This document summarizes research on the potential applications of psychedelic drugs like MDMA and psilocybin in treating anxiety disorders such as PTSD. It discusses studies that found psychedelic-assisted psychotherapy using these drugs showed promise in reducing symptoms of PTSD and depression in participants. For example, a study on MDMA-assisted therapy found one participant, Nicholas Blackston, had a realization about self-healing during a session. The document also reviews research on the mechanisms of action, risks, and legal status of psychedelics. It calls for further research with larger and more diverse cohorts and different treatment timelines.

1. Hayley Peerless – 30849137
Psychedelics and their potential applications in the treatment of PTSD & Other anxiety-related disorders
Psychoactive substances, generally defined as compounds that alter mental processes such as perception
and cognition, have had a vacillating reputation in regards to societal acceptance throughout history. Fossil
evidence provided by numerous archeologists indicates that over 10,000 years ago, humans may have not only
used psychoactive plants during ritualistic ceremonies but as intoxicants for the purpose of mind-alteration as
well. In addition, archaic Catholic texts mention the use of peyote by Native Americans, both ceremoniously and
casually, since 1000BC and throughout the 16th
century. However, over time as Christianity gained momentum,
the traditional use of psychedelics was labelled as unorthodox and their use substantially diminished but were
rediscovered by Western society during the late 1800s (The University of Cambridge 2007)i
. By the 1950s, new
techniques had emerged and the interest in psychedelic research began to increase. Humphrey Osmond and
Aldous Huxley (1953) are two of the most notable researchers who, through their own personal experimentation
and competition for best-suited generic name, coined the term "Psychedelic". Although profoundly influential, the
medical research and recreational use of psychedelics was restricted, much to the dismay of its supporters, in the
early 1960s by the United States Food and Drug Administration (Shroder, 2014)ii
. Since then there has been
minimal research into the clinical applications of Psychedelic drugs due to legislation and limited techniques for
both human and non-human subjects. However, some non-profit organizations such as MAPS – the
Multidisciplinary Association for Psychedelic Studies – which was founded in 1986, conduct research that aid in
developing medical, legal and cultural contexts for people to benefit from the careful use of Psychedelics (MAPS
2015)iii
. For example, in April of 2011, MAPS began a triple-blind pilot study on MDMA-Assisted Psychotherapy
pilot study for the treatment of Posttraumatic stress disorder (PTSD) in Charleston, South Carolina, with the hopes
of resolving previous unsuccessful attempts (Shroder 2014).
MDMA, also known as 3,4-methylenedioxymethamphetamine or 'ecstasy', is a ring-substituted
phenethylamine with a chemical structure that is similar to that of mescaline, from the Peyote cactus, and
Methamphetamine, a synthetic central nervous system (CNS) stimulant (Bouso 2008)iv
. It was originally
synthesized in 1912 by Merck, a German pharmaceutical company, to stop bleeding. However, when tested it was
found to produce intense feelings of closeness and affiliation due to its primary mechanism of action on the 5-
Hydroxytryptamine (5-HT) transporter, which results in excessive serotonin in the synaptic cleft. In addition, the
drug has also been shown to interact with other neurotransmitter systems such as dopamine and norepinephrine
(Australian Government Department of Health 2008)v
. One of the [more well-known] participants in the prior
mentioned 2011 MAPS study was Nicholas Blackston – a former marine, whom after touring in the Iraqi cities of
Fallujah and Ramadi – suffered from recurring, unwanted memories, severe emotional distress and a shift to
negative-based thinking – symptoms characteristic of PTSD. Prior to his enrollment in the study, Nicholas had
tried various homeopathic remedies such as meditation and deep breathing, in addition to medicinal cannabis use,
all with no avail. In the months following Nicholas's unsuccessful attempts at a "self-cure", a CNN news

2. Hayley Peerless – 30849137
Psychedelics and their potential applications in the treatment of PTSD & Other anxiety-related disorders
broadcast on the controversial MAPS pilot project had caught his interest, eventually bringing him to the office of
lead investigators, Michael and Annie Mithoefer, M.D. As per FDA (the United States Food and Drug
Administration) protocol, Nicholas and the other candidates underwent psychological screening and preparatory
sessions in the weeks preceding the study. All participants were then randomly assigned one of three different
