PsychedelicsEbook PDF

Psychedelics and Mental Health
Copyright © 2018 – Kelly Brogan

“...the potential significance of LSD and other psychedelics for

psychiatry and psychology was comparable to the value the
microscope has for biology or the telescope has for astronomy.”
– Stanislov Grof
I S IT POSSIBLE THAT THE GREATEST PAIN, depression, and suffering emerges

from the simple illusion of the separate self? Particularly in the West, we can get
lost in the idea that we are each individuals, a perspective that is sometimes called
atomism—feeling as if we are struggling to hack it and essentially alone, when all is
said and done. We can carve deep grooves in the negative thoughts that emerge
from this sense of alienation.
I imagine you’ve heard the trope “we are all one,” or that “love is our birthright.”
Perhaps these are more than Hallmark sayings and are, in fact, truths that need to
be felt rather than heard, learned, or understood. The same could be said for some
other disruptive concepts like sacredness and divinity. More and more of us are
encountering the seeming walls of our existence—and walking through them—in
experiences that many describe as mystical or metaphysical. We know we are
relating to something metaphysical when we experience the mystery of it all,
the great surrender to a greater design and to a beauty so chaotic that it can
only be received with gratitude.

Mystical experiences are the portal to this greater perspective, and are often
recounted as being more real than “reality” as we know it...forever etched into
consciousness as a life-defining shift. British philosopher Alan Watts defines
mystical experiences as:
“...those peculiar states of consciousness in which the individual discovers

himself to be one continuous process with God, with the Universe, with
the Ground of Being, or whatever name he may use by cultural
conditioning or personal preference for the ultimate and eternal reality.”
In a mystical experience, one becomes aware of awareness...becomes the watcher

perceiving the dissolution of all of the formerly held beliefs, opinions, and habits.
Mystical experiences have been characterized as having the dimensions of
sacredness, deep positive mood, paradoxicality, transcendence of time and space—
and ineffability, the difficulty of putting the experience into words.
What is the mystical experience?

Psychedelic researcher Robin Carhart-Harris relayed the experience of one of his
subjects, a 52-year-old man with treatment-resistant depression:
“Four decades I battled depression, the awful feeling that you don’t matter,
you’re not making a difference, that everyone else is having a better life;
the utter pointlessness of it or getting no real enjoyment from anything.”
About a guided experience with psilocybin, the subject said:
“There simply aren’t words to describe it, but I can say

that the usual negative self narration that I have had
vanished completely. It was replaced by a sense of
beautiful chaos, a landscape of unimaginable color and
beauty. I began to see that all of my concerns about

daily living weren’t relevant and that they were a result of a negative
spiral. I also felt like I was learning without being taught that intuition
was being fed. Fleeting feelings from my past came back, memories too,
both of which had seemed long forgotten.”
Then, several weeks later, he said:
“Although it’s early days yet, the results are amazing. I feel more
confident and calm than I have in such a long time. My outlook has
changed significantly too. I’m more aware that it’s pointless to get
wrapped up in endless negativity. I also feel as if I’ve seen a much
clearer picture. Another side to this is that I feel like I’ve had a second
chance, like a survivor. I can enjoy things now the way I used to without
the cynicism, without the oppression. At its most basic, I feel like I used
to before the depression.”
New glorious tracks have been laid down in this man’s life, enduring for the six
months of the study and likely beyond.
The subversive power of psychedelics

As a former atheist (a belligerent one), I certainly never thought I would be writing
this: In order to successfully come off of or avoid psychiatric medication, an
experience of conscious expansion is required. It might be called a spiritual
awakening, a deepening of personal connection to something greater, or simply a
connection to meaning.
As my patients move through this process, I watch for the window during which the
ego breaks open. The mind then engages in its death throe efforts to freak them
out, scare them, and convince them that EVERYTHING IS WRONG and nothing is
going to be okay, ever. I wait for this because it is what initiation feels like, and I
know that the light follows it.

