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Journal of Psychopharmacology
1 –9
© The Author(s) 2015
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DOI: 10.1177/0269881114565653
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Introduction
Almost half of a billion people worldwide suffer from mental
health problems, at substantial cost to society (World Health
Organization, 2001). Suicide is among the many deleterious con-
sequences of poor mental health and accounts for approximately
one million deaths across the globe annually (Hawton and van
Heeringen, 2009). Despite advances in mental health treatment
over the past 60 years, suicide rates have not significantly
declined in much of the world during this time (Varnik, 2012),
suggesting the need for more innovative and effective mental
health treatments. In response to this trend the National Institute
of Mental Health has called for research on novel interventions
that address the mechanisms underlying suicidal phenomena
(National Action Alliance for Suicide Prevention: Research
Prioritization Task Force, 2014). Treatments involving classic
psychedelics may represent one such approach.
Classic psychedelics can occasion mystical-type experiences
and have been used in sacramental healing contexts across cul-
tures since time immemorial (Johnson et al., 2008; Nichols,
2004). Among the most prominent of these substances are
dimethyltryptamine (DMT; widespread in the plant kingdom),
the semi-synthetic lysergic acid diethylamide (LSD; derived
from the ergot fungus), mescaline (the primary active constitu-
ent of peyote and other cacti), and psilocybin (the primary psy-
choactive constituent of Psilocybe and other mushroom genera),
with primary effects caused by their action as agonists on sero-
tonin 2A (5-HT2A) brain receptors (Vollenweider and Kometer,
2010). Western science devoted significant attention to classic
psychedelics from the 1950s through the early 1970s, and though
a lack of modern methodological rigor complicates interpreta-
tion, results suggested that classic psychedelics might potentiate
psychotherapeutic effectiveness (Johnson et al., 2008; Nichols,
2004; Vollenweider and Kometer, 2010). To the dismay of
responsible investigators, sensationalized media coverage of
recreational classic psychedelic use in the 1960s led to the most
severe legal restrictions, which all but eliminated the possibility
of future study that might have yielded more conclusive find-
ings. These legal restrictions were enacted in the absence of a
compelling medical or scientific rationale, and contemporary
analysis suggests that classic psychedelics are among the least
harmful of misused drugs, with limited dependence potential
(Nutt et al., 2007, 2010).
Classic psychedelic use is associated with
reduced psychological distress and suicidality
in the United States adult population
Peter S Hendricks1, Christopher B Thorne1, C Brendan Clark2,
David W Coombs1 and Matthew W Johnson3
Abstract
Mental health problems are endemic across the globe, and suicide, a strong corollary of poor mental health, is a leading cause of death. Classic
psychedelic use may occasion lasting improvements in mental health, but the effects of classic psychedelic use on suicidality are unknown. We
evaluated the relationships of classic psychedelic use with psychological distress and suicidality among over 190,000 USA adult respondents pooled
from the last five available years of the National Survey on Drug Use and Health (2008–2012) while controlling for a range of covariates. Lifetime
classic psychedelic use was associated with a significantly reduced odds of past month psychological distress (weighted odds ratio (OR)=0.81
(0.72–0.91)), past year suicidal thinking (weighted OR=0.86 (0.78–0.94)), past year suicidal planning (weighted OR=0.71 (0.54–0.94)), and past
year suicide attempt (weighted OR=0.64 (0.46–0.89)), whereas lifetime illicit use of other drugs was largely associated with an increased likelihood
of these outcomes. These findings indicate that classic psychedelics may hold promise in the prevention of suicide, supporting the view that classic
psychedelics’ most highly restricted legal status should be reconsidered to facilitate scientific study, and suggesting that more extensive clinical
research with classic psychedelics is warranted.
Keywords
Psychedelic, hallucinogen, lysergic acid diethylamide, psilocybin, mescaline, mental health, suicide, prevention
1 Department of Health Behavior, University of Alabama at Birmingham,
Birmingham, AL, USA
2 Department of Psychiatry and Behavioral Neurobiology, University of
Alabama at Birmingham, Birmingham, AL, USA
3
Department of Psychiatry and Behavioral Sciences, Johns Hopkins
University School of Medicine, Baltimore, MD, USA
Corresponding author:
Peter S Hendricks, 227L Ryals Public Health Building, 1665 University
Blvd., Birmingham, AL 35294, USA.
Email: phendricks@uab.edu
565653JOP0010.1177/0269881114565653<italic>Journal of Psychopharmacology 0(0)</italic>Hendricks et al.
