Journal of Contextual Behavioral Science 15 (2020) 39–45

Contents lists available at ScienceDirect

Journal of Contextual Behavioral Science

journal homepage: www.elsevier.com/locate/jcbs

Psychological flexibility mediates the relations between acute psychedelic T

effects and subjective decreases in depression and anxiety
Alan K. Davisa,b,∗, Frederick S. Barrettb, Roland R. Griffithsb,c
a
College of Social Work, The Ohio State University, Columbus, OH, 43210, USA
b
Center for Psychedelic and Consciousness Research, Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, 5510 Nathan Shock Drive,
Baltimore, MD, 21224, USA
c
Department of Neuroscience, Johns Hopkins School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD, 21224, USA

A R T I C LE I N FO A B S T R A C T

Keywords: Prior research has shown that acute subjective psychedelic effects are associated with both spontaneous and
Psychedelics intended changes in depression and anxiety. Psychedelics are also theorized to produce increases in psycholo-
Hallucinogens gical flexibility, which could explain decreases in depression and anxiety following a psychedelic experience.
Mechanism Therefore, the present cross-sectional survey study sought to examine whether psychological flexibility mediated
Psychological flexibility
the relationship between acute psychedelic experiences and spontaneous or intended changes in depression and
Depression
Anxiety
anxiety among a large international sample of people who reported having used a psychedelic (n = 985;
male = 71.6%; Caucasian/white = 84.1%; Mage = 32.2, SD = 12.6). A regression analysis showed that acute
effects (i.e., mystical and insightful effects) were significantly associated with decreases in depression/anxiety
following a psychedelic experience. A path analysis revealed that, while controlling for age and sex, increases in
psychological flexibility fully mediated the effect of mystical and insightful experiences on decreases in de-
pression and anxiety following a psychedelic experience. This suggests that psychological flexibility may be an
important mediator of the therapeutic effects of psychedelic drugs. Future prospective experimental studies
should examine the effect of psychedelic drug administration on psychological flexibility in order to gain a better
understanding of the psychological processes that predict therapeutic effects of psychedelics.

Financial support of these mental health conditions, numerous interventions have been
developed, which include combinations of psychotherapy and phar-
Effort for the authors was provided by NIH grants RO1DA03889 and macotherapy (Cuijpers et al., 2014; Otto and Hearon, 2016). Despite
T32DA07209, and from support from Tim Ferriss, Matt Mullenweg, evidence supporting the use of these interventions, many people do not
Craig Nerenberg, Blake Mycoskie, and the Steven and Alexandra Cohen have access to these treatments (Collins et al., 2004), and many people
Foundation. The funders had no role in study design, data collection who have access will not experience symptom relief despite interven-
and analysis, decision to publish, or preparation of the manuscript. tion (Collimore and Rector, 2014; Coull and Morris, 2011;Hofmann
et al., 2012;Sinyor et al., 2010; Koen and Stein, 2011), highlighting the
1. Introduction need for more treatment options.
One emerging area of research has examined the psychotherapeutic
Depression and anxiety disorders are common mental health pro- action of psychedelic compounds (e.g., psilocybin, LSD, ayahuasca, 5-
blems (Steel et al., 2014). Global lifetime prevalence of depression and MeO-DMT) administered in clinical trials (Carhart-Harris et al., 2016;
anxiety are approximately 10% and 13%, respectively (Steel et al., Johnson and Griffiths, 2017; Palhano-Fontes et al., 2018; dos Santos
2014;Bandelow and Michaelis, 2015). The public health burden of et al., 2016) and used in naturalistic settings (Davis et al., 2018, 2019;
depression and anxiety includes occupational impairment (Birnbaum Johnson et al., 2017). These substances act primarily as agonists of
et al., 2010), and increases the risk for chronic physical conditions such serotonin (e.g., 5-HT1A/2A/C) receptors and often produce profound
as cardiovascular disease (Katon, 2011; Niles et al., 2015). Given high changes in sensory perceptions, mood, cognitions, and behavior (Araújo
prevalence rates and the substantial public health and personal burden et al., 2015; Carhart-Harris et al., 2011; Stroud et al., 2017; Carhart-

∗
Corresponding author. The Ohio State University, 1947 College Rd, Columbus, OH, 43210, USA.
E-mail address: davis.5996@osu.edu (A.K. Davis).

https://doi.org/10.1016/j.jcbs.2019.11.004
Received 30 April 2019; Received in revised form 31 October 2019; Accepted 13 November 2019
2212-1447/ © 2019 Association for Contextual Behavioral Science. Published by Elsevier Inc. All rights reserved.
A.K. Davis, et al. Journal of Contextual Behavioral Science 15 (2020) 39–45

