***PSYCHEDELICS AND MENTAL HEALTH

The New Establishment swears it has got it all right this time after a complete reversal - The desirability of brains explained - Your brain is not capable of absorbing all of neurology - Ways to lose your brain faster in Slovenia and the UK - Preventing population stupidity as an example of psychedelics-inspired cognition in action - Stigma and the psychedelic mums - Short-lived but long-lasting effects in pork chops - Portrait of the anti-euthanasia party as a pro-suicidal young man - "Sentence first, verdict afterwards" - Devastating effect on patriotic pastime - Resilience to stress - Aspects of the ZPPPD's criminalization of self-maintenance - Battlefield uses - Triangulation of organised mendacity, criminalized cures and justifiable motives for illegality

Research into psychedelics and mental health has waxed and waned inversely with the war on mental health...sorry, drugs...but recently it has only waxed:

Original: https://onlinelibrary.wiley.com/doi/10.1111/jnc.16017 [3364]

During the psychedelic sixties and on until 1983 it was believed brain cells only died, and that no new cells were made. This was challenged in 1962 by Jozef Altman but it was not until 1983 that improved techniques made adult neurogenesis credible, and it was finally confirmed in humans in 1998. So adult neurogenesis is younger than Slovenia and only one year older than the drafting of the ZPPPD.

From being part of the Nixon-era boogaloo, when shock horror stories circulated that LSD "kills your brain cells", psychedelics have become key to the study of adult neurogenesis and consciousness. Unfortunately this research was impeded by legal obstacles as well as technical ones. Nevertheless it turned out that psychedelics stimulate adult neurogenesis, and this includes CCx.

Writing in 2020, Abdissa et al in "Review Article on adult neurogenesis in humans" say:

"It is now widely accepted that new neurons are continually generated in specific regions in the adult brain. This occurs primarily in the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus in the hippocampus. Neuroblasts from the subventricular zone migrate along the rostral migratory stream into the olfactory bulb, whereas neuroblasts from the subgranular zone show relatively little migratory behavior, and differentiate into dentate gyrus granule cells. Growth factors, neurotrophins, cytokines, and hormones are also major regulators of adult neurogenesis."
https://www.sciencedirect.com/science/article/pii/S2214854X20300133 [3821]

A literature search in January 2023 using the PubMed and ScienceDirect databases, combining the keywords psychedelics and neurogenesis along with their respective MeSH [medical subject heading] terms.

https://molmed.biomedcentral.com/articles/10.1186/s10020-024-01013-4 [3820]

Tudorancea et al (2025) have some tips on "Psychedelic interventions for major depressive disorder in the elderly: Exploring novel therapies, promise and potential":

https://pmc.ncbi.nlm.nih.gov/articles/PMC12057789/ [5112]

Why might we seek to boost neurogenesis? According to Patel et al (2024) its enemy is monotony: not all of us end up performing novel tasks each day:

"Among 443 occupations studied, percentage of deaths attributed to Alzheimers disease for taxi drivers and ambulance drivers and each of the remaining 441 occupations, adjusting for age at death and other sociodemographic factors."

And...

"Of 8 972 221 people who had died with occupational information, 3.88% (348 328) had Alzheimers disease listed as a cause of death. Among taxi drivers, 1.03% (171/16 658) died from Alzheimers disease, while among ambulance drivers, the rate was 0.74% (10/1348). After adjustment, ambulance drivers (0.91% (95% confidence interval 0.35% to 1.48%)) and taxi drivers (1.03% (0.87% to 1.18%)) had the lowest proportion of deaths due to Alzheimers disease of all occupations examined. This trend was not observed in other transportation related jobs that are less reliant on real time spatial and navigational processing or for other types of dementia. Results were consistent whether Alzheimers disease was recorded as an underlying or contributing cause of death.

"Conclusions Taxi drivers and ambulance drivers, occupations involving frequent navigational and spatial processing, had the lowest proportions of deaths attributed to Alzheimers disease of all occupations."
https://www.bmj.com/content/387/bmj-2024-082194 [4782]

As Li and Wang (2026) explain:

"Many neuropsychiatric and neurodegenerative disorders share common pathological features, notably cortical atrophy, synaptic loss, and maladaptive neural circuit connections. Conditions ranging from major depression to Alzheimer's disease (AD) involve the regression of neural structure, shrinkage of dendritic arbors, loss of dendritic spines, and elimination of synapses in critical regions that mediate cognition and emotion. Chronic neuroinflammation often accompanies these structural changes, further exacerbating neural damage. Given this convergence, compounds capable of both promoting neuronal growth and modulating inflammation have enormous therapeutic potential across a spectrum of brain disorders. Psychedelics meet these criteria: they stimulate growth-factor signaling, activate cell-survival pathways, and can have immunomodulatory effects."
https://genomicpress.kglmeridian.com/view/journals/psychedelics/aop/article-10.61373-pp026w.0006/article-10.61373-pp026w.0006.xml [6868]

A quick intro to the brain:

"Prefrontal cortex, hippocampus, striatum and cerebellum are key brain structures due to their function. The prefrontal cortex is involved in the development of working memory, executive functions like planning of movement and regulation of emotion. The hippocampus is important for memory consolidationtransferring information from short-term memory into long-term memory. The striatum is part of the reward system and is necessary for voluntary motor control. The cerebellum is responsible for motor functions, maintaining balance and control of accurate multi-joint movements; it is strongly activated when learning new activities.

"Both physiological processes, such as the development of cognitive functions, and pathological processes, such as neurodegenerative changes, are accompanied by modifications of synapse structure and function. One of the key components of those processes is proteolysis of the extracellular matrix (ECM), which constitutes the environment for surrounding neurons and glial cells, at the same time serving as a specific modifier of those cells. ECM enzymes, including matrix metalloproteinases (MMPs), are involved in degrading certain ECM proteins, modulating cellular integrity and neuroplasticity. MMPs are also involved in regulating such processes as cell differentiation and migration, regulating growth factor activity, angiogenesis and inflammation by proteolytic degradation of growth factors and cell adhesion molecules. MMP2 and MMP9, belonging to the gelatinase subgroup, play the most crucial role in synaptic plasticity.

"Enzymatic remodeling of synaptic connections involving MMP9 and MMP2 is associated with such mechanisms as late-phase of long-term potentiation (LTP) impairment within hippocampal synapses, changes in dendritic spine morphology in hippocampal neurons, regeneration of nerve fibers as a result of digestion of damaged ECM components, as well as axon regeneration and elongation. Those enzymes are also implicated in morphological changes and maturation of dendritic spines.

"MMP activity and expression are strictly controlled on several levels. One of such control mechanisms is the activity of tissue inhibitors of matrix metalloproteinasesTIMPs, among which TIMP2 is the specific inhibitor of MMP2, while TIMP3 exerts a broad-spectrum inhibitory effect against several subgroups of metalloproteinases (including MMP2 and MMP9) and adamalysins (ADAMs). TIMP2 and TIMP3 are also involved in regulating cellular processes, such as cell proliferation, apoptosis and angiogenesis through different mechanisms, not related to MMP inhibition."

The article discusses the role of TIMPs in fluorosis, a condition I witnessed in my former place of residence. Fluoride is bad for TIMP2, which is bad for inflammation and bad for cognitive function.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796218/ [1572]

Before we get going on some of the aspects of psychedelics and cognitive impairment, we need some more background about matrix metalloproteinase 9 (MMP-9):

"The MMPs constitute a large group of zinc-dependent endopeptidases which have the capability of cleaving protein constituents of the extracellular matrix; MMPs may also activate or inactivate particular signaling molecules including adhesion molecules, receptors and growth factors. MMP family members are broadly categorized into the following groups of enzymes: collagenases, stromelysins, gelatinases, and membrane-type metalloproteinases. They normally exist in an inactive pro-form and require conversion to their active forms. The activity of MMPs is also controlled by endogenous inhibitors, the tissue inhibitors of MMPs (TIMPs), and an endogenous stimulator, extracellular matrix metalloproteinase inducer (EMMPRIN). In addition, plasmin can activate MMPs to degrade a range of extracellular matrix molecules. Reactive oxygen species (ROS) also contribute to MMP activity by activating the preforms of MMPs, or inducing expression of their mRNA through signaling via NF-κB.

"Activated MMPs are implicated in many processes such as cell survival, signaling, angiogenesis, inflammation, and cell motility. They may directly injure brain cells by means of processing death molecules, disrupting myelin, and perpetuating neuroinflammation.

"Among MMP members, the most important may be MMP−9. It is implicated in the remodeling and stabilization of dendritic spines, pre and post-synaptic receptor dynamics, consolidation of long term potentiation, synaptic pruning and myelin formation. MMP-9 is also involved in the sprouting, pathfinding and regeneration of axons. MMP-9 is normally expressed in barely detectable level in the brain but after an injury, it is strongly detected in many cell types including endothelial cells and infiltrated neutrophils. MMP-9 (Gelatinase B) is induced after injury through factors such as the c-fos and c-june, immediate early genes and by the cytokines, TNF-α and interleukin-1β."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971905/ [1574]

A 2017 article in Scientific American summarises some other findings about TIMPs concerning reversal of cognitive decline and longevity:

"The researchers used radioactive labeling to show TIMP2 injected intravenously crosses the bloodbrain barrier. They then injected the protein into elderly mice with normal immune systems, and found this reproduced the beneficial effects of cord plasma on both memory performance and LTP in the hippocampus whereas mice engineered to lack TIMP2 showed reduced LTP. These results show TIMP2 is sufficient to produce beneficial effects. So to also demonstrate TIMP2 is necessary for memory function, they injected regular young mice with TIMP2-neutralizing antibodies. This made young mice perform very poorly in a spatial memory task. Finally they showed old (immunodeficient) mice treated with cord plasma from which TIMP2 had been removed presented none of the improvements in memory performance seen using normal plasma. 'We were surprised by this,' Wyss-Coray says. 'I didn't expect it would be that clear-cut.'
https://www.scientificamerican.com/article/fountain-of-youth-young-blood-infusions-ldquo-rejuvenate-rdquo-old-mice/ [1571]

As an example of the effects drugs can have upon on cognitive function at the population level, a drink-spiking gang who had succumbed to peer pressure began a scheme to do the opposite of these things - that is, lower TNF-α and IL-1β and raise IL-6 and COX-2 concentrations in their victims.

Their plans were finalised in 1968 and in 1970 the drink-spiking began. Only one of the twenty members of this drug gang had any medical training, and was one of a couple of notorious psychiatrists at a notorious local mental hospital which, then, was a sort of dumping ground for awkward relatives and oversexed ladies.

The drink spikers were generally rather pompous but unremarkable provincial people who had risen to positions of political influence in this historic city through party structures.

After this population had been spiked on and off for a decade, someone who took mushrooms arrived. Initially he believed in fluoride just like the spikers and their victims. But he was curious about all the missing information, and the answers to the questions the fluoridated people had failed to ask. What was this drug? Who were the dealers? Was what they claimed reliable? What about the quality of the drug? And many more. This curiosity he couldn't help - it was an odd and novel situation for him, the first spiked population he had lived among. And the more he looked around him, the more it became clear it was a rough place. The victims and perpetrators were both suffering from delusions. Many thought they were water. They believed the only part of them influenced by water was their teeth. The cause was American pro-drug propaganda.

Within a short period this user of psychedelics and marijuana became the first member of the public to discover the origin of the fluoride being put in them, question their dosage regimen, and create a sort of early database of information where they could find out what it does. Nowadays you can just find it on the internet. But it was not so easy or cheap then. Opponents of being spiked were scattered, with no email or Twitter, only printed newsletters and letters to the Editor which, if they were any use, would not get printed.

All of which information was and forever will be enthusiastically denied by the people who had put the fluoride in the population. The revelations were hardly trusted by many observers for various psychological reasons, while any detailed evidence of the credibility of these assertions was completely censored by the press.

Now, with the advent of such studies as [1570] and the legal outcome of Food & Water Watch Inc. et al v. United States Environmental Protection Agency in the Northern District Court of California Case No. 17-cv-02162-EMC, this Court is invited to observe that that mushroom guy was just more clued-up about what was going on around him. And that those who thought he was nuts were just typecasting him in a way they had been taught to do, like mice, Trump supporters, Brexiteers and Slovenian drug prohibition experts.

The Defence avers the unifying characteristic of these groups is that the simplistic beliefs with which followers of these have been misled, or have misled themselves out of fear or inexperience, are rather easily apparent to those outside the cult.

We cannot force these adherents to leave the cult. We do not believe in forcing them to ingest psychedelics, that our reality will be revealed to them. Many, after all, manage to be perfectly smart and balanced in their opinions without them.

Instead CaPs users have to watch them squirming around with what skewed information they have, trying to understand the ineffable in the inadequate terminologies of their various professions.

