and blind prejudice from the start.

Is the Court required, by this dogmatic property of one law insofar as it relates to CaPs, to ignore these other laws about harming and killing people? Must it remain frozen in a golden age when it seemed obvious to some thinkers (most of whom never tried them) that such drugs were dangerous because of being illegal and whatnot, and their associations with jazz, peaceniks and eco-nuts?

The Defence will demonstrate the redundancy of the ZPPPD and international prohibition measures by placing legal events into their correct temporal context [3500].

The minutiae of the origins of international drug prohibition do not zoom in adequately, to grab Slovenia's interest, on the two periods in its history, ~1919 and ~1947, to which a baseline for some kind of xenophobic or factional grudge can be attached for political campaigning purposes.

With no connection to these foundational elements of the national identity, Slovenia's jurists may fondly imagine that the possible dangers and benefits of CaPs must all have been thoroughly thrashed out by the wise elders of a previous government, or other countries' governments, in a thoroughly disinterested and earnest, scientific way.

That never happened. Plus, nothing in science is final - and certainly wasn't in 1925.

In regard to CaPs, Slovenia's ZPPPD is not prejudiced or racist, they can claim, because all the other countries were too. The Prosecution is invited to present concrete evidence of these imaginary investigations - which the Defence will demonstrate were impossible.

The Defence in its religious arguments will show that the war on drugs, as far as the relevant substances are concerned, is one of the many mass delusions to which humanity is perpetually prone, itself the product of other mass delusions about race and heredity.

Now let's put aside these societal fantasies and legal fictions and break all the rules about discussing drugs in drugs trials, with a look at what CaPs do, besides get you into trouble with people who don't want to hear about it.

This Defence disregards the supposed separation of powers. Slovenia's Executive will fail interminably to address the drug stigma and health-damaging inertia it created in the first place. And will argue in back rooms over whose associates are going to control the trade and get money when someone else legalises it and makes the stigma go away.

There will be no giveaways, no sorrys, when legalization comes to Slovenia which, with all its love slogans, greenwash, and surplus philosophers, shows little sign of ever actually making contact with the psychedelic revolution. In the 1980s Slovenia did manage to get hold of some Elton John cassettes.

Should today's Slovenian intellectual become curious about LSD, the first question he will consider is how much he should drink before taking it, to blunt the experience and give him courage (rolls eyes). It's probably the same with Slovenians' first driving lesson.

The good news is that enough of the Benedictions evidence is connected with alcohol to keep Slovenia interested. But it's all bad news for booze. Psychedelics will put you off. Especially if you use them together, only to find out what it's like being poisoned in your brain and body in atomic detail. This is why LSD was so effective in its nascent war on alcoholism, before business got its lobbyists together to get it declared medically useless.

Before looking at some ingredients of cannabis and what they do, we must explore the concept of "do", and the conceptual pitfalls around correlation versus causation arising from both languages.



It is enough to notice that in English, the word "associated" - often found in scientific results - is guilty of implying causation, even when researchers are using it precisely to avoid doing so.

"Correlated" is a better word in English, but even here there is no escape from a hint of causation. The routes of all the cars travelling along the highway are associated and can be correlated in such terms as speed and direction, but the journeys, their purposes, and the vehicles themselves are not connected.

In Slovene, if the DeepL translation is to be relied upon, there is also a dangerous lean towards belief in causation - in fact it goes beyond suggestion, if correlated is translated as "povezan" - connected.

It needs hardly be explained that shark attacks are not a consequence of ice cream sales or vice versa and are not causally connected IN THAT WAY, i.e. between themselves.

However, the possibility of shark attacks attracting crowds of onlookers to the beach, and some of these rubberneckers buying ice cream while they wait to watch more swimmers being eaten, cannot be ruled out.

Only more information from a large number of longitudinal trials could rule this in. For the faithful, it's bad news. The default assumption in science is always of NO connection. After a sufficient amount of data has been gathered, statistical tests are applied to assess the unusualness of any observed correlation. The best known is p [2363].

As you have already guessed, the real cause of the correlation between ice cream sales and shark attacks is hot weather. In general this is known as a common response. In genetics we may refer to a pleiotropic effect, where one gene predisposes an individual to two or more not obviously related phenotypes, for instance nicotine addiction and schizophrenia.

One interesting research outcome appeared in a very well-controlled 2019 study of antidepressants and dementia in Israel:

"A prospective national matched cohort study from Israel (N = 71,515) without dementia (2002–2012) aged 60 and over were followed up for incident dementia from May 2013 to October 2017. Exposure to antidepressant monotherapy was classified with Anatomical Therapeutic Chemical Codes (N06A) from January 1, 2013 to December 31, 2016. The association between antidepressant monotherapy and the risk of incident dementia was quantified with hazard ratios (HR) and their 95% confidence intervals (CI) obtained from Cox regression models unadjusted and adjusted for 42 covariates. The robustness of the results was tested with 24 sensitivity analyses: 19 analyses restricted to subsamples with plausible differential dementia risks (e.g., anxiety and depression), and 5 analyses across and within antidepressant drug classes.

"Results
In the primary analysis, the risk of incident dementia for the group exposed to antidepressant monotherapy compared to the group unexposed to antidepressants was estimated with an unadjusted HR = 4.09 (df = 1, 95% Wald CI = 3.64, 4.60) and an adjusted HR = 3.43 (df = 1, 95% Wald CI=3.04, 3.88). Across the 24 sensitivity analyses the estimated adjusted HR values ranged from 1.99 to 5.47."
https://www.sciencedirect.com/science/article/abs/pii/S1064748119303902[3307]

The caveat here is that depressed people are more likely to get dementia, so the 3 to 4-fold increase in dementia might be nothing to do with the drugs which depressed people are more likely to use.

It can equally be argued that since CaPs raise hedonic tone, if it is the depression causing the dementia and not the antidepressants, CaPs prevent dementia. This is supported by the mechanistic evidence.

Since CaPs are substitutes for antidepressants, they eliminate the possibility of antidepressant-related dementia if people can manage to stop taking antidepressants.

Anyway the Defence confesses to having no way to know how words such as "združenje" actually FEEL to the native speaker, or affect his or her belief in causation. For certain, as the word for "evidence" and the word for "proof" are the same word in Slovene, and Slovenia is a somewhat religious country, it may be that dokaz is proof, but not as we know it. For instance, I'm saying all frogs are pink. See? I've proved it. The bar for proof seems likely to be very low, and if you want Slovenians to become quiet, ask about this.

The Defendant's approach is to be wary of the tendency to believe correlation is causation, but not to the extent of ignoring data just because it is "only" an association.

Many now proven causations - smoking and lung cancer being one example - began life as mere associations and correlations.

Associations - or the lack of them - are useful. An association does not prove cause and effect. But the lack of an association shows no possibility of cause and effect, and no mechanistic research is needed to confirm what we already know to be untrue.
https://www.youtube.com/watch?v=RtBvy3qwGgI [3665]

The Court is encouraged to do its best to rely less on these problematical words, and more on the numbers: what the statistics say, and what they don't.

Equally, many correlations have lost their appeal to what we may call "common sense" thanks to new information.

For example we do not think people with an interest in herbal medicine are witches, and we do not think the weather is God's punishment for our sins. Do we?



It would be conceited and wrong to think of superstition as a behaviour confined to yesteryear. A Mr Grims, seen here on Twitter, thinks fires in churches are caused by immigrants and are certain proof of the demise of white western civilisation - and not by lightning strikes, candles, ancient wiring, fumes of turpentine or other solvents for cleaning metalware, or renovation works in hot weather.

The inconvenient facts that no arson had been reported, nor any connection with immigrants ascertained in either this or some overwhelming majority of church fires, does not affect Mr Grims' conclusion, which is a guess based upon how he feels about certain types and colours of Homo sapiens and where they should be.

As a politician vying in the democratic process he evidently calculates more voters will be turned on than off by this message, which shows the eternal tension between political inclusivity and critical thinking.
https://twitter.com/BrankoGrims1/status/1668706974588911622[2700]

Completely aware he was claiming lightning strikes are caused by immigrants, Grims took his fairytale to The European Conservative, where he claimed:

"Without Christian roots, Europe cannot exist. That is why so many historic churches are burning these days. If the extreme leftists manage to cut Christian roots out of Europe, it will never be Europe again and Western civilization will fall forever. The Right must win!"
https://europeanconservative.com/articles/interviews/without-christian-roots-europe-cannot-exist-an-interview-with-branko-grims/ [2906]

In epistemological terms this falls under the heading of foundationalism: all the terms "Christian Europe", "churches burning", and "Western civilisation" are, to the coherentist, non sequiturs or conflations of jarring proportions.

But to those who assume a priori that Europe is Christian, that its places of worship, also all Christian, are free of all other incendiary causes - from lightning to work accidents - and that there is nothing about Eastern civilisation that might be of interest to this relentlessly white and churchgoing Europe, this all makes sense.

Untroubled by his poor record at remote racist fire investigation, Mr Grims was soon at it again, with equally wrong results.


https://twitter.com/BrankoGrimsX1/status/1786379948543877416 [4631]

Infinitism argues that nothing can ever be proved, ultimately, while believers are evidently unaffected by data which do not fit, or even by a general consensus about reality. The Defence contends that prejudice and hate are more popular than statistics and null hypotheses.

Skepticism, critical philosophy, and pragmatism, however, point more towards the semi-solution offered by mathematical probability - and this is the scientific model coming out of the logical positivism of the Austrian Circle 1924-36 - a period which the Court will note largely postdates the Opium Treaty (with cannabis tacked on), and ends with the murder of the Austrian Circle's chairman on Vienna University's staircase. But also with the birth of the null hypothesis, in Fisher's seminal work The Design of Experiments (1935) - rendering possible steps towards a universal truth with its practical resolution of the Münchhausen trilemma [2755, 2912]

Mr Grims offers no statistics to support his claim of Christianity's uprooting as a causal factor in left-wing church burning. The reasoning from "church fire" to "must be immigrants" is not elaborated. There have been no sustained campaigns of ecclesiastical arson in Europe in recent times, and Mr Grims would probably rather ignore its most prominent exponent, a Mr Varg Vikernes...

"...a proponent of White nationalism, survivalism and his racialist neopagan ideology, [who] has declared that he wants to blow up Blitz House and Nidaros Cathedral. He has publicly supported black metal fans burning down eight churches in Norway."

...and who got 21 years, the maximum, for murder, arson and possession of illegal weapons (including explosives) in 1994.
https://en.wikipedia.org/wiki/Church_arson [2908]
https://en.wikipedia.org/wiki/Regress_argument [2907]

We could proceed to compare the number of right wing vs. immigrant ecclesiastical arsonists, but the point has already been made: popular thinking does not need to be rational.

From this it is easily surmised the crowd may not be the best guardian of its own wellbeing, and is in fact quite lazy-minded. The individuals in the crowd are begging for quasi-gods, whose narrow prejudices "authoritatively" confirm and sanction their own.

A division of responsibility preventing any discussion of drugs in drugs cases is a fantastic tool for doing nothing.

Mr Grims is vocal in his claim that "free speech" - the sort that makes people fear and hate immigrants - is threatened by left internationalists.

We also see precise language does not favour political or religious screeds, which is why some of the populist appeal of the "white man's logic" is so outrageous. Here, from Primorske Novice, a headline translated, and annotated in red:



However sincere and sage their opinions seem to them, such influencers completely reject empiricism as non-useful to the exercise of their opinions, to manipulate the plebs.

So how can we trust what the same people among us think about CaPs? Because of the longstanding artificial dichotomy, the whole conversation must be conducted in darkness, with the threat of exposure meaning different things to different people.

Prohibition, then, has a chilling effect on debates around prohibition. The in-your-face type of user becomes a threat to quieter users whose main aim is avoidance of the dangers of stigma, street dealing, and prosecution.

Dogmatists like Mr Grims delight in the distraction and chaos this causes. In the referendum, thanks to secret balloting, the reality burst through that the pro-cannabis lobby is not some fringe group, and not foreign either.

Slovenia's Constitution guarantees the right to belief. Before we investigate what a fair-minded person might or might not believe about cannabis and its derivatives, we need to quickly make sure we understand some terms we will encounter along the way, namely agonist and antagonist. Here's a good way to think about agonists and antagonists:

"A great analogy to think of is with a vending machine. Usually to buy a drink, you would insert a $1 coin into the machine, and the response is for it to spit out your favourite soda. An agonist in this scenario would be to use a metal disc, of the same size as a coin to insert into the machine, thus using the same coin slot with a mimic coin to obtain a soda.

"An antagonist does the opposite of an agonist. It binds to receptors, and stops the receptor from producing a desired response. Going back to the analogy, it’s like jamming the machine’s coin slot so that it is unable to perform its function until the blockage is removed."

So:

"An agonist is a drug that binds to the receptor, producing a similar response to the intended chemical and receptor. Whereas an antagonist is a drug that binds to the receptor either on the primary site, or on another site, which all together stops the receptor from producing a response."
https://lx.uts.edu.au/pharmacology/article/agonists-and-antagonists/ [2601]

An experiment might test one group with an agonist and another with an antagonist, to confirm or eliminate a particular pathway of action.

For instance, in Yu et al "Beneficial effects of cannabinoid receptor type 2 (CB2R) in injured skeletal muscle post-contusion" (2015):

"A standardized rat model of skeletal muscle contusion was established, where rats were treated with the CB2R agonist JWH-133 or antagonist AM-630. The in vivo results revealed that CB2R activation with JWH-133 significantly diminished the fibrotic areas, down-regulated the mRNA levels of collagen type I/ІІІ and augmented the number of multinucleated regenerating myofibers in the injured zones. The reasons leading to the aforementioned results were directly attributable to decreased mRNA levels of TGF-β1, FN-EIIIA and α-SMA, reduced accumulation of myofibroblasts, and concomitantly increased mRNA levels of matrix metalloproteinase-1/2. However, we observed contrasting changes in rats treated with the CB2R antagonist AM-630. These results revealed multiple effects of CB2R in systematically inhibiting fibrotic formation and improving muscle regeneration, alongside its potential for clinical application in patients with skeletal muscle injuries and diseases."

And what led Yu et al to examine anti-fibrotic properties of this synthetic cannabinoid JWH-133?

"General consensus holds that CB2R exerts antifibrosis effects in diverse organ types. For instance, CB2R activation abrogates the fibrotic process by arresting growth and triggering the apoptosis of myofibroblasts in human cirrhotic liver in vitro (Julien et al., 2005). Moreover, the selective CB2R agonist JWH133 regresses fibrosis in cirrhotic rats with apoptosis of hepatic myofibroblasts (Muñoz-Luque et al., 2008). Consequently, pharmacological intervention of the hepatic endocannabinoid pathway offers potential for the treatment of liver fibrosis. In addition, CB2R activation may protect against post-ischemia/reperfusion heart failure through direct inhibition of cardiac myocyte death and prevention of myofibroblast activation (Defer et al., 2009). Treating mice through JWH-133 also prevents the profibrotic effect of bleomycin in the skin, while inhibition of CB2R signaling augments bleomycin-induced dermal fibrosis (Akhmetshina et al., 2009). Besides, CB2R is also involved in the control of skin and lung fibrosis, and of autoimmunity in a mouse model of systemic sclerosis (SSc) induced by hypochlorite (Servettaz et al., 2010)."
https://www.hh.um.es/pdf/Vol_30/30_6/Yu-30-737-749-2015.pdf [2822]

Of course this means that not activating CB2R does not do these things.

And this is one of the achievements of the Ptuj Police when a suitable target presents itself from time to time. In fact someone should attempt to list these sorts of achievements, by which enforcement of the ZPPPD against not-Slovenian-enough people and some Slovenian criminals raises the incidence of health harms, and this the Defendant has done. Stuck in the war on drugs' ignorance-promoting idea that cannabis is one thing, the law does not wish you to know that, according to Walsh et al (2021):

"In addition to the major phytocannabinoids, Δ9-THC and CBD, cannabis produces over 120 other cannabinoids that are referred to as minor and/or rare cannabinoids. These cannabinoids are produced in smaller amounts in the plant and are derived along with Δ9-THC and CBD from the parent cannabinoid cannabigerolic acid (CBGA). While our current knowledge of minor cannabinoid pharmacology is incomplete, studies demonstrate that they act as agonists and antagonists at multiple targets including CB1 and CB2 receptors, transient receptor potential (TRP) channels, peroxisome proliferator-activated receptors (PPARs), serotonin 5-HT1a receptors and others. The resulting activation of multiple cell signaling pathways, combined with their putative synergistic activity, provides a mechanistic basis for their therapeutic actions."



"Cannabinol CBN was originally isolated from Indian hemp in 1896 making it the first phytocannabinoid identified in cannabis (Wood, et al., 1886) [error, according to the Royal Society of Chemistry it's 1896 [2701]]....CBN has been found to be highly efficacious against multiple antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), making it a potentially viable treatment for staph infections (Appendino, et al., 2008)."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669157/ [2702]

By 2022 Llinas del Torrent et al, at the Laboratory of Computational Medicine, Biostatistics Unit, Faculty of Medicine, Universitat Autònoma Barcelona, were reporting further growth, another 50% more cannabinoids since the report of Walsh et al [2702] the previous year.