Harris et al., 2017; dos Santos et al., 2016). For example, recent studies psychological flexibility are associated with positive depression and
examining psychedelics administered as an adjunct to psychotherapy anxiety outcomes (Twohig and Levin, 2017). Therefore, in a regression
have demonstrated efficacy in decreasing symptoms of anxiety and model we expect to find (Hypothesis 1: H1) acute psychedelic effects
depression (Johnson and Griffiths, 2017; Carhart-Harris et al., 2017; (mystical and insight effects) will predict changes in depression and
Ross et al., 2016; Griffiths et al., 2016; dos Santos et al., 2016). Pub- anxiety following a psychedelic experience, and in a path model we
lished reports also show that decreases in depression and anxiety occur expect to find that H2) acute psychedelic effects will be directly related
following naturalistic psychedelic use in ceremonial and recreational to increases in psychological flexibility, H3) increases in psychological
contexts (Davis et al., 2018,2019; Santos et al., 2007; Uthaug et al., flexibility will be directly related to decreases in depression/anxiety,
2018). Although more work is needed to fully understand the me- and H4) psychological flexibility will mediate the relationships between
chanisms of therapeutic action, the beneficial effects of these substances acute psychedelic effects and decreases in depression and anxiety
appear to be associated with the intensity of certain types of acute symptoms.
psychedelic effects (e.g., mystical-type phenomena, psychological in-
sight) during these experiences in both healthy (Griffiths et al., 2008, 2. Method
2011; Barrett et al., 2015) and clinical (Ross et al., 2016; Griffiths et al.,
2008, 2011, 2016; Roseman et al., 2018; Davis et al., 2018; Garcia- 2.1. Procedure
Romeu et al., 2019) populations. Potential mediators of psychedelic
effects on therapeutic outcomes have been suggested, including The current study data were collected as part of a large anonymous
changes in the entropy of brain network connectivity (Carhart-Harris internet-based cross-sectional survey of individuals who reported
et al., 2014), the importance of awe/ego dissolution (Hendricks, 2018; having a moderate to strong psychedelic experience in the past.
Preller and Vollenweider, 2018); and the possible role of changes in Specifically, people were recruited as part of a larger study examining
psychological flexibility following a psychedelic experience (Kuypers acute insight (e.g., an awareness into emotions, behaviors, beliefs,
et al., 2016; Sabucedo, 2017; Walsh and Thiessen, 2018). memories, relationships, etc.) gained as a result of a psychedelic ex-
Psychological flexibility is described as an essential set of processes perience. Recruitment from the parent study is ongoing and results will
that help people manage stressors and engage in adaptive behaviors be published in a forthcoming article. Respondents were recruited by
that promote values-driven action (Gloster et al., 2017). Psychological using electronic message postings and advertisements on several in-
flexibility is a transdiagnostic construct wherein people are thought to ternet websites (e.g., www.erowid.com; www.facebook.com; www.
have the capacity to develop skills recognizing and adapting to various reddit.com), electronic mail announcements, and via an article pub-
contextual demands, shift their mindset or behaviors during individual lished by Motherboard/VICE). Advertisements directed potential re-
and social experiences, maintain balance across important life domains, spondents to a secure web-based survey (hosted by: www.qualtrics.
and learn to be open to, aware of, and committed to behaviors that are com), and those who clicked a study link were presented with a consent
congruent with their values (Kashdan and Rottenberg, 2010). Ac- document detailing the inclusion criteria. Eligible volunteers had to
cording to this model, well-being is supported by fully contacting the endorse being at least 18 years old, able to read, write and speak
present moment as a conscious human being and changing or persisting English fluently, have taken a dose of a single psychedelic (e.g., psilo-
in a values-driven behavior regardless of what is present in each mo- cybin mushrooms, psilocybin, LSD, ayahuasca, mescaline, N,N-DMT, 5-
ment (Hayes et al., 2012). Conversely, dysfunctions in mental health, MeO-DMT, peyote, 4-Acetoxy-DMT, Salvia, Ibogaine, etc.) that pro-
including depression and anxiety disorders (Kashdan and Rottenberg, duced moderate to strong psychoactive effects, and after taking the
2010), are theorized to be the result of reduced psychological flexibility substance they must have had an experience that contributed to gaining
(or psychological inflexibility). psychological insight. Following consent, respondents completed each
Psychological interventions have been developed using this theo- study questionnaire (described below). The study was approved by the
retical framework (e.g., Acceptance and Commitment Therapy (ACT); Johns Hopkins School of Medicine Institutional Review Board and the
Hayes et al., 2006), which attempt to increase psychological flexibility full survey is available from the corresponding author. No incentives
via six interconnected processes (i.e., acceptance, defusion, being pre- were offered in this study.
sent, self-as-context, determining direction for behavior change, and
using techniques to facilitate change; Twohig and Levin, 2017). Meta- 2.2. Study recruitment flow
analyses have shown moderate to strong effects in favor of ACT inter-
ventions (compared to control conditions: waitlist, psychological pla- Respondents were recruited from June 2018 through January 2019.
cebo, and treatment as usual) in decreasing anxiety and depression Of all individuals who clicked the advertisement link (n = 14,911),
symptoms (A-Tjak et al., 2015; Hacker et al., 2016), and evidence 3080 consented and completed the survey. However, 960 of these re-
shows that the positive outcomes of this intervention are mediated by spondents were excluded because they reported using more than one
increases in psychological flexibility (French et al., 2017; Twohig and substance in their psychedelic experience. Of the remaining 2120, a
Levin, 2017). If psychedelic experiences promote increases in psycho- total of 985 were included in the final sample because they indicated
logical flexibility, then such increases could be mediating the anti- experiencing a change in anxiety or depression as a result of a psy-
depressive and anxiolytic effects observed in clinical trials (Johnson chedelic experience.
and Griffiths, 2017; Carhart-Harris et al., 2017; Ross et al., 2016;
Griffiths et al., 2016; dos Santos et al., 2016) and the associations found 3. Measures
in naturalistic psychedelic use (Davis et al., 2018, 2019; Santos et al.,
2007; Uthaug et al., 2018). This relationship could also justify a psy- 3.1. Psychedelic experience
chotherapeutic approach to psychedelic-assisted therapy that focuses
on processes of change with the psychological flexibility model. We asked respondents to report which psychedelic substance they
The present cross-sectional survey study sought to examine psy- had used (e.g., psilocybin, LSD, N,N-DMT, Ayahuasca, 5-MeO-DMT,
chological flexibility as a potential mediator of acute psychedelic ex- Mescaline, Salvia/Salvinorin A, peyote cactus, Iboga/ibogaine, or
periences on changes in anxiety/depression. Prior research has shown “Other”), the subjective level of dose (i.e., Low, Moderate, Moderately
that acute psychedelic effects are associated with reductions in de- high, High), route of administration (i.e., Oral, Sublingual, Smoked or
pression and anxiety (Davis et al., 2019; Griffiths et al., 2016; Ross Vaporized, Buccal, Intravenous, Intranasal), and length of time since
et al., 2016), that psychedelic effects are associated with changes in the experience (e.g., 3–6 months ago, 7–11 months ago, 1–2 years ago,
psychological flexibility (Kuypers et al., 2016), and that increases in etc.).