And thanks to that psychedelic guy, the Defendant, those wishing to delay the cognitive decline of their children were able to avoid being fluoridated, somewhat, and keep their marbles, somewhat, albeit at great expense and inconvenience.

And that's my little service to the world thanks to the benefits of psychedelic drugs. The Defendant is no genius nor highly qualified so there must be another explanation for his prescience, beating the California court on the topic of fluoride and brain damage by some forty years.
www.nfl.si/fi [1573]
https://childrenshealthdefense.org/wp-content/uploads/Court-Ruling.pdf [3627]

Whilst waiting for the unpsychedelic world to catch up, and in the hope of eluding unavoidable adventitious fluoridatedness, the Defendant came to Ptuj, where he was the first person to notice the Town Smell and decide to do something about it. And the rest is history.

Some of that history has been captured by Monitoring the Future Panel Study Annual Report 2024:

"Hallucinogen use in the past 12 months was reported by 4.2% of early midlife adults ages 35 to 50 in 2023, which is the highest level recorded since it was first available for the full age range in 2008 (Table/Figure 45). There have been significant increases over the past 5 years and 10 years (from 0.6% in 2013, and 1.4% in 2018; Table/Figure 45). Use ranged from 2.8% at age 50 to 9.6% at age 35 (Table/Figure 46)."

These are US trends.




What is attracting people of all ages to psychedelics? A pattern of self-reliance and a turn away from the risks of pharma is suggested. Culture writer Kat Rosenfield asked them:

"I spoke to a dozen women who use psychedelics regularly, and found them to be a diverse bunch: They come from different generations and socioeconomic backgrounds; they do drugs of different types, on different schedules, for different reasons. And despite the Goop-y vibes, none were taking psychedelics in search of a woo-woo wellness experience; indeed, many of them began experimenting with MDMA, LSD, mushrooms, or ketamine only after struggling for years within the confines of a medical system that continually failed them. Some suffered from treatment-resistant depression, or from severe anxiety, or from post-traumatic stress disorder brought on by serious trauma.

"What they all have in common is a passionate belief in psychedelics as a source of healing and a force for good, one that can sometimes verge on the evangelical. They are, however, keenly aware that their zeal is shared neither by the federal government nor the average HR department which is why everybody featured in this story has been given a pseudonym to protect their privacy. As Rachel put it: 'I like having custody of my kids.'

"The stigma surrounding these substances is a source of frustration, but also something many of these women understandparticularly the ones who came of age at the height of the 1990s-era War on Drugs and the accompanying government program D.A.R.E., a valiant but ill-fated attempt to transform the countrys middle schoolers into an army of tiny narcs. Rachel fully realized how much of the 'just say no' messaging was based on fear rather than facts when she read How to Change Your Mind, Michael Pollans book about the science of psychedelics.

"'I feel like we were just so lied to,' Rachel said. 'Mushrooms or LSD or MDMA, the way that they were sold as gateway drugs. "Youre going to end up on the street and youre going to get raped." But these are really impactful experiences.'"
https://www.thefp.com/p/female-psychedelic-users-ketamine-mushroom-mommies?utm_source=substack&utm_medium=email [3626]

America might be lagging behind. In "Psychedelics and Mental Health: A Population Study" (2013) by the Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway:

21,967 respondents (13.4% weighted) reported lifetime psychedelic use. There were no significant associations between lifetime use of any psychedelics, lifetime use of specific psychedelics (LSD, psilocybin, mescaline, peyote), or past year use of LSD and increased rate of any of the mental health outcomes. Rather, in several cases psychedelic use was associated with lower rate of mental health problems. Conclusion: We did not find use of psychedelics to be an independent risk factor for mental health problems.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747247/ [313]

Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population, says the Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, AL:

"Lifetime classic psychedelic use was associated with a significantly reduced odds of past month psychological distress (weighted odds ratio (OR)=0.81 (0.720.91)), past year suicidal thinking (weighted OR=0.86 (0.780.94)), past year suicidal planning (weighted OR=0.71 (0.540.94)), and past year suicide attempt (weighted OR=0.64 (0.460.89)), whereas lifetime illicit use of other drugs was largely associated with an increased likelihood of these outcomes."
https://pubmed.ncbi.nlm.nih.gov/25586402/ [1028]

Supportively, in psychedelic pigs with brains like ours, but which unlike ourselves can be made into pork chops any time:

"An analysis of prefrontal cortex tissue revealed that 19 genes were differentially expressed one day after psilocybin administration. But only 3 genes were differentially expressed in the brain tissue one week later.

"'This observation was unexpected, given the profound and lasting effects that have been observed after a single dose of psilocybin,' the researchers said.

"Knudsen told PsyPost that there were 'surprisingly few changes to be observed in the brain 24 hours and 7 days after a single dose of psilocybin.'

"Immune-related genes constituted the largest group of genes impacted one week after psilocybin administration, suggesting that the long-lasting effects of the psychedelic substance might be related to neuroinflammation.

"'Neuroinflammation is now recognised as key player in psychiatric diseases, such as depression, with positive outcomes of treatment with anti-inflammatory compounds,' the researchers wrote.
https://www.psypost.org/2021/01/psilocybin-produces-an-immunology-related-genetic-response-in-the-prefrontal-cortex-of-pig-brains-59115 [1623]

It seems President Nixon, the Prosecution and its witnesses, the Ptuj Police, and the ZPPPD are in favour of NEPUD-related suicidality, as according to Zhang et al (2025):

"Psilocybin is among the most extensively studied psychedelics, with previous research suggesting its potential therapeutic role in suicide prevention. However, the precise mechanisms through which psilocybin may aid in suicide prevention remain unclear. This study thus employed network pharmacology and molecular docking tools to explore the mechanisms by which psilocybin may contribute to suicide prevention. Relevant drug- and disease-related targets were identified. Overlapping drug- and disease-related targets were extracted from the bioinformatics platform and imported into the STRING database to construct a protein-protein interaction (PPI) network. Key targets were selected based on topological parameters derived from network analyses conducted using Cytoscape 3.10.1. These key targets were further analyzed using GO and KEGG enrichment approaches conducted with the DAVID tool. A drug-disease-target-pathway network was subsequently constructed in Cytoscape 3.10.1. Finally, molecular docking analyses were performed to assess psilocybins potential to interact with key targets using AutoDock Vina and the PyMOL software. A total of 46 potential targets associated with psilocybin and relevant to suicide treatment were identified, of which 13 were imported into the DAVID tool for enrichment analyses. Network analyses identified four targetsHTR2A, HTR2C, HTR7, and PRKACAthat may serve as therapeutic targets for psilocybin in suicide prevention. Enrichment analysis outcomes suggested that psilocybin may prevent suicide by modulating the serotonergic synapse and calcium signaling pathways. Molecular docking analyses revealed that HTR2A, HTR2C, HTR7, and PRKACA strongly bind to psilocybin. This study provides insights into the molecular mechanisms underlying the potential role of psilocybin in suicide prevention, offering a novel basis for further research."

Finally, in a ritual incantation required by RDTGH, the authors express concern about people's "abuse" of and "addiction" to anti-suicidality, though they immediately and rightly point to the anti-addictive effects of psychedelics.
https://www.nature.com/articles/s41398-025-03410-7 [5086]

Now research into psilocybin therapy and suicide is dogged by small numbers. According to "Effect of psilocybin therapy on suicidal ideation, attempts, and deaths in people with psychiatric diagnoses: a systematic review and meta-analysis" by Wong et al (2025):

"Nine studies involved 593 adults, comparing those who received PT (335 people) to those who did not and were in a control group (258 people).

"3. PT led to a small but significant reduction in suicidal ideation. There were no instances of suicide attempts or completed suicides reported. However, most studies did not report on suicide attempts or completed suicides."
https://pmc.ncbi.nlm.nih.gov/articles/PMC12417673 [5519]

"The Multifaceted Empathy Test (MET) was used to assess the effects of LSD on emotional empathy" by a psychopharmacological team at the University of Basel.

Oxytocin plays a role in social bonding, reproduction, childbirth, and the period after childbirth. Prohibition must be against this sort of thing, as when plasma oxytocin levels were measured,

"LSD dose-dependently increased implicit and explicit emotional empathy, with the highest 200 g LSD dose having a significant effect compared with placebo. The 200 g dose of LSD also moderately increased plasma oxytocin levels compared with placebo."

In general:

"LSD has been shown to produce empathogenic and prosocial effects (Dolder et al., 2016; Schmid et al., 2015). Specifically, LSD acutely increased feelings of subjective well-being, happiness, closeness to others, openness, and trust (Dolder et al., 2016; Schmid et al., 2015), impaired the recognition of sad and fearful faces in the Face Emotion Recognition Task, enhanced emotional empathy in the Multifaceted Empathy Test (MET), and increased prosocial behavior in the Social Value Orientation Test."
https://www.frontiersin.org/articles/10.3389/fphar.2021.711255/full [314]

In "The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs" (2014) Carhart-Harris et al note:

"Many psychiatrists working with psychedelics in the 1950s and 60s expressed great enthusiasm about their therapeutic potential (Crocket et al., 1963; Abramson, 1967; Grinspoon and Bakalar, 1979; Grof, 1980) but there was an unfortunate failure to substantiate these beliefs with properly controlled studies. Subsequent reviews and meta-analyses have suggested an impressive efficacy, especially in relation to the use of LSD in the treatment of alcohol dependence (Mangini, 1998; Dyck, 2005; Krebs and Johansen, 2012) and modern trials have lent some support to this sentiment (Moreno et al., 2006; Grob et al., 2011). For example, a single high dose of psilocybin produced profound existential experiences in healthy volunteers that had a lasting beneficial impact on subjective well-being (Griffiths et al., 2006, 2008) and a moderate single dose of psilocybin administered to patients with advanced-stage cancer significantly reduced anxiety and depression scores for months after the acute experience (Grob et al., 2011). In another study, symptoms of obsessive compulsive disorder (OCD) were significantly reduced after psilocybin (Moreno et al., 2006). Supplementing these controlled studies, we surveyed over 500 recreational drug users, and found that 67% of LSD users and 60% of psilocybin users claimed that use of these drugs had produced long-term positive effects on their sense of well-being (Carhart-Harris and Nutt, 2010), consistent with the results of the aforementioned controlled studies (Griffiths et al., 2006, 2011). To place this in a context, only 6% of alcohol users claimed such improvements from alcohol use (Carhart-Harris and Nutt, 2010). One of the most remarkable properties of psychedelics is their potential to have a lasting impact on personality and outlook (McGlothlin and Arnold, 1971; Studerus et al., 2011). Personality traits are known to be relatively fixed by adulthood (Costa and McCrae, 1997; McCrae and Costa, 1997), however, the personality trait 'openness' was found to be significantly increased over 14 months after a single controlled administration of psilocybin (MacLean et al., 2011). Moreover, neuroimaging studies (Carhart-Harris et al., 2012a) have found decreased activity and connectivity after psilocybin in brain regions (e.g., the mPFC) and networks (e.g., the DMN) that are over-engaged in depression (Greicius et al., 2007; Berman et al., 2011) but normalized by a range of effective treatments (Goldapple et al., 2004; Mayberg et al., 2005; Kennedy et al., 2007; Deakin et al., 2008)."
https://www.frontiersin.org/articles/10.3389/fnhum.2014.00020/full [4437]

Griffiths et al (2006) reported:

"Psilocybin produced a range of acute perceptual changes, subjective experiences, and labile moods including anxiety. Psilocybin also increased measures of mystical experience. At 2 months, the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained positive changes in attitudes and behavior consistent with changes rated by community observers."
https://link.springer.com/article/10.1007/s00213-006-0457-5 [3937]

According to 2020's "Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains":

"Psychedelic drugs, such as psilocybin and LSD, represent unique tools for researchers investigating the neural origins of consciousness."

I must add this interests me and no one else is going to investigate my consciousness for me...and anyone can have a go at this...you don't have to be qualified...