"There are over 180 cannabinoids out of the 1600 chemical compounds that have been isolated from Cannabis, with a characteristic oxygen containing C21 aromatic hydrocarbons. These exogenous cannabinoids can be further classified into 11 subclasses: cannabichromene (CBC), cannabidiol (CBD), cannabielsoin (CBE), cannabigerol (CBG), cannabicyclol (CBL), cannabinol (CBN), cannabinodiol (CBND), cannabitriol (CBT), (−)-Δ8-trans-tetrahydrocannabinol (Δ8-THC), (−)-Δ9-trans-tetrahydrocannabinol (Δ9-THC), and miscellaneous-type cannabinoids. The Δ9-THC subclass contains 25 compounds with common structural features such as a dibenzopyran ring and a hydrophobic alkyl chain. This class includes the most abundant phytocannabinoids: (−)-Δ9-trans-tetrahydrocannabinol (THC), which is the principal psychoactive constituent of Cannabis, and (−)-Δ9-trans-tetrahydrocannabivarin (THCV), which is homologous to THC but has a 3-carbon (propyl chain) instead of a 5-carbon (pentyl chain) in the alkyl chain (Figure 1)."
https://pubs.acs.org/doi/full/10.1021/acs.jcim.3c01054  [2985]

In September 2022 Dongping Li et al at the University of Lethbridge, with an eye on "synergistic or antagonistic effect of various cannabinoids and terpenes" published their "Analysis of Anti-Cancer and Anti-Inflammatory Properties of 25 High-THC Cannabis Extracts", in which they tested the anti-cancer potency of extracts from 25 varieties of Cannabis sativa including Elevator Kush, Sunshine Pie, Diamond Haze, Spaceman Plus, Florida Gold, Citrus Splash, Glacier Goo, and Zombie.

"In this work, we analyzed 25 cannabis extracts containing high levels of delta-9-tetrahydrocannabinol (THC). We used HCC1806 squamous cell carcinoma and demonstrated various degrees of efficiency of the tested extracts, from 66% to 92% of growth inhibition of cancer cells. Inflammation was tested by induction of inflammation with TNF-α/IFN-γ in WI38 human lung fibroblasts. The efficiency of the extracts was tested by analyzing the expression of COX2 and IL6; while some extracts aggravated inflammation by increasing the expression of COX2/IL6 by 2-fold, other extracts decreased inflammation, reducing expression of cytokines by over 5-fold. We next analyzed the level of THC, CBD, CBG and CBN and twenty major terpenes and performed clustering and association analysis between the chemical composition of the extracts and their efficiency in inhibiting cancer growth and curbing inflammation. A positive correlation was found between the presence of terpinene (pval = 0.002) and anti-cancer property; eucalyptol came second, with pval of 0.094. p-cymene and β-myrcene positively correlated with the inhibition of IL6 expression, while camphor correlated negatively. No significant correlation was found for COX2. We then performed a correlation analysis between cannabinoids and terpenes and found a positive correlation for the following pairs: α-pinene vs. CBD, p-cymene vs. CBGA, terpenolene vs. CBGA and isopulegol vs. CBGA. Our work, thus, showed that most of [the] high-THC extracts demonstrate anti-cancer activity, while only certain selected extracts showed anti-inflammatory activity. Presence of certain terpenes, such as terpinene, eucalyptol, cymene, myrcene and camphor, appear to have modulating effects on the activity of cannabinoids."
https://www.mdpi.com/1420-3049/27/18/6057/pdf?version=1663338682 [2719]

So just to be clear, the least effective extract of the 25 compositions tested inhibited the squamous cancer cells by 66%, in a well in a plate in a lab.

None of the 25 failed to inhibit cancer cell growth.

None of the 25 made it grow faster.

And the people who made it illegal for you and me to do this had no idea.

Wait a minute though. Aren't these the people we trust to know everything so that we, the anti-drug public, can be protected without having to think about these experiments?

How can we be so sure this fondly imagined phalanx of legal scholars in lab coats had no idea about the cancer-modulating effects of high THC cannabis?

Because cannabis was internationally prohibited in 1925, 1961 and 1971.

High performance liquid chromatography was not commercially available until 1967. The HCC1806 squamous cell line was not developed until 1995.
https://www.atcc.org/products/crl-2335 [2720]
https://www.aaps.ca/blog/a-history-of-how-hplc-became-common-in-pharmaceutical-testing [2721]

This research would not have been technically possible for 72% of the period from 1925 to 2022. Prior to legalisation of cannabis in Canada on October 17 2018, the legal and commercial conditions for permission to perform it would likely have been too onerous, for 96% of the period from the League of Nations Opium Treaty to its publication.

"Therapeutic potential of minor cannabinoids in psychiatric disorders: A systematic review" (2025) from Cammà et al summarises 22 preclinical studies and one clinical study:

"Δ8-tetrahydrocannabidivarin (Δ8‐THCV) exhibited potential for nicotine addiction; Δ9-tetrahydrocannabidivarin (Δ-THCV) for psychotic-like symptoms; cannabidiolic acid methyl ester (CBDA-ME) alleviated anxiety and depression-like symptoms, and cannabidivarin (CBDV) autism spectrum disorder-like symptoms."
https://www.sciencedirect.com/science/article/pii/S0924977X24007508?via%3Dihub [3807]

As for interest in terpenes, Otto Wallach was the first to investigate them generally in the 1880s, and a couple were first extracted from hashish oil by Wood, Spivey and Easterfield in 1896. Then nothing happened until 1942, when a couple more were found.
https://pubs.rsc.org/en/content/articlelanding/1942/JR/jr9420000188 [2723]

In cannabis, as many as 400 are now known. "Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity" reported LaVigne et al in 2021.
https://www.nature.com/articles/s41598-021-87740-8 [500]

One is β-caryophyllene. According to Bandaru et al (2023) β-caryophyllene is an anti-diabetes substance:

"Cannabis and a variety of culinary herbs and spices may include the naturally occurring sequiterpene β-caryophyllene. Among other things, it has antioxidant, anti-inflammatory, and anti-lipidemic properties. However, it is not yet known how β-caryophyllene affects the uptake and oxidation of glucose. Determining if β-caryophyllene has anti-diabetic properties in type-2 diabetes brought on by a high-fat diet was the objective of the current investigation. A sufficient dose of β-caryophyllene (200 mg/kg b.w.t., orally for 30 days) was given to type-2 diabetic rats fed a high-fat diet and given fructose as an inducer of diabetes to assess its anti-diabetic activity. The treatment of diabetes-induced rats with β-Caryophyllene restored the altered levels of blood glucose, serum insulin as well as the lipid parameters, oxidative stress markers, antioxidant enzymes. Our findings show that β-caryophyllene improves glycemia control by enhancing glucose absorption and oxidation in the skeletal muscle of type-2 diabetic rats. From the present findings, it is evident that β-caryophyllene can be used as an anti-diabetic drug."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563560/pdf/97320630019417.pdf [4043]

Al-Taee et al of the College of Medicine and Health Sciences, United Arab Emirates University found in "β-caryophyllene, a dietary phytocannabinoid attenuates oxidative stress, inflammation, apoptosis and prevents structural alterations of the myocardium against doxorubicin-induced acute cardiotoxicity in rats: An in vitro and in vivo study" (2019) revealed that:

"...treatment with β-caryophyllene showed significant cardioprotective effects as evidenced by favorable improvement of biochemical and molecular parameters along with remarkable preservation of cardiomyocytes in histological and ultrastructural studies. Results of the present study demonstrate that β-caryophyllene has potential to protect heart against doxorubicin-induced acute cardiotoxicity in rats. Moreover, the antioxidant and free radical scavenging properties of β-caryophyllene was confirmed by in vitro assays. Provided the anticancer and chemosensitizing properties of β-caryophyllene, the cardioprotective effects of β-caryophyllene are suggestive of its multiple properties that provides an additional basis of its possible therapeutic application in chemotherapy-associated cardiotoxicity."
https://pubmed.ncbi.nlm.nih.gov/31216443/ [4395]

"Non-small cell lung cancer (NSCLC) accounts for nearly 80-85% of total lung cancer, which is further divided into adenocarcinoma, squamous carcinoma and large-cell carcinoma based on the pathology," explain Yang et al in a 2016 study of the sesquiterpene guaiol.

"Here, we show that (-)-Guaiol significantly inhibits cell growth of NSCLC cells both in vitro and in vivo. Further high throughput analysis reveals that RAD51, a pivotal factor in homologous recombination repair, is a potential target for it. The following mechanism studies show that (-)-Guaiol is involved in cell autophagy to regulate the expression of RAD51, leading to double-strand breaks triggered cell apoptosis. Moreover, targeting RAD51, which is highly overexpressed in the lung adenocarcinoma tissues, can significantly increase the chemosensitivity of NSCLC cells to (-)-Guaiol both in vitro and in vivo. All in all, our studies provide an attractive insight in applying (-)-Guaiol into NSCLC treatments and further suggest that knockdown of oncogenic RAD51 will greatly enhance the chemosensitivity of patients with NSCLC."
https://www.oncotarget.com/article/11540/text/ [3659]

Yang et al went on to publish "(−)-Guaiol triggers immunogenic cell death and inhibits tumor growth in non-small cell lung cancer" (2023):

"To explore whether autophagy and apoptosis are involved in (−)-Guaiol-induced ICD, we used inhibitors of apoptosis and autophagy. The results showed that the release of damage-associated molecular patterns (DAMPs) was partly reversed after inhibition of apoptosis and autophagy. In conclusion, these results suggested that the (−)-Guaiol triggers immunogenic cell death and inhibits tumor growth in NSCLC."
https://link.springer.com/article/10.1007/s11010-022-04613-y [3660]

Xu et al at Shanghai's National Key Laboratory of Lead Druggability Research investigated "Chemical compounds, anti-tumor and anti-neuropathic pain effect of hemp essential oil in vivo" (2024):

"Hemp (Cannabis sativa L.), an annual dioecious plant, has shown extensive application in the fields of fibers, food, oil, medicine, etc. Currently, most attention has been paid to the therapeutic properties of phytocannabinoids. However, the pharmaceutical research on essential oil from hemp is still lacking. In this study, hemp essential oil (HEO) was extracted from hemp flowers and leaves, and the components were analyzed by GC-MS. Quantitative analysis of three main compounds β-caryophyllene, β-caryophyllene oxide, α -humulene were determined by GC-FID. The anti-tumor and anti-neuropathic pain effects of HEO were evaluated. In the paclitaxel induced neuropathic mice model, HEO reduced the serum level of inflammatory cytokines TNF-α to achieve the analgesic effect, which was tested by evaluating mechanical and thermal hyperalgesia. Further investigation with cannabinoid receptor 2 (CB2 R) antagonist AM630 revealed the mechanism of reversing mechanical hyperalgesia may be related to CB2 R. In Lewis lung cancer grafted mice model, the tumor growth was significantly inhibited, the levels of tumor inflammatory cytokines TNF-α and IL-6 were downregulated, immune organ index was modified and immune-related CD4+, CD8+ T lymphocytes level, CD4+/CD8+ ratio were increased when administered with HEO. These results reveal that HEO plays a role not only in tumor chemotherapy induced peripheral neuropathy treatment, but also in anti-tumor treatment which offers key information for new strategies in cancer treatment and provides reference for the medicinal development of hemp."
https://www.sciencedirect.com/science/article/abs/pii/S0367326X24002752?via%3Dihub [3225]

Murata et al showed the heart "defends itself" against THC through the process of macropinocytosis, stating in 2021:

"Macropinocytosis is a type of clathrin-independent endocytosis in which extracellular fluids, including nutrients, antigens, and small water-soluble molecules, are taken up nonspecifically. Macropinocytosis begins with protrusion of the plasma membrane through the polymerization of actin, followed by the engulfment of extracellular fluids via closure of the membrane protrusions at their distal margins. Then, the luminal space of macropinosomes is delivered to the lysosome to digest their contents. Although excessive macropinocytosis sometimes results in massive cytoplasmic vacuolization and resultant catastrophic cell death, referred to as methuosis, macropinocytosis ordinarily participates in cellular homeostasis, especially for tumor cell survival as a nutrients-acquiring cellular strategy. In accordance with its role in nutrient acquisition, macropinocytosis is facilitated by AMPK, which is activated during nutrient deficiency. To the best of our knowledge, macropinocytosis has not been a topic in the context of Δ9-THC cytotoxicity, in contrast to ER stress, which has been repeatedly reported in Δ9-THC-treated cells."

Their highlights:

"Δ9-THC induced ER stress in HL-1 murine cardiomyocyte.
Δ9-THC also induced macropinocytosis, which was mediated by AMPK.
AMPK-macropinocytosis axis was one of the survival pathways against Δ9-THC." [1679]

In "Role of Terpenophenolics in Modulating Inflammation and Apoptosis in Cardiovascular Diseases: A Review" (2023) Ghani et al observe that:

"One in every three deaths worldwide is caused by cardiovascular diseases (CVDs), estimating a total of 17.9 million deaths annually. By 2030, it is expected that more than 24 million people will die from CVDs related complications. The most common CVDs are coronary heart disease, myocardial infarction, stroke, and hypertension. A plethora of studies has shown inflammation causing both short-term and long-term damage to the tissues in many organ systems, including the cardiovascular system. In parallel to inflammation processes, it has been discovered that apoptosis, a mode of programmed cell death, may also contribute to CVD development due to the loss of cardiomyocytes. Terpenophenolic compounds are comprised of terpenes and natural phenols as secondary metabolites by plants and are commonly found in the genus Humulus and Cannabis. A growing body of evidence has shown that terpenophenolic compounds exhibit protective properties against inflammation and apoptosis within the cardiovascular system. This review highlights the current evidence elucidating the molecular actions of terpenophenolic compounds in protecting the cardiovascular system, i.e., bakuchiol, ferruginol, carnosic acid, carnosol, carvacrol, thymol and hinokitiol. The potential of these compounds is discussed as the new nutraceutical drugs that may help to decrease the burden of cardiovascular disorders."

On nomenclature they note:

"Aromatherapy makes use of terpenes as a constituent due to the distinctive smell they offer. In the world of aromatherapy, terpene is called terpenoids due to the presence of oxygen molecules in their molecular structure. Although terpenoids is not a chemical term, they can be used to differentiate between terpene molecules that consist of oxygen or not."

Their Table 3 provides a summary of cardioprotective effects exerted by terpenophenolic compounds published between 2017 and 2022.
https://www.mdpi.com/1422-0067/24/6/5339/pdf?version=1678447195 [2765]

Terpenes were found to have anxiolytic effects in zebrafish. Johnson et al examined beta-caryophyllene and terpinolene:

"The major therapeutic constituents in cannabis, THC and CBD, are known for their action at CB1 and CB2 receptors. THC primarily acts on presynaptic CB1 receptors which mediate an inhibitory effect on neurotransmitter release. This can create a cascading effect on neuronal activity, including an increase in transmitter release from surrounding acetylcholinergic, glutamatergic, and dopaminergic neurons. This mechanism is thought to underly the therapeutic properties of cannabis. Recent studies exploring the effects of the terpene compounds produced in the Cannabis sativa plant, such as, limonene, myrcene, pinene and β-caryophyllene (BCP), have demonstrated anxiolytic and sedative properties similar to THC and CBD. Taken together, terpene compounds targeting CB1 and CB2 receptors may have important implications for medicinal and therapeutic uses and require further investigation."
https://www.sciencedirect.com/science/article/pii/S0753332223015585?via%3Dihub [4025]

For those who would rather die than get high,

"Administration of CBD reduced average 24 h mean, systolic, and diastolic BP after 2.5 weeks (−3.22±0.90  mmHg [95% confidence interval −1.01 to −5.44 mmHg], −4.76±1.24 mmHg [−1.72 to −7.80 mmHg], and −2.25±0.80 mmHg [−0.30 to −6.01 mmHg], respectively (all p<0.05); however, these values largely remained stable following the uptitration of CBD dosing. There were no changes in liver enzymes or serious adverse events (AEs). There was no significant difference in pulse wave velocity (group×factor interaction: F=1.50, p=0.226) at different time points, regardless of the intervention arm."

"Chronic Effects of Oral Cannabidiol Delivery on 24-h Ambulatory Blood Pressure in Patients with Hypertension (HYPER-H21-4): A Randomized, Placebo-Controlled, and Crossover Study" by Dujic et al (2023) concluded from its study of 70 patients sponsored by Lexaria Bioscience Corp:

"...chronic administration of CBD reduces ambulatory BP in those with untreated and treated hypertension. In addition, lack of serious AEs implies safety and tolerability of the above-noted CBD formulation.
https://lexariabioscience.com/wp-content/uploads/2023/06/Cannabis-and-Cannabinoid-Research-Chronic-Effects-of-Oral-Cannabidiol-Delivery-on-24-h-Ambulatory-Bl.pdf [4014]

Researching neuropathic pain, Borgonetti et al (2023) found that, compared to terpene-free preparations, non-psychotropic cannabis oils with a high terpene content

"...reduced microglia pro-inflammatory phenotype through the downregulation of histone deacetylase 1 (HDAC-1) and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IKBα) and increased interleukin-10 (IL-10) expression..."
https://www.hindawi.com/journals/omcl/2020/3732718/ [2766]

Hinz and Ramer (2022), reporting on the current status of cannabinoids as anticancer drugs, report downregulation of monoglyceride lipase (MAGL or MGLL), induction of dual specificity phosphatase 1 (DUSP1), upregulated ataxia telangiectasia mutated (ATM) gene and p21 protein expression and downregulation of p53 protein expression, which subsequently resulted in decreased levels of CDK2 and CCNE and cell cycle arrest in the G0/G1 phase."

And, they said,

"β-caryophyllene showed antiproliferative and proapoptotic properties on various cancer cell lines and enhanced the cytostatic effects of classical chemotherapeutic agents such as doxorubicin and sorafenib."
https://www.nature.com/articles/s41416-022-01727-4 [2753]

In "Cannabinol inhibits cell growth and triggers cell cycle arrest and apoptosis in cancer cells" by Zhong et al at the University of Lethbridge in Alberta declared cannabiniol found that:

"Cannabinol (CBN) is a weak-psychoactive cannabinoid.

CBN reduces the proliferation of several cancer cell lines.

CBN modulates the expression of cannabinoid receptors.

CBN alters ERK1/2 and AKT pathways in cancer cells.