MDMA doses: 125 milligrams, the full active dose; 75 milligrams, partially active; and 30 milligrams, which
played the role of a placebo – Enough to be "felt" by the participant but not so high as to induce a hallucinogenic
or therapeutic effect. The personal experiences of Nicholas Blackston, whom was later revealed to be a 75
milligram recipient, were recounted verbatim by Tom Shroder – renowned journalist and therapist who was
present during the privately recorded MDMA psychotherapy sessions – in his novel Acid Test. In recounting one
of the many outré awakenings Nicholas had had during his first session, Shroder detailed "… One of them was
actually about my body. I had realized that the only thing I came into this world with, that I started off with, was
my body. And that within in my body were all the answers that I need. I was communicating with this inner
healer inside – you know, I felt this source that was within" (Shroder 2014). One critical aspect of the mild
hallucination Nicholas experienced was the connection he was able to form with himself – that is, he was able
interact with and confront a younger version of himself, allowing the realization that fear and deep-seated
insecurities were the driving force behind his PTSD manifestations. The inward realization of self-healing that
Nicholas had had, is not the first of its kind. In his research on MDMA, Timothy Amoroso notes that one of the
hallmark effects of MDMA is the feeling of closeness, with others and one's self, which has been establish in both
human and animal studies and shown to be a result of an increase in oxytocin release – a hormone predominantly
synthesized in the hippocampal region that acts as a neurotransmitter – as well as activation of additional brain
regions (Amoroso 2015vi
; Kabilan 2014vii
).
Another drug that is gaining momentum for use in psychedelic-assisted psychotherapy is Psilocybin (PY,
4-phosphophoryloxy-N, N-dimethyltryptamine). Psilocybin is a substituted indolealkylamine, belonging to the
group of hallucinogenic tryptamines, and the major psychoactive alkaloid of some species of fungi distributed
across the globe, such as Psilocybe mexicana, Psilocybe azurescens, and Psilocybe cubenis (Passie 2002)viii
. As it
is serotonergic, Psilocybin's primarily interacts with 5-HT1A, 5-HT1D, 5-HT2A & 5-HT2C receptors as well as partly
upon the dopamine (DA; D1 and D2) and adrenergic α2 receptors (Passie 2002; Vollenweider 2001ix
). Isolated
from Central American "magic mushrooms" in 1957 by Swiss chemist Albert Hofmann, and produced
synthetically for the first time in 1958, Psilocybin has been used predominantly for non-medical purposes but has
been shown to possess therapeutic potential for the delaying of transient headaches, reduction of anxiety in
terminal cancer patients and alleviation/management of depression, due to its ability to lower psychological
defences and facilitate emotional insight (Johnson 2012x
; Shumate 2013xi
; Zamaria 2014xii
).

3. Hayley Peerless – 30849137
Psychedelics and their potential applications in the treatment of PTSD & Other anxiety-related disorders
In their research, R. L. Carhart-Harris et al examined the implications of Psilocybin for psychedelic-
assisted psychotherapy – under the prediction that it would augment subjective and neural responses to personal
memories – by using functional magnetic resonance imaging (fMRI) in a cohort of 10 healthy individuals, all of
whom had recreationally used Psilocybin at least 6 weeks prior to the study (Carhart-Harris et al 2012)xiii
.
Participants were required to attend two scanning sessions, separated by at least 7 days. Psilocybin (2mg in
Saline) and placebo (saline only) injections (60s infusions) were administered on an alternating day-to-day pattern
in a balanced order across participants – That is, Psilocybin was received on one day, and a placebo on the other,
during scanning. The participants then performed the autobiographical memory condition – a fixed sequence of
rest-memory-attention that was repeated 15 times in total – with their eyes closed in order to aid recollection. The
memory portion of the sequence was conducted using personal cue cards (understandable only to the particular
participant) that were presented 6s prior to the instruction "Close your eyes" and followed by a 16s recollection
period. To ensure attention was maintained, each participant was subjected to a sequence of auditory tones of
different pitch playing in either ear in a random fashion, and required to press a button indicating the ear in which
more tones had occurred. After the fMRI sessions, participants were asked to rate each memory for vividness,
emotional intensity, valence and visual imagery. The fMRI results were then analyzed, with two primary contrasts
of interests – the early memory period v. rest and the late memory period v. rest.