"Currently, the most compelling theories of how psychedelics exert their effects is by increasing the complexity of brain activity and moving the system towards a critical point between order and disorder, creating more dynamic and complex patterns of neural activity."

and

"Lempel-Ziv complexity (LZC), is a commonly-used measure of signal complexity in consciousness studies (Schartner et al., 2015, 2017a; Schaefer et al., 2017). Lempel-Ziv complexity can be best thought of as a measure of the entropy rate of a signal, giving an estimate of the information-density per unit time (Amig et al., 2004). Alternately, it can be understood as an upper-bound on the algorithmic complexity of a time-series based on how compressible it is (Ruffini, 2017a)."

so

"20 healthy volunteers underwent two scans, 14 days apart. On one day they were given a placebo (10-mL saline) and on the other they were given an active dose of LSD (75 ​μg of LSD in 10-mL saline)."

producing this result



in which we see, from the description

"Two binarized, 1000-ROI [regions of interest, according to Yeo and Schaefer's scheme of Local/Global parcellation] adjacency matrices from a single, randomly chosen subject, and their associated functional connectivity graphs (A A, etc). In the adjacency matrices, every pixel represents an edge between two nodes: if the pixel is white, the edge exists, if black, the edge does not exist. A is the functional connectivity matrix from the placebo condition, B is the matrix from the LSD condition. While the differences in fractal character are not intuitively obvious upon visual inspection, subtle differences in the distribution of connections can be seen."
https://www.sciencedirect.com/science/article/pii/S1053811920305358 [1172]

The Schaefer Local/Global parcellation methodology is laid out at
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095216/ [1173]

"Lempel-Ziv (LZ) complexity is a relatively simple method that has been robustly applied to cognitive neuroscientific work on consciousness (Casali et al., 2013; Mediano et al., 2024; Pascovich et al., 2022; Schartner et al., 2015, 2017). LZ complexity is computed through the binarisation of the signal around its median, where all values above the median are 1, and all values below the median are 0. The binarised signal is then algorithmically scanned sequentially for novel patterns within the signal (Kaspar and Schuster, 1987), creating a dictionary of binary sequences for each timeseries. The length of this dictionary is a standardised measure of the complexity of the signal."

The research use of psychedelics to try to rationalise fun, revelation and mental stability continues - however it was decided prior to these investigations were conceived that doing your own research is illegal. Illegality influences the experience.

Quantifying every aspect of human beings being themselves has no useful outcome for the typical user. Understanding Lempel-Ziv will not make the shortcomings of your apartment more tolerable, or increase empathy between neighbours with different drug use profiles.

In terms of everyday reality the researchers are somewhat lost.

But it has to be done, and Lewis-Healey et al (2024) actually found Lempel-Ziv to be the least significant association in a study of "Time-resolved neural and experience dynamics of medium and high-dose DMT" among a dizzying array of neural markers:

"We computed a variety of neural features broadly associated with the psychedelic-state, using a similar approach to Engemann et al. (2018) and Sitt et al. (2014). On the EEG data, we computed Lempel-Ziv complexity, permutation entropy, oscillatory power (delta, theta, alpha, beta), aperiodic spectral features (offset and exponent), weighted phase lag information, and weighted symbolic mutual information. Broadly, the neural markers computed fell into three families of markers: information theory, spectral, and connectivity. Spectral and information theory markers were summarised by computing the median average from each electrode in frontal (FP1, FP2, F3, F4, F7, F8, FZ, FC1, FC2, FC5, FC6), central (C3, C4, CZ), parietal (P3, P4, P7, P8, PZ, CP1, CP2, CP5, CP6), occipital (O1, O2), temporal (T7, T8, TP9, TP10, FT9, FT10), and global (all channels) regions. For connectivity measures, the median average was taken for pairings both within and between channels contained in the defined regions above (frontal, central, parietal, occipital, temporal). Global connectivity was computed as the median connectivity value for all channel pairings."



Among the findings:

"Our targeted analyses revealed that oscillatory alpha power was significantly more associated with TET [Temporal Experience Tracing] dimensions than permutation entropy (D = 0.69, p<0.001), permutation entropy was significantly more associated with TET dimensions than LZ complexity (D = 0.25, p<0.001), and wSMI was significantly more associated with TET dimensions than wPLI (D = 0.76, p<0.001). See Figure 4D for distributions of the effect sizes across all neural markers. For all neurophenomenological associations, positive valence dimensions (i.e., Bliss and Pleasantness) yielded the opposite trends to the rest of the TET dimensions. For example, both Pleasantness and Bliss were positively associated with oscillatory alpha power, while the rest of the phenomenological dimensions were negatively associated with oscillatory alpha power. Interestingly, this is in contrast to a previous study with TET and breathwork (Lewis-Healey et al., 2024), which found positive and significant associations between both neural LZ complexity and the aperiodic exponent - but not alpha oscillatory power - and the phenomenological dimension of Bliss."
https://www.biorxiv.org/content/biorxiv/early/2024/12/20/2024.12.19.629418.full.pdf [3827]

The Defendant doesn't understand all of the content of these papers. It's not necessary to enjoy the benefits of the experience.

Slightly more approachable is the related finding that

"brain complexity may offer a proficuous way of indexing the psychological effects of mind-altering substances via their neurobiological effects."
https://www.sciencedirect.com/science/article/pii/S1053811920311381 [1174]

and the temporal dimension of consciousness interests consciousness fans because it is apparently unvarying:

"Time-dimension, unlike other three dimensions of our physical universe, is never perceived as a novelty, but only reported as the flow of time."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322218/ [1175]

The Defence doesn't necessarily agree with this value judgement. Who hasn't experienced a moment when "time stood still", or felt that "time has flown"? Are these due to not noticing time, or to seeing it in a different way?

Considering how a perception of time distortion might affect emotions, we mention the case of Lola, a 13-year-old, 13-kilogram mixed-breed dog, with a history of severe anxiety according to the canine anxiety assessment scales used.

Following administration of 5 g of 1cp-LSD:

"...specific symptoms of anxiety related to separation from her owner were mitigated, such as reduced barking, crying, and overall distress."
https://link.springer.com/article/10.1007/s11259-024-10542-6 [3570]

At any rate Lola's owner seemed satisfied with the result. In another doggy adventure from Ren et al, "Disrupted HumanDog Interbrain Neural Coupling in Autism-Associated Shank3 Mutant Dogs" (2024) we learn that:

"Dogs interact with humans effectively and intimately. However, the neural underpinnings for such interspecies social communication are not understood. It is known that interbrain activity coupling, i.e., the synchronization of neural activity between individuals, represents the neural basis of social interactions. Here, previously unknown cross-species interbrain activity coupling in interacting humandog dyads is reported. By analyzing electroencephalography signals from both dogs and humans, it is found that mutual gaze and petting induce interbrain synchronization in the frontal and parietal regions of the humandog dyads, respectively. The strength of the synchronization increases with growing familiarity of the humandog dyad over five days, and the information flow analysis suggests that the human is the leader while the dog is the follower during humandog interactions. Furthermore, dogs with Shank3 mutations, which represent a promising complementary animal model of autism spectrum disorders (ASD), show a loss of interbrain coupling and reduced attention during humandog interactions. Such abnormalities are rescued by the psychedelic lysergic acid diethylamide (LSD). The results reveal previously unknown interbrain synchronizations within an interacting humandog dyad which may underlie the interspecies communication, and suggest a potential of LSD for the amelioration of social impairment in patients with ASD."
https://onlinelibrary.wiley.com/doi/10.1002/advs.202402493 [3571]

Back at Imperial College they are making up for lost time and marching on with "Increased global integration in the brain after psilocybin therapy for depression":

"Response to psilocybin correlates with network flexibility. The specific changes in network recruitment observed 1 d after psilocybin therapy in the open-label trial were not replicated at 3 weeks in this DB-RCT [double blind random controlled trial](Supplementary Information). However, the faster fMRI scanning protocol adopted in the DB-RCT generated twice as much temporal data per scanning session (Methods). This provided the rare opportunity to examine changes in the dynamic flexibility of brain networks following psilocybin therapy.

"The metric known as 'dynamic flexibility' indexes how often brain regions change their community allegiance over time, during the course of an fMRI scan....Reduced functional dynamics have been previously associated with depression symptomology. In an exploratory analysis, post-psilocybin therapy changes in network flexibility were correlated with changes in BDI [Beck Depression Inventory] score (Fig. 5c). After FDR [false discovery rate] correction, increased EN [executive network] dynamic flexibility strongly correlated with greater symptom improvement at the 6-week primary end point for the psilocybin arm (r20=−0.76, 95% CI −0.90 to −0.50, P=0.001)."
https://www.nature.com/articles/s41591-022-01744-z.pdf [1176]

In 2023 Dunlop et al showed in the American Journal of Psychiatry that cognitive behavioural therapy (in common with psychedelics) increases functional connectivity, while antidepressants reduce it:

"Objective:
The authors sought to determine the shared and unique changes in brain resting-state functional connectivity (rsFC) between patients with major depressive disorder who achieved remission with cognitive-behavioral therapy (CBT) or with antidepressant medication.

"Methods:
The Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) trial randomized adults with treatment-naive major depressive disorder to 12 weeks of treatment with CBT (16 1-hour sessions) or medication (duloxetine 3060 mg/day or escitalopram 1020 mg/day). Resting-state functional MRI scans were performed at baseline and at week 12. The primary outcome was change in the whole-brain rsFC of four seeded brain networks among participants who achieved remission.

"Results:
Of the 131 completers with usable MRI data (74 female; mean age, 39.8 years), remission was achieved by 19 of 40 CBT-treated and 45 of 91 medication-treated patients. Three patterns of connectivity changes were observed. First, those who remitted with either treatment shared a pattern of reduction in rsFC between the subcallosal cingulate cortex and the motor cortex. Second, reciprocal rsFC changes were observed across multiple networks, primarily increases in CBT remitters and decreases in medication remitters. And third, in CBT remitters only, rsFC increased within the executive control network and between the executive control network and parietal attention regions.

"Conclusions:
Remission from major depression via treatment with CBT or medication is associated with changes in rsFC that are mostly specific to the treatment modality, providing biological support for the clinical practice of switching between or combining these treatment approaches. Medication is associated with broadly inhibitory effects. In CBT remitters, the increase in rsFC strength between networks involved in cognitive control and attention provides biological support for the theorized mechanism of CBT. Reducing affective network connectivity with motor systems is a shared process important for remission with both CBT and medication."


https://ajp.psychiatryonline.org/doi/abs/10.1176/appi.ajp.21070727 [4317]

Godfrey et al (2025) consider "Effects of psychedelics on human oscillatory brain activity" to be a sound measure of trippiness, which

"...reviews the effects of classic psychedelics on human oscillatory brain activity, as measured by resting-state electroencephalography (EEG) and magnetoencephalography (MEG). Across moderate to high doses of LSD, psilocybin, ayahuasca, and DMT, a consistent reduction in alpha power (8-13 Hz) emerges, particularly in occipital regions. Below 30 Hz, desynchronization is typical, although DMT can preserve or even increase delta/theta activity, possibly reflecting its immersive, immersive visual phenomenology. Complementing these spectral findings, measures of signal diversity (e.g., Lempel-Ziv complexity) reliably increase during psychedelic states, indicating a more variable and unpredictable pattern of neural firing. Retrospective subjective ratings of the psychedelic experience often fail to align consistently with M/EEG changes, possibly because fleeting, key experiences are obscured by data averaging or recording short segments of a long experience. In contrast, real-time evaluations of subjective intensity and plasma levels robustly covary with changes in spectral power and complexity, highlighting the potential for objective, real-time EEG biomarkers of drug activity. Limited research on functional connectivity and cortical travelling waves suggest that directed, top-down control may decrease while bottom-up signaling increases, indicating a transient reversal of typical hierarchical organization, though replications are warrented. Future work should implement more unified methodological approaches, alongside high-resolution behavioral sampling, to further our understanding of how these altered brain dynamics give rise to the distinctive qualities of the psychedelic experience. Notably, EEG has yet to be evaluated in clinical studies, and future work should aim to explore the relationship between acute EEG changes and clinical responses to psychedelic therapy."
https://pubmed.ncbi.nlm.nih.gov/40541309/ [5253]

Szafoni et al (2024) in "Unlocking the healing power of psilocybin: an overview of the role of psilocybin therapy in major depressive disorder, obsessive-compulsive disorder and substance use disorder" explain that:

"In relation to depression, the role of the glutamatergic system and modulators of glutamate receptors has been discussed extensively in the literature as potential treatments. One such substance is esketamine, an antagonist of one of the glutamate receptors N-Methyl-D-Aspartate (NMDA). It has shown rapid and sustained antidepressant effects in patients with treatment-resistant depression and major depressive disorder, raising high therapeutic hopes for other modulators of the glutamatergic system, including psilocybin. With regard to the serotonergic system itself, which probably plays a central role in the effects observed after psilocybin ingestion, the structural and chemical similarity between its metabolite psilocin and serotonin should be emphasized. In other words, this implies the possibility of binding to serotonergic receptors, which are densely localized in numerous brain regions, including those closely associated with the manifestation of depression and anxiety symptoms. Interestingly, this aspect should be of interest not only in the context of research on MDD and OCD, but also with regard to the addictions currently under discussion. It is not uncommon for individuals with substance use disorders (SUD) to experience depression and anxiety-like symptoms, especially during abrupt withdrawal. In addition, all of the patient groups we have mentioned suffer from chronic stress. This has been documented in the literature and is associated with changes in hormone levels and dysregulated function of the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis is a neuroendocrine system responsible for regulating the stress response and maintaining internal balance in the face of changing environmental conditions. The potential effect of psilocybin on this axis would be via the activation of serotonergic receptors in the hypothalamus, which trigger the secretion of corticotropin-releasing factor (CRF) and thus cause the activation of the HPA axis. Interestingly, this is consistent with reports that psilocybin can transiently increase cortisol and ACTH levels even without a stress test, with levels returning to baseline after a few hours.