CBN causes apoptosis through downregulation of p21 and p27."

and

"In this report, we characterized the anti-tumor effects of CBN on the glioma A172, liver cancer HepG2 and breast cancer HCC1806 cell lines. We found that CBN reduces the proliferation of the analyzed cancer cells and modulates the level of cannabinoid receptors, including GPR18, CB2 and GPR55. Furthermore, CBN inhibits the ERK1/2 pathway in A172 and HepG2 cells, while suppressing the AKT pathway in HCC1086 cells. Moreover, CBN may cause apoptosis through downregulation of p21 and p27 as well as a cell cycle arrest at G1 or S-phase via decreasing the CDK1, CDK2, and cyclin E1 levels. Taken together, these results offer new insights into the anti-cancer properties of CBN."
https://www.sciencedirect.com/science/article/abs/pii/S1878818123000282 [4472]

In their 2022 paper "Cannabinol inhibits oxytosis/ferroptosis by directly targeting mitochondria independently of cannabinoid receptors" Salk Institute researchers

"...found that cannabinol protects neurons from oxidative stress and cell death, two of the major contributors to Alzheimer's, says senior author Pamela Maher....'This discovery could one day lead to the development of new therapeutics for treating this disease and other neurodegenerative disorders, like Parkinson's disease.'"

One day. What use is this "one day"? Why are they pretending we don't have it already?

Remember that.

According to the authors,

"The oxytosis/ferroptosis regulated cell death pathway recapitulates many features of mitochondrial dysfunction associated with the aging brain and has emerged as a potential key mediator of neurodegeneration."

and

"Here, we demonstrate that not only does CBN protect nerve cells from oxytosis/ferroptosis in a manner that is dependent on mitochondria and it does so independently of cannabinoid receptors. Specifically, CBN directly targets mitochondria and preserves key mitochondrial functions including redox regulation, calcium uptake, membrane potential, bioenergetics, biogenesis, and modulation of fusion/fission dynamics that are disrupted following induction of oxytosis/ferroptosis."
https://www.researchgate.net/profile/Zhibin-Liang-10/publication/357646567_Cannabinol_inhibits_oxytosisferroptosis_by_directly_targeting_mitochondria_independently_of_cannabinoid_receptors/links/63f916650cf1030a564baf75/Cannabinol-inhibits-oxytosis-ferroptosis-by-directly-targeting-mitochondria-independently-of-cannabinoid-receptors.pdf [876]
https://www.salk.edu/news-release/active-ingredient-in-cannabis-protects-aging-brain-cells/ [877]

We may pause to note that

"Ferroptosis is an intracellular iron-dependent form of cell death that is distinct from apoptosis, necrosis, and autophagy. Extensive studies suggest that ferroptosis plays a pivotal role in tumor suppression, thus providing new opportunities for cancer therapy."

And with that final sentence the Defence profoundly disagrees in two important respects. One is the assumption that you have to get cancer first then fix it. The second that these opportunities for cancer prevention are or have to be new.

"Since the GPX4-centered [glutathione peroxidase 4] mechanisms of ferroptosis were established in 2014, an increasing number of studies have been conducted to identify novel mechanisms governing ferroptosis. GPX4-independent pathways also have been identified. These studies have offered a powerful theoretical framework for initiating the process of ferroptosis, which is briefly divided into the following pathways: the canonical GPX4-regulated pathway, iron metabolism pathway and lipid metabolism pathway."
https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01530-y [2703]

"'Mitochondrial dysfunction is implicated in changes in various tissues, not just in the brain and aging, so the fact that this compound is able to maintain mitochondrial function suggests it could have more benefits beyond the context of Alzheimer’s disease,' [senior author Pamela] Maher said." [872]
In "Cannabidiol induces ERK activation and ROS production to promote autophagy and ferroptosis in glioblastoma cells" Kim et al (2024) explain:

"Small molecule-driven ERK activation is known to induce autophagy and ferroptosis in cancer cells. Herein the effect of cannabidiol (CBD), a phytochemical derived from Cannabis sativa, on ERK-driven autophagy and ferroptosis has been demonstrated in glioblastoma (GBM) cells (U87 and U373 cells). CBD imparted significant cytotoxicity in GBM cells, induced activation of ERK (not JNK and p38), and increased intracellular reactive oxygen species (ROS) levels. It increased the autophagy-related proteins such as LC3 II, Atg7, and Beclin-1 and modulated the expression of ferroptosis-related proteins such as glutathione peroxidase 4 (GPX4), SLC7A11, and TFRC. CBD significantly elevated the endoplasmic reticulum stress, ROS, and iron load, and decreased GSH levels. Inhibitors of autophagy (3-MA) and ferroptosis (Fer-1) had a marginal effect on CBD-induced autophagy/ferroptosis. Treatment with N-acetyl-cysteine (antioxidant) or PD98059 (ERK inhibitor) partly reverted the CBD-induced autophagy/ferroptosis by decreasing the activation of ERK and the production of ROS. Overall, CBD induced autophagy and ferroptosis through the activation of ERK and generation of ROS in GBM cells."
https://www.sciencedirect.com/science/article/abs/pii/S0009279724001418?via%3Dihub [3848]

Will more or less ferroptosis due to cannabis legalisation reduce or increase the incidence of cancer in Slovenia?

Ferroptosis was first identified in 2003 and named in 2012.



According to Brent Stockwell in "Ferroptosis turns 10: Emerging Mechanisms, Physiological Functions, and Therapeutic Applications" (2023):

"PUFAs have been known since their discovery to be highly susceptible to peroxidation due to the presence of exceptionally weak C-H bonds in between adjacent C=C double bonds, and initially it seemed plausible that free PUFAs could be drivers of ferroptosis. However, in 2015–2017, several papers demonstrated that free fatty acids are not drivers of ferroptosis, but rather that polyunsaturated fatty acids (PUFAs) need to be activated and incorporated into membrane lipids, such as phospholipids, in in order to exert their lethal effects upon peroxidation. Identification of the specific lipids that drive the execution of cell death, as well as the enzymes that promote their generation and incorporation into cell membranes has been one of the important discoveries in the last decade of ferroptosis research."

Among the therapeutic applications, iron-overload diseases, e.g. in brain trauma, Sedaghatian-type spondylometaphyseal dysplasia (SSMD), a rare disease in newborns, organ injury, retinal degeneration, and neurodegeneration:

"...ferroptosis inhibition may be a viable strategy to prevent multi-organ injury in the critical care setting."

Plus:

"...hepatitis C viral replication is restricted by activation of ferroptosis in the host cell, and specifically under the control of Fatty Acid Desaturase 2 (FADS2)

and

"SARS-CoV-2 may activate ferroptosis during infection. Patients with COVID-19 have high serum ferritin levels, suggesting high iron exposure in tissues. SARS-Cov-2 infection of Syrian Golden Hamsters causes features of COVID-19 in humans, such as acute lung injury, inflammation and hypoxemia. In this model, lipid changes typical of ferroptosis, as well as induction of the ferroptosis marker TfR1 were reported (Bednash et al., 2021). In this hamster model, it isn’t clear if ferroptosis contributes to restricting infection, as in the HCV model, or contributes to inflammation, or is a byproduct of infection without significant consequence (Figure 3)."

and

"Autoimmune diseases
Activation of ferroptosis has been detected in models of autoimmune disorders. Systemic lupus erythematosus (SLE) is such an autoimmune disease that was linked in 2021 to ferroptosis activation in neutrophils (Li et al., 2021)."

and

"...ferroptosis in human airway epithelial cells driven by 15-lipoxygenase was reported to be associated with the release of mitochondrial DNA and consequent worsening of asthma (Nagasaki et al., 2022). Asthma, which involves overactivation of immune responses, thus may be triggered or worsened by ferroptosis in airway epithelial cells that releases immunogenic mitochondria DNA."

and

"Tumorigenesis
While ferroptosis is reported to function as a tumor-suppression mechanisms, loss of ferroptosis can drive tumorigenesis."

and

"Response to environmental heat stress
With ongoing climate change driving elevated global temperatures, heat stress is likely to become an increasingly common agricultural problem. Heat stress has been shown to induce ferroptosis in numerous organisms, including the plant Arabidopsis thaliana (Distefano et al., 2017) and in the photosynthetic cyanobacteria Synechocystis sp. PCC 6803 (Aguilera et al., 2022)."
https://pmc.ncbi.nlm.nih.gov/articles/PMC9273022/ [3849]

Clearly the effect of cannabis upon ferroptosis was not considered by General Smuts. Nor was it discussed by the League of Nations' plenipotentiaries during the Opium Convention with cannabis tacked on at the last minute. Nor by the signatories of the SCND, and nor by the authors of Yugoslavia or Slovenia's anti-drug laws.

Even had a positive discovery been made in time for the ZPPPD authors, it would not have been on the agenda as the whole point was to pass a law saying there were no medical uses, and therefore (being sarcastic) no positive effects. Any positive effects the authors did know about would have been suppressed.

Anyone brave enough to swim against the dogma would have been marginalised. With the relevance of cannabis use to ferroptosis, as with all the discoveries relating to the Benedictions, the Courts were invited to hope for the best.

Since the ZPPPD and laws like it are a kind of guess or gamble, what are the odds of winning? The odds of no cannabis being better than cannabis, at the population level, are 2 to the power of n, where n is the number of applicable conditions in which the outcome is either better or worse. The odds of no cannabis being better for six outcomes is 1 in 64, and for ten it is 1 in 1024.

Clearly ferroptosis does not begin when we first hear of its existence, nor when we get a test from the doctor, but before birth. Indeed

"...inhibiting ferroptosis might be a potential option to treat pregnancy related diseases."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031498/ [2704]

Mitochondria metabolic activity is lower in human than in mouse developing neurons, "Mitochondria metabolism sets the species-specific tempo of neuronal development" by Iwata et al announced in 2023:

"Neuronal development in the human cerebral cortex is considerably prolonged compared with that of other mammals. We explored whether mitochondria influence the species-specific timing of cortical neuron maturation. By comparing human and mouse cortical neuronal maturation at high temporal and cell resolution, we found a slower mitochondria development in human cortical neurons compared with that in the mouse, together with lower mitochondria metabolic activity, particularly that of oxidative phosphorylation. Stimulation of mitochondria metabolism in human neurons resulted in accelerated development in vitro and in vivo, leading to maturation of cells weeks ahead of time, whereas its inhibition in mouse neurons led to decreased rates of maturation. Mitochondria are thus important regulators of the pace of neuronal development underlying human-specific brain neoteny."
https://www.science.org/doi/10.1126/science.abn4705?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed [4689]

So it sounds like more ferroptosis can be good or bad, depending on the circumstances. The Salk team immediately set about trying to improve on CBN with patentable analogues - which they did:

"As shown in Fig. 1 , the structure of cannabinoids (CBN, CBD, and THC) can be divided into three substructures: a monoterpenoid fragment (left unit, LU), a phenol fragment (central unit, CU), and an aliphatic chain fragment (right unit, RU). To determine the most active and viable substructure(s) responsible for their neuroprotective effects, we first assayed the fragment compounds for the inhibition of oxytosis/ferroptosis using two different cytotoxic insults (i.e., glutamate and RSL3). Compounds were tested at three different concentrations (1, 10, 50 μM) in order to cover weak to moderate bioactivities of the fragments. CBN, CBD and THC were used as reference compounds.

"As summarized in Table 1 , for the left unit (LU) that represents cannabinoid-relevant monoterpenoids, none of them at concentrations ranging from 1 to 50 μM showed any neuroprotective activity in our assays. For the right unit (RU), different linear or branched aliphatic hydrocarbon chains (carbon numbers: C4–C9) were examined. As expected, these simple, water insoluble alkanes also showed no protective effects in our cell-based assays. Together, these results suggest that, by themselves, neither the LU nor the RU fragment of CBN, CBD or THC is a viable pharmacophore.

"For the central unit (CU) in which the benzene ring is substituted with different numbers and positions of free hydroxyl (-OH) groups, we found that in general these simple mono- (i.e., phenol), di- (i.e., resorcinol, catechol, or hydroquinone) and tri- (i.e., phloroglucinol, pyrogallol, or hydroxyquinol) hydroxy phenols at concentrations ranging from 1 to 50 μM showed limited neuroprotective activity against oxytosis/ferroptosis. The exceptions were the diphenols catechol (1,2-dihydroxybenzene) and hydroquinone (1,4-dihydroxybenzene) which both showed weak neuroprotective activities only at higher concentrations (10–50 μM). Nevertheless, the data suggest that the CU fragment containing functional antioxidant groups such as aromatic hydroxyls on the phytocannabinoids are the potential key pharmacophore required for neuroprotection in our cell-based assays."
https://www.sciencedirect.com/science/article/pii/S2213231724001149?via%3Dihub [3574]

They were able to produce analogues with greater water solubility, claiming these were "more druglike" than the original CBN. However, as can be seen in their Table 3, the half maximal effective concentration (EC50) of the analogues against amyloid is at least twice that of CBN in the case of CP1 ranging up to 114 times weaker in the case of CP4. The EC50 might mislead some readers:

"While expressing the potency of a compound by its EC50 value makes sense in a clinical context, it is counterintuitive in the context of bioactivity-guided purification, as the potency of a compound is inversely related to its EC50 value, and the most potent compound is the one with the lowest EC50. In natural products chemistry, it would be more logical if an increase in potency would be reflected by an increase of a parameter reflecting the potency. In this study, we introduce the term 'effective dilution volume (EDV50)' as the reciprocal of the EC50 (1/EC50)."
https://pubmed.ncbi.nlm.nih.gov/32330577/ [3576]

Therefore the Defence does not take the claim of "druglikeness" too seriously, especially as the whole enterprise has its back turned upon THC as a neuroprotectant, for reasons of Rather Die Than Get High (RDTGH), an outgrowth of legal dogmaticism.

The ultra-reductive and anti-nature researchers are not considering entourage effects at all. Should those in need of neuroprotection (everyone) wait for the patent to be discovered before we adopt a natural use of phytocannabinoid CBN?

More interesting to the Defence is whether neuroprotection with CBN should have been forbidden since 1925, seven years before its structure was identified, and how much neuroprotection has been unnecessarily prevented by the achievements of Smuts, Murphy, Anslinger, Ryley Cooper, Nixon et al since that original prohibition took effect on the present territory on 1 January 1930?

Of course many broke the anti-neuroprotection laws, and it is clear from these discoveries among the other Benedictions - that their punishments should be undone.

From a legal perspective, increasing ferroptosis in brain injury or in anyone who might be prone to neurodegeneration seems indefensible. That could be anyone. Not allowing someone to decrease it is indefensible too. Yet this is what is proposed by the ZPPPD.

Here we begin to see the general inapplicability of the law to particular medical outcomes. There is no one-size-fits-all solution.

Remember, the default condition is we know nothing. Before we go down any of these pathways or even consider what we do or don't know about them, what is it that the opposition to CaPs is saying?

According to the Catholic World Report in 2022:

"The Catechism of the Catholic Church (CCC) reiterates the traditional teaching that drug use is wrong because, like excessive drinking, it deprives one of the use of reason. The official Latin text specifies that it consists in abusing not any medication whatsoever but 'stupefacient medication'" (n. 2291). [not quite sure what this "but" means]

"On the strength of modern medicine, however, the Catechism stresses that taking drugs is wrong on other grounds too. It constitutes a sin against the fifth commandment: 'Thou shalt not kill!'"

This "strength of modern medicine" is typically ambiguous cant. As for loss of reason, we have already observed the troubled and less-than-accurate reasoning of Mr Grims and crowds. CaPs, however, are not modern medicines. CWR continues:

"As an abuse of medicinal substances, it constitutes a sin against temperance. However, it is an intemperate act that goes against the fifth rather than the sixth commandment (CCC, nn. 2288-2291). It does not consist of extra-marital sexual activity. Rather—like the abuse of food, alcoholic beverages, and tobacco—the intemperate abuse of stupefacient medicinal substances harms one’s own health and endangers one’s life directly. Due to their psychoactive effects, it can lead one to harm the health and endanger the life of others too. The Catechism reaches the following conclusion, therefore.

“The use of drugs inflicts very grave damage on human health and life. Their use, except on strictly therapeutic grounds, is a grave offense.” (CCC, n. 2291)

"The first sentence appeals to science. The second sentence is a moral assessment: any use of drugs which does not have a strict therapeutic justification is sinful. It is sinful because it wreaks unnecessary harm upon one’s health. It thereby goes against the fifth commandment. It is a grave sin because, going by medical research, it inflicts grave damage on one’s health.

"For this reason, the Catechism goes further than John Paul II did in 1991. It teaches that any recreational use of drugs is a grave offense. It does so on the strength of medical research, which appears to show that even the occasional or minimal use of any drug is likely to inflict grave harm on your health.

"The Catechism does not accept, therefore, the scientifically unfounded distinction that many people and some countries make between hard and soft drugs. Some drugs are more addictive and harmful than others. This does not mean though they inflict negligible harm, even when only used on the odd occasion."
https://www.catholicworldreport.com/2022/01/19/what-does-the-church-teaching-about-doing-soft-drugs/ [2705]

Here, "science" means "what we - the bishops - think". But science is not a religion.

"Going by medical research" is exactly what the Defence plans to do, in contrast to this religious hijack of science as a cloak for pre-existing prejudice against possibly anti-Christian drugs.

On ferroptosis - and it's just an example - the bishops are silent. They have passed the buck, or at least fifty cents of it, to a divine medical authority which does, after all, provide many of their horizontal customers.

Sadly medics have been kept uninformed about these "bad" drugs - the ones with no medical use like alcohol, chocolate, cannabis, and psilocybin - due to the prevailing dogma into which all later topics - ferroptosis included - have been required to fit. Papers are decorated with warnings of "abuse" and "disorders" and those showing bad drugs are bad for ferroptosis will be preferred for publication. For the majority of the last century, they succeeded in making it too awkward and expensive to research them at all. Stigma alone was enough to stop it. Until it wasn't any more.