R. L Carhart-Harris et al found that early activations were generally more subcortical, and especially
significant in amygdala, hippocampus, striatal regions (E.g. nucleus accumbens), mid-cingulate cortex, ore-
sensorimotor area and precuneus (superior parietal lobule). On the other hand, late activations were shown to be
centralized in the limbic and paralimbic regions, temporal and frontal poles, as well as the medial prefrontal
cortex – the latter two being noticeably absent in the early recollection period. Although there were no significant
differences in early phase memory activation under psilocybin v. placebo, there were greater late phase sensory
activations under psilocybin, in addition to more intense subjective effects (Carhart-Harris et al. 2012). In terms of
psychotherapy potential, the greater late phase sensory activations in response to positive memory cues and
intense subjective effects produced by Psilocybin be a viable treatment for chronic depression. The potential of
Psilocybin is also supported by the research of Charles Grob et al who found that the depression scores in patients
with anxiety were decreased 6 months after a single Psilocybin treatment – 0.2mg/kg alternated with a 250mg
placebo (Grob et al 2011)xiv
; And furthermore by Griffiths et al who performed 2-3 sessions of psilocybin
treatment, occurring two months apart, in hallucinogenic-naïve healthy participants and found that at a 14-month
follow up, most participants reported an overall increase in well-being as well as satisfaction and had rated the
psilocybin experience as a positively significant life event (Griffiths 2006)xv
.

4. Hayley Peerless – 30849137
Psychedelics and their potential applications in the treatment of PTSD & Other anxiety-related disorders
Although proven to be effective therapeutic tools for the treatment of PTSD and other anxiety-based
disorders, MDMA and its hallucinogenic analogues including, but not limited to - LSD, Mescaline, Phencyclidine
(PCP) and Psilocybin – remain highly controversial due their "overt risk for abuse" and are therefore primarily
used recreationally, despite being classified as Schedule III substances in Canada (Government of Canada
2016)xvi
, and Schedule I substances in the United States of America. In their analysis, Psychedelic medicine: A
re-emerging therapeutic paradigm, Tupper et al. state that "set (i.e. psychological expectations), setting (i.e.
physical environment) and the therapeutic clinician-patient relationship are critical elements for facilitating
healing experiences and realizing positive outcomes" and that a fundamental misunderstanding of the interaction
of these 3 factors, likely contributes to the controversial reputation they have within the general population; Media
derogation is also a contributing factor to the relatively negative image of hallucinogens, as they are often
depicted solely as "club-drugs". Furthermore, the potential harms of LSD, Psilocybin, Mescaline and MDMA are
also discussed by Tupper et al, with outcomes such as Psychosis, neurocognitive deficits such as memory
impairment, Sleep disruption, short-term depression and serotonin syndrome – a potentially life threatening
condition characterized by excessive levels of serotonin (Tupper et al 2015xvii
; U.S National Library of Medicine
2014xviii
). However, given the overwhelmingly rare occurrence of death from acute overdose of LSD, Psilocybin,
MDMA and mescaline (U.S Department of Justice Drug Enforcement Administration 2015)xix
, it is relatively safe
to state that the potential and proven positive clinical applications of psychedelics far outweigh the negative.
Future studies on the applications of psychedelics should include larger and more diverse (in ethnicity, age,
gender & size) cohorts, as the majority are middle-age Caucasians, in order to gain a better understanding of the
factors that may influence effectiveness, and should also include broader range of afflicted subjects – E.g. those
with low, moderate and severe depression or periodic vs. chronic depression, as opposed to a cohort of only
severely depressed patients, in order to study the extent to which the psychedelics alleviate suffering. In addition,
extending trial periods – i.e. several infusions over the course of a year as opposed to weeks or months – may also
be worth investigating in order to examine and gain a better understanding of the viability as a periodically
prescribed drug (E.g. for terminally ill anxiety-ridden patients), assuming the legislation of the schedule I/III
drugs are subject to possible re-evaluation.

