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Pilot Study of Psilocybin Treatment For Anxiety in Patients With Advanced-Stage Cancer
Pilot Study of Psilocybin Treatment For Anxiety in Patients With Advanced-Stage Cancer
ONLINE FIRST
Pilot Study of Psilocybin Treatment for Anxiety
in Patients With Advanced-Stage Cancer
Charles S. Grob, MD; Alicia L. Danforth, MA; Gurpreet S. Chopra, MD; Marycie Hagerty, RN, BSN, MA;
Charles R. McKay, MD; Adam L. Halberstadt, PhD; George R. Greer, MD
Context: Researchers conducted extensive investiga- of Mood States, and State-Trait Anxiety Inventory were
tions of hallucinogens in the 1950s and 1960s. By the early collected unblinded for 6 months after treatment.
1970s, however, political and cultural pressures forced
the cessation of all projects. This investigation reexam- Results: Safe physiological and psychological re-
ines a potentially promising clinical application of hal- sponses were documented during treatment sessions.
lucinogens in the treatment of anxiety reactive to ad- There were no clinically significant adverse events with
vanced-stage cancer. psilocybin. The State-Trait Anxiety Inventory trait anxi-
ety subscale demonstrated a significant reduction in anxi-
Objective: To explore the safety and efficacy of psilo- ety at 1 and 3 months after treatment. The Beck Depres-
cybin in patients with advanced-stage cancer and reac- sion Inventory revealed an improvement of mood that
tive anxiety. reached significance at 6 months; the Profile of Mood States
identified mood improvement after treatment with psi-
Design: A double-blind, placebo-controlled study of pa- locybin that approached but did not reach significance.
tients with advanced-stage cancer and anxiety, with sub-
jects acting as their own control, using a moderate dose Conclusions: This study established the feasibility and
(0.2 mg/kg) of psilocybin. safety of administering moderate doses of psilocybin to
patients with advanced-stage cancer and anxiety. Some
Setting: A clinical research unit within a large public of the data revealed a positive trend toward improved
sector academic medical center. mood and anxiety. These results support the need for more
research in this long-neglected field.
Participants: Twelve adults with advanced-stage can-
cer and anxiety. Trial Registration: clinicaltrials.gov Identifier:
NCT00302744
Main Outcome Measures: In addition to monitor-
ing safety and subjective experience before and during Arch Gen Psychiatry. 2011;68(1):71-78.
experimental treatment sessions, follow-up data includ- Published online September 6, 2010.
ing results from the Beck Depression Inventory, Profile doi:10.1001/archgenpsychiatry.2010.116
I
N RECENT YEARS, THERE HAS BEEN Today, the medical value of hallucino-
a growing awareness that the psy- gens is again being examined in formal
chological, spiritual, and existen- psychiatric settings. One substance un-
tial crises often encountered by pa- der investigation is psilocybin, 4-phos-
Author Affiliations: tients with cancer and their phoryloxy-N,N-dimethyltryptamine,
Departments of Psychiatry families need to be addressed more vigor- which occurs in nature in various species
(Drs Grob and Chopra) and ously.1-4 From the late 1950s to the early of mushrooms. Psilocybin is rapidly me-
Internal Medicine (Dr McKay), 1970s, research was carried out exploring tabolized to psilocin, which is a potent ago-
Harbor-UCLA Medical Center the use of hallucinogens to treat the exis- nist at serotonin 5-HT1A/2A/2C receptors, with
and Los Angeles Biomedical tential anxiety, despair, and isolation often 5-HT2A receptor activation directly corre-
Research Institute, Torrance associated with advanced-stage cancer.5-15 lated with human hallucinogenic activ-
(Drs Grob and McKay and Those studies described critically ill indi- ity.16 Psilocybin was studied during the
Mss Danforth and Hagerty)
viduals undergoing psychospiritual epipha- 1960s to establish its psychopharmaco-
and Department of Psychiatry,
University of California, nies, often with powerful and sustained im- logical profile; it was found to be active
San Diego, La Jolla provement in mood and anxiety as well as orally at around 10 mg, with stronger ef-
(Dr Halberstadt); and Heffter diminished need for narcotic pain medica- fects at higher doses, and to have a 4- to
Research Institute, Santa Fe, tion. Despite these promising results, there 6-hour duration of experience. Psycho-
New Mexico (Dr Greer). has been no follow-up research. logical effects were similar to those of ly-
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∗
130
The 5D-ASC demonstrated marked subjective differ-
120
ences between the psilocybin and placebo experiences.
Psilocybin particularly affected the oceanic boundless-
110
ness (F1,11 =33.12, P ⬍.001) and visionary restructural-
ization (F1,11 =18.95, P=.001) dimensions (Figure 2A).