"Given the important role of cortisol in the proper functioning of learning and memory processes, an increase in cortisol may be particularly relevant in a therapeutic context. First of all, it should be mentioned that all of the above-mentioned patient groups struggle with deficits in various memory components. The temporary increase in cortisol levels can support the patients formation of new crucial beliefs by promoting learning and memory processes and change their attitude towards various past life experiences. In this context, it is crucial to emphasize that non-adaptive and inflexible beliefs interfere with therapy and affect emotions and behavior in patients with depression, obsessive-compulsive disorder and drug addiction. For example, an alcohol-dependent person may have a fixed behavioral pattern of automatically resorting to alcohol consumption when faced with a strong stressful stimulus in order to relieve emotional tension or distance themselves from the problem at hand. A similar problem can occur in people suffering from obsessive-compulsive disorder, in which certain situations trigger cognitive or behavioral automatisms. Similarly, people with depression often have a self-propelling cycle of negative thoughts that can lead to a lack of specific, required action for the individual. Breaking these patterns requires the formation of new neural pathways that gradually become dominant over time in a given situation. These changes, supported by mechanisms that promote neuroplasticity, are among the most important in the context of psilocybin-assisted psychotherapy. The phenomenon of neuroplasticity, which characterizes the brains ability to adapt and change in response to a range of experiences, reflecting the dynamic adaptability of neural circuits, is closely related to the psychoplastogens model. This model assumes that various substances known as psychoplastogens, e.g. classical psychedelics, influence the nervous system through a kind of autoregulatory feedback loop, thus promoting neuroplasticity. In short, these substances have been shown to increase synaptic growth and dendritic complexity and increase connections between neurons. This enhanced neuroplasticity is attributed to their postsynaptic effects in the medial prefrontal cortex, specifically in the fifth layer, where they stimulate glutamate release and activate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. As a result, this process triggers the Brain-Derived Neurotrophic Factor - Tropomyosin Receptor Kinase B (BDNF-TrkB) and mTOR signaling pathways, leading to upregulation of genes associated with neuroplasticity and synaptic protein synthesis."

https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1406888/full [3137]

Johnson and Rosenblat (2024) examine "Psilocybin-assisted psychotherapy as an anti-distressant with multidimensional properties".
https://www.nature.com/articles/s44220-024-00332-z [3694]

"Psilocybin mitigates behavioral despair and cognitive impairment in treatment-resistant depression model using wistar kyoto rats" say Wang et al (2025):

"Behavioral assessments demonstrated a significant and sustained beneficial effect of psilocybin on behavioral despair and cognitive impairment. Biochemical analyses revealed psilocybin-induced increases in thyroid-stimulating hormone (TSH) levels without significant changes in the hypothalamic-pituitary-adrenal (HPA) axis. The ability of psilocybin to counter stress-induced TSH reductions suggested that TSH may serve as a proxy marker of therapeutic response, although its causal role in mood regulation remains unclear. Additionally, following psilocybin administration, changes in cannabinoid receptor type I (CB1R) suggest a potential modulation of psilocybin intervention on the component of the endocannabinoid system (ECS), though causal links remain unconfirmed without antagonist studies. These findings highlight the potential of psilocybin to treat TRD through the targeting of previously unexplored biological pathways."

And of particular note:

"The present study demonstrates that early intervention with low-dose psilocybin effectively mitigates behavioral despair and recognition impairment in a diathesis-related stress model of TRD in WKY rats. WKY rats are known for their limited responsiveness to conventional antidepressants, their exposure to the chronic SIS paradigm incorporates biological, psychological, and social stressors to create a more comprehensive and accurate TRD model involving diathesis-stress interaction. Stressed WKY rats exhibit behavioral changes including increased locomotion in the OFT, increased risk assessment behavior in the EPM, and increased immobility during the FST. Early psilocybin intervention attenuates some of these behavioral responses. Namely, psilocybin intervention significantly reduces immobility in the FST, suggesting improved passive coping strategies typically observed in depressive-like states. Furthermore, our findings corroborate previous studies that demonstrated improvements in familiarity recognition and memory retention in NOR test, along with reduced time spent on cognitively driven risk assessment behaviors in the EPM, suggesting psilocybins cognitive benefits.

"While the serotonin 2 A (5-HT2 A) receptor is commonly believed to be the primary mediator for psilocybins psychoactive effects, recent research indicates that the antidepressant effects of psilocybin may occur independently of its psychedelic properties and, therefore, may not rely on the activation of 5-HT2 A receptor. Previous research has suggested that antidepressants targeting norepinephrine (NE) typically promote climbing in the FST, whereas those affecting serotonin (5-HT) enhance swimming. In this study, psilocybin intervention decreased immobility and enhanced both swimming and climbing behaviors, suggesting that psilocybin may target NE in addition to 5-HT. Although not significant, increased general activity and open-arm exploration in SIS-PSI rats within EPM support the hypothesis that psilocybin may act through non-serotonergic pathways. These behaviors are associated with NE and dopamine (DA) signaling. Moreover, the modest increase in sucrose preference suggests psilocybin may alleviate anhedonia, a core symptom of reward deficits primarily driven by the DA system, possibly through modulation of both DA and 5-HT. Given the absence of CTL data in the SPT, the interpretation of SPT findings is constrained to stressed conditions. Incorporating CTL comparisons in future studies will benefit the full assessment of the extent of restoration. In summary, these findings highlight that psilocybin may influence the DA and NE systems in addition to its primary action on 5-HT."

Regarding thyroid stimulating hormone:

"The observed restoration of thyroid-stimulating hormone (TSH) levels following psilocybin intervention highlights a previously underexplored physiological response in the context of TRD. Previous depression studies have focused mainly on investigating disruptions to the HPA axis. Persistent elevation of CORT levels can disrupt the normal functioning of the HPA axis, leading to gradual resistance to CORTs in target tissues, including the pituitary gland and HYP. The hypothalamic-pituitary-thyroid (HPT) axis, like the HPA axis, originates in HYP and aids in regulating stress-related hormones. TSH plays a crucial role in regulating the metabolism necessary for growth, and lower TSH levels have been linked to the onset of several mental health disorders. Extensive research has demonstrated that prolonged stress and resulting hyperactivity of the HPA axis can suppress TSH production, suggesting an inverse relationship between CORTs and TSH levels. In the present study, even with heightened HPA axis resilience, psilocybin can mitigate stress-induced behavioral changes, which appear to lead to the restoration of TSH levels. This is evident from the significant reduction and subsequent restoration of TSH levels in the SIS-Sham and SIS-PSI subgroups, respectively, highlighting the potential compensatory role of TSH in mood regulation and cognitive processes, especially when HPA-axis alterations are not prominent. Future studies examining a full panel of thyroid hormones (such as triiodothyronine (T3), thyroxine (T4), and thyrotropin-releasing hormone (TRH)) will be able to provide more mechanistic insight into the direct causal modulation of psilocybin on the HPT-axis.

"Furthermore, a recent study suggested that TSH may have neuroprotective effects by increasing brain-derived neurotrophic factor (BDNF) concentrations, which aligns with our findings. Our data revealed that early psilocybin intervention restored circulating BDNF levels relative to CTL animals. In addition, Western blot analyses showed increased BDNF expression in psilocybin-treated rats compared to SIS-Sham animals within all four brain regions, although the change was not significant in the AMG. Currently, the molecular mechanism by which psilocybin acts is predominantly centered on its engagement with the 5-HT2 A receptor, which is believed to be mainly responsible for the psychedelic experience associated with psilocybin. However, recent evidence also implicates direct interaction with receptor tyrosine kinase B (TrkB), a high-affinity BDNF receptor and mediator of antidepressant response. In our study, early psilocybin intervention increased TrkB expression across all brain regions relative to the SIS-Sham group, though modest in the PFC and HYP, suggesting a potential promotive effect of psilocybin on neurotrophic TrkB signaling."

More bad news for supporters of neurological decline:

"mTOR, a serine/threonine protein kinase vital for neural development and synaptic plasticity, is activated downstream of the extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) cascades, which are activated following TrkB stimulation. Increasing evidence has emphasized the importance of mTOR as a core regulator in treating neurological disorders."
https://pmc.ncbi.nlm.nih.gov/articles/PMC12106756/ [5037]

In psychedelia's version of RDTGH the holy grail is patentable psychedelic-like antidepressives which are not hallucinogens. To this end Sekssaoui et al (2024) compared the hedonic effects of psilocybin with 2,5-Dimethoxy-4-iodoamphetamine (DOI), an unpopular psychedelic which is reportedly less safe than LSD, and seldom found in recreational use, and with lisuride, a mixed agonist and antagonist of dopamine, serotonin, and adrenergic receptors. A shadow is cast over the semantics of the research as Wikipedia reveals that "Although lisuride has widely been said to be non-hallucinogenic, this may not actually be true."
https://en.wikipedia.org/wiki/2,5-Dimethoxy-4-iodoamphetamine [5259]
https://en.wikipedia.org/wiki/Lisuride [5260]

Sekssaoui et al managed to end up showing trippy mushrooms are a rather more resilient medicine than their lab-born rivals.

"Major depressive disorder (MDD) is one of the most disabling psychiatric disorders in the world. First-line treatments such as selective serotonin reuptake inhibitors (SSRIs) still have many limitations, including a resistance to treatment in 30% of patients and a delayed clinical benefit that is observed only after several weeks of treatment. Increasing clinical evidence indicates that the acute administration of psychedelic agonists of the serotonin 5-HT2A receptor (5-HT2AR), such as psilocybin, to patients with MDD induce fast antidepressant effects, which persist up to five weeks after the treatment. However, the involvement of the 5-HT2AR in these antidepressant effects remains controversial. Furthermore, whether the hallucinogenic properties of 5-HT2AR agonists are mandatory to their antidepressant activity is still an open question. Here, we addressed these issues by investigating the effect of two psychedelics of different chemical families, DOI and psilocybin, and a non-hallucinogenic 5-HT2AR agonist, lisuride, in a chronic despair mouse model exhibiting a robust depressive-like phenotype. We show that a single injection of each drug to wild type mice induces anxiolytic- and antidepressant-like effects in the novelty-suppressed feeding, sucrose preference and forced swim tests, which last up to 15 days. DOI and lisuride administration did not produce antidepressant-like effects in 5-HT2A−/− mice, whereas psilocybin was still effective. Moreover, neither 5-HT1AR blockade nor dopamine D1 or D2 receptor blockade affected the antidepressant-like effects of psilocybin in 5-HT2A−/− mice. Collectively, these findings indicate that 5-HT2AR agonists can produce antidepressant-like effects independently of hallucinogenic properties through mechanisms involving or not involving the receptor."
https://www.nature.com/articles/s41386-024-01794-6.pdf [5261]

In "Reimagining Neuropsychiatric and Neurological Disorders through the Lens of Brain Network Dynamics: Psychedelics as Catalysts for System-Level Plasticity" Zhang, Wang and Wang (2025) reframe psychiatric diagnoses along an "ordercomplexitychaos" continuum.

They would Rather Incorporate Than Hallucinate (RITH):

"To maximize the therapeutic potential of psychedelics, research should also focus on developing next-generation psychedelic analogues with reduced hallucinatory effects but preserved plasticity-promoting properties."

Zhang et al simply do not understand the uselessness to a free individual freedom of the confinement of psychedelics use to controlled conditions. Neuroplasticity is for coping with real life, uncontrolled conditions, so non-naturalistic settings are entirely for the benefit of the researchers, as it turns out. But ordinary people with ordinary problems do not need to learn how to cope with being part of a research program.