My patients don’t take psychedelics during their tapering processes; however, they
do meet with the dark night of the soul that can be visited through the experience
of psychedelic journeys. This brink of consciousness—when traversed, embraced,
and subsumed—can represent a kind of death of a former self and a rebirth into a
new, expanded self-agency.
The survival of this trial is highly disruptive. In fact, the cost of one’s new life is
their old life. And everything is subject to review, calibration, and reintegration.
In a banned TED Talk, Graham Hancock discusses how plant medicines, and
specifically a brew of South American plants called ayahuasca, significantly threaten
the matrix of society. He goes on to say that in many ways, alcohol and prescription
drugs keep people asleep and compliant with the agenda of the orthodoxy.
Transformational substances like psilocybin, LSD, and ayahuasca blow the lid off of
the small boxes we are stuffed into.
Seemingly divined
from the most
improbable of
adf;
contexts, the overlap
in psilocybin (the
primary active
ingredient in
psychedelic
mushrooms), LSD, and
ayahuasca lies in the
activation of an inner
portal to expanded states of awareness. Often with attendant visions and journeys,
some believe that these agents simply unmask what is always present but
veiled...that we are but playing a part in a play we have forgotten is taking place.

My friend Charles Eisenstein echoes Graham’s sentiments, stating:
“Psychedelics can bestow expanded consciousness, perceptions, and

ways of being that are incompatible with those that undergird our
society. Psychedelics—also called entheogens—have the power to
subvert the alienation, competition, anthropocentrism, linear ordering
of time and space, standardization of commodities and social roles,
and reduction of reality to a collection of things that propel the world-
destroying machine of modern civilization. They disrupt the defining
mythology of our civilization, the Story of Separation.”

Scientific studies of entheogens for

depression and anxiety
A MOUNTING BODY OF SCIENTIFIC EVIDENCE has revealed the beneficial
effects of entheogens for depression1 ,2 , with psilocybin being the most
extensively studied.3 Interestingly, most studies noted that there were no serious
adverse effects, toxicities, or dependency when psychiatric patients were treated
with entheogens. In a meta-analysis of 19 studies that included 423 individuals
with psychiatric diagnoses, 79% of people who tried entheogens showed clinician-
judged improvements.3
Ayahuasca for depression

Ayahuasca has ridden a zeitgeist of popularity, as our awakening population
reaches for support in what feels like an urgent and timely need to move beyond a
paradigm that is literally killing us and this planet. Ayahuasca is a plant admixture
made from two or more plants, including a DMT-containing plant (e.g., Psychotria
viridis) and other plants that contain monoamine oxidase (MAO) inhibitors (e.g.,
Banisteriopsis caapi). While academic research would love to reduce the attendant
experience of these plants to simple brain chemicals, this approach is unlikely to
reveal the true power of entheogenic journeys. Of interest, relative to more
common experiences of psychedelics ayahuasca is typically a group experience,
facilitated by a shaman, involving what may be described as an initiation led by a
transformative feminine energy. Some meet with their own mortality, experience
the prospect of personal dissolution, and move through deep waves of bodily pain
while also experiencing bliss, expansion, and profound metaphysical insights.
1
https://www.ncbi.nlm.nih.gov/pubmed/26976063
2
3

Mechanistic studies of ayahuasca are supportive of the experience that users

describe. Brain scans suggest that ayahuasca increases blood flow to brain regions
that regulate mood.4 DMT, a component of ayahuasca, has been shown to reduce
the expression of pro-inflammatory cytokines while increasing the anti-
inflammatory cytokine IL-10 in human immune cells.5 Other research suggests that
harmine, another component of ayahuasca, is anti-inflammatory6,7 and these anti-
inflammatory effects may lead to reduction in the systemic, chronic inflammation
that can drive depressive symptoms.8,9 ,10 Further, ayahuasca may be considered an
antioxidant, as its components harmine and harmaline exert antioxidant and
neuroprotective effects through MAO inhibition.11,12
In a recent, randomized placebo-controlled trial, 35 patients with treatment-

resistant major depression showed rapid symptom improvement after just one
dose of ayahuasca.13 These findings fit with those of a previous open-label trial
showing that a single dose of oral ayahuasca allowed six volunteers to achieve
an 82% reduction in depressive symptom scores.14
4
5
6
7
8
9
10
11
12
https://www.ncbi.nlm.nih.gov/pubmed/8815918/
13
http://www.biorxiv.org/content/early/2017/01/27/103531
14