5. Hayley Peerless – 30849137
Psychedelics and their potential applications in the treatment of PTSD & Other anxiety-related disorders
References
i
The Department of History and Philosophy of Science (2007). The Medical History of Psychedelic Drugs. The
University of Cambridge, Freelane, Cambridge, UK. Pg. 4-20.
ii
Tom Shroder (2014). Acid Test. New York, NY. Blue Rider Press. Pg. 35-38, 50-51
iii
The Multidisciplinary Association for Psychedelic Studies (2015). What is Maps? Retrieved April 2016 from:
http://www.maps.org
iv
José Carlos Bouso, Rick Doblin, Magí Farré, Miguel Ángel Alcázar & Gregorio Gómez-Jarrabo (2008) MDMA-
Assisted Psychotherapy Using Low Doses in a Small Sample of Women with Chronic Posttraumatic Stress
Disorder, Journal of Psychoactive Drugs, 40:3, 225-236
v
The Australian Government Department of Health (2008). Pharmacology of MDMA (Ecstasy). Retrieved April
2016 from:
http://www.health.gov.au/internet/publications/publishing.nsf/Content/drugtreat-pubs-modpsy-
toc~drugtreat-pubs-modpsy-2~drugtreat-pubs-modpsy-2-3~drugtreat-pubs-modpsy-2-3-pmdm
vi
Timothy Amoroso B.S. (2015). The Psychopharmacology of 3,4-Methylenedioxymethamphetamine and its Role
in the Treatment of Posttraumatic Stress Disorder, Journal of Psychoactive Drugs, 47:5, 337-344
vii
Anirudha Kabilan (2014). The Pharmacological Role of Oxytocin – A short Review. Journal of Pharmacology.
Sci & Res. Vol. 6(2), 220-223
viii
Torsten Passie, Juergen Seifert, Udo Schneider & Hinderk M Emrich (2002). The Pharmacology of Psilocybin.
Addition Biology 7, 357-364.
ix
Franz X Vollenweider (2001). Brain mechanisms of hallucinogens and entactogens. Dialogues Clin Neurosci.
3(4): 265-279
x
Matthew W. Johnson. R. Andrew Sewell & Roland R. Griffiths (2012). Psilocybin dose-dependently causes
delayed, transient headaches in healthy volunteers. Drug Alcohol Depend. 123(1-3): 132-140
xi
Timothy Shumate (2013). The Benefits of Psychedelic Drug Application for Clinical Treatment of Mental
Illness. The Journal of Undergraduate Nursing Writing. Vol. 6 (1)
xii
Joseph A. Zamaria (2014). A Phenomenological Examination of Psilocybin use and its positive and persisting
aftereffects. California School of Professional Psychology. ProQuest LLC.
xiii
R. L. Carhart-Harris, R. Leech, T.M Williams et al (2012). Implications for Psychedelic-assisted
Psychotherapy: functional magnetic resonance imaging and Psilocybin. The British Journal of Psychiatry 200:
238-244
xiv
Grobs CS, Danforth AL, Chopra GS, Hagerty M, McKay CR, Halberstadt Al, et al. (2011) Pilot study of
psilocybin treatment for anxiety in patients with advanced-stage cancer Arch Gen Psychiatry. 68: 71-8
xv
Griffiths RR, Richards WA, McCann U, et al (2006). Psilocybin can occasion mystical-type experiences having
substantial and sustained personal meaning and spiritual significance. Psychopharmacology (Berl) 187:268–83
xvi
The Government of Canada (1996; Amended 2016). Controlled Drugs and Substances Act. Retrieved April
2016 from:
http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-14.html#h-30
xvii
Kenneth W. Tupper, Evan Wood, Richard Yensen, Matthew W. Johnson (2015). Psychedelic medicine: A re-
emerging therapeutic paradigm. CMAJ 187(14)
xviii
U.S National Library of Medicine (2014). MedlinePlus. Retrieved April 2016 from:
https://www.nlm.nih.gov/medlineplus/ency/article/007272.htm
xix
U.S Department of Justice Drug Enforcement Administration [DEA] (2015). Drugs of Abuse. Retrieved April
2016 from:
http://www.dea.gov/pr/multimedia-library/publications/drug_of_abuse.pdf#page=68