40
A.K. Davis, et al. Journal of Contextual Behavioral Science 15 (2020) 39–45

3.2. Acute mystical experiences 3.4. Anxiety and depression

The Mystical Experiences Questionnaire (MEQ) was used to assess The Depression, Anxiety, and Stress Scale (DASS-21) was used to
subjective mystical-type phenomena that may have occurred after assess for anxiety and depression symptoms during the 3 months before
taking the psychedelic (Maclean et al., 2012; Barrett et al., 2015). Re- and 3 months after the psychedelic experience. This 21-item scale
spondents were asked to think back on their experience with a psy- (Lovibond and Lovibond, 1995) examines the core negative emotional
chedelic and then to rate the extent to which each of 30 descriptors experiences of depression and anxiety that respondents reported ex-
applied at any point during their session on a 6-point scale from periencing. The DASS-21 is comprised of three subscales: depression,
0 = “None; not at all” to 5 = “Extreme (more than ever before in my anxiety, and stress, of which we used a subscale consisting of the
life).” Similar to prior research (Davis et al., 2018, 2019), we calculated combined depression and anxiety subscales in the current study. There
a total mean score of all items on the questionnaire. Internal con- are seven items in each subscale and respondents are asked to respond
sistency reliability of the total scale was excellent (alpha = .94). to each item on a scale from 0 = “Never” to 3 = “Almost always.”
Internal consistency reliability was good for the before measures (de-
pression subscale alpha = .91; anxiety subscale alpha = .80) and
3.3. Acute insight experiences adequate-to-good for the after measures (depression subscale
alpha = .84; anxiety subscale alpha = .69). In the present study, we
The Psychological Insight Questionnaire (PIQ) was created to assess examined subjective changes in depression and anxiety following a
the degree to which respondents experienced acute insight (e.g., gained psychedelic experience by calculating a mean total change score by
an awareness into your emotions, behaviors, beliefs, memories, or re- subtracting the total depression and anxiety after scores from the total
lationships) that sometimes occurs after taking a psychedelic. depression and anxiety before scores for each respondent (e.g., negative
Respondents were asked to think back on their experience with a psy- scores represent a decrease in depression/anxiety). A single measure
chedelic and then to rate the intensity with which they experienced combining depression and anxiety subscales (depression/anxiety) was
each of 28 insight experiences at any point during their session, and analyzed as the dependent measure in analyses reported in this report.
similar to the MEQ they rated each item on a 6-point scale from Separate analyses for depression and anxiety subscales are reported in
0 = “No; not at all” to 5 = “Extremely (more than ever before in my supplementary material.
life).” A total score was calculated as the mean of the responses to each
item, and the internal reliability of this total score was excellent
3.5. Psychological flexibility
(alpha = .93). The PIQ is under development and the psychometric
properties of this questionnaire will be reported in a forthcoming
The Acceptance and Action Questionnaire II (AAQII; Bond et al.,
manuscript. See Table 1 for items, item means (and standard devia-
2011) was developed as a measure of psychological inflexibility, and in
tions), and percent endorsement of each item ('No, not at all' = 0 and
the present survey it was used to assess the degree of psychological
all other response options = 1).
flexibility respondents experienced before and after the psychedelic
experience. The AAQII is comprised of 7 items and respondents were
asked to respond to each item on a scale from 1 = “Never true” to

Table 1
Psychological Insight Questionnaire item means and standard deviations (N = 985).
Item Mean(SD) Proportion of sample that endorsed at any intensity levela

Realized how current feelings or perceptions are related to events from my past 3.51 (1.52) 93.1%
Awareness of uncomfortable or painful feelings I previously avoided 3.17 (1.67) 88.1
Realized ways my beliefs may be dysfunctional 3.53 (1.55) 91.4
Discovered how aspects of my life are affecting my well-being 3.93 (1.21) 97.6
Gained a deeper understanding of events/memories from my past 3.48 (1.52) 93.4
Experienced validation of my life, character, values, or beliefs 3.71 (1.43) 94.5
Realized the importance of my life 3.84 (1.48) 92.8
Awareness of dysfunctional patterns in my actions, thoughts, and/or feelings 3.66 (1.43) 94.2
Discovered specific techniques for coping with difficulties 3.19 (1.57) 90.6
Realized how critical or judgmental views I hold towards myself are dysfunctional 3.58 (1.50) 93.3
Discovered I could explore uncomfortable or painful feelings I previously avoided 3.47 (1.55) 91.7
Gained a deeper understanding of previously held beliefs and/or values 3.84 (1.27) 97.1
Discovered a vivid sense of the paradoxes in life 3.63 (1.57) 92.0
Realized I could experience memories previously too difficult to experience 2.37 (1.86) 72.9
Awareness of beneficial patterns in my actions, thoughts, and/or feelings 3.29 (1.45) 93.1
Discovered a clear pattern of avoidance in my life 2.76 (1.72) 83.1
Realized the nature and/or origins of my defenses or other coping strategies 3.04 (1.63) 88.0
Discovered new insights about my work or career 2.29 (1.88) 70.6
Gained resolution or clarity about past traumas or hurtful events 2.91 (1.78) 83.6
Discovered clear similarities between my past and present interpersonal relationships 2.83 (1.74) 83.1
Discovered new feelings or perspectives about significant relationships in my life 3.65 (1.48) 93.0
Realized certain actions I should take in regards to important relationships in my life 3.42 (1.56) 91.4
Discovered new actions that may help me achieve my goals 3.28 (1.53) 91.7
Realized the point of view or actions of others that had been difficult to understand previously 3.25 (1.61) 89.7
Discovered clarity or creative solutions about how to solve a problem in my life 3.28 (1.55) 91.7
Awareness of information that helped me understand my life 4.14 (1.14) 97.8
Discovered ways to see my problems with more clarity 3.81 (1.30) 96.0
Awareness of my life purpose, goals, and/or priorities 3.77 (1.42) 94.7

Note. Range of scores of all items was 0–5.

a
Response options were on a scale from 0 = “No, Not at all” to 5 = “Extremely (more than ever before in my life)”. Data in this column show the proportion of
respondents who endorsed any option other than “No, Not at all.”.

41
A.K. Davis, et al. Journal of Contextual Behavioral Science 15 (2020) 39–45

Table 2 psychological flexibility have a direct effect on changes in depression/

Means, standard deviations, and correlations among variables included in path anxiety) and mediation effects (H4): Intensity of psychological insight
analysis (i.e., mystical experiences score, psychological insight score, depres- and mystical effects are indirectly related to changes in depression/
sion/anxiety symptom change score, psychological flexibility change score; anxiety via and the path analyses. Analyses were conducted in SPSS v
N = 985).
25 (IBM Corp, 2018) and MPlus version 7.0 using weighted least square
M (SD) 1 2 3 4 5 6 mean and variance estimators (Muthén and Muthén 1998-2017).