LSD research
Accidentally developed in 1938 by Dr. Albert Hofmann, who was
searching for a drug to induce labor from ergot fungus, LSD-25 (the
25th isolate he extracted from ergot) was extensively studied for
psychiatric applications from the 1950s to 1970s. Thousands of people
ingested LSD under the guidance of psychiatrists, therapists, and
researchers in the context of addiction, anxiety, and depression. In fact,
40,000 patients were prescribed some form of LSD therapy between
1950 and 1965, and over 1,000 scientific papers about the effects of LSD
were published—though the methods were often subpar and the sample
sizes too small to draw meaningful conclusions.15
LSD was adopted by the growing countercultural movement of the 60s due in
part to individuals like psychologist Timothy Leary—who brought the mantra “turn
on, tune in, and drop out” to American students—and to the psychedelic-influenced
music scene, which helped it gain global penetrance as a recreational substance.
But then the moral panic of the 60s ensued and the US government outlawed LSD
in 1968, causing its research and experimentation to go underground. There was
a renewed interest in the therapeutic potential of LSD in the 1990s, and the
advent of molecular brain imaging has given us insights into how this substance
impacts the body.
For example, brain scan studies reveal that LSD increases resting-state functional
connectivity within the default-mode network (DMN). The DMN has been associated
with introspection, meditation, and daydreaming, and in one study brain scans
show that increased DMN connectivity causes the lines between self and
environment to blur.16 The same study also found that LSD increased the level of
communication between normally separate brain networks, and that this increased
15
https://www.theguardian.com/science/neurophilosophy/2014/sep/02/psychedelic-psychiatry
16
http://www.cell.com/current-biology/fulltext/S0960-9822(16)30062-8

connectivity was associated with subject-reported “ego dissolution.” Another fMRI

study showed that LSD reduced reactivity of the left amygdala and right medial
prefrontal cortex, compared to the placebo group, which decreased the response
of the amygdala to fearful stimuli.17
The first American study published in over 40 years on LSD administered it to

people diagnosed with life-threatening diseases in a much more rigorous setting: a
double-blind, randomized, placebo-controlled trial. This study found that LSD-
assisted psychotherapy effectively reduced people’s anxiety immediately and up to
12 months later.18 A 2015 clinical trial found that LSD increases subjective well-
being, happiness, closeness to others, openness, and trust—which may be partially
mediated with increases in prolactin and oxytocin19; a 2016 trial replicated these
findings and showed that LSD enhanced participants’ desire to be with other people
and increased prosocial behavior.20
The sense of reconnection fostered by these therapeutic experiences appears to

have been a cornerstone of clinical improvement, an imperative now supported by
more recent research implicating isolation and social disconnection in
inflammatory processes.21
17
https://www.nature.com/articles/tp201754
18
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086777/
19
20
21
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5143485/pdf/npp2016141a.pdf

Psilocybin for depression

Psilocybin, a naturally occurring substance found in some types of mushrooms, has
been diligently studied as an antidepressant. In a 2016 trial, two doses of psilocybin
were given to 12 patients with treatment-resistant major depression. Eight of the
12 patients achieved complete remission of symptoms one week after
treatment, and seven patients remained free of depressive symptoms at a
three-month follow-up evaluation.22
In a follow-up study, the same researchers used

fMRI brain scans to understand how psilocybin
alters brain function.23 They found that psilocybin
decreases cerebral blood flow in the temporal
cortex, including the amygdala (which is sometimes
called the reptilian brain), and that this decreased
blood flow tracked with reduced depressive
symptoms. These findings fit with those of previous
studies that used brain scans to show that
psilocybin decreases the reactivity of the
amygdala and enables positive affective states
—similar to LSD.24 Other fMRI studies found that
psilocybin dampens amygdala activation in
response to visual threats, and also decreases the connectivity of the amygdala to
the primary visual cortex.25
A high-profile 2017 study showed that psilocybin decreased connectivity in the