Despite this somewhat inevitable blindness to researcher-effect, the authors conclude encouragingly that

"...psychedelics represent a promising shift in the treatment of neuropsychiatric and neurological disorders, offering a novel approach that transcends the limitations of traditional target-based pharmacologies. By modulating brain network dynamics and facilitating neural reorganization, psychedelics have the potential to create lasting changes that improve cognition, emotion, and behavior. However, to fully realize their therapeutic potential, future research must address remaining gaps in our understanding of how psychedelics work at the network level, and how their effects can be optimized for different patient populations. This integrative, network-based approach may catalyze the next era of brain medicine, offering transformative treatments for a range of complex conditions that have long defied conventional therapies."
https://pubs.acs.org/doi/full/10.1021/acsptsci.5c00379 [5262]

To this end, Purple et al (2025) examined "Short- and long-term modulation of rat prefrontal cortical activity following single doses of psilocybin"

"We quantify cellular- and circuit-resolution neural network dynamics following therapeutically relevant doses of the psychedelic psilocybin. Using chronically implanted Neuropixels probes, we recorded local field potentials (LFP) alongside action potentials from hundreds of neurons spanning infralimbic, prelimbic and cingulate subregions of the medial prefrontal cortex of freelybehaving adult rats. Psilocybin (0.3 mg/kg or 1 mg/kg i.p.) unmasked 100 Hz high frequency oscillations that were most pronounced within the infralimbic cortex, persisted for approximately 1 h post-injection and were accompanied by decreased net neuronalfiring rates and reduced spike-train complexity. These acute effects were more prominent during resting behaviour than during performance of a sustained attention task. LFP 1-, 2- and 6-days post-psilocybin showed gradually-emerging increases in beta and low-gamma (2060 Hz) power, specific to the infralimbic cortex. These findings reveal features of psychedelic action not readily detectable in human brain imaging, implicating infralimbic network oscillations as potential biomarkers of psychedelic-induced network plasticity over multi-day timescales."
https://www.nature.com/articles/s41380-025-03182-y.pdf [5360]

Despite finding, in "Evaluation of behavioural and neurochemical effects of psilocybin in mice subjected to chronic unpredictable mild stress", that the psychedelic "reversed impairments in anhedonia and behavioural despair dimensions of depressive phenotype but not in apathy-related behaviour" and that "psilocybin administration was also able to exert an anxiolytic-like effect on treated animals," Erkizia-Santamara et al (2025) did not find BDNF or SV2A increased. This they explain thus:

"In the present study, no effect of psilocybin was observed on cortical expression of BDNF. Previous studies have also reported transient increases of BDNF following psychedelic administration in plasma of healthy subjects or in rodent brain. Although the predominant mode of BDNF secretion is from presynaptic sites, BDNF can be synthesized and secreted from different components of the synapse including astrocytes, microglia and post-synaptic dendrites. Thus, it is feasible to speculate that psychedelic-induced neuroplastic effect could be mediated by the selective increase of BDNF from precise subcellular localizations, and a more specific look into local production of BDNF in the dendritic compartment may shed light into their mechanism of action. Moreover, discrepancy between different studies could be due to the desynchronised timing between tissue harvest (14 days after the last dose in the present work) and the 'window of neuroplasticity' opened by psilocybin.

"Additionally, we measured the 12-transmembrane domain glycoprotein SV2A. This protein is expressed in synaptic vesicles throughout the brain and is considered to reflect presynaptic density. One study performed in pigs has reported increases in cortical SV2A seven days after one single intravenous administration of psilocybin. Kiilerich et al., have also measured increases in SV2A levels in the paraventricular thalamic nucleus after repeated low doses of psilocybin in mice. Unfortunately, the present work was not able to replicate such results, which could be due to differences in the methodological approach, species, region-specificity or experiment timing."
https://www.nature.com/articles/s41398-025-03421-4.pdf [5080]

SV2A in pigs: "A Single Dose of Psilocybin Increases Synaptic Density and Decreases 5-HT2A Receptor Density in the Pig Brain" by Raval et al (2021).
https://www.mdpi.com/1422-0067/22/2/835 [5328]

The origins of consciousness in evolution are not understood, but it is very old. The octopus, an invertebrate with which we appear to have very little in common, is a better performer at visual tasks than the pigeon, respond to rewards, can recognise people, like to play, and play tricks. They are adapted to be both cunning and scary.
https://www.bbc.co.uk/programmes/articles/2KzKVBXNXFtz4bYDWGNkqxS/10-incredible-facts-about-octopuses [1249]

Perhaps it is time to recognise, legally, to whom people's consciousness belongs, as Lord Donaldson describes [966]. And time to recognise that doctors don't possess any automatic rights over it or them. The right to reject a medical or psychiatric dogma is fundamental to the right to treatment when desired.

Causing hyperinsulinemia now or in the future, by prohibiting anti-obesogenic cannabis now, is the functional equal of taking away a diabetic's insulin later, when their own internal supply is depleted.

The criminalisation of self-maintenance, and the perception which supports it, is functionally equivalent to the denial of treatment.

And of course ruinous to the mental health of the criminalised individual, who is literally "guilty of health".

In case you're wondering if people can tell LSD and psilocybin apart...they can't.

"In terms of blinding, no participant could distinguish between doses of psilocybin/LSD but the placebo was easily identified by participants. When asked to identify the doses, 15 mg psilocybin was mostly mistaken for 30 mg psilocybin, 30 mg psilocybin was mostly mistaken for 100 g LSD, 100 g LSD was mostly mistaken for 15 mg psilocybin, and 200 g LSD was mostly mistaken for 100 g LSD. Nonetheless, this study indicates that any differences between LSD and psilocybin are dose-dependent rather than substance-dependent and is another significant contribution to psychedelic medicine by them at the University of Basel."
https://blossomanalysis.com/papers/direct-comparison-of-the-acute-effects-of-lysergic-acid-diethylamide-and-psilocybin-in-a-double-blind-placebo-controlled-study-in-healthy-subjects/ [1029]
https://pmc.ncbi.nlm.nih.gov/articles/PMC10517157/ [3877]

These findings were reinforced when in 2026 Nature Medicine published "An international mega-analysis of psychedelic drug effects on brain circuit function" combining data from 11 brain-imaging studies, which in turn include more than 500 brain scans of 267 people. Girn et al report the consensus that

"...psychedelics decrease FC within and increase FC between most large-scale cortical networks - a finding first observed by Roseman and colleagues with psilocybin, and which has since been reported for additional drugs and datasets."


https://www.nature.com/articles/s41591-026-04287-9 [6139]

In "Synergistic, multi-level understanding of psychedelics: three systematic reviews and meta-analyses of their pharmacology, neuroimaging and phenomenology" Shinozuka et al (2024) notes:

"Pharmacologically, LSD induces significantly more inositol phosphate formation at the 5-HT2A receptor than DMT and psilocin, yet there are no significant between-drug differences in the selectivity of psychedelics for the 5-HT2A, 5-HT2C, or D2 receptors, relative to the 5-HT1A receptor."
https://www.nature.com/articles/s41398-024-03187-1 [3757]

However, in another study, subjects were able to distinguish between natural psilocybin mushrooms and lab-made pure psilocybin without the usual natural congeners. The artificial stuff was ok, and considered therapeutically better than nothing, but in "'The mushroom was more alive and vibrant': Patient reports of synthetic versus organic forms of psilocybin". Kryskow et al (2024), the non-blinded comparison was based on subjective reports of the participants.

"There was consensus among participants that the preferred form was the whole mushroom. The reasons given for this include the feeling that the whole mushroom is sacred, alive, unmanipulated by humans and natural. Individuals found the whole mushroom and mycological extract forms to have a gentler onset and comedown, and cited this as a factor that made the forms superior to the synthetic variant. At the same time, the experience of synthetic psilocybin in pill form was described as feeling more like medicine and being a dummied-down experience that was generally viewed as inferior to the organic forms. Despite not being the first choice, participants agreed that synthetic psilocybin was still therapeutic. Some explained that during the peak of the experience, the different forms of psilocybin had the same effect.

"Emotional and psychological effects
Emotional and psychological effects were reported by participants. During and following their psilocybin experiences, participants reported feeling heightened emotions, and empathy and compassion with all three forms. Overall, emotions experienced during the sessions were described as positive and empowering. Some spoke about the empowering feeling of joining generations of people who had taken psilocybin before them. In addition, participants spoke of breakthroughs in their emotional processing in their day-to-day lives following dosing sessions with both synthetic and whole mushrooms. There were reports of participants feeling more comfortable with death and using their psilocybin experiences as a touchstone to alleviate anxiety in moments of dysregulation. However, while synthetic psilocybin was described as therapeutic, this form was also reported as inducing less emotion and less euphoria compared to the whole mushroom.

"Spiritual and mystical experiences
Another central theme that emerged was spiritual and mystical experiences with all three forms of psilocybin. Participants spoke of non-ordinary experiences of consciousness which included feelings of rebirth, feelings of unity with the universe, and feeling as if they ceased to exist. They also described feeling more spiritual, both during and following the session. Psilocybin delivered in pill form (mycological extract and synthetic) was perceived as less spiritual because participants felt it was manmade and less traditional. The texture of the synthetic experience was further described as mechanical rather than alive as with other forms. In contrast, while taking psilocybin in whole mushroom form, some felt connected to the cycle of life or felt as if they were participating in a ceremony. Experiences that were longer in duration (mycological extract and the whole mushroom) were also perceived as more spiritual in part because there was more time to go deeper. There was agreement among participants that the whole mushroom felt more sacred and spiritual than other forms.

"Onset and comedown
Participants discussed the onset and comedown phases of their psychedelic dosing experiences. Their discussion revealed significant variation among participants' perceptions of each forms' respective onset and comedown phases. Synthetic, mycological extract and whole mushroom were all described as having a rapid and sharp onset by some, as well as a gentle and slow onset by others. For some participants, the transitional periods at the beginning and end of the experience were identical for both of the naturally derived forms when the whole mushroom was consumed with citrus juice. It was noted that a gentle transition period is more comfortable, can facilitate integration and allows for the ability to meditate into the experience. On the other hand, it was pointed out that too long of an onset can lead to anxiety if the participant doesn't have anything to occupy themselves with. Thus, there was also no consensus as to whether a sharp or gentle onset was superior. Some mentioned that beside the onset and comedown, the three forms are very similar to each other.

"Mild and transient side effects
Transient side effects during the various dosing experiences were brought up at points during the interviews. Physical symptoms were scarcely mentioned and included mild nausea, which resolved on their own without intervention. In terms of emotional distress, participants cited external factors such as group dynamics as being influential. This included being affected by others' panic and feeling worried about people in the session who were crying out for help. Some complaints also included how the prolonged onset of the whole mushroom caused anxiety. A lack of response following the session was also associated with the feeling of failure for not having an experience that was as profound as everyone else."
https://akjournals.com/view/journals/2054/aop/article-10.1556-2054.2024.00379/article-10.1556-2054.2024.00379.xml [3652]

Martin-Guerrero et al (2025) found differences between psychedelic and non-psychedelic compounds with a similar structure:

"Of note, phosphorylation of FOXK2 at S360 was among the sites showing the largest differences between compound classes (Fig. 4a and 4b). FOXK2 is a transcription factor implicated in the regulation of glucose homeostasis and aerobic glycolysis, consistent with the ontology analysis revealing an enrichment of these processes within the hallucinogenic signature (Fig. 3c). These observations led us to hypothesize that phosphorylation-dependent activation of FOXK2 may enhance glycolytic flux. To test this possibility, we performed lactate production assays to determine whether FOXK2 phosphorylation was associated with increased glycolytic activity. Treatment with hallucinogenic compounds elevated lactate levels by approximately 2- to 4.5-fold relative to vehicle, whereas their non-hallucinogenic counterparts produced no effect (Fig. 4c). Together, the results shown in Fig. 4 demonstrate a clear association between the hallucinogenic potential of the compounds, phosphorylation of FOXK2 S360, and lactate production. This finding is in line with recent proteomic studies in human cerebral organoids treated with LSD, which revealed significant alterations in proteins involved in glycolysis and oxidative phosphorylation. However, our phosphoproteomic data reveal for the first time that enhanced glycolytic activity is a distinctive feature of psychedelics with hallucinogenic properties, and that this property is not shared by their non-hallucinogenic analogs. This discovery has potential physiological significance as it links, at the intracellular signaling level, the altered states of consciousness produced by hallucinogenic psychedelics with those induced by physiological anoxia. Indeed, our study suggests that these two interventions converge on enhancing glycolytic metabolism and result in transiently modified states of awareness, which in both cases may ultimately contribute to their restorative or therapeutic effects."
https://www.biorxiv.org/content/biorxiv/early/2025/11/26/2025.11.24.690190.full.pdf [5729]

The rather shocking claim that LSD increases aggression...