1. Age 32.19 07 .09 -.09 .14 -.07

(12.6) 4. Results
2. Sexa 1.27 (0.45) .09 .01 -.06 .08
3. Mystical Experiences 3.80 (0.89) .41 -.19 .28
4. Psychological Insight 3.38 (0.91) -.31 .50 4.1. Respondent characteristics
5. Decreaae in anxiety/depression −6.80 -.62
(5.61) Most of the sample reported they were male (72%), Caucasian/
6. Increase in psychological 2.09 (1.44) white (84%), never married (51%), currently live in the United States
flexibilityb
(65%) and earned $35,000 or more in income (60%). Average age in
Note. Bolded items were considered statistically significant (p < .001) and the sample was 32.2 (SD = 12.6). Over three-quarters of the sample
meaningful (coefficient > 0.20). reported that their psychedelic experience was occasioned by LSD
a
Sex coded Male = 1, Female = 2. (42%) or psilocybin/mushrooms (38%) as the psychedelic substance
b
The AAQII was originally developed as a measure of psychological inflex- used to occasion their experience. Furthermore, about one-half of the
ibility. Reduction in AAQ scores indicates an increase in psychological flex- sample reported that the dose was moderately-high (36%) or high
ibility. However, to ease interpretation, we have calculated a positive change (21%). The psychedelic experience had occurred at least 1 year prior to
score to denote increases in psychological flexibility. the survey in 75% of the sample. Overall, there was a mean decrease in
depression/anxiety (M = −6.80; SD = 5.61; Range: −21 to +9), and
7 = “Always true.” Lower scores on this measure indicate greater a mean increase in psychological flexibility (M = 2.01; SD = 1.44;
psychological flexibility. Internal consistency reliability was good for Range: −4.14 to +6), from before to after the psychedelic experience.
the psychological flexibility before measure (alpha = .88) and the Additional details about respondent characteristics are shown in
psychological flexibility after measure (alpha = .88). We examined Supplemental Table 1.
changes in psychological flexibility by calculating a mean change score. Associations between acute psychedelic effects and psychological
This calculation involved subtracting the mean psychological flexibility flexibility and depression/anxiety change scores.
before score from the mean psychological flexibility after score for each A series of point-biserial correlations revealed that the type of
respondent in order to ease interpretation (i.e., we calculated a positive psychedelic drug used by respondents (Psilocybin: No = 0, Yes = 1;
change score to denote increases in psychological flexibility). This LSD: No = 0, Yes = 1; Other Psychedelic: No = 0, Yes = 1) was
change score was used in all analyses. unrelated (range: −0.19 to 0.14) to all other variables (age, sex, acute
insight and mystical effects, depression/anxiety change score, and
3.6. Demographics psychological flexibility change score). Additionally, as Table 2 shows,
the intensity of mystical effects was moderately correlated with insight
We included items inquiring about the age, sex, gender, race, eth- effects and to a lesser degree with decreases in depression/anxiety and
nicity, country/region of residence, income, level of education, and increases in psychological flexibility. Intensity of psychological insight
relationship status of each respondent. was moderately correlated with decreases in depression/anxiety; and
the intensity of psychological insight and decreases in depression/an-
3.7. Data analyses xiety were correlated with increases in psychological flexibility.

Data Quality. Study completion time was examined in order to 4.2. Regression analysis
identify cases of rushed and possibly careless responding. Overall, re-
spondents completed the survey in approximately 47 min. Only 3 re- Table 3 shows data from the multiple linear regression including
spondents took less than 15 min to complete the survey; 25% of the acute mystical (M = 3.81; SD = 0.89) and insight effects (M = 3.38;
sample completed the survey in less than approximately 33 min; and SD = 0.91) as predictors of decreases in depression/anxiety
75% of the sample completed the survey in less than approximately (M = −6.80; SD = 5.61). The overall model was significant
67 min. Although 3 respondents completed the survey in less than (p < .001), accounting for 10% of the variance in depression/anxiety
15 min, a review of their responses did not provide any indication of change scores (H1). Although accounting for a relatively small amount
careless responding. This pattern of response time suggests that careless of variance in this model, the intensities of both mystical and insight
responding was not a concern. effects were associated with decreases in depression/anxiety (see
Analytic Plan. First, descriptive statistics for demographic and Table 3).
background characteristics for all study variables were calculated.
Pearson and point biserial correlation coefficients were calculated to Table 3
examine the relationships among all primary study variables (age, sex, Summary of multiple linear regression showing significant predictors of
acute insight and mystical effects, depression/anxiety change score, and changes in depression or anxiety (spontaneous and intended) from before to
psychological flexibility change score). Given the large number of re- after a psychedelic experience (N = 985).
spondents in the sample, we used a coefficient cutoff of 0.20, and used Variables B SE B β t p
an alpha cutoff of p < .001, to determine whether a correlation was
both meaningful and statistically significant, respectively. Next, a re- Constant .90 .83
gression analysis was used to test (H1): acute mystical and insight ex- Mystical effects -.51 .21 -.08 −2.428 .015*
Psychological insight effects −1.71 .20 -.28 −8.395 .000***
periences will be negatively associated with depression/anxiety change Adjusted R2 .10
score. A path analysis was then used to test hypothesized direct effects
(H2–H3: Intensity of psychological insight and mystical effects have a Note. The overall model was significant, F(2, 984) = 55.675, p < .001.
direct effect on changes in psychological flexibility, and changes in *p < .05; ***p < .001.