Any good news about a particular drug, cannabis, and a process, ferroptosis, was like Mr Grims and the multiple alternative causes of ecclesiastical infernos besides immigrants.

According to this self-serving ecclesiastical view, drugs - pluralised for a conflationary PR effect - are inherently unhealthy BECAUSE their use is breaking the rules. Duh! Now the doctors have got it all wrong. Illness CAN caused by a curse or sin! Anything which makes these rules look stupid or out of date is eschewed in favour of vague semantic concepts: drugs, intoxication, loss of reason, and in the eyes of the church and the law, the otherwise virtuous user's greatest sin is non-dependence on churches and doctors.

And the clincher is "science", in the very wrong sense described above.

This religiosity involves telling the population WHAT TO THINK. Which turns out to be as little as possible.

Original thinking based on personal perceptions, not theological teachings, is condemned.

Which makes their mission to crackdown on CaPs all the more critical.

The vintnering bishops are as reliable in their drug advice as in their sex advice, childcare, and ISP stewardship. Like Mr Grims and the immigrant fires, their "facts" are made up to fit the dogma, and avoid being tested by ongoing empirical evidence.

The problem is not drug users' loss of reason, but that the Church does not understand their reason, and does not want to. Its own reasoning is rather limited, archaic, circular, lost in linguistic and confirmation bias, sunk cost error, argument to authority - many would say a fictional authority - and other fallacies.

What most regard as fun, the church regards as pathological. Everything in its philosophy leads back to the motives and will to power of the churchmen themselves. Having no medical or legal authority, everything they order about drugs, legally, all comes back to the Constitution:



Why do laws die? Change of ruler. Change of perceptions. Modern humans spend less time farming and so the Courts no longer need to determine whether a donkey was previously of good character.

Better informed beliefs replace older ones. The modern internet-equipped individual is better informed and has a wider range of information to choose from.

He or she is less dependent on a particular doctor or a particular medical philosophy than ever in history.

Misinformation and scams exist, both in orthodox medicine, and the alternatives. Drugs may be legal, tested, but harmful. Drugs may be prescription only or not allowed at all. He can buy them anyway [2644].

"Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses" from Walsh et al (2021) reveals:

"Cannabichromene CBC is one of the most abundant minor cannabinoids found in cannabis....CBC may be beneficial in cancer treatment due to its ability to increase blood levels of AEA (see above). AEA has been shown to inhibit breast cancer cell proliferation and induce death of colon cancer cells (De Petrocellis, et al., 1998; Patsos, et al., 2005). CBC was also shown to inhibit cell migration and disrupt the cell cytoskeleton in an in vitro model of urothelial cancer (Anis, et al., 2021). In one study that examined the anti-tumor effects of several minor cannabinoids, only CBG was more potent than CBC at inhibiting the growth of several cancer cell lines (Ligresti, et al., 2006)."

and

"A cannabis fraction containing high amounts of CBGA was reported to have cytotoxic activity against colon cancer cells (Nallathambi, et al., 2018). Interestingly, synergistic toxic effects were observed when CBGA was given with a cannabis fraction high in THCA. These two fractions also prevented the growth and proliferation of adenomatous colon polyps that are colon cancer precursors. When tested at micromolar concentrations, CBGA was also shown to have cytotoxic actions in human leukemia cancer cell lines (Scott, et al., 2013). In further support of cannabinoid synergism, the IC50 for CBGA leukemia cell toxicity was reduced when co-applied with CBD (Scott, et al., 2013; Scott, et al., 2017)."
https://pmc.ncbi.nlm.nih.gov/articles/PMC8669157/ [3635]

According to Vernail et al at the Department of Neural and Behavioral Sciences, Penn State College of Medicine (2022), "Acute CBG Lowers Blood Pressure, but Does Not Alter Heart Rate or Locomotor Activity":

"Acute CBG administration elicited a significant decrease in mean blood pressure compared with vehicle (Figure 1A). There was no apparent dose responsiveness for the CBG doses used in this study (Figure 1B; Δ from baseline: −22 ± 2 at 3.3 mg/kg versus −28 ± 2 mmHg at 10 mg/kg). On average, the peak decrease in mean blood pressure elicited by CBG was observed at 90-min post-administration, with no difference between doses (Figure 1C). CBG also significantly lowered systolic and diastolic blood pressure compared with vehicle (Table 1), again with no dose responsiveness. There were no differences in heart rate responses following CBG versus vehicle administration (Table 1). There were also no differences in locomotor activity over the study period across treatment groups (Figure 1D)."


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124753 [4697]

Moreover, and leaning heavily on the idea that CBG must be good medicine because it doesn't get you high, Vernail et al showed the same year that "Acute CBG Lowers Blood Pressure via an α2AR Mechanism":

"While cannabigerol can bind to classical cannabinoid receptors, it is also an agonist at α2- adrenoreceptors (α2AR) which, when activated, inhibit presynaptic norepinephrine release. This raises the possibility that cannabigerol could activate α2AR to reduce norepinephrine release to cardiovascular end organs to lower blood pressure. Despite this possibility, there are no reports examining cannabigerol cardiovascular effects. In this study, we tested the hypothesis that acute cannabigerol administration lowers blood pressure. Blood pressure was assessed via radiotelemetry at baseline and following intraperitoneal injection of cannabigerol (3.3 and 10 mg/kg) or vehicle administered in a randomized crossover design in male C57BL/6J mice. Acute cannabigerol significantly lowered mean blood pressure (−28 ± 2 mmHg with 10 mg/kg versus −12 ± 5 mmHg vehicle, respectively; p = 0.018), with no apparent dose responsiveness (−22 ± 2 mmHg with 3.3 mg/kg). The depressor effect of cannabigerol was lower in magnitude than the α2AR agonist guanfacine and was prevented by pretreatment with the α2AR antagonist atipamezole. These findings suggest that acute cannabigerol lowers blood pressure in phenotypically normal mice likely via an α2AR mechanism, which may be an important consideration for therapeutic cannabigerol administration."
https://www.frontiersin.org/articles/10.3389/fphys.2022.871962/pdf[1816]

"We hypothesized that CBG would not impair memory, but our finding that CBG significantly enhanced verbal memory was unexpected," say Cuttler et al in "Acute effects of cannabigerol on anxiety, stress, and mood: a double-blind, placebo-controlled, crossover, field trial" (2024):

"CBG received little research interest initially, due in part to the overwhelming focus on the effects of THC and CBD. Subsequent pre-clinical investigations involving the administration of CBG to animals, however, have demonstrated a broad spectrum of potential therapeutic effects including potent antibiotic and antifungal activity. CBG also appears to have anti-hypertensive effects, it reduces intra-ocular pressure and keratinocytes in a psoriasis model, it has possible efficacy in inflammatory bowel disease and it may have analgesic effects. Moreover, CBG has been demonstrated to have antidepressant-like effects in a rodent tail suspension model while lacking cannabimimetic effects indictive of THC."
https://www.nature.com/articles/s41598-024-66879-0 [3310]

"THCA was recently shown to possess potent anti-inflammatory activity in mice fed a high fat diet (HFD) (Palomares, et al., 2020; Carmona-Hidalgo, et al., 2021). THCA treatment reduced the expression of inflammatory molecules including tumor necrosis factor alpha (TNF-α) and cytokine interleukin 10 (IL-10) in the HFD mice. This effect was mediated via PPARγ stimulation (Palomares, et al., 2020). THCA also improved glucose tolerance and attenuated liver fibrosis in the HFD mice (Carmona-Hidalgo, et al., 2021). Using an in vitro COX-1/COX-2 assay it was determined that Δ9-THCA inhibits both COX-1 and COX-2 enzymes with a concentration causing 50% inhibition (IC50) in the high micromolar range (Ruhaak, et al., 2011)."

Tenascins are a family of large glycoproteins present in cellular matrix, overexpressed in tumors compared to healthy tissues, and

"...tenascin-C inhibits the spreading of fibroblasts by blocking the interaction of fibronectin with cellular syndecan-4 (Huang et al., 2001), a mechanism that indirectly inhibits full activation of integrin α5β1 and the RhoA/ROCK pathway (Midwood and Schwarzbauer, 2002). Presumably as a consequence of this 'anti-adhesive' (or rather anti-spreading) activity, tenascin-C negatively affects the growth of normal fibroblasts (Orend et al., 2003), but stimulates proliferation and migration of cancer cells (Ruiz et al., 2004, Orend, 2005). On the other hand, tenascin-C appears to be a bona fide cell adhesion protein for lymphoid and certain other cell types, mediating direct interactions with cellular integrin α9β1 (Schreiber et al., 2009, Ellis et al., 2013). Such a Janus-like activity can have paradoxical effects. As a substrate for embryonic sensory ganglion explants, for example, tenascin-C promotes neurite growth but at the same time inhibits glial cell migration (Wehrle-Haller and Chiquet, 1993). Similar bimodal activities have been ascribed to tenascin-R and tenascin-W (Chiquet-Ehrismann and Tucker, 2011)."
https://www.sciencedirect.com/science/article/pii/S0945053X14000080 [1552]

Carmona-Hildago et al explain the role of tenascin C and alanine transaminase in THCA anti-fibrogenic activity:

"CCl4-induced fibrosis also increased the protein level of tenascin C (TNC), an early fibrotic marker in liver (Kasprzycka, Hammarström, and Haraldsen 2015), compared to control mice. Treatment with 20 and 40 mg/kg of Δ9 -THCA significantly reduced liver TNC-stained area 44% and 57%, respectively, compared to CCl4-vehicle mice (Figure 1C). CCl4-induced fibrosis led to a 2.3-fold increase in ALT activity compared to control mice. High dose of Δ9 -THCA induced a significant 1.3-fold reduction of ALT activity compared to CCl4-vehicle mice (Supplementary figure 2). Altogether our results showed that Δ9 -THCA was able to prevent fibrogenesis in the liver."

Tenascins are shown in part D of Figure 2


"Δ9-THCA significantly attenuated CCl4-induced liver fibrosis and inflammation and reduced T cell and macrophage infiltration. Mice fed HFD for 23 weeks developed severe obesity (DIO), fatty liver and marked liver fibrosis, accompanied by immune cell infiltration. Δ9-THCA, significantly reduced body weight and adiposity, improved glucose tolerance, and drastically attenuated DIO-induced liver fibrosis and immune cell infiltration. Conclusions: Δ9-THCA prevents liver fibrogenesis in vivo, providing a rationale for additional studies on the medicinal use of this cannabinoid, as well as cannabis preparations containing it, in the treatment of liver fibrosis and the management of NAFLD [non-alcoholic fatty liver disease]."
https://www.biorxiv.org/content/10.1101/2020.05.11.088070v1.full.pdf [1551]

"CBDV has been investigated as a treatment for symptoms associated with autism spectrum disorder (ASD) such as repetitive behaviors, cognitive challenges and issues with communication and social functioning (Mouro, et al., 2019). Mice carrying mutations in the MeCP2 gene and MeCP2 null mice develop Rett Syndrome (RTT), a neurodevelopment disease related to ASD. CBDV treatment (2 mg/kg) was found to rescue both behavioral and phenotypic changes in the RTT mice model (Vigli, et al., 2018)....Similar behavioral improvements were reported using CBDV in a valproic acid-induced model of ASD."

"THCV regulates blood glucose levels suggesting it might be useful in weight reduction and treating diabetes. In mice with dietary-induced obesity (DIO), THCV improved fasting plasma glucose and glucose tolerance in a dose-dependent manner."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669157/ [854]

In mice, they found that THC, THCA, and THCV—but not CBD—reduced pain, while THC, CBD, THCA, THCV, and CBG all had a positive impact on anxiety. The authors concluded THCA and THCV, which bound both CB1 and CB2, may be able to reduce pain, inflammation, and anxiety when either is used in the absence of other cannabinoids. This finding is significant since there is a growing interest in the clinical applications of single-cannabinoid preparations.
https://www.nature.com/articles/s41598-020-77175-y [511]

As mentioned in [854], at the same time a 14-strong team in Cordoba, Spain, was coming to similar conclusions, beginning with an anti-fun value judgement, namely:

"Medicinal cannabis has remarkable therapeutic potential, but its clinical use is limited by the psychotropic activity of Δ9-tetrahydrocannabinol (Δ9-THC)."

The Defence disagrees with this value judgement, which resembles the a priori of the bishops. Unlike the misery required of the pious, the Defendant is quite content to be happy whilst also not getting fat. Palomares et al continue:

"However, the biological profile of the carboxylated, non-narcotic native precursor of Δ9-THC, the Δ9-THC acid A (Δ9-THCA-A), remains largely unexplored. Here we present evidence that Δ9-THCA-A is a partial and selective PPARγ modulator, endowed with lower adipogenic activity than the full PPARγ agonist rosiglitazone (RGZ) and enhanced osteoblastogenic effects in hMSC. Docking and in vitro functional assays indicated that Δ9-THCA-A binds to and activates PPARγ by acting at both the canonical and the alternative sites of the ligand-binding domain. Transcriptomic signatures in iWAT from mice treated with Δ9-THCA-A confirmed its mode of action through PPARγ. Administration of Δ9-THCA-A in a mouse model of HFD-induced obesity significantly reduced fat mass and body weight gain, markedly ameliorating glucose intolerance and insulin resistance, and largely preventing liver steatosis, adipogenesis and macrophage infiltration in fat tissues. Additionally, immunohistochemistry, transcriptomic, and plasma biomarker analyses showed that treatment with Δ9-THCA-A caused browning of iWAT and displayed potent anti-inflammatory actions in HFD mice. Our data validate the potential of Δ9-THCA-A as a low adipogenic PPARγ agonist, capable of substantially improving the symptoms of obesity-associated metabolic syndrome and inflammation."
https://pubmed.ncbi.nlm.nih.gov/31706843/ [922]

Also in Cordoba, Hildago et al an overlapping team with that of [922] found that:

"Δ9-THCA prevents TGFβ-induced fibrotic markers in vitro and liver inflammation and fibrogenesis in vivo, providing a rationale for additional studies on the medicinal use of this cannabinoid, as well as cannabis preparations containing it, for the treatment of liver fibrosis and the management of NAFLD."
https://pubmed.ncbi.nlm.nih.gov/33341026/ [923]

Still in Cordoba, Nadal et al had also concluded, in "Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity" in 2017 in which

"The in vivo neuroprotective activity of Δ9-THCA was investigated in mice intoxicated with the mitochondrial toxin 3-nitropropionic acid (3-NPA)."

that

"Cannabinoid acids bind and activate PPARγ with higher potency than their decarboxylated products. Δ9-THCA increased mitochondrial mass in neuroblastoma N2a cells and prevented cytotoxicity induced by serum deprivation in STHdh Q111/Q111 cells and by mutHtt-q94 in N2a cells. Δ9-THCA, through a PPARγ-dependent pathway, was neuroprotective in mice treated with 3-NPA, improving motor deficits and preventing striatal degeneration. In addition, Δ9-THCA attenuated microgliosis, astrogliosis and up‐regulation of proinflammatory markers induced by 3-NPA."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731255/ [1543]

In the context of astrogliosis and microgliosis, we note in passing that:

"Matschke et al. reported astrogliosis in 86% of individuals who died following a diagnosis of SARS-CoV-2 infection. In agreement, snRNA-seq data show that the main markers of reactive astrocytes are enriched in samples from the medial frontal cortex of patients with COVID-19 compared with noninfected patients, supporting the hypothesis that reactive astrogliosis is a feature of COVID-19 (SI Appendix, Fig. S11). Astrocytes are also relevant in the regulation of synapses (and neural networks) and have been linked to the manifestation of depression, anxiety symptoms, and memory impairment, all of which have been observed in our post-COVID infection cohort."
https://www.pnas.org/doi/10.1073/pnas.2200960119 [4550]

Much more on Covid and cannabinoids to come, in which we shall see how the Ptuj Police tried to make the pandemic worse. To top it off, Palomares and team add that:

"Δ9-THCA-A alleviated collagen-induced arthritis in mice, through CB1 receptor and PPARγ pathways."
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC5731255/ [1071]

As investigation of PPAR-cannabinoid interactions reached its teenage years, Advances in Pharamacology reported:

"All PPAR isoforms appear to be activated by cannabinoids, but the majority of evidence is for PPARα and γ. To date, little is known about the potential interaction of cannabinoids with other nuclear hormones. At least some (but not all) of the well-known biological actions of cannabinoids including neuroprotection, antiinflammatory action, and analgesic effects are partly mediated by PPAR-activation, often in combination with activation of the more traditional target sites of action. This has been best investigated for the endocannabinoid-like compounds palmitoylethanolamide and oleoylethanolamine acting at PPARα, and for phytocannabinoids or their derivatives activation acting at PPARγ. However, there are still many aspects of cannabinoid activation of PPAR and the role it plays in the biological and therapeutic effects of cannabinoids that remain to be investigated."
https://www.sciencedirect.com/science/article/abs/pii/S1054358917300364 [936]

In mitophagy, "PPARγ is an E3 ligase that induces the degradation of NFκB/p65" say Hou et al (2012).

