06/17/2015 Studying the Effects of Psilocybin in Humans:
The re-emergence of psychedelics in clinical science
Albert Garcia-Romeu, PhD
1 06/17/2015 Psychedelics (Psilocybin, LSD)
! Primarily
serotonergic, acting
as agonists at 5-HT2A
receptor subtypes
(among others)
2 06/17/2015 Psychedelics = Mind manifesting?
“To fathom hell, or soar angelic, take a pinch of psychedelic.” -Dr. Humphrey Osmond in a letter to Aldous Huxley, (1957)
From Greek ‘psyche’ for mind, and ‘delos’ for manifest.
Psychedelics
“A psychedelic drug is one which has small
likelihood of causing physical addiction, craving,
major physiological disturbances, delirium,
disorientation, or amnesia, produces thought,
mood, and perceptual changes otherwise rarely
experienced except perhaps in dreams,
contemplative and religious exaltation, flashes of
vivid involuntary memory and acute psychoses.”
- Dr. Lester Grinspoon
3 06/17/2015 4 06/17/2015 5 06/17/2015 6 06/17/2015 Psilocybin (O-phosphoryl-4-hydroxyN,N-dimethyltryptamine)
! 
! 
Active agent in over 100 species of mushrooms, most in
Psilocybe genus
Ancient history of use by various indigenous cultures
7 06/17/2015 Overview
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Initial psilocybin study in 36 healthy volunteers (2006)
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14 month persisting effects of psilocybin (2008)
! 
Dose effects of psilocybin in 18 healthy volunteers (2011)
! 
Effects of psilocybin on personality (2011)
! 
Psilocybin for smoking cessation in 15 smokers (2014)
! 
Psilocybin for anxiety in 44 cancer patients (in preparation)
! 
Psilocybin’s effects on spirituality and meditation in 75
healthy volunteers (in preparation)
Initial psilocybin study in our research group
!
(Griffiths, Richards, McCann, Jesse, 2006, Psychopharmacology)
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Broadly assessed effects of a high dose of
psilocybin in 36 high functioning, spiritually
involved people with no history of hallucinogen
use
Compared 30 mg/70 kg psilocybin to 40 mg/70
kg methylphenidate as an active comparator.
8 06/17/2015 Pahnke-Richards Mystical Experience
Questionnaire -- 7 hours after session
Spiritual
significance:
2 Months after
sessions
9 06/17/2015 Change in
Well-Being:
2 Months after
sessions
Community ratings of participants’ behavior &
attitudes 2 months after sessions
10 06/17/2015 Mystical-type
experiences
occasioned by
psilocybin mediate the
attribution of personal
meaning and spiritual
significance 14
months later.
Griffiths et al. (2006, 2008)
Drug sessions
The 8-hr drug sessions are conducted in a
living-room-like environment !  Two monitors are present throughout the
session
!  Participants asked to:
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lie on the couch
wear eye masks and headphones
listen to a program of music
focus attention inward
trust, let go, be open
11 06/17/2015 Human Hallucinogen Research:
Guidelines For Safety
(Johnson Richards Griffiths, 2008, J Psychopharm)
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Safety profile of classic hallucinogens
Volunteer screening and selection
Training of study personnel
Physical session environment
Preparation of volunteers
Conduct of hallucinogen administration sessions
Post-session volunteer follow up procedures
12 06/17/2015 Psilocybin Occasioned Mystical-type Experiences:
Immediate And Persisting Dose-related Effects
(Griffiths Johnson Richards Richards McCann Jesse, 2011, Psychopharmacology)
18 participants, similar to previous study
!  Methods very similar to 2006 study
!  5 sessions 1 month apart
!  Doses: 0, 5, 10, 20, and 30 mg/70 kg
!  Half received ascending doses, other descending
!  Placebo quasi-randomly inserted
!  Persisting effects assessed at 3 weeks post
session
! 
13 06/17/2015 The dark side
39% of participants (7 of 18) had extreme
ratings of fear, fear of insanity, or feeling trapped
!  6 cases: 30 mg/70 kg
!  1 case: 20 mg/70 kg
!  But small increase in mystical experience scores
!  Potential for dangerous behavior if unsupervised
! 
Unpredictable timing
14 06/17/2015 Mystical experiences occasioned by the hallucinogen psilocybin lead
to increases in the personality domain of openness
(MacLean Johnson Griffiths, 2011, J Psychopharmacol)
NEO Personality Inventory: Neuroticism, Openness, Extroversion,
Agreeableness, and Conscientiousness
Openness: aesthetic appreciation and sensitivity, imagination and
fantasy, and broad-minded tolerance of others’ viewpoints and values
15 06/17/2015 Why use a psychedelic"
to treat addiction?