42
A.K. Davis, et al. Journal of Contextual Behavioral Science 15 (2020) 39–45

increases in psychological flexibility mediated the relationships be-

tween acute psychedelic effects and decreases in depression and anxiety
symptoms (H4). Findings from our regression and path analysis models
supported each of these hypotheses. Consistent with prior studies
(Davis et al., 2019; Griffiths et al., 2016; Ross et al., 2016), in the
present study mystical experiences were associated with decreases in
depression and anxiety. Importantly, these observations were extended
by showing that experiences of psychological insight during a psyche-
delic experience are also associated with decreases in depression and
anxiety. Further, when mystical and psychological insight effects were
included simultaneously as predictors of changes in our models, results
Fig. 1. Path analysis showing that increases in psychological flexibility mediate showed that psychological insight stands out as a more robust predictor
relationship between acute effects of psychedelics and decreases in depression/ of change, as evidenced by the larger direct (Insight: β = 0.46 versus
anxiety (full sample, N=985). **p < .01, ***p < .001.
Mystical: β = 0.09) and indirect (Insight: β = 0.29 versus Mystical:
β = 0.06) coefficients in the path analysis.
4.3. Path analysis That psychological insight is strongly related to decreases in de-
pression and anxiety is perhaps not surprising given the history of in-
As shown in Fig. 1, the path analysis controlling for age and sex sight-oriented therapies (Connolly Gibbons et al., 2007), but it has also
revealed that greater mean intensity of acute mystical and psycholo- been questioned whether gaining insight is sufficient in and of itself to
gical insight effects were directly related (Mystical: β = 0.09, p < .01; produce lasting changes in behavior or mental health functioning
Insight: β = 0.46, p < .001) to mean increases in psychological (Kuncewicz et al., 2014; Leichsenring et al., 2006). To this point, our
flexibility (Mincrease = 2.09; SD = 1.44; supporting H2), mean increases models also showed that psychological insight was predictive of change
in psychological flexibility were directly related (β = −0.62, when accounting for the correlation between insight and mystical ex-
p < .001) to mean decreases in depression/anxiety (supporting H3), periences. Insightful as well as mystical-type experiences have been
and indirect effects were found wherein psychological flexibility identified as subtypes of the phenomenon of quantum change, which
mediated the relationships between the intensity of acute mystical refers to a sudden, distinctive, benevolent, and enduring experience
(β = 0.06, SE = 0.02, p < .01) and insight (β = 0.29, SE = 0.02, resulting in personal transformations that affect a broad range of per-
p < .001) effects and mean decreases in depression/anxiety (sup- sonal emotions, cognitions and behaviors (Miller and C'de Baca, 2001;
porting H4). Model fit was good: root mean square error of approx- Miller, 2004). Such experiences after taking a psychedelic have also
imation = .055 (95% CI: 0.01, 0.12); comparative fit index = 0.995; been implicated in decreases in alcohol use among individuals with
weighted root-mean-square residual = 0.394. alcohol use disorder (Garcia-Romeu et al., 2019).
Furthermore, findings from the present study underscore a potential
4.4. Supplementary analyses explanation for how acute psychedelic experiences, including gaining
psychological insight and mystical experiences, may exert such
The sample used for our primary analyses (described above) was a changes. Specifically, we demonstrated the importance of increases in
group of individuals who reported a spontaneous or intended change in psychological flexibility as a mediator of the positive therapeutic ef-
anxiety (intended N = 142; spontaneous N = 197) or depression (in- fects. Although several other mechanisms have been proposed at var-
tended N = 366; spontaneous N = 280) following a psychedelic ex- ious levels of functioning, from changes in the entropy of brain network
perience. In the path analysis shown in Fig. 1, we collapsed these connectivity (Carhart-Harris et al., 2014) to the importance of awe/ego
groups into one sample (N = 985), and averaged measures of depres- dissolution (Hendricks, 2018; Preller and Vollenweider, 2018), findings
sion and anxiety into a single measure, in order to examine our primary from this study are consistent with evidence demonstrating that psy-
study hypotheses in a more concise manner. However, we also analyzed chedelic effects are associated with changes in psychological flexibility
all study hypotheses (H1–H4) within each of these subgroups using the among a small sample of subjects who use the psychedelic ayahuasca
same analytic approach described above, and these tables and figures (Kuypers et al., 2016), and research showing that increases in psycho-
are available in supplementary files (Suppl. Tables 1-4; Suppl. Figures logical flexibility is associated with positive depression and anxiety
1-4). In short, all hypotheses were replicated in each subsample, with outcomes (Twohig and Levin, 2017).
two notable exceptions. Among those who intended to change their Although the exploration of potential mediators of psychedelic ef-
anxiety after a psychedelic experience, the regression analyses (Suppl. fects on therapeutic outcomes is in its early stages, if psychological
Table 3) showed that intensity of mystical effects was not significantly flexibility emerges as a consistent and robust mediator of effects in
associated with decreases in anxiety (contrary to H1). Furthermore, in prospective clinical trials, then the field of psychedelic-assisted psy-
the path analysis (Suppl. Figure 3), intensity of mystical effects was not chotherapy should consider integrating psychedelic administration
significantly associated with increases in psychological flexibility with contextual behavioral therapies (e.g., ACT; Hayes et al., 2006) or
(contrary to H2), nor were there indirect relationships between acute other therapies designed to target psychological flexibility. Such
mystical effects and decreases in anxiety via increases in psychological therapies are designed to enhance processes of change by supporting
flexibility. However, all other findings showed that our models were increases in psychological flexibility which could be enhanced through
identical regardless of whether one had a spontaneous or intended the administration of a psychedelic. Moreover, it is possible that some
change in these their anxiety/depression. acute psychedelic effects overlap with the core processes of the ACT
model of psychopathology (Hayes et al., 2006). For example, consistent
5. Discussion with the core processes of ACT, qualitative analysis of first-hand ac-
counts of tobacco smokers in a clinical trial examining the effect of
The present retrospective cross-sectional survey study examined psilocybin-assisted therapy (Johnson et al., 2014; Noorani et al., 2018),
whether psychedelic occasioned mystical-type or psychological insight suggested that their psychedelic experiences helped them see them-
experiences predicted decreases in depression and anxiety following a selves in the context of their addiction (i.e., self as context), realize that
psychedelic experience (H1), acute psychedelic effects predicted in- they are not the labels (e.g., smoker) which they previously identified
creases in psychological flexibility (H2), increases in psychological as (i.e., defusion), understood their values more clearly than before
flexibility predicted decreases in depression/anxiety, (H3) and whether (i.e., values), and connected with the fullness of the present moment