research-article2014
Original Paper
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2 Journal of Psychopharmacology
The past three decades have witnessed a gradual return to
research on classic psychedelics. Though limited in number,
these studies indicate that classic psychedelics may warrant the
attention they received five decades ago, not least in part because
they appear to target a number of factors that modulate suicide
risk. For instance, affective disturbance is one of the most promi-
nent contributors to suicidality (Hawton and van Heeringen,
2009). Under carefully controlled conditions, a single adminis-
tration of psilocybin can occasion profoundly meaningful experi-
ences that bring about persisting elevations in mood among
healthy, hallucinogen-naïve volunteers (Griffiths et al., 2006,
2008, 2011). In a pilot trial among individuals with advanced-
stage cancer a single dose of psilocybin was associated with
long-term reductions in anxiety and depression (Grob et al.,
2011), and in a pilot trial among individuals with life-threatening
diseases two administrations of LSD produced lasting reductions
in anxiety (Gasser et al., 2014; in press). Substance misuse also is
robustly related to suicide risk (Borges et al., 2000; Britton and
Conner, 2010; Center for Substance Abuse Treatment, 2008;
Hawton and van Heeringen, 2009; Wilcox et al., 2004), and sev-
eral lines of research suggest that classic psychedelics have anti-
addictive effects (Bogenschutz and Pommy, 2012). For example,
a recent meta-analysis of six randomized clinical trials of treat-
ment for alcoholism conducted between 1966–1970 found that a
single dose of LSD reduced the probability of alcohol misuse
almost two-fold relative to comparison conditions (Krebs and
Johansen, 2012). Furthermore, a single-arm trial of smoking ces-
sation involving up to three administrations of psilocybin yielded
abstinence rates of 80% at long-term follow-up, more than dou-
bling abstinence rates typical of approved contemporary tobacco
dependence interventions (Johnson et al., 2014). Moreover, natu-
ralistic hallucinogen use predicted a reduced likelihood of recidi-
vism among more than 25,000 individuals under community
corrections supervision with a history of substance involvement
(Hendricks et al., 2014). Additional prominent suicide risk fac-
tors include impulsive-aggressive personality characteristics and
early traumatic life events (Hawton and van Heeringen, 2009).
Psilocybin may occasion enduring improvements in inner peace,
patience, good-natured humor/playfulness, interpersonal regard,
anger, and compassion (Griffiths et al., 2006, 2011), and may
facilitate processing of prior trauma by enhancing recall of auto-
biographical memories (Carhart-Harris et al., 2012a). Finally,
classic psychedelics may boost spirituality (Bogenschutz and
Pommy, 2012; Griffiths et al., 2011), which has been shown to
protect against suicidality (Rasic et al., 2009, 2011; Weber and
Pargament, 2014). Although sample sizes in recent medical
administration studies have been limited, no serious adverse
events were reported, consistent with historical data indicating
that these substances can be administered safely in medical con-
texts by using appropriate safeguards (Johnson et al., 2008).
Neurobiological experiments echo clinical findings, adding
further evidence to suggest that classic psychedelics may modify
processes implicated in suicidality. Increased 5-HT2A receptor
density in the prefrontal cortex is associated with suicide risk fac-
tors (e.g. major depression) and suicidal behavior, and may
reflect compensatory up-regulation of 5-HT2A receptors stem-
ming from dysfunctional serotonergic transmission (Bhagwagar
et al., 2006; Carballo et al., 2008; Meyer et al., 2003; Shelton
et al., 2008). Classic psychedelic use down-regulates 5-HT2A
receptors in the prefrontal cortex which may, in turn, normalize
limbic hyperactivity associated with affective disturbance
(Baumeister et al., 2014, Kraehenmann et al., in press;
Vollenweider and Kometer, 2010). Reduced neuroplasticity (i.e.
expression of brain-derived neurotrophic factor) is also associ-
ated with affective disturbance and suicide, and classic psyche-
delic use may elicit neuroplastic adaptation via glutamatergic
transmission (Baumeister et al., 2014; Bogenschutz and Pommy,
2012; Dwivedi, 2010; Dwivedi et al., 2003; Vollenweider and
Kometer, 2010). Furthermore, the default mode network (DMN)
is hyperactive and hyperconnected among those with affective
disorders, a state that may underpin negative rumination and
rigid pessimism characteristic of these conditions (Carhart-Harris
et al., 2014; Whitfield-Gabrieli and Ford, 2012). Classic psyche-
delics may normalize the DMN, thereby reducing this cognitive
fixedness (Carhart-Harris et al., 2012b; Carhart-Harris et al.,
2014; Muthukumaraswamy et al., 2013; Roseman et al., 2014;
Tagliazucchi et al., 2014). In support of this view, a single dose of
psilocybin increased personality openness 14 months post-
administration (MacLean et al., 2011). Some studies show that
openness may protect against suicide in older adults, though find-
ings are mixed (Segal et al., 2012). Finally, emerging evidence
suggests that classic psychedelics might reduce markers of cen-
tral nervous system inflammation that are implicated in a host of
mental health conditions and suicidal behavior (Black and Miller,
in press; Szabo et al., 2014).
Despite evidence suggesting safety and efficacy, the legal sta-
tus of classic psychedelics has not changed since 1971. Classic
psychedelics remain Schedule I substances (designated as having
a high potential for abuse, no currently accepted medical use, and
a lack of accepted safety under medical supervision), rendering
clinical research with these drugs extremely difficult to conduct
(Nutt et al., 2013). Consequently, an understanding of the impact
of classic psychedelics on mental health and suicidality remains
incomplete. Given the regulatory difficulty associated with
administering classic psychedelics to humans, population-based
survey studies represent one means for examining the relation-
ships of classic psychedelic use with mental health and suicidal-
ity. What population-based survey studies sacrifice in internal
validity afforded by experimental methodology, they gain in
external validity provided by large samples, minimal inclusion
and exclusion criteria, and assessment of subjects in real-world
settings (Kelley et al., 2003). To our knowledge, only one prior
investigation has evaluated the population-level associations of
classic psychedelic use with mental health. Using data drawn
from 2001–2004 of the National Survey on Drug Use and Health
(NSDUH), Krebs and Johansen (2013) tested the relationships of
lifetime classic psychedelic use with worst month of the past year
psychological distress, past year mental health treatment use, and
past year Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition (DSM-IV; American Psychiatric Association,
1994) symptom indicators among over 130,000 USA adults.
