Effects of Naturalistic Psychedelic Use on Depression, Anxiety, and Well-Being: Associations With Patterns of Use, Reported Harms, and Transformative Mental States

This survey study (n=2,150) assessed the associations between the amount of psychedelic use and behavioural outcomes, as well as the frequency of harms ascribed to psychedelic use. Psychedelic use was associated with significant improvements in depressive and anxious symptoms and with increased emotional well-being and these improvements increased in magnitude with increasing psychedelic exposure. Thirteen per cent of the survey sample (n=330) endorsed at least one harm from psychedelic use, and these participants reported less mental health benefit.

Abstract

“Survey-based studies suggest naturalistic psychedelic use provides mental health benefits similar to those observed in clinical trials. The current study sought to confirm these findings in a large group of psychedelic users and to conduct a novel examination of associations between the amount of psychedelic use and behavioural outcomes, as well as the frequency of harms ascribed to psychedelic use. A cross-sectional, online survey was completed by 2,510 adults reporting at least one-lifetime psychedelic experience. Participants retrospectively completed a battery of instruments assessing depression, anxiety, and emotional well-being prior to and following psychedelic exposure. Participants also reported preferred psychedelic agents, the number of uses, and the harms attributed to psychedelic use. Psychedelic use was associated with significant improvements in depressive and anxious symptoms and with increased emotional well-being. These improvements increased in magnitude with increasing psychedelic exposure, with a ceiling effect. However, improvements were noted following a single lifetime use. Strong evidence for benefit of one preferred psychedelic agent over another was not observed, but enduring increases in factors related to mystical experience and prosocial perspective-taking associated with enhanced mental health. Thirteen per cent of the survey sample (n = 330) endorsed at least one harm from psychedelic use, and these participants reported less mental health benefit. Results from the current study add to a growing database indicating that psychedelic use—even outside the context of clinical trials—may provide a wide range of mental health benefits, while also posing some risk for harm in a minority of individuals.

Authors: Charles L. Raison, Rakesh Jain, Andrew D. Penn, Steven P. Cole & Saundra Jain

Summary

INTRODUCTION

Psychedelics were long stigmatized as drugs of abuse, but in recent years several publicly traded companies have entered the psychedelic development space to jostle for early supremacy.

Several factors have converged to fuel this psychedelic gold rush, including preliminary findings that psychedelics are effective in treating a variety of psychiatric and addictive conditions, and a perception that psychedelic treatment will demand a longed for, but previously unattainable, integration of pharmacology and psychotherapy.

Despite the current cultural and commercial enthusiasm for psychedelics, current data from clinical trials leave many questions unanswered. Fortunately, a growing database from prior large-scale survey-based studies has provided insight into a wide range of associations between psychedelic use and various positive outcomes.

Few large-scale survey studies have used a validated scale to examine whether naturalistic psychedelic use associates with reduced symptoms of major depressive disorder or generalized anxiety disorder in addition to enhanced well-being, and no study has examined associations between number of lifetime psychedelic experiences and changes in depressive and anxious symptoms.

The Psychedelics and Wellness Study was designed to examine associations between past psychedelic use and current levels of emotional wellness, as well as the prevalence and types of harms engendered by past use.

Participant Recruitment and Enrollment

Participants were recruited through free online platforms, social media, word-of-mouth, in-person, flyers/postcards, email, and snowball sampling. They answered inclusion questions related to age (18 and older) and use of psychedelics (at least one time) and signed an online consent form.

Study Design

The PAWS Study used an online platform to deliver a survey instrument to assess participants’ retrospective perspectives on the mental health effects of classic psychedelic use.

The survey asked participants to rate their mental health status prior to first psychedelic use and then after psychedelic use. Depressive, anxious and well-being symptoms were assessed using the PHQ-9, GAD-7 and HERO Wellness Scale.

Participants completed a 26-item battery of questions following their psychedelic experience to assess change in variables related to their mental health/well-being.

Survey Instruments and Questions Participant Demographics, Psychedelic Use, and Preferences

The PAWS survey anonymously collected participant, age, sex, education level, preferred psychedelic drug, estimated number of lifetime psychedelic uses, and history of micro-dosing.

Nine-Item Patient Health Questionnaire

The PHQ-9 is a widely used self-report instrument that queries each of the nine symptoms that comprise major depressive disorder (MDD) in the DSM 5. It has good internal reliability and construct validity.

Seven-Item Generalized Anxiety Disorder Scale

The GAD-7 is a self-report instrument widely used for screening and assessment of symptom severity of generalized anxiety disorder. It has an internal consistency of 0.92 and has been validated in primary care and larger treatment settings.

HERO Wellness Scale

The HERO Wellness Scale is a five-item self-report inventory that measures happiness, enthusiasm, resilience, optimism and overall mental wellness. It has good internal consistency and adequate corrected item-total correlations.

Twenty Six-Item Psychedelic Change Questionnaire

The PCQ-26 was created specifically for this study, and queries a mixture of emotional states that often occur during the psychedelic experience itself, as well as symptoms common to a variety of mental disorders and substance misuse.

Eight-Item Negative Consequences Inventory

The NCI-8 was created to measure the potential negative outcomes of psychedelic use, including increased suicidal desire, criminal impulses/behaviors, aggressive impulses/behaviors, alcohol misuse, cigarette smoking, cannabis/marijuana misuse, benzodiazepine misuse, and opiate/opioid misuse.