...turns out to be based on experiments involving giving a dozen rats LSD every other day, presumably without any therapy or counselling.
https://www.jneurosci.org/content/41/5/891 [998]

Contrast this with the results of the British Army's Operation Moneybags: as the intro notes, "This drug has been widely used in hospitals for the treatment of mental disorder." One day one, without drugs, the troops are alert and properly paranoid. On day two, they relax, stop taking cover, become insurbordinate, stroll and around and giggle. One can't aim his rocket launcher. The troops huddle together instead of spreading out. Defensive positions are not adopted and the soldiers quickly lose interest when not stimulated by mission objectives, "relapsing into laughter and inconsequential behaviour." One nearly chops down a substantial tree with only a spade. Another climbs a tree, and after 70 minutes the commander gives up and rolls around on the ground laughing. Apart from the tree-chopping incident, the problem is undoubtedly not aggression, but the impossibility of mustering any aggression. On Day 3 they are back to their usual efficient selves, achieving all their objectives in three hours.
https://www.youtube.com/watch?v=ziqpwkhqTRs [999]

The Czechoslovak army also had a trial, with similar results.
https://youtu.be/5HXMHdhQL_8?t=102 [1003]

"The protagonists of Experiment (1968) are four genuine officers of the Czechoslovak army who voluntarily take a dose of LSD. They are then tasked with drawing up a warfare plan, which of course they fail to do while the camera carefully records the complete mental disengagement of the military. The officers, however, appear quite satisfied. They take off their uniforms, giggle, and apparently have great fun. The narrator declares: 'Hallucinogens give us hope for an imminent end to deadly wars.'"
https://przekroj.pl/en/society/a-communist-lsd-trip-aleksander-kaczorowski [1004]

An interesting anecdotal use of LSD to cure post-Covid anosmia
https://sashachapin.substack.com/p/covid-19-took-my-sense-of-smell-then [315]

Why DMT works all the time and LSD won't - Tobias Buchborn
https://www.youtube.com/watch?v=fng6ODKvJdU [316]

"N, N-Dimethyltryptamine, a natural hallucinogen, ameliorates Alzheimers disease by restoring neuronal Sigma-1 receptor-mediated endoplasmic reticulum-mitochondria crosstalk" say Cheng et al (2024):

"The current study demonstrated that the anti-AD effects of DMT are associated with its restoration of neuronal ER-mitochondria crosstalk via the Sig-1r activation. DMT modulates the mitochondrial calcium uptake and ER-mitochondrial contacts in the in vivo and in vitro models, facilitates the TCA cycle, and protects against mitochondrial dysfunction in Alzheimer disease."

https://alzres.biomedcentral.com/articles/10.1186/s13195-024-01462-3 [4627]

Gendra et al (2026) are interested in restoring oscillatory dynamics in Alzheimer's disease:

"By modulating the excitability of layer 5 pyramidal neurons, our models reproduce hallmark changes in EEG power spectra observed under psychedelics, including alpha power suppression and gamma power enhancement. These spectral shifts are shown to correlate strongly with the regional distribution of serotonin 2A receptors. Furthermore, simulated EEG reveals increased complexity and entropy, suggesting restored network function. These findings underscore the potential of serotonergic psychedelics to reestablish healthy oscillatory dynamics in the prodromal and early phases of Alzheimer's disease and offer mechanistic insights into their potential therapeutic effects in neurodegenerative disorders."
https://pmc.ncbi.nlm.nih.gov/articles/PMC13108508/ [6153]

In the Journal of Psychopharmacology, a ten-person team at Palo Alto University reported in a follow-up study using psilocybin for depression. At the four-and-a-half year follow-up, 71 to 100 percent of participants credited improvements in levels of anxiety and depression to the single-dose psilocybin and therapy combination of the study. The participants further "rated it among the most personally meaningful and spiritually significant experiences of their lives."

Actually millions of people knew that already, but didn't know that would have to wait to become part of a statistically significant sample to transform this fact into official fact. And there are plenty more depressed people who shouldn't need to wait another 70 years for the government and judges to find out. And they aren't going to wait. The biggest fear they have in confronting their mental situation is the fear placed in their mind by the prohibitionists in advance of taking the plunge, i.e. people who are causing them anxiety, who haven't taken the plunge themselves but think they have the right to stop others.
https://journals.sagepub.com/doi/10.1177/0269881119897615 [319]

In 2021 University of Pretoria researchers Sanah Malomile Nkadimeng, Christiaan ML Steinmann, and Jacobus N Eloff finally got round to making some mushroom tea, in "Anti-Inflammatory Effects of Four Psilocybin-Containing Magic Mushroom Water Extracts in vitro on 15-Lipoxygenase Activity and on Lipopolysaccharide-Induced Cyclooxygenase-2 and Inflammatory Cytokines in Human U937 Macrophage Cells"

Using four species, Panaeolus cyanescens, Psilocybe natalensis, Psilocybe cubensis, Psilocybe cubensis A+ strain, they found

"TNF-α and IL-1β significantly and lowered IL-6 and COX-2 concentrations in treated human U937 macrophage cells. Water extracts also increased percentage viability of treated cells and levels of anti-inflammatory IL-10 non-significantly. Conclusion: The study suggested that the hot-water extracts of the four psilocybin-containing magic mushrooms have potential anti-inflammatory effects executed by downregulating pro-inflammatory mediators."

https://www.dovepress.com/anti-inflammatory-effects-of-four-psilocybin-containing-magic-mushroom-peer-reviewed-fulltext-article-JIR [1570]

In "Moderating factors in psilocybin-assisted treatment affecting mood and personality: A naturalistic, open-label investigation" by Irrmischer et al (2025):

"At baseline, 1 week and 3 months after the psilocybin program participants completed the Generalized Anxiety Disorder Assessment (GAD-7), Patient Health Questionnaire (PHQ-9), PTSD Checklist for DSM-5 (PCL-5) and NEO Five-Factor Inventory-3 (NEO-FFI-3). In addition, after the dosing the Mystical Experiences Questionnaire (MEQ-30), Posttraumatic Growth Inventory (PTGI) and Emotional Breakthrough Inventory (EBI) were administered. Moderation effects were established using linear mixed-model analysis." https://link.springer.com/article/10.1007/s00213-024-06733-3 [5333]

See KZ-1 Article 32 on when the benefits of an allegedly criminal act outweigh harms. The Defence, separately, does not detect the elements of a crime in the prevention of suicide, violence, or depression, or the enhancement of empathy and meaning in life.

A different Article 32 refers to public benefit. The benefits described here are demonstrated in mass populations, relevant cohorts, and case studies.

"The decisions referring to the public benefit tend to be more general in nature. In most cases, the Constitutional Court uses the term public benefit as a general term, without providing specific and detailed content (e.g., Decision Up-2501/08, 19 February 2009, in which the Constitutional Court only refers to provisions as set in Administrative Dispute Act, second paragraph of Article 32 (Official Gazette of the Republic of Slovenia, no. 105/06 and amendments), which define thatif an applicant demonstrates that enforcing a decision (act) would cause irreparable harm, the court will temporarily halt the measure until a decision becomes final. The court must consider the balance between the applicants potential damage, public benefit, and the interests of other parties, ensuring a proportional approach.)."
https://journals.uni-lj.si/CEPAR/article/download/20572/16988 [5128]

Haden and Woods found three reports of LSD overdoses:

"The first case report documents significant improvements in mood symptoms, including reductions in mania with psychotic features, following an accidental lysergic acid diethylamide (LSD) overdose, changes that have been sustained for almost 20 years. The second case documents how an accidental overdose of LSD early in the first trimester of pregnancy did not negatively affect the course of the pregnancy or have any obvious teratogenic or other negative developmental effects on the child. The third report indicates that intranasal ingestion of 550 times the normal recreational dosage of LSD was not fatal and had positive effects on pain levels and subsequent morphine withdrawal."

The first case is the most interesting and relevant to his section.

"Her initial diagnosis [age 12] was unspecified psychotic disorder (with psychotic depression, bipolar disorder, and schizophreniform disorder as possible diagnoses). She was started on an antidepressant medication (sertraline) in May 1998, when she reported worsening depressive symptoms without evidence of psychosis. Her symptoms improved and stabilized until the fall of 1999, when her depression worsened. A light box (Levitt et al., 1996) was introduced in November 1999 for the treatment of a seasonal (winter) depression, and shortly thereafter she started to show signs of hypomania (decreased need for sleep, elevated mood, increased chattiness, increased productivity, and 'obsessive 'cleaning'). The light box treatment was discontinued and the sertraline was reduced. Over the Christmas holidays, she admitted to using Ecstasy (presumably 3,4-methylenedioxymethamphetamine [MDMA]) twice, the last time being on New Years Eve 1999. Her hypomanic symptoms continued, and she was assessed by her psychiatrist on January 19, 2000. A urine drug screen was done that day, which was positive only for cannabis. She was diagnosed with bipolar II disorder and instructed to discontinue the sertraline. She refused a mood stabilizer at this time. She was hospitalized voluntarily on February 17, 2000, to recover in a low stimulation environment and was discharged after 3 days, prematurely. Although AV was using cannabis, she had not used any stimulants since New Years Eve. Lithium 150 mg two times a day was started on an outpatient basis on March 2, which she agreed to take as this was 'a natural salt.' She stopped taking it by the end of March, as she reported 'feeling like myself again.' Her symptoms of hypomania, however, only intensified. Her second hospitalization, on April 19, 2000, was precipitated by an incident where she bit her mother. She was committed under the provincial Mental Health Act because of safety concerns. At this point, she was not sleeping and she had grandiose delusions, including that she could purchase a town in Mexico and become the mayor, that she was enlightened, and that she could speak all languages. Hospital notes documented that she was grandiose, paranoid, irritable, and disorganized. The lithium was restarted. After a 20-day admission, she was discharged on lithium 300 mg two times a day and olanzapine 57.5 mg at bedtime. Her diagnosis was changed to bipolar I disorder, as she had had a full-blown manic episode with psychotic features. AV reported in retrospect that she did not feel well in between hospital admissions, nor for several months afterward, and that she did not use much cannabis in those intervening months.

"Drug use history
AVs first cannabis use was at age 11 with no effect. She used again at age 12 and began using regularly, escalating through ages 1314, when she was using it daily (1998 1999). She reported infrequent use of psilocybin mushrooms (in 1998) and LSD on one prior occasion (Remembrance Day, November 11, 1999). She used Ecstasy (likely MDMA) twice with her initial use in December 1999. It is noteworthy that her symptoms of hypomania emerged shortly after initiation of light box treatment, which was before her first use of Ecstasy. Urinalysis on January 14, 2000, was positive only for cannabis. AV reported that she never used cocaine, methamphetamine, or opiates.

"Mental health family history
Mental health concerns existed in her family of origin, with bipolar diagnoses in two paternal relatives and alcoholism and trauma in her maternal lineage. Psychosocial issues AVs home life was turbulent, with parental separation, an incarcerated father (1996, when she was age 12), subsequent ostracization by peers, the death of her grandmother (1998, when she was age 14), and school changes. AV was unable to function in the normal school system because of disruptive and defiant behavior and was moved to an alternative school at age 13 (in 1997).

"LSD overdose incidentJune 20, 2000
The LSD overdose incident occurred during a summer solstice party (June 20, 2000, at age 15), where the supplier of the liquid LSD made a decimal place error when preparing individual dosages diluted in glasses of water. Specifically, what were intended to be 100 mcg dosages (a normal recreational dosage) were actually 1,000 mcg per glass. AV drank one glass and subsequently drank the 'leftover drops' from two other glasses. Her total dosage was therefore in the range of 1,1001,200 mcg, which was ingested at 10:00 p.M. on a relatively empty stomach. Although no lethal overdoses of LSD have been documented, it is estimated that the lethal dose in a human is 14,000 mcg (Klock et al., 1973). Observers subsequently reported erratic behavior for the next 6.5 hours, followed by what they believed to be a seizure, as she was lying in a fetal position with her arms/ fists clenched tightly. An ambulance was called at 4:30 a.M., and by the time the paramedics arrived 10 minutes later she was alert and oriented. She was transported to a local hospital where she was diagnosed with a seizure, as this is what the witnesses reported. This conclusion is questionable as subsequent interviews with AV and observers revealed no loss of bladder or bowel control, no biting of her tongue, no clonic movements in any limbs, and only a brief period of confusion after the clenching episode. It was unclear whether she had a loss of consciousness or whether she was intensely preoccupied with her experience at the time. Although extremely uncommon, grand mal seizures after LSD ingestion have been reported in the historical literature (Fisher & Ungerleider, 1967). AVs father reported that when he entered the hospital room the next morning, AV stated, 'Its over.' He believed she was referring to the LSD overdose incident, but she clarified that she meant her bipolar illness was cured.

"Mental health team case notes The case notes from AVs mental health team psychiatrist and therapist subsequent to the overdose incident reported a significant change in her mental illness symptoms.

"June 28, 2000: A second EEG was ordered, which was normal.

"July 11, 2000: AV 'came in today with a lovely fine balance and a glint in her eye and she is maintaining a happy and credible mood balance ever since the unfortunate incident that provoked her seizure three weeks ago' and AV 'has not presented with as easy and healthy a presentation in many, many months.'

"July 19, 2000: AV 'is entirely stable at present' and 'she has an excellent perspective on her illness and some things she can do to keep herself well.'

"September 6, 2000: She has remained remarkably stable this summer with no evidence of recurrent depression or mania and AV is doing remarkably well even compared to last year at this time when she was noticeably depressed.

"February 14, 2001: AV discussed tapering off her lithium with her psychiatrist, who observed at the end of the case note that, her insight and self-awareness are quite remarkable.

"May 30, 2001: AV 'has gone off her lithium and there are more mood instabilities as a result of that but no evidence of clinical hypomania or depression' and 'we spoke carefully with mother, father, and AVit is clear that no one has seen symptoms of clinical depression . . . ' and 'she has had a fairly successful school year other than the one term out of four and has not had a breakthrough of clinical levels of depression or mania.'"

"AVs father observed that his daughter appeared to be completely recovered from her mental health concerns after the overdose incident.

