***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]
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, in,
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]
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."
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]
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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