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Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences

In an online survey of 1,993 people about their worst "bad trip" on psilocybin mushrooms, most (84%) reported some benefit but a minority experienced acute harms (11% put themselves or others at risk, 2.6% were aggressive, 2.7% sought medical help) and 7.6% of episodes older than one year led to treatment for persistent psychological symptoms (including three apparent new psychoses and three suicide attempts). Higher estimated dose, greater subjective difficulty and lack of physical comfort or social support predicted acute risk, degree of difficulty was positively associated with enduring increases in well‑being while duration was negatively associated, and harms were much rarer in well‑controlled laboratory settings.

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Authors

Roland Griffiths
Matthew Johnson
Frederick Barrett

Published

September 27, 2016

Journal of Psychopharmacology

individual Study

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Abstract

Acute and enduring adverse effects of psilocybin have been reported anecdotally, but have not been well characterized. For this study, 1993 individuals (mean age 30 yrs; 78% male) completed an online survey about their single most psychologically difficult or challenging experience (worst “bad trip”) after consuming psilocybin mushrooms. Thirty-nine percent rated it among the top five most challenging experiences of his/her lifetime. Eleven percent put self or others at risk of physical harm; factors increasing the likelihood of risk included estimated dose, duration and difficulty of the experience, and absence of physical comfort and social support. Of the respondents, 2.6% behaved in a physically aggressive or violent manner and 2.7% received medical help. Of those whose experience occurred >1 year before, 7.6% sought treatment for enduring psychological symptoms. Three cases appeared associated with onset of enduring psychotic symptoms and three cases with attempted suicide. Multiple regression analysis showed degree of difficulty was positively associated, and duration was negatively associated, with enduring increases in well-being. Difficulty of experience was positively associated with dose. Despite difficulties, 84% endorsed benefiting from the experience. The incidence of risky behavior or enduring psychological distress is extremely low when psilocybin is given in laboratory studies to screened, prepared, and supported participants.

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Research Summary of 'Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences'

Introduction

Psilocybin, the principal psychoactive compound in Psilocybe and related mushrooms, has a long history of use in certain cultural and religious contexts. Previous literature indicates that psilocybin has low physiological toxicity and low addictive potential, but it can occasion acute distressing psychological reactions and, more rarely, persisting adverse psychiatric outcomes. Emergency-department and poison-centre data show that medical presentations involving psilocybin are uncommon relative to many other drugs, yet case reports and anecdotal evidence document instances of short-term fear, risk-taking behaviour, and longer-term psychiatric problems following non‑clinical use. This study set out to characterise psychologically difficult or challenging experiences—commonly described as “bad trips”—following ingestion of psilocybin mushrooms. Carbonaro and colleagues conducted a large anonymous internet survey asking respondents to report in detail on a single worst challenging psilocybin session, including demographics, set and setting, dose and duration, acute and enduring negative and positive consequences, and use of strategies to alleviate the experience. The aim was to quantify the nature, acute harms, and longer-term outcomes of difficult psilocybin experiences occurring outside laboratory contexts and to examine factors associated with increased risk of harm.

References (17)

Papers cited by this study that are also in Blossom

Abnormal visual experiences in individuals with histories of hallucinogen use: A web-based questionnaire

Baggott, M. J., Coyle, J. R., Erowid, E. et al. · Drug and Alcohol Dependence (2011)

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Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin

Barrett, F. S., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2015)

Experienced drug users assess the relative harms and benefits of drugs: a web-based survey

Carhart-Harris, R. L., Nutt, D. J. · Journal of Psychoactive Drugs (2013)

Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance

Griffiths, R. R., Richards, W. A., Mccann, U. et al. · Journal of Psychopharmacology (2006)