"AV reports that she was free from all mental illness symptoms (bipolar or other) for the subsequent 13 years until she gave birth and experienced postpartum depression. The birth of her second child in 2017 was also associated with a turbulent emotional period. AV reports that after the LSD overdose incident she experienced life with a normal brain, whereas her brain felt chemically unbalanced before the incident.

"AVs cannabis use was unchanged by the overdose event and she continues to use cannabis regularly.

"Currently, AV has stable employment, stable positive friendships, and good work relationships.

"Case 1: Conclusion
This case report documents a significant improvement in mood symptoms, including reductions in mania with psychotic features, following an accidental LSD overdose, changes that have been sustained for almost 20 years."
https://www.researchgate.net/publication/339234169_LSD_Overdoses_Three_Case_Reports/link/5e5d4c09a6fdccbeba1449b6/downloa [4008]

CNN, reporting on the paper, also writes, that mistaking it for cocaine:

"A 46-year-old woman snorted a staggering 550 times the normal recreational dose of LSD and not only survived, but found that the foot pain she had suffered from since her 20s was dramatically reduced.

and

"'No clinical trial research could be done with dosages this high and there are no publications exploring the positive outcomes of very large dosages of LSD,' the authors said."

'To understand the effects of extremely high dosages of psychedelics such as LSD, an examination of overdoses in naturalistic settings is required.'"
https://edition.cnn.com/2020/02/27/health/lsd-overdoses-case-studies-wellness/index.html#:~:text=They%20noted%20that%20in%20CB's,levels%20and%20subsequent%20morphine%20withdrawal.%E2%80%9D [4009]

About those naturalistic settings. Card et al in "Therapeutic Potential of Psilocybin for Treating Psychological Distress among Survivors of Adverse Childhood Experiences: Evidence on Acceptability and Potential Efficacy of Psilocybin Use" (2023) state:

"Survivors of adverse childhood experience are at elevated risk for psychological distress. In recent years, renewed interest in psychedelic medicine has highlighted the therapeutic potential of psilocybin for those who have experienced childhood adversity. However, recreational psilocybin use remains illegal and access to approved therapies is difficult. Such use provides an opportunity to explore the therapeutic potential of psilocybin for psychological distress among people with adverse childhood experiences. Therefore, we conducted an online survey to assess interest in, acceptability of, and experiences with psilocybin. We further explored whether the association between Adverse Childhood Experiences Questionnaire (ACEQ) scores and psychological distress was lower among those who had used psilocybin in the past three months. Results showed high levels of interest in and acceptability of psilocybin that did not differ across ACEQ scores. Results also showed that the effect of adverse childhood experiences on psychological distress was lower for people who had recently used psilocybin (p = .019). Taken together, these findings suggest that psilocybin therapy may be potentially acceptable and may feasibly help in supporting survivors of adverse childhood experiences with particularly strong benefits to those with more severe childhood adversity."
https://www.tandfonline.com/doi/abs/10.1080/02791072.2023.2268640 [4049]

and

"The study surveyed 1,249 people in Canada, ages 16 and older, who completed a questionnaire used to assess experiences of childhood trauma. They were also asked about psilocybin use, including when they last consumed the substance, their frequency of use and how strong the doses were.

We found that the effect of adverse childhood experiences on psychological distress was lower among those who had used psilocybin compared to those who had not, the study says, suggesting potential benefit of psilocybin in treating the psychological consequences of adverse childhood experiences.

The authors said their findings aligned with other published research, such as a study of more than 213,000 U.S. adults that found that lifetime use of psilocybin was associated with lower odds of a past-year major depressive episode.

Taken together, our results and the existing literature point to a positive therapeutic potential of psilocybin, the report says. While naturalistic use of psilocybin is very different from therapeutic trials, our findings converge with emerging evidence from clinical trials and suggest that there may be benefits of use outside of therapeutic settings.

"Of the respondents, nearly half (49.9 percent) said they often or always used psilocybin to address mental health or emotional challenges, while 32.2 percent said they sometimes used psilocybin for that purpose. People who scored high for adverse childhood experiences were significantly more likely to use psilocybin for mental health, although high adverse experiences scores werent associated with increased likelihood to use psilocybin for other reasons, such as to enhance the senses, for pleasure, to connect with others, to relieve boredom, for spiritual purposes and for self-enhancement and -understanding.

"'Importantly,' wrote researchers, 'there appears to be a dose response effect, with more exposure to psychedelics being associated with greater psychological effect and improvements to psychological well-being.'"
https://www.marijuanamoment.net/psilocybin-eases-psychological-distress-in-people-who-experienced-childhood-trauma-study-suggests/ [4050]

Reasons people use psilocybin, according to Oregon Psilocybin Services:

https://psychedelicalpha.com/news/oregon-psilocybin-services-tracker-q1-2025 [5145]

Another naturalistic study, "Investigation of self-treatment with lysergic acid diethylamide and psilocybin mushrooms: Findings from the Global Drug Survey 2020" by Kopra et al (2023)

"...investigated the patterns of use, self-reported outcomes and outcome predictors of psychedelic self-treatment of mental health conditions or specific worries/concerns in life.

"Methods:
We use data from the Global Drug Survey 2020, a large online survey on drug use collected between November 2019 and February 2020. In all, 3364 respondents reported their self-treatment experiences with lysergic acid diethylamide (N = 1996) or psilocybin mushrooms (N = 1368). The primary outcome of interest was the 17-item self-treatment outcome scale, items reflecting aspects of well-being, psychiatric symptoms, social-emotional skills, and health behaviours.

"Results:
Positive changes were observed across all 17 outcome items, with the strongest benefits on items related to insight and mood. Negative effects were reported by 22.5% of respondents. High intensity of psychedelic experience, seeking advice before treatment, treating with psilocybin mushrooms and treating post-traumatic stress disorder were associated with higher scores on the self-treatment outcome scale after averaging values across all 17 items. Younger age, high intensity of experience and treating with LSD were associated with increased number of negative outcomes.

"Conclusions:
This study brings important insights into self-treatment practices with psychedelics in a large international sample. Outcomes were generally favourable, but negative effects appeared more frequent than in clinical settings. Our findings can help inform safe practices of psychedelic use in the community, and inspire clinical research. Future research can be improved with utilisation of prospective designs and additional predictive variables."
https://pmc.ncbi.nlm.nih.gov/articles/PMC10350727/ [3879]

Herrmann et al (2025) had 19 parameters when "Exploring the potential psychological predictors associated with changes in depression, anxiety, and well-being following naturalistic psychedelic use":

"Although research shows that psychedelic use may lead to improvement in mental health and well-being, the underlying changes in psychological predictors associated with these improvements remain unclear. 161 participants were recruited in a prospective online survey assessing naturalistic psychedelic use. We used lasso regression to assess how 19 distinct changes in psychological variables (e.g., meaning in life, mindfulness) were linked to future changes in depression, anxiety, and well-being changes. We found increases in meaning in life (β = 0.229, 95 % CI [0.101, 0.357], p < 0.01), agreeableness (β = 0.193, [0.077, 0.361], p < 0.05), mindfulness (β = 0.174, [0.022, 0.383], p < 0.05), and extraversion (β = 0.135, [0.002, 0.246], p = 0.046) to be the variables most strongly associated with future increases in well-being. Increases in mindfulness (β = −0.347, [-0.481, −0.220], p < 0.001), emotional stability (β = −0.158, [-0.279, −0.020], p < 0.05), and extraversion (β = −0.147, [0.022, 0.383], p < 0.05) were the most strongly associated with future decreases in anxiety. Lastly, increases in self-esteem (β = −0.216, [-0.365, −0.056], p < 0.05) were most strongly associated with changes in depression. Changes in mindfulness and emotional stability were also associated with depression; however, they were not significant. Mindfulness was the sole predictor that ranked within the top three across all outcomes. These findings suggest that these differing predictors may underpin the observed psychological improvements following naturalistic psychedelic use."
https://www.sciencedirect.com/science/article/abs/pii/S0022395625005205 [5421]

Discussing the motives for use of serotonergic psychedelics, Basedow and Kuitunen-Paul (2022) report

"In this systematic review, we investigated which use motives for the substance class of SPs are reported for different user populations. The most prominent motive for the use of SPs across all 37 studies was expansion. Nonetheless, over half of the studies also reported coping and enhancement reasons, while social and conformity reasons were rarely involved in the use of SPs. Opposed to our expectation quantitative and qualitative approaches were not related to different proportions of reported use motives. Furthermore, SP use motives did not differ between users of different substances, by year of publication or between different participant populations.

"It seems that a strong public presence of SPs as agents with properties related to coping has not led to a strong presence of this motive in user reports. In contrast, the motive that was most often reported was expansion. The expansion motive was added to the classic four-factor structure, based on and replicated in studies with alcohol-users, to explain motives that seemed to be reported frequently and exclusively in users of cannabis. It relates to processes of subjectively increasing self-knowledge and creativity, as well as changes in awareness and perception. Adding this motive to the use motive structure was likely due to cannabis' psychedelic properties. Therefore, it is fitting that a large proportion of SP users reports expansion motives, since the motive was created specifically to capture psychedelic subjective effects. Interestingly, cannabis use, for which the motive was specifically created, is linked to enhancement more strongly than to the expansion motive.

"Additionally, we showed that reported motives do not differ between questionnaire types, indicating that the five factor use motives apply well to the lived experience of SP users. However, we did observe a small, but non-significant, difference for coping motives, in the sense that qualitative reports more frequently led to the report of coping motives compared to quantitative reports (75% vs. 59% respectively). Coping motives describe substance use as a form of emotion regulation, specifically the regulation (and reduction) of negative affective states. One reason might be the wording of structured coping questions. These are often focused on general negative affect instead of describing specific negative states. This general description might lead people not to identify with the item in question and therefore respond with disagreement. On the other hand, in qualitative reports, participants have the opportunity to explain how they use SPs to cope with specific ailments or emotional states. What they frequently do not have is the opportunity to add individual motives to the questionnaire-specific set of motives. This might result in non-reporting and underreporting of motives which were not covered by the applied questionnaire as previously shown for certain cannabis use motive measures, for example using because of substance-specific craving. Another explanation of this potential finding is a reduction of social desirability bias in qualitative interviews. While in standard survey research social desirability is an issue, in qualitative interviews the interviewer might have built enough trust with the interviewee, which in turn could lead to more honest answers.

"We observed no differences in terms of the year of publication, the investigated SPs or participant populations. This observation, in combination with the above finding related to different questionnaire types, supports the conclusion that the motives for SP use are remarkably similar across contexts. The motive of expansion being the most common holds up across substances, contexts and time. This finding supports the classification of SPs as a homogeneous class of substances, even though singular members of this group might differ in terms of pharmacology or subjective effects. The distinction of SPs as a coherent class is further supported by previous research showing that other substances, such as cannabis and MDMA are more often associated with the motive of enhancement instead of expansion."


https://onlinelibrary.wiley.com/doi/full/10.1111/dar.13480 [4263]

"Depression affects an estimated 300 million people around the world, an increase of nearly 20% over the past decade. Worldwide, depression is also the leading cause of disability."

...explain Metaxa and Clarke for the BMJ in "Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis" (2024) and their results are condensed into the following figures.

And the scientists "discovered" that what you expect to happen plays an important role in the efficacy of psychedelics.

"Treatment effects of psilocybin were significantly larger among patients with secondary depression, when self-report scales were used to measure symptoms of depression, and when participants had previously used psychedelics. Further research is thus required to delineate the influence of expectancy effects, moderating factors, and treatment delivery on the efficacy of psilocybin as an antidepressant."
https://www.bmj.com/content/385/bmj-2023-078084 [4626]

Because this news about expectation will always be news to somebody, the Defence reminds the Court that officialdom and other random people who spread scare stories about psychedelics tend to create the very negative results they claim to be observing, via expectancy or hesitancy.

Most of the political commentators have never observed or experienced any bad trips themselves - consequently all their "knowledge" comes from hearsay, with a high degree of propagandising, political targeting, and media amplification. All in all it is an area badly in need of secularisation. The less bad trips are discussed, the fewer there will be.

And what could be a worse trip than not only spending your declining decades confused and unable to function effectively, but also preventing others from avoiding the same?

In "Psilocybin for dementia prevention? The potential role of psilocybin to alter mechanisms associated with major depression and neurodegenerative diseases" Haniff et al (2024) examine the mechanisms by which psilocybin exerts its neuroprotective effects, first by explaining:

"Adult hippocampal neurogenesis (AHN) is a phenomenon that describes the birth of new neurons in the dentate gyrus throughout life and it is associated with spatial learning, memory and mood regulation. Microglia are innate immune system macrophages in the central nervous system that carefully regulate AHN via multiple mechanisms. Disruption in AHN is associated with both dementia and major depression and microgliosis is a hallmark of several neurodegenerative diseases.