43
A.K. Davis, et al. Journal of Contextual Behavioral Science 15 (2020) 39–45

and their experience of it (i.e., contact with the present moment). Al- such therapeutic effects can be further enhanced by using a psy-
though not highlighted in the qualitative reports per se, another com- chotherapeutic approach to psychedelic-assisted therapy that specifi-
ponent of the ACT model, committed action, was demonstrated in the cally targets processes of change within a transdiagnostic psychological
clinical trial by the high rates (80%) of biologically verified abstinence flexibility model.
at 6 months post-treatment (Johnson et al., 2014). These data suggest
that psychedelics appear to occasion both mindfulness/acceptance Declaration of competing interests
processes as well as commitment and behavior change processes.
However, more research is needed to systematically investigate these Dr. Griffiths is a board member of Heffter Research Institute and Dr.
processes in rigorous longitudinal trials among individuals with de- Davis is a board member of Source Research Foundation. Neither or-
pression or anxiety in order to replicate these findings in this popula- ganization was involved in the design/execution of this study or the
tion. interpretation or communication of findings.
This study has several limitations. Internet-based recruitment and
data collection procedures were anonymous. Although this likely in- Appendix A. Supplementary data
creased participation from individuals from a variety of geographical
locations, it would have excluded people who are unable or prefer not Supplementary data to this article can be found online at https://
to participate in research conducted on the internet. Further, a limita- doi.org/10.1016/j.jcbs.2019.11.004.
tion of survey methods is that all reports are retrospective, increasing
the likelihood that current affect and personality bias could influence References
recollection of subjective psychedelic experiences as well as depression
and anxiety symptoms that were experienced many years ago. A-Tjak, J. G. L., Davis, M. L., Morina, N., Powers, M. B., Smits, J. A. J., & Emmelkamp, P.
However, this potential confound is not expected to be more or less M. G. (2015). A meta-analysis of the efficacy of acceptance and commitment therapy
for clinically relevant mental and physical health problems. Psychotherapy and
than similar confounds in other retrospective survey research (Davis Psychosomatics, 84, 30–36.
et al., 2018,2019). Additionally, the parent study from which the data Araújo, A. M., Carvalho, F., Bastos, M.de. L., Guedes de Pinho, P., & Carvalho, M. (2015).
were drawn, was designed to investigate the acute effect of gaining The hallucinogenic world of tryptamines: An updated review. Archives of Toxicology,
89, 1151–1173.
insight during a psychedelic experience. Although the mean score of the Bandelow, B., & Michaelis, S. (2015). Epidemiology of anxiety disorders in the 21st
intensity of mystical experiences in this sample was similar to prior century. Dialogues in Clinical Neuroscience, 17, 327–335.
studies (Davis et al., 2018), suggesting comparably strong mystical ef- Barrett, F. S., Bradstreet, M. P., Leoutsakos, J.-M. S., Johnson, M. W., & Griffiths, R. R.
(2016). The Challenging Experience Questionnaire: Characterization of challenging
fects in addition to insight effects, we cannot rule out the possibility
experiences with psilocybin mushrooms. Journal of Psychopharmacology, 30,
that recruiting people who specifically reported gaining insight as part 1279–1295.
of a psychedelic experience accounts for some of the differential Barrett, F. S., Johnson, M. W., & Griffiths, R. R. (2015). Validation of the revised Mystical
Experience Questionnaire in experimental sessions with psilocybin. Journal of
strength in the association between acute insight and other study
Psychopharmacology, 29, 1182–1190.
variables. Birnbaum, H. G., Kessler, R. C., Kelley, D., Ben-Hamadi, R., Joish, V. N., & Greenberg, P.
Another limitation to this study is that, despite our efforts to recruit E. (2010). Employer burden of mild, moderate, and severe major depressive disorder:
individuals with diverse backgrounds by placement of notices on a Mental health services utilization and costs, and work performance. Depression and
Anxiety, 27, 78–89 1091–4269.
variety of internet forums, respondents were primarily young, white, Bond, F. W., Hayes, S. C., Baer, R. A., Carpenter, K. M., Guenole, N., Orcutt, H. K., et al.
and male. Although our sample is consistent with prior studies of psy- (2011). Preliminary psychometric properties of the acceptance and action
chedelic users using similar recruitment procedures (Barrett et al., questionnaire–II: A revised measure of psychological inflexibility and experiential
avoidance. Behavior Therapy, 42, 676–688.
2016; Davis et al., 2018), similar to Michaels et al. (2018) we strongly Carhart-Harris, R. L., Bolstridge, M., Rucker, J., Day, C. M. J., Erritzoe, D., Kaelen, M.,
encourage future researchers to continue efforts in recruiting a diverse et al. (2016). Psilocybin with psychological support for treatment-resistant depres-
sample. There are several possible explanations for the lack of diverse sion: An open-label feasibility study. The Lancet Psychiatry, 3, 619–627.
Carhart-Harris, R. L., Leech, R., Hellyer, P. J., Shanahan, M., Feilding, A., Tagliazucchi, E.,
representation in psychedelic survey studies. For example, it could be et al. (2014). The entropic brain: A theory of conscious states informed by neuroi-
that the topic of these studies are not interesting to some potential re- maging research with psychedelic drugs. Frontiers in Human Neuroscience, 8.
spondents, that there is a perceived risk involved with reporting an il- Carhart-Harris, R. L., Roseman, L., Bolstridge, M., Demetriou, L., Pannekoek, J. N., Wall,
M. B., et al. (2017). Psilocybin for treatment-resistant depression: FMRI-measured
legal behavior, or that the internet computer format excluded in- brain mechanisms. Scientific Reports, 7, 13187.
dividuals from differing socio-economic backgrounds. Efforts to Carhart-Harris, R. L., Williams, T. M., Sessa, B., Tyacke, R. J., Rich, A. S., Feilding, A.,
overcome these factors could include a community-based participatory et al. (2011). The administration of psilocybin to healthy, hallucinogen-experienced
volunteers in a mock-functional magnetic resonance imaging environment: A pre-
research methodology (Israel et al., 2005), wherein the study is de-
liminary investigation of tolerability. Journal of Psychopharmacology, 25, 1562–1567.
signed through engagement with leaders from a variety of diverse Collimore, K. C., & Rector, N. A. (2014). Treatment of anxiety disorders with comorbid
backgrounds, with the intention of better understanding the ways in depression: A survey of expert CBT clinicians. Cognitive and Behavioral Practice, 21,
which the study can be designed to connect with individuals from these 485–493.
Collins, K. A., Westra, H. A., Dozois, D. J. A., & Burns, D. D. (2004). Gaps in accessing
communities. treatment for anxiety and depression: Challenges for the delivery of care. Clinical
Psychology Review, 24, 583–616.
6. Conclusion Connolly Gibbons, M. B., Crits-Christoph, P., Barber, J. P., & Schamberger, M. (2007).
Insight in psychotherapy: A review of empirical literature. In L. Castonguay, & C. Hill
(Eds.). Insight in psychotherapy (pp. 143–165). Washington, DC: APA Press.
The findings from the present study highlight the role of psycho- Coull, G., & Morris, P. G. (2011). The clinical effectiveness of CBT-based guided self-help
logical flexibility as a mediator of acute psychedelic effects and de- interventions for anxiety and depressive disorders: A systematic review. Psychological
Medicine, 41, 2239–2252.
creases in depression/anxiety. Future studies should examine the effect Cuijpers, P., Sijbrandij, M., Koole, S. L., Andersson, G., Beekman, A. T., & Reynolds, C. F.,
of psychedelic drug administration on psychological flexibility in a la- III (2014). Adding psychotherapy to antidepressant medication in depression and
boratory setting using a controlled trial design in order to ascertain the anxiety disorders: A meta-analysis. World Psychiatry, 13, 56–67.
Davis, A. K., Barsuglia, J. P., Lancelotta, R., Grant, R., & Renn, E. (2018). The epide-
causal influences of psychological processes that predict therapeutic miology of 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) use: Benefits, con-
effects of hallucinogens. Such work should include measurement of the sequences, patterns of use, subjective effects, and reasons for consumption. Journal of
core processes of ACT (e.g., defusion, values, self as context, etc.) in Psychopharmacology, 32, 779–792.
Davis, A. K., So, S., Lancelotta, R., Barsuglia, J. P., & Griffiths, R. R. (2019). 5-Methoxy-
order to examine whether changes in these core processes occur and
N,N-Dimethyltryptamine (5-MeO-DMT) used in a naturalistic setting is associated
predict enduring effects of psychedelic substances on therapeutic out- with unintended improvements in depression and anxiety. The American Journal of
comes. If psychological flexibility continues to be shown to mediate Drug and Alcohol Abuse, 45, 161–169.
positive therapeutic outcomes, future research should explore whether French, K., Golijani-Moghaddam, N., & Schröder, T. (2017). What is the evidence for the