"Lys28 is required for PPARγ-mediated p65 degradation."
https://www.nature.com/articles/ncomms2270 [4693]

In section 6.3 of the 2021 review of "The Role of Phytoconstituents as PPAR Agonists: Implications for Neurodegenerative Disorders", Gachon University researchers summarise some investigations of the cannabinoids Δ9-THC, ∆9-THCA, CBDA, CBG and CBGA, on PPARγ and other markers with implications for neuroinflammation, Huntington's Disease, Alzheimer's Disease, Parkinson's Disease, ischemia and multiple sclerosis in their Table 3:

"In a human cell culture model of PD (SH-SY5Y), delta-9-tetrahydrocannabinol (Δ9-THC) was found to have PPARγ-mediated neuroprotective properties. In SH-SY5Y cells, Δ9-THC alleviated 1-methyl-4-phenylpyridinium iodide (MPP+), MPP+-driven cell death, reduced cleaved caspase 3 and ROS levels, and promoted PPARγ expression (Table 3). PPAR antagonist (T0070907) was reported to disrupt Δ9-THC neuroprotective, antioxidant, and apoptotic effects. These effects were not inhibited by CB1 receptor blockade. The study suggested that activation of PPARγ leads to antioxidant mediating neuroprotective effects of Δ9-THC. Similarly, Zeissler et al. revealed that Δ9-THC had therapeutic effects on MPP+-driven SH-SY5Y cells by restoring mitochondrial biogenesis proteins in a PPAR-dependent manner. It was found to prevent cell death and induce PPARγ, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), mitochondrial transcription factor (TFAM), and mitochondrial DNA (Table 3). The authors also described that in comparison to pioglitazone, Δ9-THC provides neuroprotection through PPARγ-dependent renewal of mitochondrial content, which may be useful in treating PD."
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8698906/ [1043]

As Zeissler et al [1113] explain:

"...activation of the PPARγ receptor can also regulate the de novo synthesis of mitochondria by inducing the expression of PPARγ coactivator-1α (PGC-1α) as well as the mitochondrial transcription factor A (TFAM), both of which are key regulators of mitochondrial biogenesis."

and some further details:

"Reduction in mitochondrial complex 1 activity is known to be a key feature in sporadic PD and complex 1 inhibitors are therefore widely used as a model for mitochondrial dysfunction in PD. We used MPP+ as a means to model PD-associated mitochondrial dysfunction in differentiated SH-SY5Y cells to further investigate the PPARγ mediated anti-oxidant effect of D9-THC. The suitability of differentiated human dopaminergic SH-SY5Y cells in Parkinson’s disease research is still a subject of debate with some arguing for differentiation, and some against. However, differentiated cells are susceptible to MPP+ and express the required dopamine and noradrenalin transporters for uptake of the neurotoxin. Furthermore, differentiation leads to a reduction in cell proliferation and the induction of a predominantly mature dopaminergic-like neurotransmitter phenotype. We therefore used differentiated SH-SY5Y cells in our study." [1113]

"Cannabidiol and (−)Δ9-tetrahydrocannabinol are neuroprotective antioxidants" declared Hampson et al of the Laboratory of Cellular and Molecular Regulation, National Institutes of Mental Health, Bethesda, MD, back in 1998, i.e. two years prior to the ZPPPD.

"The neuroprotective actions of cannabidiol and other cannabinoids were examined in rat cortical neuron cultures exposed to toxic levels of the excitatory neurotransmitter glutamate. Glutamate toxicity was reduced by both cannabidiol, a nonpsychoactive constituent of marijuana, and the psychotropic cannabinoid (−)Δ9-tetrahydrocannabinol (THC). Cannabinoids protected equally well against neurotoxicity mediated by N-methyl-d-aspartate receptors, 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid receptors, or kainate receptors. N-methyl-d-aspartate receptor-induced toxicity has been shown to be calcium dependent; this study demonstrates that 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid/kainate receptor-type neurotoxicity is also calcium-dependent, partly mediated by voltage sensitive calcium channels. The neuroprotection observed with cannabidiol and THC was unaffected by cannabinoid receptor antagonist, indicating it to be cannabinoid receptor independent. Previous studies have shown that glutamate toxicity may be prevented by antioxidants. Cannabidiol, THC and several synthetic cannabinoids all were demonstrated to be antioxidants by cyclic voltametry. Cannabidiol and THC also were shown to prevent hydroperoxide-induced oxidative damage as well as or better than other antioxidants in a chemical (Fenton reaction) system and neuronal cultures. Cannabidiol was more protective against glutamate neurotoxicity than either ascorbate or α-tocopherol, indicating it to be a potent antioxidant. These data also suggest that the naturally occurring, nonpsychotropic cannabinoid, cannabidiol, may be a potentially useful therapeutic agent for the treatment of oxidative neurological disorders such as cerebral ischemia."

and

"Cells use easily oxidizable compounds such as glutathione, ascorbate, and α-tocopherol as antioxidants that protect important cellular structures (e.g., DNA, proteins, and membranes) from ROS damage. Studies have suggested that ROS damage may be involved in glutamate neurotoxicity. To investigate whether cannabinoids could protect neurons against glutamate by reacting with ROS, the antioxidant properties of cannabidiol and other cannabinoids were assessed. Cyclic voltametry, a procedure that measures the ability of a compound to accept or donate electrons under a variable voltage potential, was used to measure the oxidation potentials of several natural and synthetic cannabinoids. Cannabidiol, THC, and the synthetic cannabinoid HU-211 all donated electrons at a similar potential as the antioxidant BHT. Anandamide (arachidonyl-ethanolamide), which is not a cannabinoid in structure but is an endogenous ligand for the cannabinoid receptor, did not undergo oxidation in this assay (Fig. 4A)."

and

"Unlike cannabidiol, THC is a ligand for the brain cannabinoid receptor, and this action has been proposed to explain the ability of THC to protect neurons from NMDAr toxicity in vitro. However, in AMPA/kainate receptor toxicity assays, THC and cannabidiol were similarly protective, suggesting that cannabinoid neuroprotection may be independent of cannabinoid receptor activation. This was confirmed by inclusion of a cannabinoid receptor antagonist, SR-141716A (Fig. 3). Neither THC or cannabidiol neuroprotection was affected by cannabinoid receptor antagonist."

For sure in 1998 research grant availability suggested we would rather fry (in our own reactive oxygen species) than get high, and so the discussion ultimately leans towards CBD, while the equal or greater contribution of THC was mildly downplayed in this study.
https://www.pnas.org/doi/10.1073/pnas.95.14.8268 [4004]

From the range of spectrophotometric methods available to them, to measure the antioxidant properties of various minor cannabinoids, Dawidowicz et al chose four. An idea of this range of methods can be gleaned from



"According to the literature, CBD and Δ9-THC exhibit strong antioxidant activity, stronger than vitamins C, A and E."

and they say

"The presented data prove that all the examined cannabinoids - CBG, CBD, Δ9-THC, CBN, CBGA CBDA and Δ9-THCA - exhibit antioxidant activity manifesting itself in their ability to scavenge free radicals, to protect oxidation process and to reduce metal ions. Although, the intensity of these activities for individual cannabinoids is not the same, it is generally comparable to that of E vitamin. It should be noticed, however, that the magnitude of the deviation from this approximate and simplified observation depends on the method applied in estimating the antioxidant properties of cannabinoids. Careful consideration of the obtained results leads to the following conclusions:

"1. Two types of electron sources (i.e. antioxidant centers) transferring electrons to the reduced radical/metal ion can be distinguished in CBG, CBD, Δ9-THC, CBN, CBGA CBDA, and Δ9-THCA: phenolic groups and double bonds. Their significance depends on the type of electron-accepting species.

"2. The antioxidant activity of the examined neutral cannabinoids (CBG ,CBD, Δ9-THC and CBN) is higher than that of [antioxidant standard] Trolox when radicals/metal ions are reduced by electron transfer from phenolic groups following the SET mechanism. It is evident from the results obtained by ABTS [2,2'-azino-bis(3-ethylbenz-thiazoline-6-sulfonic acid, see [3094]], CUPRAC [CUPric Reducing Antioxidant Capacity: based on the absorbance measurement of Cu(I)-neocuproine, see [3095]] and FRAP [Ferric Reducing Antioxidant Power: some disadvantages re low pH, see [3096]] and slightly less so by DPPH. [α, α-diphenyl-β-picrylhydrazyl, for developments see [3097] and see [3098] for a discussion of these and other spectrophotometric methods]

"3. The antioxidant activity of neutral cannabinoids is lower than that of Trolox [a water-soluble analog of vitamin E used in biological and biochemical applications to reduce oxidative stress or damage] when the adduct formation mechanism dominates in the radical scavenging process (see the results from beta-carotene assays).

"4. Although the hydrogen bond between the phenolic single bondOH group and the carboxyl group in cannabinoid acids may account for their lower antioxidant activity, it is not necessarily the case. At the presence of basic radicals (see ORAC) or in an environment with pH greater than the pKa of cannabinoid acids (see CUPRAC), their antioxidant activity is equal to or even greater than that of their neutral counterparts.

"5. The analysis of the obtained results shows that in the case of cannabinoids with two hydroxyl groups, only one of them exhibits antioxidant activity when the SET and/or HAT mechanism dominates in the electron transfer process.

"6. The importance of the cannabinoids' double bond in the radical scavenging process– is revealed in the adduct formation mechanism (see beta-carotene, DPPH and ORAC results)."





https://www.sciencedirect.com/science/article/pii/S0367326X21000903[1806]
https://pubmed.ncbi.nlm.nih.gov/27406072/ [3094]
https://www.sciencedirect.com/science/article/abs/pii/S0165993611000173 [3095]
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002788 [3096]
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551182/ [3097]
https://www.mdpi.com/2076-3921/11/11/2213# [3098]

The results of Dawidowicz et al should be placed into the context of the antioxidant equivalents of common foods in terms of Trolox equivalent, from watermelon (1.4), tomato (3.4), broccoli (15.9), macadamia nut (17), and raisins (30.4) up to plums (62.4), pecan (179) and rice bran (242.9). [check that these units are both TE/g and not e.g. TE/100mg]
https://www.biologydiscussion.com/herbal-drugs/antioxidant-history-measurement-and-antioxidant-capacity/25176 [3099]

What, you may ask, of the antioxidant activity of the endocannabinoids? As Scott et al at the University of Missouri, Kansas, explain in "Cannabinoids and endocannabinoids hold promise for use as disease modifiers and therapeutic agents for the prevention or treatment of neurodegenerative diseases and neurological disorders" in the journal Neural Regeneration Research (2024, online 2023).

"Endocannabinoids cannot act as direct antioxidants due to their molecular structure, but phytocannabinoids have a multi-ring structure containing a phenolic group that can act as a direct antioxidant."

Commercial objections pretending to be moral objections pretending to be legal objections pretending to be medical objections will continue to insist that we must not "interfere with nature" by using phytocannabinoids to prevent neurodegenerative and neurological disorders, which is the position the ZPPPD took 23 years before this particular paper appeared. Indeed, such an article could not have been published before the ZPPPD's enactment as:

"The psychotropic and medicinal properties of the plant, Cannabis sativa, have been known to humans for thousands of years....In the last 20 years, however, the medicinal properties of cannabinoids have been the focus of much research and important discoveries have been made."

and

"In recent years, new experimental models are being implemented that circumvent the limitations of single cell and whole animal models. Some of these models include 3-dimensional cell cultures, ex vivo cultures and organotypic explant cultures. Organotypic cultures have been widely used due to the preservation of tissue architecture and the maintenance of native cellular function (Jones et al., 2010; Landucci et al., 2022).

"These experimental models have allowed scientists to determine the receptors, enzymes, and signaling pathways that cannabinoids affect, and have supported the idea that cannabinoids are generally safe, have physiological effects on multiple organ systems and are readily metabolized and removed from tissues (Table 3). "
https://journals.lww.com/nrronline/fulltext/2024/04000/cannabinoids_and_endocannabinoids_as_therapeutics.22.aspx [4027]

The Defence contends that proving their right to prevent their neurodegenerative diseases and neurological disorders, by a law that was contemporaneously and necessarily ignorant of this, is not a reasonable demand to be placed upon the public, who should be free to choose to try to do this.

Nor is it acceptable for the ZPPPD to proceed to remain willingly ignorant now. Rather, the law should be seen for what it is: an attack on the largest possible politically disenfranchised group, unhealthy, cruel, damaging, and out of date.

To the groups whose longevity and quality of life is detrimented by the ZPPPD we can recently add those born with Leigh syndrome, also known as subacute necrotic encephalopathy. Its prevalence is reckoned by the Viljem Julijan Society to amount to between 1 in 33,000 and 100,000.
https://viljem-julijan.si/opisi-redkih-bolezni/leighov-sindrom/ [3536]

But according to Lim et al (2022):

"The birth prevalence of Leigh syndrome is estimated to be 1 in 40,000 but rises to 1 in 2,000 in certain isolated populations."

In their study 39% had consanguineous parents.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9534328 [3537]

The new research on CBD may be viewed as an extreme version of the anti-neurodegenerative properties of cannabinoids in healthy and not-so-healthy subjects. As "Cannabidiol ameliorates mitochondrial disease via PPARγ activation in preclinical models" (2024) explains:

"Mutations in mitochondrial energy-producing genes lead to a heterogeneous group of untreatable disorders known as primary mitochondrial diseases (MD). Leigh syndrome (LS) is the most common pediatric MD and is characterized by progressive neuromuscular affectation and premature death. Here, we show that daily cannabidiol (CBD) administration significantly extends lifespan and ameliorates pathology in two LS mouse models, and improves cellular function in fibroblasts from LS patients. CBD delays motor decline and neurodegenerative signs, improves social deficits and breathing abnormalities, decreases thermally induced seizures, and improves neuropathology in affected brain regions. Mechanistically, we identify peroxisome proliferator-activated receptor gamma (PPARγ) as a key nuclear receptor mediating CBD’s beneficial effects, while also providing proof of dysregulated PPARγ expression and activity as a common feature in both mouse neurons and fibroblasts from LS patients. Taken together, our results provide the first evidence for CBD as a potential treatment for LS."

CBD extended the median life of the mice by 23%. Puighermanal et al might have obtained better results with a combination of CBD, THC, and other phytogenic constituents. However they only tried CBD and THC alone. THC alone did not have any effect in Gad2:Ndufs4cKO lifespan. Their results point to CBD's life-extending role in LS via PPARγ rather than cannabinoid receptor involvement, the proof being that:

"PPARγ blockade reduces CBD-induced beneficial effects in complex I deficient mice."

The results:

"CBD prolongs lifespan and improves fitness in Ndufs4-deficient mice

"Ndufs4 knockout (Ndufs4KO) mice, a well characterized mouse model of LS, display a progressive neurodegenerative phenotype, which resembles the human disease including retarded growth rate, lethargy, loss of motor skills, and premature death. To assess the therapeutic potential of CBD, we first examined the effects of daily CBD treatment (100 mg/kg, i.p.) beginning promptly after weaning (Postnatal day [PND] 23-29). CBD treatment significantly extended the lifespan of Ndufs4KO mice. Median survival was 57 and 70 days for vehicle and CBD groups, respectively (Fig. 1a). CBD treatment significantly delayed the onset of common clinical signs associated with neurological decline, such as clasping, twisting, and curling, compared to vehicle-treated mice (Fig. 1b). A progressive decrease in motor function also appears as a consequence of the neurological decline present in Ndufs4KO mice. CBD treatment also delayed this observed motor decline (Fig. 1c), as measured by rotarod tests conducted at PND30, 40 and 50."
https://www.nature.com/articles/s41467-024-51884-8 [3535]

Like the Ugandan chimpanzee [3154, 3155], to keep ourselves in good condition, we members of the species Homo sapiens quite commonly autonomously select things from the environment around us. To the

"...anti-inflammatory, anti-oxidant, anti-bacterial, anti-aging, anti-fatigue, anti-tumor, anti-constipation, neuroprotective, lipoid-regulating, hepatoprotective, and immunomodulatory properties"
https://pubmed.ncbi.nlm.nih.gov/39278423/ [3538]

...of cannabis fructus (hemp seed) we can add the famously antioxidant food well-known as a liver treatment: turmeric.

"Pure curcumin has the potential to reduce MDA concentration and increase total antioxidant capacity." say Jakubczyk et al in "Antioxidant Potential of Curcumin—A Meta-Analysis of Randomized Clinical Trials" (2020).
https://www.mdpi.com/2076-3921/9/11/1092 [4024]

Salehi et al (2020) add:

"Curcumin has been shown to play a critical role in the survival of alcoholic hepatocellular tissue. It has been shown that curcumin can induce and trigger mitochondrial biogenesis and, by this mechanism, prevent the occurrence of both intrinsic and extrinsic apoptosis pathways in liver cells that have been impaired by alcohol. According to this mechanism, curcumin may protect hepatocellular tissue from alcohol-induced cell degeneration and may therefore survive alcoholic hepatocellular tissue. Based on these mechanisms, the protective functions of curcumin against alcohol-induced cell degeneration due to oxidative stress, inflammation, and apoptosis events in hepatocellular tissue have been recorded."



"Besides, it was shown that some parts of curcumin were mediated against alcohol-induced direct and indirect inflammatory by down-regulating the function of various signaling mediators, including down-regulation of Cyclooxygenase-2 (COX-2), mitogen-activated and Janus kinases, and inhibiting the generation of TNF-alpha, IL-1,IL-2,IL-6,IL-8, IL12, IL12 [sic], and 5′-Adenosine monophosphate-activated protein kinase. Curcumin also acts as an anti-inflammatory agent by inhibiting the generation of nitric oxide (NO) as well as the inducible expression in hepatocellular nitric oxide synthase (iNOS). The effect of curcumin in reducing inflammation is believed to be due to inhibition of the production of alcohol-induced TNF-α. Some parts of the anti-inflammatory effect of curcumin have been mediated by its protective effects in the mitochondria of the liver. This agent activates and regulates mitochondrial membrane potential (MMP) and causes mitochondrial permeability transition biogenesis (MPT) activity which results in hepatocellular survival in inflammatory events such as alcohol administration. All these findings suggest that curcumin possesses the potential for anti-inflammatory properties in alcohol-exposed animal or human hepatic cells. However, because inflammation is involved in most of the hepatic tissue fibrosis induced by alcohol; studies have investigated the potential protective effect of curcumin as an anti-inflammatory agent in inflamed liver induced by alcohol."


https://brieflands.com/articles/ijpr-124352.html [4018]

The Defence defines Cannabis Component X (CCx) as any cannabinoid, a terpene, or other pharmacologically-active phytogenic constituent.