Suggestive anthropological evidence
! 
Reports suggest that hallucinogen use within the
ritualized practices of indigenous cultures may
be efficacious in the treatment of a variety of
forms of drug dependence, with reported high
rates of recovery and prolonged abstinence
! 
Peyote and the Native American Church in the US
(Albaugh & Anderson, 1974; Bergman, 1971; Blum et al., 1977;
Calabrese, 1997; Garrity, 2000; Menninger, 1971; Pascarosa et
al., 1976; Roy, 1973)
! 
! 
Ayahuasca ceremonies within certain Amazonian
societies (Dobkin de Rios et al., 2002)
Correlational; not possible to separate role of
hallucinogen from the larger context of religious
guidance and social support
16 06/17/2015 Krebs T S , Johansen P J Psychopharmacol 2012;26:994-1002
Across studies, LSD doubled the odds a patient would be
alcohol free at the 1st follow up (N=536)
Our laboratory findings suggest
anti-addiction possible efficacy
Evidence of potential long term antidepressant-like effects
!  Evidence of behavior change from
volunteers and community observers
!  Highly salient, often mystical-type effects
with sustained personal meaning and
spiritual significance
!  Increased personality openness, possibly
affording openness to personal change,
including changes in self-identity
! 
17 06/17/2015 Pilot feasibility study: Smoking
Develop approach and demonstrate
feasibility
!  Cigarette smoking selected as model
system of drug dependence
! 
! 
! 
Relative lack of social & economic impairment
that often accompanies other drug
dependencies
Anecdotal reports of quitting after psilocybin
or LSD
Study design
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• 
• 
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Combined cognitive behavior therapy with 3
psilocybin sessions: 20 mg/70 kg on target quit date
(week 5), 30 mg/70 kg 2 weeks later, optional 3rd
dose 8 weeks later.
Participants: 15 otherwise healthy adult smokers in
the Baltimore area; 93% White; Mode education
level: College degree.
Mean Age = 50.6 yrs. (10.5 yrs.); Sex: 10 Male, 5
Female
Mean Cigarettes per Day: 18.7 (2.9); Mean Years
Smoking: 31.3 (9.9); Mean Previous Quit
Attempts=6.2 (3.6); Mean FTND score at intake: 5.3
(1.3)
10 reported previous psychedelic use (minimal), 5
hallucinogen naïve
18 06/17/2015 Timeline Follow-back (N = 15)
7-day Point Prevalence Abstinence (N = 15)
p < .001
30
Cigarettes per day
% Abstinent
100
80
Results
60
40
20
25
20
15
10
Smoking Status by self-report, breath 5CO, and cotinine:
•  80% abstinent at 15 weeks (12 of 015)
• BL 80%
abstinent
at 30mo*
6 months (12 of 15) BL 10wks 6mo 12mo
10wks
6mo 12mo
•  67% abstinent
Timepoint
Timepoint at 12 months (10 of 15)
0
Exhaled Carbon Monoxide (N = 15)
Urinary Cotinine (N = 15)
Urinary Cotinine (ng/ml)
Breath CO (ppm)
80
60
40
20
0
BL
10wks
6mo
6000
4000
2000
0
BL
12mo 30mo*
Mean (SEM) SASE Temptation Score
Mean (SEM) SASE Confidence Score
80
60
Results
BL
6mo
12mo 30mo*
Temptation to Smoke (N = 15)
Confidence to Abstain (N = 15)
100
20
10wks
Timepoint
Timepoint
40
30mo*
100
80
60
40
20
7-day
Point
Abstinence
(N =6mo15)12mo
10wks
6mo
12moPrevalence
30mo*
BL
10wks
Timeline Follow
30mo*
p<
Timepoint
Timepoint
Smoking Craving (N = 15)
100
30
BL
Cigarettes per day
40
80
60
40
20
10wks
6mo
12mo
30mo*
Timepoint
0
25
20
15
10
5
0
BL
10wks
6mo
12mo 30mo*
BL
10wks
Tim
Timepoint
Exhaled Carbon Monoxide (N = 15)
80
60
Urinary Coti
nine (ng/ml)
80
% Abstinent
120
O (ppm)
Mean (SEM) QSU Score
160
6000
19 4000
06/17/2015 Results
Self-reported cigarettes / day before, and after study
Timeline Follow-back (N = 15)
evalence Abstinence (N = 15)
p < .001
Cigarettes per day
30
25
20
15
10
5
0
0wks
6mo
12mo 30mo*
BL
6mo
12mo 30mo*
Timepoint
Timepoint
arbon Monoxide (N = 15)
Urinary Cotinine (ng/ml)
Urinary Cotinine (N = 15)
6000
How4000does it work?