Ethical Considerations

The PAWS study was conducted on a completely anonymous basis, and no personally identifying data was collected. It was determined to be exempt under 45 CFR 46.104(d) (2).

Statistical Analyses

Frequency distributions were calculated for all measures and means, and standard deviations were computed for all continuous measures. Significant deviations from normality were examined, but bootstrap simulations demonstrated that underlying distributions were normally distributed.

To optimize its use in subsequent analyses, exploratory factor analysis was applied to the PCQ-26 to examine potential underlying structures and reduce dimensionality. Three factors were identified and included as predictors in a regression model for each of the primary outcomes as dependent variables.

Paired sample t-tests, linear regressions and multiple regressions were used to evaluate the impact of psychedelic use on PHQ-9, GAD-7 and HERO scores. The effect of each individual predictor variable on the dependent variable was compared using standardized beta coefficients.

Demographics

2,510 adults with a range of ages from 18 to 86 completed a survey on psychedelic use. Most reported psilocybin or LSD as their preferred psychedelic.

Association of Lifetime Psychedelic Use With Depression, Anxiety and Emotional Well-Being

As shown in Table 2, survey respondents reported significant reductions in depressive and anxious symptoms and increases in emotional well-being following psychedelic exposure.

PCQ-26: Factor Analysis and Association With Lifetime Psychedelic Use

The relationship with your life partner item was considered inapplicable by 31.3% of the respondents, so a mean substitution of missing data procedure was used. Three factors were identified, and a Monte-Carlo simulation confirmed the appropriateness of a three-factor solution.

The PCQ-26 items that loaded onto each factor are presented as a pattern matrix in Table 3. The items in Factor 1 are frequently endorsed as being experienced during the acute psychedelic experience itself, while the items in Factor 2 overlap with emotional and physical states/functions that are reliably altered in depressive/anxious conditions.

Psychedelic usage improved factor 1, factor 2, and factor 3 on the PCQ-26.

Negative Outcomes Associated With Lifetime Psychedelic Use

Participants who endorsed at least one negative outcome as a result of psychedelic use were divided between behavioral disturbance and substance misuse.

Participants with one or more negative outcomes derived significantly less benefit from psychedelic use than those with none, despite showing no differences in their assessment of pre-psychedelic symptom status.

Psychedelic use was associated with greater reductions in scores on the PHQ-9 and GAD-7 scales, and greater increases on the HERO scale. The sigmoidal curve best explained the association between lifetime use and HERO scores.

We examined the effect of psychedelic use in 90 survey respondents who reported only one lifetime use. We found that these participants experienced significant reductions in depression and anxiety and increases in emotional well-being.

The majority of respondents felt that psilocybin or LSD had been most beneficial for them, but no differences were seen in pre-exposure HERO, PHQ-9 or GAD-7 scores when comparing each of these agents vs. all others. Participants who preferred ayahuasca reported enhanced improvements in well-being vs. all other agents, but these effects were accounted for by the fact that these participants reported lower pre-psychedelic scores and higher post-psychedelic scores.

Factors Independently Associated With Change in Depression, Anxiety and Emotional Well-Being

Multiple regression identified demographic, PCQ-26 and patterns of use variables independently associated with change in PHQ-9, GAD-7, and HERO scores from pre- to post-lifetime psychedelic use.

DISCUSSION

In the current study, participants who reported using psychedelics in the past reported large effect size reductions in depression and anxiety, and marked improvements in emotional well-being. These benefits increased with self-reported psychedelic use, but even participants with a single life-time exposure reported improvements in mental health.

Most participants reported mental health benefits from psychedelic use, including increased self-perceived altruism and prosocial behavior, but 13 percent identified at least one harm.

The current study has several limitations, including its retrospective design, reliance on self-report, and inability to confirm that respondents actually took the psychedelics as reported or took them the number of times reported. However, the study provides a window into relationships between self-reported depression, anxiety and well-being and patterns of psychedelic use.

These findings suggest that psychedelics may require a significant degree of redosing for maximal therapeutic effect, and that there is a point of diminishing returns in regard to the mental health benefits individuals tend to receive from psychedelic use in naturalistic settings.

Because the PAWS study specifically sought out participants with psychedelic experience, it is possible that bias in recruitment and demand characteristics inflated the improvements in mental health ascribed to psychedelic use. However, a minority of participants reported being harmed by psychedelic use. Participants who endorsed any of the negative outcomes derived significantly less therapeutic benefit from their psychedelic use, which provides additional face validity to the reality of these harms. However, the study did not enroll a population-based sample, and the study did not assess the contexts in which psychedelics were used. Studies consistently find that psychedelics induce acute perceptual/cognitive/emotional states that predict later mental health benefits. The question is whether these acute experiences persist and whether their persistence associates with mental health improvements.

Results suggest that mystical/breakthrough/insight perspectives are capable of producing long-term increases in these states and that such increases associate with improvements in mental health.

Results from the current study suggest several potentially fruitful lines of future research, including survey-based studies of naturalistic psychedelic use, more exhaustive studies of the types of harms that naturalistic psychedelic use may engender, and more research into the risks involved with psychedelic use in the general population.