They found that lifetime classic psychedelic use was largely
unassociated with these outcomes, though some findings indi-
cated that lifetime classic psychedelic use was associated with a
decreased likelihood of certain mental health indices (e.g. past
year mental health treatment utilization). The purpose of the cur-
rent study was to examine the relationships of lifetime classic
psychedelic use with past month psychological distress and past
year suicidality using data drawn from the last five available
years of the NSDUH at the time of analysis (2008–2012).
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Hendricks et al. 3
Considering multiple lines of research indicating that classic
psychedelics may be protective with regard to mental health
problems and suicidality, we hypothesized that lifetime classic
psychedelic use would be associated with a decreased likelihood
of past month psychological distress, past year suicidal thinking,
past year suicidal planning, and past year suicide attempt.
Methods
The NSDUH survey of the Substance Abuse and Mental Health
Services Administration of the United States Department of
Health and Human Services is conducted annually to estimate the
prevalence of substance use and mental illness in the general
USA civilian non-institutionalized population using a complex,
probability sampling design (United States Department of Health
and Human Services, 2009, 2010, 2011, 2012, 2013). NSDUH
interviewers met with individuals in their homes, who listened to
prerecorded survey questions on headphones and provided
responses via computer. Participants in the current study were
adult (>18 years old) respondents of the NSDUH survey pooled
across years 2008–2012 with valid data on the primary independ-
ent variable (lifetime classic psychedelic use) and all covariates
(see below). These cross-sectional data were pooled across years
2008–2012 because standardized assessment procedures intro-
duced in 2008 yielded the same variables for analysis. Weighted
interview response rates were approximately 75%. Detailed
information on NSDUH methodology is available elsewhere
(https://nsduhweb.rti.org/respweb/homepage.cfm). The NSDUH
survey was approved by the institutional review board of the
Research Triangle Institute and the current analyses were
approved by the institutional review board of the University of
Alabama at Birmingham.
Data analysis
A unique identifier was created for each unique NSDUH respond-
ent from years 2008–2012 using the Cantor pairing function.
Respondents reporting they had ever, even once, used DMT
(code 616 from variables HALNEWA, HALNEWB, HALNEWC,
HALNEWD, or HALNEWE=1), ayahuasca (a South American
drink that contains DMT; code 6103 from variables HALNEWA,
HALNEWB, HALNEWC, HALNEWD, or HALNEWE=1),
LSD (variable LSDFLAG=1), mescaline (variable MESC2=1),
peyote or San Pedro (cacti that contain mescaline; variable
PEYOTE2=1 or code 6077 from variables HALNEWA,
HALNEWB, HALNEWC, HALNEWD, or HALNEWE=1), or
psilocybin (variable PSILCY2=1) were coded as positive for life-
time classic psychedelic use; those indicating that they had never
used any of these substances were coded as negative. We consid-
ered coding individuals who responded in the affirmative to a
query concerning use of DMT, alpha-methyltryptamine (AMT),
and 5-methoxy-N, N-diisopropyltryptamine (5-MeO-DIPT)
(“Have you ever, even once, used any of the following: DMT,
also called dimethyltryptamine, AMT, also called alpha-methyl-
tryptamine, or Foxy, also called 5-MeO-DIPT?”; variable
TRYPTM=1) as lifetime classic psychedelic users, but since
DMT use in particular could not be determined from this query,
and because the classification of AMT and 5-MeO-DIPT as
classic psychedelics is inconclusive, this query was not used to
classify lifetime classic psychedelic users (post-hoc analyses
determined that doing so contributed only 362 additional indi-
viduals to the group of lifetime classic psychedelic users and had
no meaningful impact on the results). A single variable corre-
sponding to lifetime classic psychedelic use (yes =1 or no=0) was
the primary independent variable in analyses.
The primary outcome variables included past month psycho-
logical distress (variable SPDMON; yes=1 or no=0) as measured
by the widely used and well-validated Kessler Psychological
Distress Scale (K6; Kessler et al., 2002, 2010; Khan et al., 2014),
past year suicidal thinking (“At any time in the past 12 months…
did you seriously think about trying to kill yourself?”; variable
MHSUITHK; yes=1 or no=0), past year suicidal planning
(“During the past 12 months, did you make any plans to kill your-
self?”; variable MHSUIPLN; yes=1 or no=0), and past year sui-
cide attempt (“During the past 12 months, did you try to kill
yourself?”; variable MHSUITRY; yes=1 or no=0). Multivariate
logistic regression was used to test the associations between life-
time classic psychedelic use and the primary outcomes while
controlling for the following covariates: age in years (18–25,
26–34, 35–49, 50–64, or 65 or older); gender (male or female);
ethnoracial identity (non-Hispanic White, non-Hispanic African
American, non-Hispanic Native American/Alaska Native, non-
Hispanic Native Hawaiian/Pacific Islander, non-Hispanic Asian,
non-Hispanic more than one race, or Hispanic); educational
attainment (5th grade or less, 6th grade, 7th grade, 8th grade, 9th
grade, 10th grade, 11th grade, 12th grade, freshman college year,
sophomore or junior college year, or senior college year or more);
annual household income (less than $20,000, $20,000–$49,999,
$50,000–$74,999, or $75,000 or more); marital status (married,
divorced/separated, widowed, or never married); self-reported
engagement in risky behavior (“How often do you like to test
yourself by doing something a little risky?”; never, seldom,
sometimes, or always) and lifetime illicit use of cocaine, other
stimulants, sedatives, tranquilizers, heroin, pain relievers, mari-
juana, 3,4-methylenedioxymethamphetamine (MDMA)/ecstasy,
phencyclidine (PCP), and inhalants (each aforementioned drug
category coded as separate covariates). All analyses were con-
ducted in SAS version 9.3 using PROC SURVEYLOGISTIC and
accounted for the complex study design variables and sampling
weights as recommended by the NSDUH.