Methods

Participants were recruited primarily through psychedelic-focused websites, email invitations, and online social networks between January and July 2013. Interested individuals were directed to an online SurveyMonkey questionnaire describing the study aims; participation was anonymous and voluntary. The Johns Hopkins Institutional Review Board approved the procedures. Inclusion required being at least 18 years old, English fluent, reporting a psilocybin mushroom dose that produced moderate to strong effects, endorsing having had a psychologically difficult/challenging experience with psilocybin (a “bad trip”), reporting that the selected experience occurred aged 18–70 outside a university or hospital study, and not having previously completed the survey. Respondents were instructed to answer about their single most psychologically difficult session. Cases attributed to co‑consumption of substances other than psilocybin, or whose open‑ended comments raised validity concerns, were excluded. The survey took roughly 45 minutes (median completion time 59 minutes) and included demographic items, lifetime hallucinogen use, session‑specific questions (estimated dose, set and setting, duration, intentions, presence of a guide, co‑use of other drugs), and three psychometric instruments commonly used in psychedelic research: the Hallucinogen Rating Scale (HRS), the 30‑item Mystical Experience Questionnaire (MEQ30), and selected subscales of the 5D‑ASC. Qualitative retrospective ratings solicited perceived difficulty, personal meaningfulness, spiritual significance, and change in well‑being attributed to the session. Optional open‑ended written comments were collected. Statistical analyses used descriptive statistics, Pearson correlations to explore associations among difficulty, duration, meaning, spiritual significance and well‑being, and multiple regression to examine the relative contributions of difficulty and duration on those outcomes. Correlations and binary logistic regression (odds ratios) evaluated relationships between dose, setting, concurrent drug use, age, past hallucinogen experience, and endorsement of putting self or others at risk. For enduring effects, analyses focused on participants whose session occurred at least 1 year prior to survey completion. The survey flow is reported: 5,850 started the survey; after exclusions and non‑completion, 1,993 provided usable data.

Results

Sample and session characteristics: Of the 1,993 respondents analysed, mean age at survey was 29.8 years and 78% were male; 89% identified as White and 51% had a college or graduate degree. Median lifetime uses of psilocybin prior to the chosen session fell in the 6–10 range, and 93% had used psilocybin more than twice. The median reported weight of dried mushrooms among those who knew weight was 4 g (n = 1,203); fresh mushroom median weights clustered at 21–30 g (n = 148). Sixty‑eight percent reported taking a moderately high or high dose for the session, and 36% were attempting a larger than usual dose. Session contexts varied: 25% were alone, 24% with one person, 39% with a few people, 9% in a small/medium group and 4% in a large gathering. Only 25% had any sitter or guide present, and 2.7% reported a trusted sober guide experienced in psychedelic support. Cannabis or alcohol use immediately before or during the session was reported by 53% and 19%, respectively. Median reported age at the chosen session was 23.3 years, and the session occurred on average 6.5 years before survey completion. Qualitative outcomes and psychometric scores: Participants rated the chosen session as highly challenging: 62% considered it among the top 10 most psychologically difficult episodes of their lives, 39% among the top five, and 11% as the single most challenging. Despite this, many reported positive longer‑term effects: 76% indicated the session led to increases in well‑being or life satisfaction and 84% reported benefiting from the experience. Thirty‑four percent and 31% rated the session among the top five personally meaningful and spiritually significant experiences of life, respectively. HRS subscale means (SEM) were reported (e.g. Intensity 2.62 (0.01), Perception 2.54 (0.02)). MEQ30 subscale means included Ineffability 69.24 (0.58) and a total score mean 50.26 (0.54); 20.5% fulfilled criteria for a “complete” mystical experience (scores ≥60% on each MEQ30 subscale). Relations among difficulty, duration, dose and setting: Duration of the difficult portion correlated positively with degree of difficulty (r = 0.30) but correlated negatively, or less strongly, with personal meaning, spiritual significance and enduring well‑being. Degree of difficulty correlated positively with personal meaning (r = 0.41) and, to a lesser extent, with spiritual significance and enduring well‑being. Multiple regression showed that higher difficulty predicted greater personal meaning, spiritual significance and enduring increases in well‑being, whereas longer duration predicted lower ratings on those outcomes. Risk and acute harms: Endorsement of putting self or others at risk of physical harm was reported by 10.7% of respondents; 2.6% reported behaving in a physically aggressive or violent manner and 2.7% sought medical help at a hospital or emergency department during the occasion. Endorsement of risk was positively correlated with estimated dose (HRS item) (r = 0.071, p < 0.01), degree of difficulty (r = 0.154, p < 0.001), and duration (r = 0.157, p < 0.001). In logistic regression, better physical comfort reduced odds of endorsing risk (odds ratio = 0.562, p < 0.001, 95% CI 0.416–0.760) and greater social support also reduced odds (odds ratio = 0.657, p = 0.004, 95% CI 0.493–0.875). Weight of dried mushrooms, age, past hallucinogen experience, emotional state before ingestion, and use of cannabis or other mood‑altering drugs were not significantly associated with endorsement of risk. Strategies to alleviate the experience: Most participants (91%) tried at least one strategy to stop the challenging experience. Common attempts included calming the mind (69%) and changing location (63%); 33–40% tried shifting body posture, changing music or the social environment, or asking for help. About 25% used cannabis and smaller proportions used alcohol (5%) or another drug (3%). Participants judged these strategies to be modestly effective overall: on average, strategies reported as having helped substantially were about 57% as frequent as strategies attempted. Suicidality and enduring problems: Independent review of open‑ended comments identified both increased suicidality (five cases) and decreased suicidality (six cases) attributed to the psilocybin session. Three respondents described suicide attempts or severe self‑harm behaviour linked temporally to their session. To assess enduring effects, analyses focused on participants whose session was ≥1 year prior (n = 1,339). In that subgroup, 24% reported experiencing one or more negative psychological symptoms lasting ≥1 week attributed to the session (fear 13%, anxiety 16%, depression 12%, paranoia 9%, other 12%); 10% reported symptoms lasting ≥12 months and 7.6% sought professional treatment for these symptoms. Of those who sought treatment after the session, 28 individuals (2.1% of the 1,339) had reported no prior symptoms or treatment. Prior treatment history strongly predicted post‑session treatment: 14.3% of those with prior treatment sought help after the session compared with 6% without prior treatment (p < 0.001). Review of open‑ended data identified three cases in which respondents attributed onset of enduring psychotic symptoms to the challenging psilocybin session; all three were White males aged 18–21 at the time of the session and reported no prior psychotic symptoms.