How does curcumin rank compared to CCx?

"ABTS: The TEAC values of quercetin and curcumin were about 2.02 and 0.50. 1 g DL-alpha-tocopherol and anthocyanins were equivalent to 2.06 mmol, 2.897 mmol of Trolox in scavenging free radicals capacity. FRAP: Used 1.0 mmol/L FeSO4 as the reference standard, quercetin, curcumin and Trolox equivalent molar about 5.73, 1.18 and 2.09. DL-alpha-tocopherol, antioxidant activity of proanthocyanidins were 207.7mg and 156.36 mg."
https://pubmed.ncbi.nlm.nih.gov/19548565/ [4016]

Khopde et al obtained a TEAC result of 2.61 ± 0.15.
https://scholar.google.si/scholar_url?url=https://www.academia.edu/download/31493013/BioChem.pdf&hl=en&sa=X&ei=zi01ZaXnF_G-y9YP5PKv2AM&scisig=AFWwaebZG9DNqVvn4vd7ToM8oCuK&oi=scholarr  [4020]

But like CCx, curcumin exerts its effects in multiple pathways. According to Casas-Grajales, P. Muriel, in "Liver Pathophysiology", 2017:

"Curcumin is a well-known hepatoprotector, therefore, we suggest that curcumin also exerts its hepatoprotective effects through other mechanisms altogether with its antioxidant properties. One of these mechanisms is the induction of enzymatic antioxidants such as GST [glutathione transferase], HO-1 [haeme-oxygenase-1], and CAT [catalase] (Rivera-Espinoza and Muriel, 2009). Other mechanism proposed is by the inhibition of NF-κB that is a transcriptional factor activated by endotoxins, cytokines, and oxidative stress and is involved in the expression of genes related to the inflammation process (Samuhasaneeto et al., 2009). In different models of liver damage, the inhibition of NF-κB by curcumin results in the prevention of the increase of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6 (Reyes-Gordillo et al., 2007), expression of iNOS (Shapiro et al., 2006), PPARγ (Samuhasaneeto et al., 2009), and COX-2 (Nanji et al., 2003), which are also implicated in the inflammation process."
https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/trolox-equivalent-antioxidant-capacity [4017]

How can these effects from CCx be so bad, when in curcumin they are so great? It's all about the sin. When considering the potential synergies of CCx a further fact about turmeric stands out. from "Curcumin: A Review of Its Effects on Human Health" (2017):

"There are several components that can increase bioavailability. For example, piperine is the major active component of black pepper and, when combined in a complex with curcumin, has been shown to increase bioavailability by 2000%."

You do not have to be ill to take curcumin or black pepper. You don't need a prescription.

"One study on healthy adults aged 40–60 years used an 80 mg/day dose of a lipidated form of curcumin. Subjects were given either curcumin (N = 19) or a placebo (N = 19) for four weeks. The treatment was 400 mg powder per day containing 80 mg curcumin. Blood and saliva were taken before and after the four weeks. Curcumin significantly lowered triglyceride levels but not total cholesterol, LDL, or HDL levels. There was a significant increase in nitrous oxide (NO) and in soluble intercellular adhesion molecule 1 (sICAM), a molecule linked to atherosclerosis. Inflammation-related neutrophil function increased, as measured by myeloperoxidase concentration, but c-reactive protein and ceruloplasmin did not. There was a decrease in salivary amylase activity, which can be a marker of stress, and an increase in salivary radical scavenging capacities and plasma antioxidant enzyme catalase, but not in super oxide dismutase or glutathione peroxidase. In addition, there was a decrease in beta amyloid plaque, a marker of brain aging, and in plasma alanine amino transferase activities, a marker of liver injury. This indicates that a relatively low dose of curcumin can provide health benefits for people that do not have diagnosed health conditions."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664031 [4022]

In the above there are two errors, however. Instead of nitric oxide (NO), the authors say nitrous oxide (N2O). Secondly the authors they are citing, DiSilvestro et al, do say nitric oxide increased, but not sICAM:

"Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities."

and

"In this study, curcumin showed signs of both direct and indirect antioxidant actions. The curcumin-induced increase in salivary radical scavenging capacity is consistent with a direct antioxidant action (elimination of free radicals by curcumin and/or its metabolites). Curcumin has shown this type of activity in vitro. In the present study, curcumin also showed indirect antioxidant action by elevating plasma activities of the endogenous antioxidant enzyme catalase. Interestingly, low plasma catalase is associated with a high risk for one form of cardiovascular disease."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518252 [4023]

It's almost as if curcumin users are trying to defy God's plan by interfering in these pathways. The Court can see for itself that CCx share many of the beneficial properties of curcumin, are comparable in terms of what amount might reasonably be consumed, and that while curcumin may be uhelpful in certain rare combinations of conditions, and while dangerously foreign for a Slovenian audience, anyone who proposed it should be criminalised or compusorily medicalized, or legal to possess but not to sell, would be regarded as mad.
https://onlinelibrary.wiley.com/doi/10.1111/j.1478-3231.2009.02086.x [4019]

Ginger is another crop whose health benefits closely correspond with those of cannabis, as illustrated in this figure from "Ginger for Healthy Ageing: A Systematic Review on Current Evidence of Its Antioxidant, Anti-Inflammatory, and Anticancer Properties" by Ozkur et al (2022):


https://onlinelibrary.wiley.com/doi/epdf/10.1155/2022/4748447 [3816]

More about how the minor cannabinoids and terpenes fit together with the main course, as it were, in the "Entourage effects" medical segment of the Defence. But for now, a few permutations of CCx known to exist in evidence before we sum up the mission of the seeker after knowability. According to the recent "Cannabis-Based Phytocannabinoids: Overview, Mechanism of Action, Therapeutic Application, Production, and Affecting Environmental Factors" by Jurga et al in Poland, the main course THC itself acts through multiple pathways:

"The effects of THC are observed through its broad effects on various receptors. THC ranges from acting as a partial agonist for the CBR1 and CBR2 receptors to being a full agonist for the GPR55/GPR18, TRPV2-4/TRPA1, PPARa/y receptors to being an antagonist for the TRPM8/5HT3A receptor."
https://pmc.ncbi.nlm.nih.gov/articles/PMC11508795/ [3662]

In 2018 Blasco-Benito et al at Complutense University Madrid

"...compared the antitumor efficacy of pure THC with that of a botanical drug preparation (BDP). The BDP was more potent than pure THC in producing antitumor responses in cell culture and animal models of ER+/PR+, HER2+ [estrogen positive, progesterone positive, human epidermal growth factor receptor 2] and triple-negative breast cancer. This increased potency was not due to the presence of the 5 most abundant terpenes in the preparation. While pure THC acted by activating cannabinoid CB2 receptors and generating reactive oxygen species, the BDP modulated different targets and mechanisms of action. The combination of cannabinoids with estrogen receptor- or HER2-targeted therapies (tamoxifen and lapatinib, respectively) or with cisplatin, produced additive antiproliferative responses in cell cultures. Combinations of these treatments in vivo showed no interactions, either positive or negative. Together, our results suggest that standardized cannabis drug preparations, rather than pure cannabinoids, could be considered as part of the therapeutic armamentarium to manage breast cancer."
https://pubmed.ncbi.nlm.nih.gov/29940172/ [3636]

Co-author Cristina Sanchez summarises the findings in this video:
https://www.youtube.com/watch?v=KQUSoIJkaWg [3637]

Using the HOCl scavenging assay of their reference 5, Hacke et al "Probing the antioxidant activity of Δ9-tetrahydrocannabinol and cannabidiol in Cannabis sativa extracts" (2019) had reported on the synergistic effect of the two boss cannabinoids:

"Herein, we report the antioxidant activity of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) in pure and mixed solutions at different ratios, as well as of six different Cannabis sativa extracts containing various proportions of CBD and THC by using spectrophotometric (reducing power assay, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), hypochlorous acid (HOCl) scavenging assays) and electrochemical methods (cyclic voltammetry and differential pulse voltammetry). The isolated cannabinoids, the different stoichiometric ratios of CBD and THC, and the natural extracts proved to have remarkable antioxidant properties in all the methods employed in this work. The antioxidant activity of CBD and THC was compared against that of the well-defined antioxidants such as ascorbic acid (AA), resveratrol (Resv) and (−)-epigallocatechin-3-gallate (EGCG). Clear evidence of the synergistic and antagonistic effects between CBD and THC regarding to their antioxidant activities was observed. Moreover, a good correlation was obtained between the optical and electrochemical methods, which proved that the reported experimental procedures can easily be adapted to determine the antioxidant activity of extracts from various Cannabis sativa species and related compounds."
https://pubs.rsc.org/en/content/articlelanding/2019/AN/C9AN00890J [4000]

With a view to mashing up, for their antioxidative potential, the discarded leaves of hemp grown for seeds or fibre, Stasiłowicz-Krzemien et al of Poznan University in "Determining Antioxidant Activity of Cannabis Leaves Extracts from Different Varieties—Unveiling Nature’s Treasure Trove" (2023) used the same four methods as Dawidowicz to test different extraction processes.

"The results revealed that the selection of extractant and extraction conditions significantly influenced the active compounds’ extraction efficiency and antioxidant activity. Among the tested conditions, ultrasound assisted extraction using methanol yielded the highest cannabinoid profile: CBD = 184.51 ± 5.61; CBG = 6.10 ± 0.21; ∆9-THC = 0.51 ± 0.01; and CBC = 0.71 ± 0.01 µg/g antioxidant potential in Białobrzeska leaf extracts."
https://www.mdpi.com/2076-3921/12/7/1390/pdf [4002]

"Numerous studies have demonstrated the necessity of antioxidants, but currently, the preferred choice of determination method is a controversial challenge." say Christodoulou et al. [3098]

And to conclude our dip into the topic of antioxidation, Cásedas et al add the superoxide radical method, in "Evaluation of two different Cannabis sativa L. extracts as antioxidant and neuroprotective agents" (2022), explaining that

"The substrate xanthine and the enzyme xanthine oxidase can be used to measure the potential reduction of superoxide radical by the formation of the NBT-radical superoxide complex."

And apparently:

"Cannabis sativa L. is a plant that contains numerous chemically active compounds including cannabinoids such as trans-Δ-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and flavone derivatives, such as luteolin-7-O-glucuronide and apigenin glucuronide. In particular, the polar fraction of hemp including many phenolic compounds has been overlooked when compared with the more lipophilic fraction containing cannabinoids. Therefore, the aim of this study was to assess two extracts of industrial hemp (C. sativa) of different polarity (aqueous and hexane) by evaluating their antioxidant profile and their neuroprotective potential on pharmacological targets in the central nervous system (CNS). Several assays on in vitro antioxidant capacity (DPPH, superoxide radical, FRAP, ORAC), as well as inhibition of physiological enzymes such as acetylcholinesterase (AChE) and monoaminooxidase A (MAO-A) were carried out in order to find out how these extracts may be helpful to prevent neurodegenerative disorders. Neuro-2a cell line was selected to test the cytotoxic and neuroprotective potential of these extracts. Both extracts showed striking antioxidant capacity in the FRAP and ORAC assays, particularly the hexane extract, and interesting results for the DPPH and superoxide radical uptake assays, with the aqueous extract standing out especially in the latter. In enzyme inhibition assays, the aqueous extract showed AChE and MAO-A inhibitory activity, while the hexane extract only reached IC50 value for AChE inhibitory bioassay. Neuro-2a assays demonstrated that polyphenolic extract was not cytotoxic and exhibited cytoprotective properties against hydrogen peroxide and antioxidant response decreasing reactive oxygen species (ROS) production. These extracts could be a source of compounds with potential benefit on human health, especially related to neurodegenerative disorders."
https://www.frontiersin.org/articles/10.3389/fphar.2022.1009868/full [4001]

Therefore whatever the bishops think about our loss of reason, reason is actually on the side of the cannabis proponents. The ZPPPD represents an unnatural and unhelpful restriction on the free trade in antioxidant health benefits.

If the bishops worry that this might also make us happy, they had their chance to vote in the referendum like everyone else (except people who don't speak Slovene).

The ZPPPD, either through promulgating fear or confiscation, reduces the antioxidant capacity available to the general population.

Indeed prohibition increases, for users, the stresses of stigma and criminality, which in turn produce oxidative stress, and thus they require more antioxidants, which may be obtained by recreational cannabis use.

All recreational use is therefore medical use.

"Chronic Stress and Oxidative Stress as Common Factors of the Pathogenesis of Depression and Alzheimer’s Disease: The Role of Antioxidants in Prevention and Treatment" by Juszcryk et al (2021) confirms the negative role of the ZPPPD:

"Stress is defined as a response to potentially threatening stimuli. Although moderate acute stress may be beneficial by enhancing memory performance as well as increasing proliferation of hippocampal cells and neurogenesis, chronic stress may be a cause of deleterious alterations in the brain. Long-lasting stress leads to suppressed cell proliferation and reduced neurogenesis, thus playing an important role in pathogenesis of depression and AD. Environmental stress factors cause symptoms through immune and hormonal effects, neuroplastic changes resulting in neurogenesis, and impairment of neurotransmission. Ultimately, this can lead to neurodegenerative changes and, consequently, to dementia and cognitive decline."
https://pmc.ncbi.nlm.nih.gov/articles/PMC8470444/ [3661]

This may explain why cannabis use sometimes falls after legalization.

A reminder this decision was made in 1925, 31 years after the first experiment regarding a free radical reaction in 1894; just three years after the discovery of vitamin E; six years before vitamin C; 39 years before the identification of THC; 93 years before THC was found to restore cognitive function in old mice; and 100 years prior to the identification of the role of the mTOR pathway in THC-induced anti-aging and cognitive repair in 2024.

When did these free radicals become important in terms of the drug legislation? J A Knight of the Department of Pathology, University of Utah School of Medicine, was able to look back in 1998, explaining that

"...the presence of free radicals in biological systems was not generally considered likely until the discovery of superoxide dismutase in 1969, although in the 1950s the basis of oxygen toxicity and X-irradiation was proposed to be by a common free radical mechanism and the radical theory of aging was hypothesized. Oxyradicals are now widely accepted as being very important, not only in the aging process but also in numerous human diseases/disorders where they have either a primary or secondary role."
https://pubmed.ncbi.nlm.nih.gov/9846200/ [4021]

Sagredo et al (2011) examined "Neuroprotective effects of phytocannabinoid-based medicines in experimental models of Huntington's disease" at Universidad Complutense, Madrid and reported that:

"The administration of Δ(9)-THC- and CBD-enriched botanical extracts combined in a ratio of 1:1 as in Sativex attenuated 3NP-induced GABA deficiency, loss of Nissl-stained neurons, down-regulation of CB(1) receptor and IGF-1 expression, and up-regulation of calpain expression, whereas it completely reversed the reduction in superoxide dismutase-1 expression. Similar responses were generally found with other combinations of Δ(9)-THC- and CBD-enriched botanical extracts, suggesting that these effects are probably related to the antioxidant and CB(1) and CB(2) receptor-independent properties of both phytocannabinoids. In fact, selective antagonists for both receptor types, i.e., SR141716 and AM630, respectively, were unable to prevent the positive effects on calpain expression caused in 3NP-intoxicated rats by the 1:1 combination of Δ(9)-THC and CBD. Finally, this combination also reversed the up-regulation of proinflammatory markers such as inducible nitric oxide synthase observed in malonate-lesioned rats. In conclusion, this study provides preclinical evidence in support of a beneficial effect of the cannabis-based medicine Sativex as a neuroprotective agent capable of delaying disease progression in HD, a disorder that is currently poorly managed in the clinic, prompting an urgent need for clinical trials with agents showing positive results in preclinical studies."
https://pubmed.ncbi.nlm.nih.gov/21674569/ [1802]

In 2012 Fishbein et al at The Adelson Center for the Biology of Addictive Diseases and The Mauerberger Chair in Neuropharmacology, Sackler Faculty of Medicine, Tel-Aviv University say:

"We have previously reported that a single injection of an ultra-low dose of delta-9-tetrahydrocannabinol (THC; the psychoactive ingredient of marijuana) protected the brain from pentylenentetrazole (PTZ)-induced cognitive deficits when applied 1-7 days before or 1-3 days after the insult. In the present study we expanded the protective profile of THC by showing that it protected mice from cognitive deficits that were induced by a variety of other neuronal insults, including pentobarbital-induced deep anesthesia, repeated treatment with 3,4 methylenedioxymethamphetamine (MDMA; 'ecstasy') and exposure to carbon monoxide. The protective effect of THC lasted for at least 7 weeks. The same ultra-low dose of THC (0.002 mg/kg, a dose that is 3-4 orders of magnitude lower than the doses that produce the known acute effects of the drug in mice) induced long-lasting (7 weeks) modifications of extracellular signal-regulated kinase (ERK) activity in the hippocampus, frontal cortex and cerebellum of the mice. The alterations in ERK activity paralleled changes in its activating enzyme MEK and its inactivating enzyme MKP-1. Furthermore, a single treatment with the low dose of THC elevated the level of pCREB (phosphorylated cAMP response element-binding protein) in the hippocampus and the level of BDNF (brain-derived neurotrophic factor) in the frontal cortex. These long-lasting effects indicate that a single treatment with an ultra-low dose of THC can modify brain plasticity and induce long-term behavioral and developmental effects in the brain."
https://pubmed.ncbi.nlm.nih.gov/22821081/ [1779]

These are the "well-known" neuroprotective, antiinflammatory, anticonvulsive and analgesic benefits of smoking marijuana, whether it produces the dreaded Δ9-THC or not. If you want these toning effects without getting high, you have more of a problem than the people who don't mind getting high, as pure THCA isn't obtainable legally or otherwise.