Results
Of the 191,382 respondents, 27,235 reported lifetime classic psy-
chedelic use (13.6% weighted). Of these, 391 reported lifetime
DMT use (0.1% weighted), 26 reported lifetime ayahuasca use
(0.008% weighted), 18,152 reported lifetime LSD use (10.2%
weighted), 4687 reported lifetime mescaline use (3.5% weighted),
3540 reported lifetime peyote or San Pedro use (2.4% weighted),
and 20,274 reported lifetime psilocybin use (8.9% weighted). In
addition, 12,657 of the respondents reported past month psycho-
logical distress (4.8% weighted), 10,445 reported past year sui-
cidal thinking (3.8% weighted), 3157 reported past year suicidal
planning (1.1% weighted), and 1716 reported past year suicide
attempt (0.5% weighted).
Table 1 displays the characteristics of lifetime classic psyche-
delic users versus non-lifetime classic psychedelic users. Lifetime
classic psychedelic use was concentrated among 26–64 year olds
and rare among those aged 65 years and older. Furthermore, life-
time classic psychedelic use was more common among men,
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4 Journal of Psychopharmacology
Table 1. Characteristics of lifetime classic psychedelic users versus non-lifetime classic psychedelic users.
Feature Lifetime classic
psychedelic users
Non-lifetime classic
psychedelic users
p value
Weighted % Weighted %
Age, years <0.0001
18–25 13.6 14.9
26–34 21.3 14.9
35–49 33.7 26.3
50–64 29.4 24.4
65 and older 2.0 19.4
Gender <0.0001
Male 62.8 46.0
Female 37.2 54.0
Race <0.0001
Non-Hispanic White 83.3 65.2
Non-Hispanic African American 3.9 12.7
Non-Hispanic Native American/Alaska Native 1.1 0.4
Non-Hispanic Native Hawaiian/Pacific Islander 0.2 0.4
Non-Hispanic Asian 1.3 5.2
Non-Hispanic more than one race 2.0 1.1
Hispanic 8.3 15.0
Education <0.0001
5th grade or less 0.3 1.6
6th grade 0.1 1.5
7th grade 0.2 0.6
8th grade 1.0 1.8
9th grade 2.0 2.5
10th grade 3.2 2.9
11th grade 4.8 4.5
12th grade 28.1 30.9
Freshman college year 10.1 8.7
Sophomore or junior college year 20.0 16.4
Senior college year or more 30.3 28.7
Annual household income <0.0001
Less than $20,000 16.9 18.5
$20,000–$49,999 30.0 33.3
$50,000–$74,999 17.8 17.2
$75,000 or more 35.3 31.0
Marital status <0.0001
Married 47.3 54.5
Divorced/separated 18.3 13.1
Widowed 1.8 6.7
Never married 32.6 25.7
Self-reported engagement in risky behavior <0.0001
Never 27.8 55.6
Seldom 44.1 32.4
Sometimes 25.3 11.0
Always 2.8 1.0
Lifetime illicit substance use
Lifetime cocaine use 71.4 7.5 <0.0001
Lifetime other stimulant use 37.1 3.7 <0.0001
Lifetime sedative use 17.9 1.2 <0.0001
Lifetime tranquilizer use 37.5 5.0 <0.0001
Lifetime heroin use 10.6 0.4 <0.0001
Lifetime pain reliever use 46.5 9.5 <0.0001
Lifetime marijuana use 97.7 36.2 <0.0001
Lifetime MDMA/ecstasy use 33.0 2.1 <0.0001
Lifetime PCP use 18.0 0.4 <0.0001
Lifetime inhalant use 39.5 3.8 <0.0001
All percentages were rounded to the nearest 0.1%. Rao-Scott chi-square tests were used to examine the characteristics of lifetime classic psychedelic users versus non-
lifetime classic psychedelic users. MDMA: 3, 4-methylenedioxymethamphetamine; PCP: phencyclidine.