100 Psilocybin had smaller but significant effects on anx-
ious ego dissolution (F1,11 =4.91, P =.049) and auditory
0 alterations (F1,11 =5.93, P=.03). The item clusters with
marked differences between the subjective states pro-
duced by psilocybin and niacin included a significant in-
C
80
crease (P ⬍.05) in psilocybin-invoked states of positive
†
† derealization, positive depersonalization, altered sense
†
† of time, positive mood, manialike experiences, elemen-
Diastolic Blood Pressure, mm Hg
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60 Placebo 70
∗ Psilocybin, 0.2 mg/kg † †
50 60 †
†
∗
% of Maximum Score
% of Maximum Score
50 †
40
40 †
†
†
30 † †
30 †
20
†
20
†
10 10
0 0
OB AED VR AA RV n ion e d ce n r
ion ol ol ns ns sia ts n n
tio zat Tim oo en tio rde lus ntr ntr tio tio the ep tio tio
5D-ASC Dimension a liza ali of eM p eri a liza D iso De Co Co ina ina es erc oll
ec g ina
ere n e iv Ex ere
t y c c n P c ma
rso ns sit g ht
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ou B
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sit eD ere xio of ss tar eu e ilit ilit
Po iv Alt Ma An os
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Figure 2. Subjective effects of psilocybin as measured by the 5-Dimension Altered States of Consciousness profile (5D-ASC). A, Five main 5D-ASC dimensions are
shown: oceanic boundlessness (OB), anxious ego dissolution (AED), visionary restructuralization (VR), auditory alterations (AA), and reduced vigilance (RV). B, Item
clusters comprising the OB, AED, and VR dimensions are shown. Values are the mean (SEM) percentages of the total possible score. *P⬍.01, †P⬍.05 for psilocybin
vs niacin placebo control (1-way analyses of variance were used to compare niacin and psilocybin effects on individual 5D-ASC dimensions and 5D-ASC item clusters).
A A Placebo
25 Placebo 14 Psilocybin, 0.2 mg/kg
Psilocybin, 0.2 mg/kg
12 †
20
10
POMS Score
BDI Score
15 8
6
10
4
5
2
0 0
1 d Before 1 d After 2 wk After 1 d Before 6 h After 1 d After 2 wk After
B B
25 14
12
20
10
POMS Score
BDI Score
15 8
6
10 †
4
5
2
0 0
1d 1 mo 2 mo 3 mo 4 mo 5 mo 6 mo 1d 1 mo 2 mo 3 mo 4 mo 5 mo 6 mo
Before Before
Assessment Time Assessment Time
Figure 3. Beck Depression Inventory (BDI) scores. A, Mean (SEM) BDI Figure 4. Profile of Mood States (POMS) scores. A, Mean (SEM) POMS
scores 1 day before, 1 day after, and 2 weeks after administration of scores 1 day before, 6 hours after, 1 day after, and 2 weeks after
psilocybin or niacin placebo are shown. B, Six months of mean (SEM) BDI administration of psilocybin or niacin placebo are shown. B, Six months of
follow-up data are shown. The BDI was administered at monthly intervals for mean (SEM) POMS follow-up data are shown. The POMS was administered
6 months after the second treatment session, and the 6 sets of monthly at monthly intervals for 6 months after the second treatment session, and
follow-up data were compared with the scores obtained the first time the the 6 sets of monthly follow-up data were compared with the scores
participants filled out the instruments (ie, 1 day before the first treatment obtained the first time the participants filled out the instruments (ie, 1 day
session). †P⬍ .05 for psilocybin vs the value from 1 day before the first before the first treatment session). †P ⬍ .05 for psilocybin vs niacin placebo
treatment session (t tests were used to compare individual monthly control (1-way analyses of variance were used to compare niacin and
follow-up values with values on the day before the first session). placebo effects at individual times).
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35 35
30 30
25 25
20 20
1 d Before 6 h After 1 d After 2 wk After 1 d Before 6 h After 1 d After 2 wk After
C D
50 50
45 45
STAI State Anxiety Score
30 30
25 25
20 20
1d 1 mo 2 mo 3 mo 4 mo 5 mo 6 mo 1d 1 mo 2 mo 3 mo 4 mo 5 mo 6 mo
Before Before
Assessment Time Assessment Time
Figure 5. Mean (SEM) State-Trait Anxiety Index (STAI) state anxiety scores (A) and trait anxiety scores (B) 1 day before, 6 hours after, 1 day after, and 2 weeks
after administration of psilocybin or niacin placebo are shown. Six months of mean (SEM) STAI state anxiety follow-up data (C) and trait anxiety follow-up data
(D) are shown. The STAI was administered at monthly intervals for 6 months after the second treatment session, and the 6 sets of monthly follow-up data were
compared with the scores obtained the first time the participants filled out the instruments (ie, 1 day before the first treatment session). *P ⬍ .01, †P ⬍ .05 for
psilocybin vs the value from 1 day before the first treatment session (t tests were used to compare individual monthly follow-up values with values on the day
before the first session).
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