High levels of personal meaning and mysticaltype2000
effects were associated with decreased
craving, and increased confidence to abstain.
nce to Abstain (N = 15)
50
BL
10wks
0
12mo 30mo*
r = 0.68, p = 0.005
r = -0.65,
p = 0.009
100
80
60
90
0
-50
2
12mo
Timepoint
ing Craving (N = 15)
30mo*
4
6
Personal Meaning
SOCQ Mystical Experience
(% of maximum possible score)
6mo
50
100
Temptation to Smoke (N = 15)
-100
-200
30
6mo
Timepoint
50
-50
-150
C
Change in SASE
Temptation to Smoke
Timepoint
B
Change in SASE
Confidence to Abstain
12mo 30mo*
0
Mean (SEM) SASE Temptation Score
6mo
Change in Craving (QSU)
A
10wks
ks
10wks
8
r = -0.7
0
-50
-100
2
4
Personal Me
60
40
20
BL
10wks
6mo
Timepoint
12mo
30mo*
20 06/17/2015 Table 2. Verbatim written comments for all volunteers who demonstrated biologically verified
smoking abstinence at 6-month follow-up (n=12). These comments were excerpted from the
States of Consciousness Retrospective Questionnaire (administered at end of treatment, in week
15) that asked open-ended questions about what was most memorable and what was most
spiritually significant about the psilocybin session experiences.
______________________________________________________________________________
Participant ID Verbatim Comments
______________________________________________________________________________
402
Feelings of gratefulness, a great (powerful) remembrance of humility… of my
experience of being, the experience of my being in and within the infinite.
403
Not at all religious but significant in motivating me to nurture my spiritual life.
405
It changes what I believe… We are all one and divine.
406 1
The awareness that all is one and then the realization that I am an integral piece of the
one's puzzle.
410
Oneness with universe; being forgiven.
413
Rich joy and awe. My body melting and becoming one with the universe felt both
painless and profound… Feeling complete as a person and physically a part of all thin
416
There is a meaningful presence that humbles any human heart.
417
Simultaneously being aware and saturated in the majesty of existence.
421
Seeing God speaks for itself; seeing and feeling forever was like traveling through
space-time.
422
The sessions permitted me to go inside and see and feel the nature of the mind.
423
Recognizing the source and manifestation of visions… source of unconscious content.
427
I believe I channeled the power of the Goddess and that I hold that power in me. I
believe she exists everywhere and I look for her to add spark, life, and joy to
everyday ordinary situations.
_____________________________________________________________________________
1
This participant was out of the country at end of treatment, and provided these retrospective comments
at 12-month follow-up.
“Effects of psychedelic-occasioned experiences on higher-order psychological
constructs have also been implicated. For instance, reductions in craving and anxiety,
increases in motivation and self-efficacy, and acute alterations in autobiographical
recall and cognitive bias have been hypothesized to mediate potential efficacy of
psychedelics in clinical treatment contexts. Furthermore, the ability of psychedelics to
elicit mystical, transcendent, or peak experiences has also been proposed as a
potential psychological mechanism in precipitating insight and behavior change”
(Garcia-Romeu et al., 2015)
21 06/17/2015 Psilocybin treatment of cancer related
anxiety and depression
Following up of older research using LSD
!  Currently analyzing data from study of 44
individuals. Initial findings from UCLA
promising.
! 
Effects of Psilocybin on Spiritual Practice
75 individuals completed study
!  Examining whether psilocybin occasioned
mystical experience can increase adoption of, or
increase the benefits of, a meditation program
! 
22 06/17/2015 Acknowledgements: Thanks to our funders at the Heffter
Research Institute, and the Beckley
Foundation, and NIDA Grants T32DA07209
& R01DA003889. Thanks to Principal Investigator Matthew W. Johnson, CoInvestigators Roland R. Griffiths, Annie Umbricht, Elliot Stein,
John Fedota, and our research team: Mary Cosimano, Maggie
Klinedinst, Lettie Nanda, Patrick Johnson, Matthew
Bradstreet, Fred Barrett, Fred Reinholdt, Samantha Gebhart,
Bill Richards, Katherine MacLean, Theresa Carbonaro, Taylor Marcus, Toni White, Allie Matous, and all of our participants for making this work possible.
! Contact: [email protected]
23