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Hendricks et al. 5
non-Hispanic Whites and Native Americans/Alaska Natives,
those with greater educational attainment and income, individuals
who were divorced/separated or who had never been married,
those with greater self-reported engagement in risky behavior, and
those who reported lifetime illicit use of each of the other sub-
stances. Among lifetime classic psychedelic users, only 240 (0.9%
weighted) reported never having used any other illicit substance
whereas among non-lifetime classic psychedelic users, 85,601
(58.2% weighted) reported never having used any other illicit
drug. Figures 1–4 show the results of multivariate logistic regres-
sion models predicting past month psychological distress, past
year suicidal thinking, past year suicidal planning, and past year
suicide attempt. As shown in these figures, lifetime classic psy-
chedelic use was associated with a decreased likelihood of past
month psychological distress (weighted OR=0.81 (0.72–0.91),
p=0.0002), past year suicidal thinking (weighted OR=0.86 (0.78–
0.94), p=0.001), past year suicidal planning (weighted OR=0.71
(0.54–0.94), p=0.01), and past year suicide attempt (weighted
OR=0.64 (0.46–0.89), p=0.008). Conversely, lifetime illicit use of
other substances was either not related with or associated with an
increased odds of these outcomes, with odds ratios (ORs) for all
relationships exceeding 1.0 except lifetime PCP use and past
month psychological distress, and lifetime MDMA/ecstasy use
and past year suicidal thinking, past year suicidal planning, and
past year suicide attempt (no OR significantly different than 1.0).
Discussion
The objective of the current study was to evaluate the associa-
tions of classic psychedelic use with psychological distress and
suicidality in a large sample generalizable to the USA adult popu-
lation. Consistent with hypotheses, lifetime classic psychedelic
use was associated with a 19% reduced likelihood of past month
psychological distress, a 14% reduced likelihood of past year sui-
cidal thinking, a 29% reduced likelihood of past year suicidal
planning, and a 36% reduced likelihood of past year suicide
attempt. These findings comport with the accumulating literature
indicating that classic psychedelics may remediate a number of
risk factors associated with suicide. Indeed, if the current results
reflect a direct causal chain between classic psychedelic use and
decreased suicidality, the mechanisms described in the introduc-
tion may have explanatory value. By contrast, lifetime illicit use
of all other substances was by and large associated with an
increased likelihood of psychological distress and suicidality at
or above the trend level. These results align with data indicating
that non-psychedelic substance use is a suicide risk factor (Borges
et al., 2000; Britton and Conner, 2010; Center for Substance
Abuse Treatment, 2008; Hawton and van Heeringen, 2009;
Wilcox et al., 2004).
An obvious limitation of the current research is its reliance on
self-report. Biases in responding may have obscured the true rela-
tionships of classic psychedelic use with psychological distress
and suicidality. Also, analyses were restricted to the available
data, which precluded testing more nuanced associations (e.g.
dose-response relationships). Furthermore, as with any cross-
sectional study, the associations reported here may not necessarily
indicate causation. Population survey studies cannot control for
all possible sources of confounding and therefore we cannot rule
out that a shared underlying factor may have contributed to both
classic psychedelic use and decreased psychological distress and
Figure 1. Result of multivariate logistic regression model predicting past month psychological distress. Diamonds are weighted odds ratio point
estimates and error bars are 95% confidence intervals. Associations of demographic variables and self-reported engagement in risky behavior with
psychological distress are not presented. n=191,369 due to missing data on the dependent variable. MDMA: 3, 4-methylenedioxymethamphetamine;
PCP: phencyclidine.
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6 Journal of Psychopharmacology
suicidality. Psychedelic drug users commonly report autognostic
(Móró et al., 2011), “mind expansion,” spiritual, and curiosity
motives for such use (Lyvers and Meester, 2012). Although these
interests may be lasting effects of classic psychedelic drug use,
they may also represent predrug characteristics among classic
psychedelic users that might protect against suicide as well (e.g.
openness, curiosity, and spiritual tendencies; Carhart-Harris et al.,
2014; Kashdan et al., 2004; Rasic et al., 2009, 2011; Weber and
Pargament, 2014). Lerner and Lyvers (2006) found that classic
psychedelic users reported less materialistic values and greater
Figure 2. Result of multivariate logistic regression model predicting past year suicidal thinking. Diamonds are weighted odds ratio point estimates and
error bars are 95% confidence intervals. Associations of demographic variables and self-reported engagement in risky behavior with suicidal thinking are
not presented. n=190,728 due to missing data on the dependent variable. MDMA: 3, 4-methylenedioxymethamphetamine; PCP: phencyclidine.
Figure 3. Result of multivariate logistic regression model predicting past year suicidal planning. Diamonds are weighted odds ratio point estimates and
error bars are 95% confidence intervals. Associations of demographic variables and self-reported engagement in risky behavior with suicidal planning are
not presented. n=190,713 due to missing data on the dependent variable. MDMA: 3,4-methylenedioxymethamphetamine; PCP: phencyclidine.
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Hendricks et al. 7
mysticism, spirituality, and concern for others than non-classic
psychedelic drug users, and speculated that both predrug factors
and classic psychedelic drug effects contributed to group differ-
ences. This too may be the case with regard to the present find-
ings. However, as classic psychedelic use was associated with
self-reported engagement in risky behavior and illicit substance
use, some who use classic psychedelics may also have a premor-
bid liability for suicidality. The picture is undoubtedly complex.
Nevertheless, future research should attempt to delineate longitu-
dinal predictors of classic psychedelic use that also relate to men-
tal health and suicidal behavior.