As the Daily Telegraph explained in 2016:

"British Sugar will be swapping tomato plants for cannabis seedlings after signing a long-term contract to supply the crop to drugs company GW Pharmaceuticals.

"The marijuana plants, which are of a non-psychoactive variety, will be grown in British Sugar’s 18-hectare glasshouse in Wissington, Norfolk, where the company, a subsidiary of Associated British Foods, is currently cultivating tomatoes. The space is the equivalent of 23 football pitches."
https://web.archive.org/web/20230331031141/https://www.telegraph.co.uk/business/2016/10/25/british-sugar-to-cultivate-cannabis-plants-in-norfolk-for-gw-pha/ [4186]

In a 2014 patent 20140377382 assigned to GW Pharma,

"The invention relates to the use of cannabinoid-containing plant extracts in the prevention or treatment of neural degeneration. In particular, the invention relates to use of one or more cannabinoid-containing plant extracts in the prevention or treatment of neural degeneration, wherein the one or more cannabinoid-containing plant extracts comprise: i) a cannabinoid-containing fraction; and ii) a non-cannabinoid containing fraction."

Claims in support of this include:

"[0020] Surprisingly the applicants have found that the administration of cannabinoid-containing plant extracts, are more efficacious than essentially pure cannabinoids in the prevention of neural degeneration. In particular cannabinoid-containing plant extracts comprising as a predominant cannabinoid either tetrahydrocannabinol (THC) or cannabidiol (CBD) were particularly efficacious in the prevention of neural degeneration."

and

"[0030] The "major cannabinoid" is herein defined as the predominant cannabinoid in the cannabinoid-containing plant extract. In the case of a plant extract from a cannabis plant bred to contain a high content of THC the major cannabinoid will be THC.

"0031] The "minor cannabinoid" is herein defined as the second most predominant cannabinoid in the cannabinoid-containing plant extract. In the case of a plant extract from a cannabis plant bred to contain a high content of THC the minor cannabinoid will usually be CBD.

"[0032] The "other cannabinoids" are herein defined as all of the remaining cannabinoids that are present in a cannabis plant extract when the major and the minor cannabinoids have been accounted for. In the case of a plant extract from a cannabis plant bred to contain a high content of THC the other cannabinoids will include cannabigerol (CBG), cannabichromene (CBC), tetrahydrocannabidivarin (THCV) and tetrahydrocannabinolic acid (THCA)."

and

"[0053] Preferably the neurodegenerative disease is taken from the group: Alzheimer's disease; Parkinson's disease; amyotrophic lateral sclerosis; Huntington's disease; frontotemporal dementia; prion disease; Lewy body dementia; progressive supranuclear palsy; vascular dementia; normal pressure hydrocephalus; traumatic spinal cord injury; HIV dementia; alcohol induced neurotoxicity; Down's syndrome; epilepsy or any other related neurological or psychiatric neurodegenerative disease.

"[0054] The cannabinoid-containing plant extracts are used in the manufacture of a pharmaceutical formulation for use in the prevention or treatment of ischemic disease.

"[0055] Preferably the ischemic disease is taken from the group: stroke; cardiac ischemia; coronary artery disease; thromboembolism; myocardial infarction or any other ischemic related disease.

"[0056] The cannabinoid-containing plant extracts are used in the manufacture of a pharmaceutical formulation for use in the prevention or treatment of brain injury or damage.

"[0057] Preferably the brain injury or damage is a traumatic brain injury.

"[0058] A traumatic brain injury can include but is not limited to: diffuse axonal injury; concussion; contusion; whiplash or any other traumatic head or brain injury.

"[0059] More preferably the brain injury or damage is an acquired brain injury.

"[0060] An acquired brain injury can include but is not limited to: stroke; anoxic brain injury; hypoxic brain injury or any other acquired brain injury.

"[0061] More preferably the brain injury or damage is a closed head injury or an open head injury or any other head injury.

"[0062] The cannabinoid-containing plant extracts are used in the manufacture of a pharmaceutical formulation for use in the prevention or treatment of age related inflammatory or autoimmune disease."

About some experiments done by the applicant,

"[0123] As can be seen above, all of the samples were able to reduce the concentration of intracellular calcium ions, showing that they have the potential to be neuroprotective.

"[0124] The essentially pure CBD was shown to produce a far greater reduction in the concentration of the intracellular calcium ions in comparison to the other test samples.

"[0125] Although this response appears to show that the essentially pure CBD would be more beneficial as a neuroprotective agent than that of the other test articles, this is not necessarily the case.

"[0126] Drugs that are able to strongly interfere with the action of NMDA tend to cause side effects on learning and memory. This is due to the requirement in the brain for low concentrations of glutamate for functions involved with learning and memory. When a drug is able to reduce the effects at the NMDA receptor to such a large degree although the neurones will be protected, a patient's cognition is likely to be impaired at the same time.

"[0127] All of the other test articles gave similar reductions in the concentration of intracellular calcium ions of around 20-30% reduction. This reduction is more likely to be neuroprotective without harmful cognitive effects."
https://www.patentsencyclopedia.com/app/20140377382 [4184]

According to a May 2018 report by the BBC:

"The company began growing a non‐psychoactive variety of cannabis at its plant in Wissington, Norfolk, last year for use in children's epilepsy medicine.

"It was in the news in June after people living nearby complained of a smell of 'weed' after the plants were harvested."

A further reason to suppose THC/CBD drugs must prevent neurodegeneration is because the boss of British Sugar's wife is the now former Conservative Health Minister Victoria Atkins.

She has prosecuted people for cannabis, and therefore used her skills to try impede her partly fluoridated Lincolnshire constituents' prevention of their neurodegeneration. In the political medical model, you see, first you create a problem, then you sell the solution.

"Speaking in parliament in July last year, she said: 'I must first declare an interest, because my husband works for a company that has a license to grow non-psychoactive versions of cannabis to treat epileptic conditions in children.

"'It is groundbreaking work, but I thought I should declare it, given that I will be talking about the psychoactive version of cannabis in due course - a very different substance.'"
https://www.bbc.com/news/uk-england-lincolnshire-44109060[4185]

Yet it can be seen from GW Pharma's patent that they are very much interested in major cannabinoids, psychoactive or not. Tory voters are typically low on neuroplasticity, so they won't have noticed Ms Atkins' Janus-esque misdirection. She did, however, recuse herself from cannabis policy, for what it's worth.
https://www.pulsetoday.co.uk/analysis/politics/who-is-new-health-secretary-victoria-atkins/ [4188]

At the same time this shapes a future market for the sale of more anti-neurodegenerative cannabinoid drugs, after the patients have neurodegenerated - instead of before, which latter strategy it is the aim of the Defence to show, is a right belonging to the owner of the nervous system, and not British Sugar, GW Pharma, the Ministry of Health, selected Harley Street doctors, cannabis shop proprietors, or the favoured friends and relatives of politicians.

Claims of another patent, 20100292345, this one solely for cannabigerol, include:

"5. Use as claimed in any of claims 1 to 4, wherein the diseases or conditions to be treated are taken from the group: pain (including but not limited to acute pain; chronic pain; neuropathic pain and cancer pain), neurodegenerative disease (including but not limited to Alzheimer's disease; Parkinson's disease; amyotrophic lateral sclerosis; Huntington's disease; multiple sclerosis; frontotemporal dementia; prion disease; Lewy body dementia; progressive supranuclear palsy; vascular dementia; normal pressure hydrocephalus; traumatic spinal cord injury; HIV dementia; alcohol induced neurotoxicity; Down's syndrome; epilepsy or any other related neurological or psychiatric neurodegenerative disease), ischemic disease (including but not limited to stroke; cardiac ischemia; coronary artery disease; thromboembolism; myocardial infarction or any other ischemic related disease), brain injury or damage (including but not limited to traumatic brain injury is taken from the group: diffuse axonal injury; concussion; contusion; whiplash or any other traumatic head or brain injury), acquired brain injury (including but not limited to stroke; anoxic brain injury; hypoxic brain injury or any other acquired brain injury), age related inflammatory or autoimmune disease, cachexia (including related conditions such as AIDS wasting disease, weight loss associated with cancer, chronic obstructive pulmonary disease or infectious diseases such as tuberculosis), nausea and vomiting, glaucoma, movement disorders, rheumatoid arthritis, asthma, allergy, psoriasis, Crohn's disease, systemic lupus erythematosus, diabetes, cancer, osteoporosis, renal ischemia and nephritis."
https://www.patentsencyclopedia.com/app/20100292345 [4188]

While another, patent 20100317729 from 2010, proposes treatment with tetrahydrocannabidivarin (THCV) and cannabidiol for

"[0014] Examples of diseases and conditions that are the result of the background tone of constitutively active cannabinoid receptors include but are not limited to obesity, schizophrenia, epilepsy, cognitive disorders such as Alzheimer's disease, bone disorders such as osteoporosis, bulimia, obesity associated with type II diabetes (non-insulin dependant diabetes), the treatment of drug, alcohol and nicotine abuse or dependency and inflammatory disorders (Pertwee, R. G., 2000)."
https://www.patentsencyclopedia.com/app/20100317729 [4189]

So how does accessibility to these weird and wonderful individual cannabis components work for the wannabe lawful citizen?

The Court may agree that if it wants to support the anti-nature interests of patentable cannabis-based pharmaceutical medicine against the interests of accessible public health using the intact phytogenic form of the plant, the number of judgements it must make about CCx is no less than the number of affected variables for each treatable condition multiplied by the number of treatable conditions multiplied by the combinatory product of n(CCx).

For example if n(CCx)=100, the number of pair combinations is 4950. The number of trio combinations is 161700, and the number of combinations containing 50 constituents is one hundred octillion eight hundred and ninety-one septillion three hundred and forty-four sextillion five hundred and forty-five quintillion five hundred and sixty-four quadrillion one hundred and ninety-three trillion three hundred and thirty-four billion eight hundred and twelve million four hundred and ninety-seven thousand two hundred and fifty-six (100891344545564193334812497256) requiring to be multiplied by the number of conditions and variables thereto.

How many illnesses are there? Examining the provenance of a claim that there are "10,000 diseases. Only 500 treatments"...

"Margaret Anderson, the executive director of Faster Cures, said the group hired an economist to go through a data set maintained by Orphanet and counted 9,235 'orphan diseases,' meaning rare diseases that affect fewer than 6 out of 10,000 patients. (The European Union and Japan have even more restrictive definitions.) That’s how they came up with '10,000 diseases', though she acknowledged it was not a 'perfect science.'

"She also pointed to a World Health Organization statement that 'scientists currently estimate that over 10,000 of human diseases are known to be monogenic,' meaning involving a single gene."
https://web.archive.org/web/20230221221900/https://www.washingtonpost.com/news/fact-checker/wp/2016/11/17/are-there-really-10000-diseases-and-500-cures/ [2623]

The Executive continues to hold the awed public in its thrall. It is unlikely to process all these combinations. The victims, trying not to neurodegenerate, grow fat, diabetic or get cancer, have only the Courts to impress upon this opponent the folly of its policies.

So to elucidate the number of judgements the Court can use in support of prejudice against cannabis and to delay legalisation, we can take a shot with 9235 diseases. Each will have an average number of variables to consider: for instance any enzyme will have a catalytic active site and a substrate recognition site upon which our combinations of cannabis ingredients may act, proteins upstream and downstream which may be affected, the patient may have a high BMI or live in an atmosphere containing 50 trillion Town Smell ingredient combinations, and so on.

Let's take ten as an average number of variables or confounders. So our number of determinations standing in the way of legal access to the Benedictions would amount to 9235 x 10 x 100891344545564193334812497256.

Which gives a total of three hundred and fifty-four decillion seven hundred and sixty nonillion three hundred and forty-four octillion eight septillion two hundred and eleven sextillion four hundred and ninety-two quintillion four hundred and sixty-five quadrillion five hundred and forty-six trillion two hundred and fourteen billion eight hundred and eighty-two million forty-five thousand nine hundred and forty-two (354,760,344,008,211,492,465,546,214,882,045,942) legal determinations with which to stall legalisation of this plant while you all become fat, get cancer, drink to lose your memories and die.

The outcome of banning cannabis in the population is either good or bad and cannot be both. Ignoring the remote possibility of a neutral result, the number of outcomes for each individual is likewise 2.

Was General Smuts or the Slovenian government right or wrong to stop the world? Since we have this number handy, the odds of either one having guessed correctly in all (or none) of the above discussed cases is 1 in 2^{354,760,344,008,211,492,465,546,214,882,045,942}.

Square that answer for both of them. Or cube it to include the SCND's superstitious guess too.

Fortunately the equihuman condition of Homo sapiens offers the Court a shortcut in its search for the veracity of cannabis-derived prophylaxis. Specifically, the experiences of much larger jurisdictions where cannabis has been legalised to a greater or lesser extent, where, as usual, none of the dire predictions of the bishops have materialized.

However, in a discussion of the differences between US and European patent law, in the opinion of Simmons and Simmons, an international law firm...

"...in order to satisfy the requirement that the natural product produces a useful effect, it is important for the patent application as filed to include supporting data to demonstrate this effect (at least plausibly). For a cosmetic or personal care product, this effect could be, for example, reducing the appearance of wrinkles or blemishes, or improving skin hydration. For a food or dietary supplement, this could be, for example, improving health or nutrition."
https://www.simmons-simmons.com/en/publications/ckfxuqnou6mkn0a25dlew2v44/patenting-natural-products-part-1-newly-isolated-material [2680]

And in US20130059018 filed on 11 March 2011 by GW Pharma Ltd and Otsuka Pharmaceutical Co Ltd, and granted on 29 July 2014

"Cannabis has been ascribed to be both a carcinogen and anti-cancer agent. In particular smoking cannabis is known to be carcinogenic as the cannabis smoke contains at least 50 different known carcinogenic compounds, many of which are the same substances found in smoked tobacco. One of these carcinogens, benzopyrene is known to cause cancer as it alters a gene called p53, which is a tumour suppressor gene. Cannabis contains the substance tetrahydrocannabinol (THC) which has been shown to cause benzopyrene to promote the p53 gene to change.

"Researchers however have discovered that some cannabinoids, including THC and cannabidiol (CBD) are able to promote the re-emergence of apoptosis so that some tumours will heed the signals, stop dividing, and die. The process of apoptosis is judged by observation of several phenomena including: reduced cellular volume, condensation of nuclear chromatin, changes in distribution of phospholipids in plasma membrane phospholipids, and cleavage of chromatin into DNA fragments called DNA ladders."

The patent US20130059018 and its citations represent an established legal basis for the utility of cannabis ingredients inter alia in cancer prophylaxis:

"This invention relates to the use of phytocannabinoids, either in an isolated form or in the form of a botanical drug substance (BDS), as a prophylactic or in the treatment of cancer. Typically the cancer to be treated is a cancer of the: prostate, breast, skin, glioma, colon, lung or a bone or lymph metastasis. The phytocannabinoids may be used in combination with other cancer treatments."

With regard to specific references to prophylaxis:

"In a fourth aspect of the present invention there is provided one or more phytocannabinoids, either in an isolated form or in the form of a botanical drug substance (BDS), as a prophylactic or in the treatment of cancer

"In a fifth aspect of the present invention there is provided one or more phytocannabinoids taken from the group selected from: THCV, CBDV, THCVA, THCA, CBDA, CBD, CBG, and CBC, for use in the treatment of prostate cancer, wherein the THCVA is present as an isolated phytocannabinoid, the THCA, CBDA CBD, CBG or CBC are present in the form of a BDS, and the THCV or CBDV are present in either an isolated form or in the form of a BDS."

and

"The application WO 2008/129258 describes the use of cannabinoid-containing plant extracts in the prevention or treatment of diseases or conditions that are alleviated by blockade of one or more types of TRP channel. Different binding potentials of the cannabinoid-containing plant extracts at the TRPA1 and TRPM8 channels are described. The diseases and conditions to be prevented or treated include: neuropathic pain, inflammation, vasoconstriction or cancer.

"The TRPM8 receptor has also been found in breast, colon and skin cancers."

and

"The application WO/2006/037981 describes the use of the cannabinoid CBD to prevent tumour cells migrating or metastisising from an area of uncontrolled growth to an area away from the original tumour site."

and referring to Table 5.1

"As can be seen the phytocannabinoid THCA was most effective at inhibiting DAGL and the all the phytocannabinoid acids (THCA, CBDA and CBGA) were effective at inhibiting MAGL. These data infer that these phytocannabinoid might be useful in the treatment of cancer as they are able to prevent the endogenous cannabinoid 2-AG from being hydrolysed and as such may prevent cancerous cell formation."

and

"CBD BDS is able to statistically significantly reduce the numbers of ACF [Aberrant crypt foci are clusters of abnormal tube-like glands in the lining of the colon and rectum. Aberrant crypt foci form before colorectal polyps and are one of the earliest changes seen in the colon that may lead to cancer] per mouse in comparison to the control.

"FIG. 5 b) shows that the CBD BDS is more effective at reducing the number of polyps per mouse at a statistically significant level in comparison to the control animals.

"FIG. 5 c) shows that the CBD purified compound significantly reduced the numbers of tumours per animal.

"FIG. 6 (a-c) demonstrate the data obtained for isolated CBG and CBDV in addition to that obtained for CBG BDS and CBDV BDS.

"All of the phyto cannabinoids exerted a protective effect against the experimentally induced colon carcinogenesis as is shown in FIG. 6 a) with isolated CBG giving the most statistically significant results.

"FIG. 6 b) demonstrates that the protective effect was even more pronounced on the formation of ACF with 4 or more crypts. These type of crypts are predictive of the final incidence of colon cancer and on the formation of tumours. As is shown isolated CBG gave the most statistically significant data demonstrating such a protective effect that there were no ACF with greater than 4 crypts produced in the animals given isolated CBG.