DMN immediately after treatment, and increased connectivity one day post-
22
http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(16)30065-7/abstract
23
https://www.nature.com/articles/s41598-017-13282-7
24
25

treatment.26 This increased DMN functional connectivity was maintained for at least
five weeks and tracked with the reduction in depressive symptoms. The authors of
this study suggest that psilocybin may provide a “reset” mechanism in which
acute disintegration of the DMN later enables a reintegration.
Another fMRI study showed that psilocybin consistently deactivates the medial
prefrontal cortex, a brain region that has been shown to be hyperactive in
people diagnosed with depression.27 Therefore, this deactivation may be one way
that psilocybin alleviates depressive symptoms. Other researchers posit that
entheogens like psilocybin destabilize local brain network hubs, ultimately
allowing brain networks to reorganize after the acute effects have resolved.
Said another way, entheogens could literally rewire your brain.
Figure adapted from “Psychedelics as Medicine: An Emerging New Paradigm” 28
26
https://www.nature.com/articles/s41598-017-13282-7
27
28

Psilocybin for anxiety

Psilocybin has also been studied as a treatment for anxiety. In one trial, 12 patients
with advanced-stage cancer who had been diagnosed with cancer-related anxiety
were given oral psilocybin or niacin as a placebo. People given psilocybin showed
significant improvements in mood and reduction in anxiety scores with no
clinically significant adverse effects.29 In a similar trial, 29 cancer patients with
associated depression or anxiety were given a single dose of psilocybin or niacin,
and psilocybin produced immediate and sustained improvements in anxiety and
depression.30 At a six-and-a-half-month follow-up appointment, 60–80% of
participants continued to enjoy clinically significant reductions in depression
or anxiety, and even exhibited improved attitudes toward death.
In an even larger randomized, double-blind, crossover clinical trial, 51 cancer

patients with associated depression and/or anxiety were given either a very low
(placebo-like) dose of psilocybin or a high dose of psilocybin.31 Interestingly, both
groups showed significant reduction in depression or anxiety scores that
were sustained for at
least six months, with
the higher dose of
adf;
psilocybin enabling
better outcomes. Six
months after treatment,
about 80% of participants
showed clinically
significant decreases in
symptoms of anxiety and
depression. Consistent
29
http://www.sciencedirect.com/science/article/pii/S2215036616300657?via%3Dihub
30
31

with many psychedelic studies, the depth of a person’s mystical experience proved
predictive of therapeutic efficacy.
Figures from [23]
Perhaps the largest study of all was a 2016 meta-analysis conducted by Roland
Griffiths, a very active entheogen researcher from Johns Hopkins. This study
analyzed 191,832 survey respondents to determine if lifetime entheogen use
corresponded with psychological distress, suicidal thinking, and suicide
attempts.32 Respondents were categorized into four groups:
✦ Psilocybin only (i.e., lifetime use of psilocybin but no other classic

psychedelic) 2.47%
✦ Psilocybin & other psychedelics (i.e., use of psilocybin and other classic
psychedelics) 6.49%
✦ Non-psilocybin psychedelics only (i.e., use of any classic psychedelic with the
exception of psilocybin) 4.59%
✦ No psychedelics (i.e., those reporting no lifetime use of any classic
psychedelic) 86.42%
Researchers carefully controlled for age, gender, educational status, ethnoracial

identity, household income, marital status, and lifetime illicit use of other drugs.
Ultimately, the analysis found that the “psilocybin only” group had the lowest
odds of past suicidal thinking, psychological distress, and suicide attempts,
suggesting that psilocybin alone may be protective against stress
and suicidality.
32

Spirituality/mindfulness/cooperation
In addition to psychedelics being studied for psychiatric diagnoses, several studies
have shown that these entheogens can lead to increased mindfulness,
cooperation, and pro-environmental behaviors.
In one study that explored the potential of ayahuasca to increase mindfulness