We also cannot rule out the possibility that classic psychedelic
use may have caused harm at the individual level. Indeed, classic
psychedelic use may exacerbate schizophrenia or other psychotic
disorders, can be dangerous in hazardous physical environments,
and can sometimes elicit feelings of anxiety, fear, panic, and par-
anoia (Johnson et al., 2008). Nevertheless, the associations
reported here suggest that if individual-level harms occurred,
they failed to obscure the apparent protective effect of classic
psychedelic use on psychological distress and suicidality at the
population level. Considering that carefully controlled conditions
are ideal in the administration of classic psychedelics (Johnson
et al., 2008), it is noteworthy that naturalistic classic psychedelic
use demonstrated evidence of benefit. Not only could classic psy-
chedelic users have used in suboptimal settings, they could have
ingested substances of unknown purity and/or at sub- or suprath-
erapeutic doses. If the results do reflect salubrious effects of clas-
sic psychedelic use, these may very well be potentiated in
specialized treatment settings designed to maximize safety and
efficacy (Johnson et al., 2008).
Given the grave and chronic nature of suicide (Hawton and
van Heeringen, 2009; Varnik, 2012) and the call for research on
innovative treatments that target suicide pathogenisis (National
Action Alliance for Suicide Prevention: Research Prioritization
Task Force, 2014), the current findings set the stage for more
extensive clinical research with classic psychedelics. Despite mil-
lennia of use in sacred healing rituals, and accruing scientific evi-
dence suggesting safety and efficacy when administered in
clinical settings with appropriate safeguards (Johnson et al.,
2008), classic psychedelics remain Schedule I substances.
Accordingly, evaluating the clinical application of classic psych-
edelics remains an arduous challenge secondary to regulatory hur-
dles and scarce funding, among other obstacles (Nutt et al., 2013).
The present results reinforce the perspective that the designation
of these substances should be reconsidered to allow further scien-
tific inquiry. Regardless, priorities for future investigation include
evaluating the efficacy of classic psychedelics in treating suicidal-
ity as well as pathologies associated with increased suicide risk
including affective disturbance, substance misuse, dysfunction
marked by impulsive-aggressive personality traits, trauma seque-
lae, and neurocognitive deficits. Mediators of classic psyche-
delics’ effects should be carefully evaluated so as to better
understand their mechanisms of action. Elucidating such mecha-
nisms is critical to optimizing the benefits of classic psychedelics
and their concomitant psychotherapeutic components.
Conclusion
Classic psychedelics carry a contentious recent history and
barriers to their clinical evaluation remain. Growing evidence
Figure 4. Result of multivariate logistic regression model predicting past year suicide attempt. Diamonds are weighted odds ratio point estimates and
error bars are 95% confidence intervals. Associations of demographic variables and self-reported engagement in risky behavior with suicide attempt
are not presented. n=190,709 due to missing data on the dependent variable. MDMA: 3,4-methylenedioxymethamphetamine; PCP: phencyclidine.
at JOHNS HOPKINS UNIVERSITY on January 15, 2015jop.sagepub.comDownloaded from
8 Journal of Psychopharmacology
including the present research suggests that classic psyche-
delics may have the potential to alleviate human suffering
associated with mental illness. Further rigorous research is
warranted to better understand these substances, with the ulti-
mate goal of taking full advantage of their latent therapeutic
capacity.
Acknowledgements
NSDUH data are available to the public and archived at http://www.icpsr.
umich.edu/icpsrweb/SAMHDA/series/64. The authors thank Mallory
Cases, Michael Scott Crawford, Noah Wiles Sweat, and Jacqueline Upp
for their work on the project.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the
research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship,
and/or publication of this article.
References
American Psychiatric Association (1994) Diagnostic and statistical man-
ual of mental health disorders. 4th ed. Washington, DC: American
Psychiatric Association.
Baumeister D, Barnes G, Giaroli G, et al. (2014) Classical hallucinogens
as antidepressants? A review of pharmacodynamics and putative
clinical roles. Ther Adv Psychopharmacol 4: 156–169.
Bhagwagar Z, Hinz R, Taylor M, et al. (2006) Increased 5-HT2A recep-
tor binding in euthymic, medication-free patients recovered from
depression: A positron emission study with [11C] MDL 100,907. Am
J Psychiatry 163: 1580–1587.
Black C and Miller JM (in press) Meta-analysis of cytokines and che-
mokines in suicidality: Distinguishing suicidal versus non-suicidal
patients. Biol Psychiatry. doi: 10.1016/j.biopsych.2014.10.014
Available online 30 October 2014
Bogenschutz MP and Pommy JM (2012) Therapeutic mechanisms of
classic hallucinogens in the treatment of addictions: From indirect
evidence to testable hypotheses. Drug Test Anal 4: 543–555.
Borges G, Walters EE and Kessler RC (2000) Associations of substance
use, abuse, and dependence with subsequent suicidal behavior. Am J
Epidemiol 151: 781–789.
Britton PC and Conner KR (2010) Suicide attempts within 12 months
of treatment for substance use disorders. Suicide Life Threat Behav
40:14–21.
Carballo JJ, Akamnonu CP and Oquendo MA (2008) Neurobiology of
suicidal behavior. An integration of biological and clinical findings.
Arch Suicide Res 12: 93–110.
Carhart-Harris RL, Erritzoe D, Williams T, et al. (2012b) Neural cor-
relates of the psychedelic state as determined by fMRI studies with
psilocybin. Proc Natl Acad Sci U S A 109: 2138–2143.
