Psilocybin is a naturally occurring
psychedelic compound found in many species of mushrooms. In this form it
has a long history of use by Man in the context of healing and
divination, and it is still employed in this manner today by indigenous
groups such as the Mazatec. Since the 1960’s awareness of psilocybin and
the fungi within which it resides has spread into the Western world.
Following the legal clamp down that resulted from widespread use of this
and other psychedelics like LSD and mescaline at this time, scientific
research into this compound and other psychedelics all but drew to a
halt. In the last few years regulatory red tape has been loosening to
some degree, and scientists have began studying psilocybin for a number
of reasons. It appears that psilocybin is a highly multifaceted compound
and has the capacity to act as a profound tool in the study of the
brain and consciousness, as well as act as a treatment for a variety of
psychological conditions.
Psilocybin is a compound of very low physical toxicity, but it can
exert very powerful psychological effects, and the correct set and
setting are of key importance when the drug is administered to reduce
the chances of adverse reactions and to maximise potential benefits. On
ingestion, psilocybin is dephosphorylated into the pharmacologically
active molecule psilocin which closely resembles a key neurotransmitter
serotonin in structure, and because of this it had a high affinity for
5-HT
2A and 5-HT
1 serotonin receptors where it
mimics the effect of the neurotransmitter. The psychedelic effects of
psilocybin can be prevented by the chemical ketanserin, which acts as a
5-HT
2A receptor antagonist, blocking psilocybin’s access to
the receptor sites and preventing it from exerting an effect
(Vollenweider
et al. 1999). These receptors are located at
varying densities in many parts of the brain, and play important roles
in mood and motivation regulation, among other things. At medium doses
psilocybin has also been found to increase an increase in cerebral
metabolic rate of glucose, particularly in the frontomedial and
frontolateral cortex (24.3%), anterior cingulate (24.9%) and
temporomedial cortex (25.3%) brain regions (Vollenweider
et al. 1997).
Recent technological developments such as functional magnetic
resonance imaging (fMRI) are allowing researchers to examine the brain
with greater precision and less invasively than ever before. Brain
imaging studies of healthy volunteers under psilocybin have found that
brain activity was reduced in the default-mode network via a reduction
in blood flow, and hub regions such as the thalamus and anterior and
posterior cingulate cortex were affected, and this in turn has
downstream effects on consciousness, leading to a more unconstrained,
expansive and free flowing state when compared to cognition in a sober
state (Carhart-Harris
et al. 2012). An overactive default mode
network is associated with depressive states and obsessive rumination,
so a reduction in activity of this network may have important
implications for the treatment of depression. A reduction of activity in
the default-mode network is also linked to experiences of ego
dissolution commonly associated with psilocybin. This network is linked
to our personality and sense of self, with the latter being experienced
as less solid under psilocybin, and there is a sense of novelty, with
people commonly describing experiencing the world akin to new, as
through child like eyes. Activity in the medial prefrontal cortex was
consistently decreased by psilocybin, which is of interest as this area
has been observed to be hyperactive in people experiencing major
depressive episodes. Mindfulness meditation has also been found to
reduce activity in these same brain regions.
More brain imaging research has also shown the psilocybin enhances
autobiographical recollection and facilitates the recall of memories in a
vivid fashion in healthy volunteers, and that there was a correlation
between vividness of memories and subjective well being at a two week
follow up after the session. Increased activity in brain regions that
process visual and other sensory information was also observed. This
aspect of psilocybin suggests it may be an aid to psychotherapy as a
tool to facilitate the recall of salient memories or to aid in the
reduction of fixation on negative memories, while also having the
potential to enhance creative thinking (Carhart-Harris
et al. 2012).