capacities, researchers used The Five Facet Mindfulness Questionnaire (FFMQ) and
the Experiences Questionnaire (EQ), which measures centeredness. This study
found that ayahuasca indeed reduced judgmental processing and inner
reactivity, which are goals of meditation practices.33 Another study evaluated
the effects of ayahuasca by using creativity tests, including the “pattern/line
meanings test” (PLMT) and the “picture concept test” (PCT) to assess divergent and
convergent thinking. This test showed that ayahuasca significantly increased
divergent thinking and decreased convergent thinking, suggesting that this
entheogen enhances creativity and decreases a person’s sense of
limitations.34 Interestingly, people with more psychedelic experiences are more
likely to construe themselves as part of nature and feel interconnectedness, leading
to pro-environmental behavior.35
Part of the undermining capacity of entheogens is that they can foster a deep sense
of connectedness to the web of life—to the natural world, to each other, to the
cosmos. This connection makes it impossible to proceed with life as it is offered by
33
34
35
https://www.ncbi.nlm.nih.gov/pubmed/28631526/

the dominant paradigm, where nature is something to be managed and utilized,

where production of goods and procurement of money matters, and where our
bodies are machines prone to senseless malfunction. Many people describe a
difference between life before even a single psychedelic experience and life after.
And the “after” is characterized by a deep sense of existential arrival and ease—an
experience of clarity offered, often, through a harrowing journey wherein the ego is
shed, fractured, and left by the side of the road.
While these fast-track opportunities can offer an embodied experience of contact

with the spiritual realm, they typically still entail spiritual work and
commitment to integrate epiphanic realizations into daily life. In fact, this
integration and the ability to hold Reality alongside reality is why and how these
agents can sometimes be destabilizing to the unprepared journeyer. For these
reasons, the proper context, guidance, support, and informed consent is a vital part
of the potential for healing that these experiences can offer.
Once the emblem of a revolutionary counterculture, psychedelics are now the

subject of medical research, further revealing an gradual breakdown of beliefs
underlying the status quo, and paving the way toward an unknown but altogether
promising future.

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Psychedelics and Mental Health

Copyright © 2018 – Kelly Brogan

“...the potential significance of LSD and other psychedelics for

I S IT POSSIBLE THAT THE GREATEST PAIN, depression, and suffering emerges

Copyright © 2018 – Kelly Brogan

“...those peculiar states of consciousness in which the individual discovers

In a mystical experience, one becomes aware of awareness...becomes the watcher

What is the mystical experience?

About a guided experience with psilocybin, the subject said:

“There simply aren’t words to describe it, but I can say

Copyright © 2018 – Kelly Brogan

Then, several weeks later, he said:

The subversive power of psychedelics

Copyright © 2018 – Kelly Brogan

Copyright © 2018 – Kelly Brogan

My friend Charles Eisenstein echoes Graham’s sentiments, stating:

“Psychedelics can bestow expanded consciousness, perceptions, and

Copyright © 2018 – Kelly Brogan

Scientific studies of entheogens for

Ayahuasca for depression

Copyright © 2018 – Kelly Brogan

Mechanistic studies of ayahuasca are supportive of the experience that users

In a recent, randomized placebo-controlled trial, 35 patients with treatment-

Copyright © 2018 – Kelly Brogan

Copyright © 2018 – Kelly Brogan

connectivity was associated with subject-reported “ego dissolution.” Another fMRI

The first American study published in over 40 years on LSD administered it to

The sense of reconnection fostered by these therapeutic experiences appears to

Copyright © 2018 – Kelly Brogan

Psilocybin for depression

In a follow-up study, the same researchers used

A high-profile 2017 study showed that psilocybin decreased connectivity in the

Copyright © 2018 – Kelly Brogan

Figure adapted from “Psychedelics as Medicine: An Emerging New Paradigm” 28

Copyright © 2018 – Kelly Brogan

Psilocybin for anxiety

In an even larger randomized, double-blind, crossover clinical trial, 51 cancer

Copyright © 2018 – Kelly Brogan

Figures from [23]

✦ Psilocybin only (i.e., lifetime use of psilocybin but no other classic

Researchers carefully controlled for age, gender, educational status, ethnoracial

Copyright © 2018 – Kelly Brogan

In one study that explored the potential of ayahuasca to increase mindfulness

Copyright © 2018 – Kelly Brogan

the dominant paradigm, where nature is something to be managed and utilized,

While these fast-track opportunities can offer an embodied experience of contact

Once the emblem of a revolutionary counterculture, psychedelics are now the

Copyright © 2018 – Kelly Brogan

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