Carhart-Harris RL, Leech R, Williams TM, et al. (2012a) Implications
for psychedelic-assisted psychotherapy: Functional magnetic reso-
nance imaging study with psilocybin. Br J Psychiatry 200: 238–244.
Carhart-Harris RL, Leech R, Hellyer PJ, et al. (2014) The entropic brain:
A theory of conscious states informed by neuroimaging research
with psychedelic drugs. Front Hum Neurosci 8: 20.
Center for Substance Abuse Treatment (2008) Substance abuse and
suicide prevention: Evidence and implications—A white paper.
DHHHS Pub. No. SMA-08–4352. Rockville, MD: Substance Abuse
and Mental Health Services Administration.
Dwivedi Y (2010) Brain-derived neurotrophic factor and suicide patho-
genesis. Ann Med 42: 87–96.
Dwivedi Y, Rizavi HS, Conley RR, et al. (2003). Altered gene expression
of brain-derived neurotrophic factor and receptor tyrosine kinase B
in postmortem brain of suicide subjects. Arch Gen Psychiatry 60:
804–815.
Gasser P, Holstein D, Michel Y, et al. (2014) Safety and efficacy of lyser-
gic acid diethylamide-assisted psychotherapy for anxiety associated
with life-threatening diseases. J Nerv Ment Dis 202: 513–520.
Gasser P, Kirchner K and Passie T (in press) LSD-assisted psychotherapy
for anxiety associated with a life-threatening disease: A qualitative
study of acute and sustained subjective effects. J Psychopharmacol
29: 57–68.
Griffiths RR, Johnson MW, Richards WA, et al. (2011) Psilocybin occa-
sioned mystical-type experiences: Immediate and persisting dose-
related effects. Psychopharmacology 218: 649–655.
Griffiths RR, Richards WA, Johnson MW, et al. (2008) Mystical-type
experiences occasioned by psilocybin mediate the attribution of per-
sonal meaning and spiritual significance 14 months later. J Psycho-
pharmacol 22: 621–632.
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
187: 268–283.
Grob CS, Danforth AL, Chopra GS, et al. (2011) Pilot study of psilocybin
treatment for anxiety in patients with advanced-stage cancer. Arch
Gen Psychiatry 68: 71–78.
Hawton K and van Heeringen K (2009) Suicide. Lancet 373: 1372–1381.
Hendricks PS, Clark CB, Johnson MW, et al. (2014) Hallucinogen use
predicts reduced recidivism among substance-involved offenders
under community corrections supervision. J Psychopharmacol 28:
62–66.
Johnson MW, Garcia-Romeu A, Cosimano MP, et al. (2014) Pilot study
of the 5-HT2AR agonist psilocybin in the treatment of tobacco
addiction. J Psychopharmacol 28: 983–992.
Johnson MW, Richards WA and Griffiths RR (2008) Human hallucinogen
research: Guidelines for safety. J Psychopharmacol 22: 603–620.
Kashdan TB, Rose P and Fincham FD (2004) Curiosity and exploration:
Facilitating positive subjective experiences and personal growth
opportunities. J Pers Assess 82: 291–305.
Kelley K, Clark B, Brown V, et al. (2003). Good practice in the con-
duct and reporting of survey research. Int J Qual Health Care 15:
261–266.
Kessler RC, Andrews G, Colpe LJ, et al. (2002) Short screening scales to
monitor population prevalences and trends in non-specific psycho-
logical distress. Psychol Med 32: 959–976.
Kessler RC, Green JG, Gruber MJ, et al. (2010) Screening for serious
mental illness in the general population with the K6 screening scale:
Results from the WHO World Mental Health (WMH) survey initia-
tive. Int J Methods Psychiatr Res 19: 4–22.
Khan A, Chien CW and Burton NW (2014) A new look at the construct
validity of the K6 using Rasch analysis. Int J Methods Psychiatr Res
23: 1–8.
Kraehenmann R, Preller KH, Scheidegger M, et al. (in press) Psilocybin-
induced decrease in amygdala reactivity correlates with enhanced
positive mood in healthy volunteers. Biol Psychiatry. doi:10.1016/j.
biopsych.2014.04.010 Available online 26 April 2014
Krebs TS and Johansen PØ (2012) Lysergic acid diethylamide (LSD) for
alcoholism: Meta-analysis of randomized controlled trials. J Psycho-
pharmacol 26: 994–1002.
Krebs TS and Johansen PØ (2013) Psychedelics and mental health: A
population study. PLoS One 8: e63972.
Lerner M and Lyvers M (2006) Values and beliefs of psychedelic
drug users: A cross-cultural study. J Psychoactive Drugs 38:
143–147.
at JOHNS HOPKINS UNIVERSITY on January 15, 2015jop.sagepub.comDownloaded from
Hendricks et al. 9
Lyvers M and Meester M (2012) Illicit use of LSD or psilocybin, but
not MDMA or nonpsychedelic drugs, is associated with mystical
experiences in a dose-dependent manner. J Psychoactive Drugs 44:
410–417.
MacLean KA, Johnson MW and Griffiths RR (2011) Mystical experi-
ences occasioned by the hallucinogen psilocybin lead to increases
in the personality domain of openness. J Psychopharmacol 25:
1453–1461.
Meyer JH, McMain S, Kennedy SH, et al. (2003) Dysfunctional attitudes
and 5-HT2 receptors during depression and self-harm. Am J Psychia-
try 160: 90–99.