44
A.K. Davis, et al. Journal of Contextual Behavioral Science 15 (2020) 39–45

efficacy of self-help acceptance and commitment therapy? A systematic review and Analysis of the mystical experience questionnaire: A study of experiences occasioned
meta-analysis. Journal of Contextual Behavioral Science, 6, 360–374. by the hallucinogen psilocybin. Journal of the Scientific Study of Religion, 51, 721–737.
Garcia-Romeu, A., Davis, A. K., Erowid, F., Erowid, E., Griffiths, R. R., & Johnson, M. W. Michaels, T. I., Purdon, J., Collins, A., & Williams, M. T. (2018). Inclusion of people of
(2019). Cessation and reduction in alcohol consumption and misuse after psychedelic color in psychedelic-assisted psychotherapy: A review of the literature. BMC
use. Journal of Psychopharmacology, 33, 1088–1101. Psychiatry, 18, 245.
Gloster, A. T., Meyer, A. H., & Lieb, R. (2017). Psycholiogical flexibility as a malleable Miller, W. R. (2004). The phenomenon of quantum change. Journal of Clinical Psychology,
public health target: Evidence from a representative sample. Journal of Contextual 60, 453–460.
Behavioral Science, 6, 166–171. Miller, W. R., & C'de Baca, J. (2001). Quantum change: When epiphanies and sudden insights
Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, transform ordinary lives. Guilford Press.
B. D., et al. (2016). Psilocybin produces substantial and sustained decreases in de- Muthén, L. K., & Muthén, B. O. (1998–2017). Mplus User's Guide (8th ed.). Los Angeles,
pression and anxiety in patients with life-threatening cancer: A randomized double- CA: Muthén and Muthén.
blind trial. Journal of Psychopharmacology, 30, 1181–1197. Niles, A. N., Dour, H. J., Stanton, A. L., Roy-Byrne, P. P., Stein, M. B., Sullivan, et al.
Griffiths, R. R., Johnson, M. W., Richards, W. A., Richards, B. D., McCann, U., & Jesse, R. (2015). Anxiety and depressive symptoms and medical illness among adults with
(2011). Psilocybin occasioned mystical-type experiences: Immediate and persisting anxiety disorders. Journal of Psychosomatic Research, 78, 109–115.
dose related effects. Psychopharmacology, 218, 649–665. Noorani, T., Garcia-Romeu, A., Swift, T. C., Griffiths, R. R., & Johnson, M. W. (2018).
Griffiths, R. R., Richards, W., Johnson, M., McCann, U., & Jesse, R. (2008). Mystical-type Psychedelic therapy for smoking cessation: Qualitative analysis of participant ac-
experiences occasioned by psilocybin mediate the attribution of personal meaning counts. Journal of Psychopharmacology, 32, 756–769.
and spiritual significance 14 months later. Journal of Psychopharmacology, 22, Otto, M. W., & Hearon, B. A. (2016). Combination treatment for anxiety and mood dis-
621–632. orders: Benefits and issues for the combination of cognitive-behavioral therapy and
Hacker, T., Stone, P., & MacBeth, A. (2016). Acceptance and commitment thearpy – do we pharmacotherapy. The Oxford handbook of cognitive and behavioral therapies (pp. 482–
know enough? Cumulative and sequential meta-analyses of randomized controlled 493). New York, NY: Oxford University Press.
trials. Journal of Affective Disorders, 190, 551–565. Palhano-Fontes, F., Barreto, D., Onias, H., Andrade, K. C., Novaes, M. M., Pessoa, J. A.,
Hayes, S. C., Luoma, J. B., Bond, F. W., Masuda, A., & Lillis, J. (2006). Acceptance and et al. (2018). Rapid antidepressant effects of the psychedelic ayahuasca in treatment-
commitment therapy: Model, processes and outcomes. Behaviour Research and resistant depression: A randomized placebo-controlled trial. Psychological Medicine,
Therapy, 44, 1–25. 49, 655–663.
Hayes, S. C., Strosahl, K. D., & Wilson, K. G. (2012). Acceptance and commitment therapy: Preller, K. H., & Vollenweider, F. X. (2018). Phenomenology, structure, and dynamic of
The process and practice of mindful change (2nd ed.). New York, NY: Guilford Press. psychedelic states. Current Topics In Behavioral Neurosciences, 36, 221–256.
Hendricks, P. S. (2018). Awe: A putative mechanism underlying the effects of classic Roseman, L., Nutt, D. J., & Carhart-Harris, R. L. (2018). Quality of acute psychedelic
psychedelic-assisted psychotherapy. International Review Of Psychiatry (Abingdon, experience predicts therapeutic efficacy of psilocybin for treatment-resistant de-
England), 30, 331–342. pression. Frontiers in Pharmacology, 8, 974.
Hofmann, S. G., Asnaani, A., Vonk, I. J., Sawyer, A. T., & Fang, A. (2012). The efficacy of Ross, S., Bossis, T., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B., et al. (2016). Rapid