Further brain imaging research has built on this past research and
shown that psilocybin increases the amplitude of activity in brain
regions that are reliably activated during dream sleep and which form
part of the brains more ancient and primitive emotion system. At the
same time an expanded state of consciousness is facilitated, with
respect to an increased breadth of associations made by the brain under
the drug and the ease with which this occurs compared to sober states
(Tagliazucchi
et al. 2014). This research indicates that
psilocybin may allow access to waking dream states, and so allow active
unconscious emotional processing and learning that is associated with
dreaming, while also being an aid in creative thinking and problem
solving, while having therapeutic applications for its ability to access
the primal parts of the brain. It appears the state of consciousness
resulting from psilocybin ingestion leads to disorganised and reduced
activity in the ego system which in turn permits disinhibited and
increased activity on the emotion system. This builds on evidence in
other studies with the compound that psilocybin may be a useful aid for
certain forms of psychotherapy.
Further analysis of the recent MRI findings of human brains under
psilocybin has shown that the drug increases connection and
communication between brain regions that are usually more disconnected
in a sober state, and in an organised and stable fashion; the brain’s
connectivity pattern is distinctly different under psilocybin. It is
possible that experiences such as synaesthesia reported under
psychedelics, where different sensory perceptions cross over and merge,
may occur due to these alterations in brain connectivity. The function
of the brain under psilocybin can be described as less constrained and
more intercommunicative compared to a sober brain state (Petri et al.
2014).
More recent research has shown that psilocybin administration results
in reduced amygdala reactivity, which in turn is correlated with
positive mood in healthy volunteers (Kraehenmann
et al. 2014).
Thus, psilocybin may have potential as a treatment for anxiety and
depression, with amygdala overactivity linked with negative mood states
in patients with major depression. Research into psilocybin’s role as a
treatment for depression and anxiety is ongoing. Current anti-depressant
treatments only dampen symptoms, require chronic use to be effective,
are only effective for a certain proportion of people, they tend to come
with a range of side effects, and for some such as the commonly
prescribed SSRI’s, withdrawals can be prolonged. Psilocybin could
provide an alternative, more effective way of treating depression than
is currently employed.
Research supported by MAPS and led by Francisco Moreno at the
University of Arizona compromised the first FDA approval clinical pilot
study of psilocybin in the US since 1970, and it was focussed on the
treatment of obsessive-compulsive disorder (OCD). It was found that
psilocybin administration resulted in a significant reduction in OCD
symptoms in a number of patients (Moreno
et al. 2006), and this
is hypothesised to occur via a downregulation of serotonin receptors,
resulting in a reduced responsiveness to serotonin (Halberstadt &
Geyer 2011).
Psilocybin has been found to reduce the pain and symptoms of cluster
headaches (Vollenweider & Kometer 2010; Sun-Edelstein & Mauskrop
2011) which are highly debilitating, are considered one of the most
painful syndromes known to Man and are linked to a high suicide rate. No
other treatments are known to stop cluster headache cycles and
sub-psychedelic doses of psilocybin (and LSD) are effective. Psilocybin
has been found to decrease blood flow in the hypothalamus, where blood
flow increases during cluster headache episodes, which may partly
explain its efficacy in treating this condition (Carhart-Harris
et al. 2012). Further research in this area is certainly warranted.
Recent studies have used psilocybin in the treatment of alcoholism
and tobacco addiction. A recently completed pilot study with 15
participants using medium and large doses of the drug yielded highly
promising preliminary results, and further research is certainly
warranted. 12 of 15 study participants (80%) showed abstinence at a six
month follow up, while current treatments for tobacco addiction have a
much lower success result, not exceeding 35% (Johnson
et al.
2014). This was a small pilot study to test the feasibility of using
psilocybin to treat tobacco addiction so it is important not to draw any
definitive conclusions regarding the efficacy of psilocybin in treating
tobacco addiction, but the results are certainly encouraging and
supportive of further research.
Psychedelics like psilocybin act in a number of different ways in the
brain to affect addictive syndromes. They act on the receptors in the
brain associated with drug seeking behaviour, while reducing blood flow
to areas of the brain associated with emotional processing and higher
function that tend to be overactive in depressives. This can restrain
negative circular thought patterns associated with addiction. The
temporary chaotic state induced by psychedelics seems to weaken
reinforced brain connections and dynamics and the experience provides a
window of reflection where people can view their life and addiction
issues from a wider perspective. People who were more successful in
quitting smoking had higher ‘mystical experience’ scores, and in other
studies, the psilocybin induced mystical experience was found to cause
positive changes in measures of life satisfaction and well being, as
well as long term personality change, particularly in openness.