Móró L, Simon K, Bárd I, et al. (2011) Voice of the psychonauts: Coping,
life purpose, and spirituality in psychedelic drug users. J Psychoac-
tive Drugs 43: 188–198.
Muthukumaraswamy SD, Carhart-Harris RL, Moran RJ, et al. (2013)
Broadband cortical desynchronization underlies the human psyche-
delic state. J Neurosci 33: 15171–15183.
National Action Alliance for Suicide Prevention: Research Prioritization
Task Force (2014) A prioritized research agenda for suicide preven-
tion: An action plan to save lives. National Institute of Mental Health
and the Research Prioritization Task Force, Rockville, Maryland.
Nichols DE (2004) Hallucinogens. Pharmacol Ther 101: 131–181.
Nutt DJ, King LA and Nichols DE (2013) Effects of Schedule I drug
laws on neuroscience research and treatment innovation. Nature Rev
Neurosci 14: 577–585.
Nutt DJ, King LA and Phillips LD (2010) Drug harms in the UK: A mul-
ticriteria decision analysis. Lancet 376: 1558–1565.
Nutt D, King LA, Saulsbury W, et al. (2007) Development of a rational
scale to assess the harm of drugs of potential misuse. Lancet 369:
1047–1053.
Rasic DT, Belik SL, Elias B, et al. (2009) Spirituality, religion and sui-
cidal behavior in a nationally representative sample. J Affect Disord
114: 32–40.
Rasic D, Robinson JA, Bolton J, et al. (2011) Longitudinal relationships
of religious worship attendance and spirituality with major depres-
sion, anxiety disorders, and suicidal ideation and attempts: Findings
from the Baltimore epidemiologic catchment area study. J Psychiatr
Res 45: 848–854.
Roseman L, Leech R, Feilding A, et al. (2014) The effects of psilocybin
and MDMA on between-network resting state functional connectiv-
ity in healthy volunteers. Front Hum Neurosci 8: 204.
Segal DL, Marty MA, Meyer WJ, et al. (2012) Personality, suicidal ide-
ation, and reasons for living among older adults. J Gerontol B Psy-
chol Sci Soc Sci 67: 159–166.
Shelton RC, Sanders-Bush E, Manier DH, et al. (2009). Elevated 5-HT
2A receptors in postmortem prefrontal cortex in major depression is
associated with reduced activity of protein kinase A. Neuroscience
158: 1406–1415.
Szabo A, Kovacs A, Frecska E, et al. (2014) Psychedelic N, N-dimethyl-
tryptamine and 5-methoxy-N, N-dimethyltryptamine modulate innate
and adaptive inflammatory responses through the sigma-1 receptor
of human monocyte-derived dendritic cells. PLoS One 9: e106533.
Tagliazucchi E, Carhart-Harris R, Leech R, et al. (2014) Enhanced rep-
ertoire of brain dynamical states during the psychedelic experience.
Human Brain Mapp 35: 5442–5456.
United States Department of Health and Human Services. Substance
Abuse and Mental Health Services Administration. Center for
Behavioral Health Statistics and Quality (2009) National Survey
on Drug Use and Health, 2008. Ann Arbor, MI: Inter-university
Consortium for Political and Social Research.
United States Department of Health and Human Services. Substance
Abuse and Mental Health Services Administration. Center for
Behavioral Health Statistics and Quality (2010) National Survey
on Drug Use and Health, 2009. Ann Arbor, MI: Inter-university
Consortium for Political and Social Research.
United States Department of Health and Human Services. Substance
Abuse and Mental Health Services Administration. Center for
Behavioral Health Statistics and Quality (2011) National Survey
on Drug Use and Health, 2010. Ann Arbor, MI: Inter-university
Consortium for Political and Social Research.
United States Department of Health and Human Services. Substance
Abuse and Mental Health Services Administration. Center for
Behavioral Health Statistics and Quality (2012) National Survey
on Drug Use and Health, 2011. Ann Arbor, MI: Inter-university
Consortium for Political and Social Research.
United States Department of Health and Human Services. Substance
Abuse and Mental Health Services Administration. Center for
Behavioral Health Statistics and Quality (2013) National Survey
on Drug Use and Health, 2012. Ann Arbor, MI: Inter-university
Consortium for Political and Social Research.
Varnik P (2012) Suicide in the world. Int J Environ Res Public Health
9: 760–771.
Vollenweider FX and Kometer M (2010) The neurobiology of psyche-
delic drugs: Implications for the treatment of mood disorders. Nature
Rev Neurosci 11: 642–651.
Weber SR and Pargament KI (2014) The role of religion and spirituality
in mental health. Curr Opin Psychiatry 27: 358–363.
Whitfield-Gabrieli S and Ford JM (2012) Default mode network activ-
ity and connectivity in psychopathology. Annu Rev Clin Psychol 8:
49–76.
Wilcox HC, Conner KR and Caine ED (2004) Association of alcohol and
drug use disorders and completed suicide: An empirical review of
cohort studies. Drug Alcohol Depend 76: S11–S19.
World Health Organization (2001) The World health report 2001: Mental
health: New understanding, new hope. Geneva, Switzerland: World
Health Organization.
at JOHNS HOPKINS UNIVERSITY on January 15, 2015jop.sagepub.comDownloaded from