"FIG. 6 c) details the number of tumours that occurred in each animal. Again the data produced in the mice given isolated CBG was such that no tumours were produced in these animals.

"In summary these data demonstrate the protective effects of phytocannabinoids in the prevention of colon cancer. Of significance is the phytocannabinoid CBG which exerts a strong protective effect against colon cancer particularly when it is in an isolated form."
https://patents.google.com/patent/US20130059018 [2681]

To which we can add the discovery of Kwon et al in Kawngwon, South Korea that "Metallothionein Family Proteins as Regulators of Zinc Ions Synergistically Enhance the Anticancer Effect of Cannabidiol in Human Colorectal Cancer Cells" (2023), published in the International Journal of Molecular Sciences, who say:

"CBD treatment regulated the expression of genes related to DNA repair and cell division, with metallothionein (MT) family genes being identified as having highly increased expression levels induced by CBD. It was also found that the expression levels of MT family genes were decreased in colorectal cancer tissues compared to those in normal tissues, indicating that the downregulation of MT family genes might be highly associated with colorectal tumor progression. A qPCR experiment revealed that the expression levels of MT family genes were increased by CBD. Moreover, MT family genes were regulated by CBD or crude extract but not by other cannabinoids, suggesting that the expression of MT family genes was specifically induced by CBD. A synergistic effect between CBD and MT gene transfection or zinc ion treatment was found. In conclusion, MT family genes as novel target genes could synergistically increase the anticancer activity of CBD by regulating the zinc ions in human colorectal cancer cells."
https://www.mdpi.com/1422-0067/24/23/16621/pdf?version=1700655118 [4262]

Yüksel et al (2023) mixed it up when they

"...investigated a plausible therapeutic synergism of a triple combination of CBD/CBG, curcumin, and piperine in the colon adenocarcinoma using HCT116 and HT29 cell lines. Potential synergistic effects of various combinations including these compounds were tested by measuring cancer cell proliferation and apoptosis. Our findings revealed that different genetic backgrounds of HCT116 and HT29 cell lines resulted in divergent responses to the combination treatments. Triple treatment showed synergism in terms of exhibiting anti-tumorigenic effects by activating the Hippo YAP signaling pathway in the HCT116 cell line."
https://www.frontiersin.org/articles/10.3389/fphar.2023.1145666/full [2732]

With regard to the formation of the carcinogen benzo alpha pyrene from the combustion of smoked drugs, the evidence favours cannabis strains with a relatively high ratio of desirable ingredients to cellulose - combustion of cellulose is the source of the polycyclic aromatic hydrocarbons:

"The formation of polycyclic aromatic hydrocarbons (PAHs) from the pyrolysis of cellulose over the temperature range of 300-650° C has been investigated. Detectable amounts (microgram per gram) of 2-4 ring PAHs were observed at and above 400° C. Benzo[a]pyrene and benz[a]anthracene were observed at and above 500° C. Changing the gas phase residence time from 2 to 18 s and the sample size from 200 to 500 mg did not significantly affect the yields of PAHs formed over this low temperature range. The addition of oxygen to the carrier gas stream significantly reduced the yields of PAHs. The pathway to PAH formation in the 300-650° C temperature range is believed to proceed via the carbonization process where the solid residue undergoes a chemical transformation and rearrangement to give a more condensed polycyclic aromatic structure. The evolution profiles of PAHs from the solid residue suggests that smaller 2-3 ring PAHs evolve first and pass through a maximum at a slightly lower temperature than the larger 4-5 ring PAHs. The yields of PAHs obtained from the pyrolysis of d-glucose and sucrose are comparable to those obtained from cellulose."
https://www.infona.pl/resource/bwmeta1.element.elsevier-b4826b42-deb5-393e-bc12-348766dc6e22 [2682]

And just how much heat is required to ignite cellulose? According to researchers from the Department of Chemical and Process Engineering, University of Strathclyde, Glasgow, and the School of Mechanical and Aerospace Engineering, Queen's University of Belfast:

"The results showed that the identified ignition temperatures of cellulose, hemicellulose and lignin are 410°C, 370°C and 405°C, respectively. It has been found that the influence of their interactions on the ignition behaviour of mixtures is insignificant, indicating that the ignition behaviour of various biomass feedstock could be predicted with high accuracy if the mass fractions of cellulose, hemicellulose and lignin are known."
https://pureadmin.qub.ac.uk/ws/files/159093540/ExStudy.pdf [2683]

There is an inverse relationship between cellulose and useful ingredients, so the best strategy - to keep Slovenia's oncologists busy with cancer, and confirm the bishops' superstitions about the sins of drugs except the ones they take - is to place some limit on the useful ingredients, as the association between cellulose and their employment is positive, although the association with public health is not.

Aguzzi et al (2024) report "Anticancer effect of minor phytocannabinoids in preclinical models of multiple myeloma":

"Multiple myeloma (MM) is a blood cancer caused by uncontrolled growth of clonal plasmacells. Bone disease is responsible for the severe complications of MM and is caused by myeloma cells infiltrating the bone marrow and inducing osteoclast activation. To date, no treatment for MM is truly curative since patients relapse and become refractory to all drug classes....Here, we examined the cytotoxic activity of CBG, CBC, CBN, and CBDV in vitro in MM cell lines, their effect in modulating MM cells invasion toward bone cells and the bone resorption. Subsequently, according to the in vitro results, we selected CBN for in vivo study in a MM xenograft mice model. Results showed that the phytocannabinoids inhibited MM cell growth and induced necrotic cell death. Moreover, the phytocannabinoids reduced the invasion of MM cells toward osteoblast cells and bone resorption in vitro. Lastly, CBN reduced in vivo tumor mass. Together, our results suggest that CBG, CBC, CBN, and CBDV can be promising anticancer agents for MM."
https://iubmb.onlinelibrary.wiley.com/doi/full/10.1002/biof.2078 [3278]

McKallip et al (2002) looked into "Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease":

"In the current study, we examined whether ligation of CB2 receptors would lead to induction of apoptosis in tumors of immune origin and whether CB2 agonist could be used to treat such cancers. Exposure of murine tumors EL-4, LSA, and P815 to delta-9-tetrahydrocannabinol (THC) in vitro led to a significant reduction in cell viability and an increase in apoptosis. Exposure of EL-4 tumor cells to the synthetic cannabinoid HU-210 and the endogenous cannabinoid anandamide led to significant induction of apoptosis, whereas exposure to WIN55212 was not effective. Treatment of EL-4 tumor-bearing mice with THC in vivo led to a significant reduction in tumor load, increase in tumor-cell apoptosis, and increase in survival of tumor-bearing mice. Examination of a number of human leukemia and lymphoma cell lines, including Jurkat, Molt-4, and Sup-T1, revealed that they expressed CB2 receptors but not CB1. These human tumor cells were also susceptible to apoptosis induced by THC, HU-210, anandamide, and the CB2-selective agonist JWH-015. This effect was mediated at least in part through the CB2 receptors because pretreatment with the CB2 antagonist SR144528 partially reversed the THC-induced apoptosis. Culture of primary acute lymphoblastic leukemia cells with THC in vitro reduced cell viability and induced apoptosis."
https://ashpublications.org/blood/article-pdf/100/2/627/1684292/h81402000627.pdf [3686]

The purpose of the foregoing is to merely show a sample of some positive influences of various CCx in the prevention and treatment of illness. Psychedelics will be dealt with in detail separately elsewhere.

It should be evident to the most inexperienced investigator that none of the above examples could have been known to League of Nations racists in 1924, or by Slovenian racists drafting their facsimile law in 2000.

Probably, though, the latter were advised not to look at any information about drugs when they were copying out their drug law, thanks to which any information about the effects of not taking these drugs is supposedly excluded from the consequent trials.

It's just the present Prosecutor's hard cheese to have been assigned to this case. By the sheer law of averages they were bound, eventually, to get a Defendant who could read.

For cannabis there are two options facing the health-conscious population faced with the ZPPPD. They can wait for all the research on the 354 decillion combinations of CCx and disease to be fought out one by one in Slovenia's courts, dying in the meantime.

Or they can just get some weed. We'll get into the statistics once we've established that the ZPPPD does not supervene other laws, against unnecessary mortality and morbidity.

The Benedictions section which follows is a non-exhaustive condensed summary of the positive outcomes attested to in the evidence in this case, covering some of the abovementioned orphan diseases, but mainly oriented toward the most common causes of morbidity and mortality, in three sections devoted to cannabis, classical psychedelics, and Benedictions common to both.

The Benedictions enumerate in the briefest way possible what the Defendant and a putative minimum of 354,845 Slovenian fellow-deviants want.

Conversely, they are what the ZPPPD and the Republic of Slovenia wants to prevent the 354,845 Slovenian recipients of the Benedictions (ROBs) having, and prevent the 116,434 facilitators of the Benedictions (FOBs) required to supply them, supplying [3179].

Until Slovenia can make it legal but bureaucratically unfeasible, monopolize the market with an inferior product, and hoover up all the money from it in ancillary costs.

Slovenia is not interested in affordable health solutions, only how much health solution you can afford.

The cannabis black market will therefore be largely unaffected by legalisation, Slovenia-style. And that's just the way Slovenia likes it: chaotic, destructive, and arbitrary, and preferably left in an uncleaned-up sticky mess, full of broken glass.

Like the Defendant, the 354,845 want to activate their receptors, upregulate or downregulate their gene expression, affect their protein synthesis, alter their microbiome and lipid metabolism howsoever they choose. Just like you, with yours.

They own their receptors, genes, proteins, bugs and fats. Their bodies do not belong to a legal fiction, to racists from history, to a doctor, or to any government. Just like yours.

Any responsible adult is entitled to be skeptical of the longstanding dogma, and to act upon what this Defence sets out to prove are more accurate and credible beliefs.

The Defendant stands for the rights of everyone disadvantaged, discriminated against, persecuted, and prosecuted on the false or absent bases of prohibition, and also believes the victims of these officially-sanctioned prejudices have been appallingly treated and should be pardoned and compensated.

The Defendant requests the return of his CaPs and other rightful property, for whose distraint Slovenia has proffered no credible excuse or cause.

The Benedictions represent both empirical entities as well as beliefs. Beliefs which the Defence evidence shows may be reasonably and earnestly held about the positive benefits of CaPs at the population level, in which the good overwhelmingly outweighs the bad. This is the latest version of this dynamic list.


THE BENEDICTIONS


Roche biochemical pathways can be searched at:

Part 1: Metabolic Pathways
http://biochemical-pathways.com/#/map/1 [1977]

Part 2: Cellular and Molecular Processes
http://biochemical-pathways.com/#/map/2 [1978]

These are some of the benefits to which to which the Defence claims a right, based on the evidence of the probability of their resulting from the use of cannabis and/or psychedelics at the population level. Implicit in this claim is that these benefits outweigh any deleterious effects claimed by the proponents of prohibition, based on their evidence of equal or better quality.

All the methods and materials to be found in the evidence supportive of the Benedictions additionally form part of the beliefs in which the public may invest, and consequent behavioural choices to which it is constitutionally entitled.

Thus the creeds of this particular belief system contain no dragons, wizards or evil spirits. Rather they are to be found in the scientific and general literature on the subjects at issue in the evidence.

One piece of good news for the prohibition side is that although the Benedictions are demonstrated at a population or experimental cohort level, or by laboratory observation, the prohibitionist is only liable in tort, for denial or removal of the Benedictions, towards the individuals in whose wellbeing it has actively interfered.

To this end the Court is invited to intervene on the issue of who should have known what and when. Most of the evidence includes dates of publication. Some excerpts appear in chronological or reverse-chronological order to elucidate the arc of discovery.

For legal purposes, the wannabe healthy and lawful citizen can belong to one of three groups A, B and C.

All three groups A, B and C are confronted with evidence of desirable effects: that is, any number or combination of desirable effects revealed in this evidence including, but not limited to the above Benedictions.

Now let's look at the legal positions of each of the three Groups and their relationship to each n(CCx) x treatable conditions x variables.

Group A consists of those who smoke normal cannabis, receiving a mixture of THC and other cannabinoids. According to evidence, Group A receives the Benedictions.

Group B is for the no THC-anything people. These are ones who insist that feeling good has no place in medicine, a dogma paralleling that of the bishops. Their treatment regimens are in the RDTGH group: they would rather die than get high.

The anti-euphoria brigade doesn't really make much sense. Its philosophy is post-Augustinian in origin. For centuries, medicine wasn't working if it wasn't hurting, or at least unpleasant. Most of these old treatments are now thought fantastical. But the idea has somehow lingered on that feeling well mustn't involve too much feeling good.

Group B will, according to the evidence, reject any Benedictions involving psychoactivity (except any psychoactivity that they enjoy), get fat and fall ill sooner or more often - out of principle. Group B accepts an irrational definition of psychoactivity.



The Defendant enjoys psychoactivity and, like it or not, the members of Group B contain the endogenous THC and CBD homologues AEA and 2-AG like everyone else. And also endogenous DMT. This topic requires extra-strong denial, as the Prosecution's ignorance of the ECS just makes the ZPPPD look even more stupid and their position more untenable. Actually it was always untenable. But no foreigner came to tell them.

Refusing to supplement their endocannabinoids could be a legal principle. Group B could be acting from professional ethics, fear of "drugs" except those they take but don't think of as drugs, fear of drug tests, or be otherwise reputationally-motivated. Group B get a reduced set of Benedictions, with a worst possible outcome of zero effect.

Group C wants everyone to wait until every single drug or their ingredients' effects have been tested against every single one of our putative three hundred fifty-four decillion seven hundred and sixty nonillion three hundred and forty-four octillion eight septillion two hundred and eleven sextillion four hundred and ninety-two quintillion four hundred and sixty-five quadrillion five hundred and forty-six trillion two hundred and fourteen billion eight hundred and eighty-two million forty-five thousand nine hundred and forty-two biological processes, plus probably every sociological process, and every other -ological process, to find out what people who smoke weed already know.

For context there are an estimated 200 sextillion stars in the universe. And for that figure I am obliged to
https://theconversation.com/how-many-stars-are-there-in-space-165370 [2663]

The European Space Agency offers a range of 10 sextillion to one septillion stars.
https://www.esa.int/Science_Exploration/Space_Science/Herschel/How_many_stars_are_there_in_the_Universe [2664]

Possibly Slovenia's favourite, Group C will die out of principle before it becomes possible for them to receive the Benedictions. Some members of Group C hope for for a population chained, in the future, to some patentable Frankenstein variant of CCx.

Group C also contains religious people and others who deny, or are unaware of, the existence of the Benedictions, or caution against allowing them for prejudiced or non-empirical reasons, and who say "more research is necessary".

Now as a member of Group A, the Defendant has no objection whatsoever to Groups B or C, who would rather do without the Benedictions, who would RDTGH, who prefer being ill to breaking the law or facing the stigma, or who are super-cautious except for alcohol, or who do not know the Benedictions exist. To be fair this last group is large.

But in contrast, Groups B and C do object to Group A getting the Benedictions. Which is to say they wish to impose their medical opinions, prohibitions, and sanctions on Group A and everything connected with it.

In terms of Constitutional right to belief it looks like this:




What gives them the right to inflict their - hopelessly wrong - choice upon the minority who have got it right? The answer is the ZPPPD.

Could they, for instance, pounce on the Defendant's inappropriateness for eating a pot of yoghurt? No, because yoghurt is not a proscribed substance.

Could they achieve their aims by insisting the Defendant dine morning, noon and night on bureks until reaching a massive girth and keeling over? Or that the Defendant must drink too much, while frowning at any suggestion of his that we don't?

Booze and bureks could achieve with compulsion what can be achieved voluntarily and willingly by Group B.

But prohibition of Group A produces outcomes comparable with an excess of booze and bureks.

The effect of the compulsory fare on the one hand and the prohibited Benedictions on the other is one and the same.

Compelling people to eat and drink might seem a little too much, an assault on the unwilling, really.

Yet eliciting the same results by banning CaPs is regarded as a legal duty.

What evidence is there that the Benedictions are not only ameliorative of morbid conditions, but also preventative, as implied by these two studies [922,923]?

The mechanistic targets enumerated in the Benedictions do not begin to exist only when we feel ill, get a diagnosis, or a lab test.

Cannabis users in population cohorts are among those with a healthier BMI. What are we arguing about and what is the ZPPPD, though obsolescent before it was born, achieving? What are prosecutions for these tortless acts trying to achieve? Are these achievements of the ZPPPD - e.g. fatter people with more cancer - worth the cost?

Prohibition intends, mostly unsuccessfully, to deprive users of these effects, and therefore of their human right to not be a big fat drunk heart failure victim, their human right to all the Benedictions, both those known and yet to be discovered.

Since there is no registered source of refined THCA as a low adipogenic PPARγ agonist, antifibrogen, or for the rest of the Benedictions, the only way to obtain it is along with all the congeners available in ordinary cannabis, with which the symbiotic relationship between humans and cannabis has evolved.

Do Ptuj people, with wine and tobacco in hand, uttering a stream of racist epithets, and with their irrational fondness for their Town Smell, really believe they will be better off by depriving others of the Benedictions?

Is getting the foreigner, with his unfashionably adequate accommodation and language, really so important for Slovenia, to be worth depriving an estimated minimum of 354,845 of their fellow-citizens of years of life and laughter? Is it smart to want that?

Although the Court is trying to ignore it, its prosecution is a hate crime, at both the microscopic and macroscopic levels. Is the hate generated worth preventing all the Benedictions?

The Defence concludes the present submission on the alleged inadmissibility of facts about drugs in drugs cases with the claim that with respect to CaPs, the ZPPPD is nothing more than an obsolete, dreary assault on public health, defended by those who insist on using their education to strain every sinew of the law, simply to avoid finding anything out.

You can search CCx by medical condition at https://acannability.com/periodictable/ [3714]