cognitive behavioral therapy: A review of meta-analyses. Cognitive Therapy and and sustained symptom reduction following psilocybin treatment for anxiety and
Research, 36, 427–440. depression in patients with life-threatening cancer: A randomized controlled trial.
IBM Corp. (2018). IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp. Journal of Psychopharmacology, 30, 1165–1180.
Israel, B. A., Eng, E., Schulz, A. J., & Parker, E. A. (2005). Methods in community-based Sabucedo, P. (2017). The psychological flexibility model from a cultural perspective: An
participatory research for health. San Francisco: Jossey-Bass. interpretive analysis of two native American healing rituals. Internaltional Journal of
Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P., & Griffiths, R. R. (2014). Pilot study Culture and Mental Health, 10, 367–375.
of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. Journal of Santos, R. G., Landeira-Fernandez, J., Strassman, R. J., Motta, V., & Cruz, A. P. M. (2007).
Psychopharmacology, 28, 983–992. Effects of ayahuasca on psychometric measures of anxiety, panic-like, and hope-
Johnson, M. W., Garcia-Romeu, A., Johnson, P. S., & Griffiths, R. R. (2017). An online lessness in Santo Daime members. Journal of Ethnopharmacology, 112, 507–513.
survey of tobacco smoking cessation associated with naturalistic psychedelic use. dos Santos, R. G., Osório, F. L., Crippa, J. A. S., Riba, J., Zuardi, A. W., & Hallak, J. E. C.
Journal of Psychopharmacology, 31, 841–850. (2016). Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin,
Johnson, M. W., & Griffiths, R. R. (2017). Potential therapeutic effects of psilocybin. and lysergic acid diethylamide (LSD): A systematic review of clinical trials published
Neurotherapeutics, 14, 734–740. in the last 25 years. Therapeutic Advances in Psychopharmacology, 6, 193–213.
Kashdan, T. B., & Rottenberg, J. (2010). Psychological flexibility as a fundamental aspect Sinyor, M., Schaffer, A., & Levitt, A. (2010). The sequenced treatment alternatives to
of health. Clinical Psychology Review, 30, 865–878. relieve depression (STAR*D) trial: A review. Canadian Journal of Psychiatry, 55,
Katon, W. J. (2011). Epidemiology and treatment of depression in patients with chronic 126–135.
medical illness. Dialogues in Clinical Neuroscience, 13, 7–23. Steel, Z., Marnane, C., Iranpour, C., Chey, T., Jackson, J. W., Patel, V., et al. (2014). The
Koen, N., & Stein, D. J. (2011). Pharmacotherapy of anxiety disorders: A critical review. global prevalence of common mental disorders: A systematic review and meta-ana-
Dialogues in Clinical Neuroscience, 13, 423–437. lysis 1980–2013. International Journal of Epidemiology, 43, 476–493.
Kuncewicz, D., Lachowicz-Tabaczek, K., & Załuski, J. (2014). Why insight in psy- Stroud, J. B., Freeman, T. P., Leech, R., Hindocha, C., Lawn, W., Nutt, D. J., et al. (2017).
chotherapy does not always lead to behaviour change? Polish Journal of Applied Psilocybin with psychological support improves emotional face recognition in
Psychology, 12, 99–122. treatment-resistant depression. Psychopharmacology, 235, 459–466.
Kuypers, K. P. C., Riba, J., de la Fuente Revenga, M., Barker, S., Theunissen, E. L., & Twohig, M. P., & Levin, M. E. (2017). Acceptance and commitment therapy as a treatment
Ramaekers, J. G. (2016). Ayahuasca enhances creative divergent thinking while for anxiety and depression: A review. Psychiatric Clinics of North America, 40,
decreasing conventional convergent thinking. Psychopharmacology, 223, 3395–3403. 751–770.
Leichsenring, F., Hiller, W., Weissberg, M., & Leibing, E. (2006). Cognitive-behavioral Uthaug, M. V., van Oorsouw, K., Kuypers, K. P. C., van Boxtel, M., Broers, N. J., Mason, N.
therapy and psychodynamic psychotherapy: Techniques, efficacy, and indications. L., et al. (2018). Sub-acute and long-term effects of ayahuasca on affect and cognitive
American Journal of Psychotherapy, 60, 233–259. thinking style and their association with ego dissolution. Psychopharmacology, 235,
Lovibond, P. F., & Lovibond, S. H. (1995). The structure of negative emotional states: 2979–2989.
Comparison of the depression anxiety stress scales (DASS) with the beck depression Walsh, Z., & Thiessen, M. S. (2018). Psychedelics and the new behaviourism: Considering
and anxiety inventories. Behavior Research and Therapy, 33, 335–343. the integration of third-wave behavior therapies with psychedelic-assisted therapy.
Maclean, K. A., Leoutsakos, J.-M. S., Johnson, M. W., & Griffiths, R. R. (2012). Factor International Review of Psychiatry, 30, 343–349.

45