Low doses of the compound, and chronic high doses have recently been
found to increase hippocampal neurogenesis in mice, and increased the
speed of their ‘unlearning’ of negative fear behaviour responses when
compared to drug free controls, an effect that may hold promise in the
treatment of post-traumatic stress disorder (PTSD) and related
pathologies (Catlow
et al. 2013). Thus psilocybin may have
applications for treating PTSD in humans, a syndrome characterised by
highly abnormal brain function, including impaired hippocampal function
(Shin
et al. 2006). Impaired hippocampal neurogenesis has also
been implicated in cognitive disorders such as anxiety, depression,
post-traumatic stress disorder (PTSD), addiction (Canales 2013) and
neurodegenerative diseases. The psilocybin was also found to decrease
activity in the medial frontal cortex regions of the mice, this area
being linked to overactivity in sufferers of PTSD, and this has also
been observed in human studies (Carhart-Harris
et al. 2012). It
may be that psilocybin, like ketamine, alters glutamatergic
neurotransmission, this being linked with neurogenesis and
neuroplasticity in the brain (Vollenweider & Kometer 2010).
Psilocybin is being studied for its efficacy at assisting terminally
ill cancer patients by easing their psychological suffering implicated
with their approaching death. Initial results, where low doses of the
drug are employed, combined with supportive psychotherapy, show great
promise in psilocybin assisting people by reducing anxiety and
existential angst, reducing dependency on pain medication following the
session and allowing people to make the most of their remaining time.
Effects from a single psilocybin session can be long term, with effects
lasting from two weeks up to six months and beyond (Vollenweider &
Kometer 2010; Grob
et al. 2011). Further research in this area
is ongoing, and is being conducted by Dr Stephen Ross of New York
University with support from the Heffter Research Institute.
Research with high doses of psilocybin have found it can induce long
term, positive changes in personality and feelings of life satisfaction
and well being (Griffiths
et al. 2011). Openness is one of the
five measures of personality, and can be significantly changed in the
long term by a single dose of psilocybin, especially if people have a
mystical experience during a session (Griffiths
et al. 2011).
This is of great interest, as after the age of 30 personality is thought
to be generally fixed in the individual, and openness is thought to
decline with age, hinting that psilocybin can influence neuroplasticity
of the brain. This change in personality remained as strong 14 months
after the session, and appears to be long term (Griffiths
et al.
2011). Openness covers personality traits such as an appreciation for
new experiences, broadness of imagination and finding value in
aesthetics, emotion, curiosity and creativity, with an increased hunger
for knowledge (MacLean
et al. 2011).
Psilocybin may have application in psychical research. In 1997 there
was some research into how psilocybin could influence results from
remote viewing conducted by students at the University of Amsterdam. In
the experiment, test-subjects under the influence of cannabis selected
the right target only slightly above chance expectancy. Test-subjects
under the influence of psilocybin selected the target with a success
rate of 58.3%, which is a statistically significant result. The
experiment was small however with only 12 subjects, but further research
with larger sample sizes is warranted (Millay 1999).
This is an exciting time for psilocybin research. The last few years
has seen an explosion in research, and this itself indicates that the
strongly anti psychedelic mind-set in scientific circles, a hangover
from the 1960’s, is beginning to dissipate, and researchers now have
cutting edge technologies such as fMRI to aid them in the work and
increase the precision and breadth of their findings. Research in many
areas is ongoing, and new avenues for enquiry are opening up. David Nutt
and his team at Imperial College are conducting a study on the efficacy
of psilocybin as a treatment for depression, building on their previous
work there. Just months ago a pilot study was completed in the US,
based at John Hopkins University, looking at the effects of psilocybin
on behaviour, psychology and brain function in long-term meditators.
Psilocybin has a long history of use by Man, and has been revered as a
powerful medicine and ally for a very long time. Modern science is
confirming and building on ancient wisdom to allow us to better
understand this amazing and highly multifaceted molecule, in order that
we can better utilise its tremendous capacity to heal people.
Notes
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