"Emerging evidence suggests that psychedelics promote neuroplasticity, including neurogenesis, and may also be immunomodulatory. In this context, psilocybin, a serotonergic agonist with rapid-acting antidepressant properties has the potential to ameliorate intersecting pathophysiological processes relevant for both major depression and neurodegenerative diseases. In this narrative review, we focus on the evidence base for the effects of psilocybin on adult hippocampal neurogenesis and microglial form and function; which may suggest that psilocybin has the potential to modulate multiple mechanisms of action, and may have implications in altering the progression from major depression to dementia in those at risk."

And they say

"...mechanisms connecting AHN and microglia, perhaps mediated by prolonged or inappropriate inflammatory processes, play a role in major depression and cognitive impairment (Fang et al., 2023; Herman, Simkovic, & Pasinetti, 2019) illustrated in Fig. 1. The downstream effect of innate immune system dysregulation may exacerbate inflammation and lead to subsequent neurodegeneration (Hayley, Hakim, & Albert, 2021; Herman, Simkovic, & Pasinetti, 2019)."


https://www.sciencedirect.com/science/article/pii/S0163725824000615 [3847]

One "prolonged or inappropriate inflammatory process" still hanging around is Covid. At the Cognitive Neuroscience Unit, School of Psychology, SRH University of Applied Sciences Heidelberg, Meyer and Zaiser (2025) have extended the knowledge of adult hippocampal neurogenesis with some "Insights on the neurocognitive mechanisms underlying hippocampus-dependent memory impairment in COVID-19" employing an ingenious indirect measure via psychological tests the mnemonic similarity task (MST) and relational elaboration and coherence (REC):

"Given the susceptibility of hippocampal neurogenesis to COVID-19 and its potential impact on pattern separation, cognitive consequences related to memory precision were anticipated. Specifically, we expected significant deficits in mnemonic pattern separation among individuals who had tested positive for COVID-19, compared to previously not infected participants, while other mnemonic functions, such as item recognition memory, would largely remain intact. Our results exactly confirm this hypothesis, showing that previously infected individuals exhibited a marked and selective impairment in mnemonic discrimination, which relies on hippocampus-dependent pattern separation, leaving item recognition memory intact. This suggests that compromised hippocampal neurogenesis following SARS-CoV-2 infection may contribute to the memory deficits observed in COVID-19 survivors. However, while the MST is a valuable tool for assessing cognitive functions related to pattern separation, it is important to acknowledge that it serves only as an indirect measure of neurogenesis and the integrity of the DG. To account for cognitive processes beyond hippocampus-dependent pattern separation, we also examined the REC score, which assesses item recognition memory (i.e., the ability to recognize a target item as 'old') that should be less reliant on hippocampal processing and rather reflect the integrity of other memory-related structures of the medial temporal lobe, such as the perirhinal cortex....The absence of significant group differences in REC scores suggests that item memory remains intact in COVID-19 survivors, further supporting the specificity of the observed deficits in hippocampus-dependent processes. This distinction further emphasizes the MSTs utility in isolating hippocampus-dependent processes, specifically pattern separation, from other cognitive functions, such as item recognition memory, which rely on perirhinal cortex integrity. However, it is important to note that the MSTs reliance on behavioral performance to infer hippocampal function means that it cannot directly measure neurogenesis or the structural integrity of specific hippocampal regions."
https://www.nature.com/articles/s41598-025-04166-2 [5100]

More on the REC paradigm:
https://mural.maynoothuniversity.ie/id/eprint/4952/1/YBH_sketch.pdf [5101]

Describing "Serotonin, immune function, and psychedelics as potent anti-inflammatories" Nichols and Foster (2025) report that:

"Some psychedelics, but not all, have been found to have powerful anti-inflammatory and immunomodulatory effects through activation of 5-HT2A receptors in preclinical experimental systems and models of human inflammatory diseases. Human studies examining anti-inflammatory effects of psychedelics are limited but suggestive that psychedelics may represent a new strategy to treat inflammatory diseases. In this review we will present an overview of serotonergic modulation of immune function, the role of 5-HT2A receptors in these processes, and a summary of key findings with psychedelics with regards to anti-inflammatory efficacy."
https://www.sciencedirect.com/science/article/abs/pii/S0074774225000261 [5102]

Legal scholars will be reaching for their antidepressants when they read this paper by Reiche et al (2025) indicating the problems suffered by victims of NEPUD, which found no cognitive deficits found in sporadic psychedelic users compared to non-users, sporadic lifetime use of psychedelics associates with increased cognitive flexibility, and that the amount of lifetime psychedelic use predicts degree of increased cognitive flexibility.

"From 2611 screened individuals, N = 136 participants (84 psychedelic users and 52 controls) were included. Participants were aged 1850 years. Neuropsychological performance was broadly equivalent between users and controls. However, matched-pair analyses showed that psychedelic users had a modest advantage in executive functions, especially superior performance on the Wisconsin Card Sorting Test (WCST) (p < .05). Dose-response analyses further corroborated these findings, indicating a positive association between lifetime psychedelic use and performance on the WCST, specifically total errors (p < .001), perseverative responses (p < .001), perseverative errors (p < .001), non-perseverative errors (p = .008), and conceptual level responses (p = .004).

"Conclusions
The study did not detect any negative associations between sporadic lifetime psychedelic use and cognition. Instead, a moderate association with executive functioning was found, indicating increased cognitive flexibility in users. Dose-response analyses further supported this relationship."
https://www.sciencedirect.com/science/article/pii/S0278584625001071?via%3Dihub [4904]

Meanwhile, back in the laboratories of the University of Michigan Ann Arbor, with an improved experimental methodology Brouns et al (2025) find that "Single-dose psychedelic enhances cognitive flexibility and reversal learning in mice weeks after administration":

"Psychedelic compounds have demonstrated remarkable therapeutic potential for treating neuropsychiatric disorders by promoting sustained neuroplasticity in the prefrontal cortex (PFC). Cognitive flexibilitythe ability to adapt previously learned rules to novel situationsrepresents a critical PFC function that is frequently impaired in depression, PTSD, and neurodegenerative conditions. In this study, we demonstrate that a single administration of the selective serotonin 2A receptor agonist 25CN-NBOH produces significant, long-lasting improvements in cognitive flexibility in both male and female mice when measured 23 weeks posttreatment. Using a novel automated sequential learning paradigm, psychedelic-treated mice showed superior adaptability in rule reversal tasks compared to saline controls, as evidenced by enhanced poke efficiency, higher percentages of correct trials, and increased reward acquisition. These behavioral findings complement existing cellular research showing psychedelic-induced structural remodeling in the PFC and uniquely demonstrate sustained cognitive benefits persisting weeks after a single psychedelic dose. Our automated behavioral task provides a high-throughput method for evaluating cognitive flexibility effects of various psychedelic compounds, offering important implications for therapeutic applications in conditions characterized by cognitive rigidity, including depression, PTSD, and potentially Alzheimer's disease."
https://genomicpress.kglmeridian.com/view/journals/psychedelics/aop/article-10.61373-pp025r.0002/article-10.61373-pp025r.0002.xml [5297]

Considering that the morality-enhancing effects of psychedelics outweigh the moral principles upon which their prohibition is based, Vojin Rakić of the Center for the Study of Bioethics (CSB), Belgrade (2025) writes:

"A contribution of major importance to our understanding of psilocybin as a moral enhancer is the first path-breaking academic publication on this topic, 'Psychedelic Moral Enhancement' by Brian Earp. Building on Earp, Rakić argues that psilocybin is, for two reasons, a more effective moral bio-enhancer than non-psychedelic substances, such as oxytocin, SSRIs, and vasopressin. First, it tends to create sensations of selflessness and oneness with the world. These sensations are directly linked to altruism and integrated love, which is a cornerstone of morality. Non-psychedelic substances, even the ones with the strongest potential to morally enhance their consumers, might stimulate empathy, which, in turn, may strengthen altruism. Hence, their effects are mediated and therefore indirect. On the other hand, the effects of psilocybin on altruism and love, and consequently on morality, are not mediated via empathy, but have a more direct effect. Second, psilocybin stimulates happiness. As happiness and morality are in a circularly supportive relationship, psilocybin might also, in that manner, function as a moral enhancer."
https://onlinelibrary.wiley.com/doi/10.1111/bioe.70043 [5558]

Five years after Ptuj police took away all of the above a further meta-analysis of psilocybin and depression, including 26 papers, appeared in the Journal of Affective Disorders in December 2025. According to Khan et al:

"Psilocybin's regulation of serotonin 5-HT2A receptors, which improves neuroplasticity, disrupts maladaptive cognitive processes and encourages emotional integration, is the backend of its therapeutic benefits. The meta-analysis results indicate that psilocybin has an outstanding capacity to reduce the symptoms of anxiety/MDD (SMD = −1.438, 95 % CI: −1.729 to −1.146, p < 0.001) and mood disorders (SMD = −1.476, 95 % CI: −1.773 to −1.178, p < 0.001). Sustained improvements are frequently observed after a single therapy session."
https://www.sciencedirect.com/science/article/abs/pii/S0165032725023249 [5755]

And three months after that, in March 2026, Verónica Mäki-Marttunen looked again at existing datasets, finding that "Psilocybin shapes the slow, global propagation of brain activity over the cortical layout of 5HT2a receptors" as

"...faster propagation speed was related to increased total functional connectivity and a contraction of the principal gradient. The results support the view that these functional connectivity indices obtained from entire signal time courses reflect the modulation of specific global events of propagation. Furthermore, we found that the cortical distribution of 5HT2a receptors could contribute to the modulation of travelling wave propagation by psilocybin. These findings provide a link between macroscopic signatures of neuromodulatory activity, global brain events and receptor action, with relevance for understanding the mechanisms of psychedelic effects."
https://www.nature.com/articles/s42003-026-09912-4_reference.pdf [6072]

Parker Singleton et al (2026) report in Nature Mental Health

"Over 130 clinical trials on the therapeutic potential of psilocybin have been initiated in the past two decades, sponsored by over 100 different institutions, and there is estimated to be a potential market size of $10.75 billion for the clinical use of psychedelics by 2027. Thirty-nine of these initiated trials are for treatment-resistant depression or major depressive disorder, for which the US Food and Drug Administration has granted psilocybin Breakthrough Therapy designation to accelerate the approval process. The largest published trial to date assessed a single dose of psilocybin for a treatment-resistant episode of major depression in 233 individuals, finding that 25 mg, but not 10 mg, of psilocybin reduced depression scores significantly more than a 1 mg dose at 3 weeks."
https://www.nature.com/articles/s44220-026-00630-8.epdf [6076]

"Changes in anxiety, quality of life, and functioning following psilocybin-assisted therapy in veterans with treatment-resistant depression" (2026) by Kelly et al found "Psilocybin produced large, sustained reductions in anxiety scores up to 12 months; Quality of life and functional impairment improved early but waned later; PTSD symptoms showed sizable yet variable reductions over follow up; While improvements in exploratory outcomes tracked with depressive symptom changes, subjective experience measures did not correlate with treatment response."
https://www.sciencedirect.com/science/article/abs/pii/S0165032726009158 [6203]

Lago et al (2026) present a remarkable case history in "Transient multidomain functional improvement in advanced Alzheimer's disease following high-dose psilocybin-containing mushroom administration: a case report" (2026).

Before:

"The patient was an octogenarian Japanese-American woman who lived with continuous family supervision and caregiver support. Progressive cognitive and functional decline had evolved over approximately 10 years. During the preceding 5 years, verbal output became predominantly monosyllabic, accompanied by severe reduction in spontaneous interaction, chronic urinary incontinence, executive dysfunction, impaired mobility, dysphagia, and marked dependence in activities of daily living."

Afterwards...

"One month after the initial session, the patient remained continent and functionally improved compared with baseline. A second supervised psilocybin session using 3 g was subsequently performed and was associated with greater verbal expressivity, improved facial mimicry, spontaneous humor, emotionally valenced autobiographical imagery, and increased agility while walking.

"The patient spontaneously stated: 'It is pleasant to come here.'"

https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2026.1813281/full [6202]

As reported by medicalxpress.com,

"They found that after taking a single high dose of psilocybin, the patient regained several abilities she had lost years earlier. Within 19 hours of taking the dose, she was able to hold hourlong conversations about her life, whereas before the study her speech had been limited to one or two words at a time. She began to show emotions and respond to humor.

"Not only did her bladder control improve, but her diapers remained dry even overnight, and she also started dressing herself. She began to maintain eye contact and smile back at people. Many of the gains persisted for weeks, with some continuing after the second, lower dose."

https://medicalxpress.com/news/2026-06-high-dose-psilocybin-temporarily-lost.html [6204]

In Slovenia they would all have been fined and the therapists fired.

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The Englishman 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 Englishman 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. Below, the latest version of this dynamic list.


THE BENEDICTIONS                            REFERENCES                        TIMELINE OF DRUG LAW v. SCIENCE