Discussion

Carbonaro and colleagues interpret their findings as evidence that psychologically difficult experiences after taking psilocybin mushrooms can lead to both acute harms (dangerous behaviour, need for emergency care) and enduring psychological problems, while also producing lasting benefits for many individuals. The survey of nearly 2,000 respondents who reported on their single worst challenging session found that although substantial proportions rated the session as highly meaningful or spiritually significant and reported increases in well‑being, nontrivial percentages reported acute risk‑taking (11% putting self or others at risk), emergency care (2.7%), aggressive behaviour (2.6%), and longer‑term treatment‑seeking (7.6% among those whose session occurred ≥1 year earlier). Three cases were reported as possibly linked to onset of enduring psychotic symptoms and three to attempted suicide. The authors place these results in the context of controlled laboratory research, where rates of acute and enduring problems are substantially lower. They note that only a small minority (2.1%) of survey respondents had session conditions approximating laboratory standards (conducive emotional state, physical comfort, social support and trusted sober guide). Reported risk factors in the survey included larger estimated dose, greater subjective difficulty and longer duration of the difficult experience, and lack of physical comfort and social support. From a therapeutic perspective, the authors suggest that interventions during a challenging experience might usefully prioritise reducing the duration of acute difficulty rather than attempting to blunt peak intensity, since duration was negatively associated with later meaning, spiritual significance and well‑being. Several limitations are acknowledged. As an anonymous internet survey, the data rely on self‑report and the veracity of respondents cannot be independently verified; non‑completion rates were high and the sample lacked demographic diversity (78% male, 89% White, 87% with some college). The recruitment strategy, focused on psychedelic‑oriented online media, produced a sample enriched for individuals who had experienced a challenging session and who may retain favourable interest in psychedelics, limiting generalisability and precluding population‑level prevalence estimates. The authors also note the survey did not assess hallucinogen persisting perception disorder specifically. Finally, differences between reported median doses (4 g dried, roughly estimated as ~25 mg psilocybin equivalent) and laboratory dosing contexts are discussed: although some psychometric indices (HRS Intensity) were comparable to controlled 20 mg/70 kg administration, MEQ30 scores and rates of “complete” mystical experience were lower in the survey sample than in lab studies, consistent with the survey focusing on the most challenging session rather than a randomly sampled session. Overall, the investigators conclude that psychologically difficult psilocybin experiences occurring outside controlled settings can involve acute danger and enduring harm for a minority, but also that many participants report lasting benefit. They emphasise that risks appear to be extremely low in laboratory studies that employ screening, preparation, and supportive monitoring during and after psilocybin administration, reinforcing the importance of set and setting when psilocybin is used clinically or recreationally.

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INTRODUCTION

Psilocybin, the principal psychoactive component of the Psilocybe and other genera of mushrooms, has likely been used for millennia within some cultures for religious or divinatory purposes. Of the US population aged 12 years or older, 8.7% (22.9 million people) reported lifetime use of psilocybin.(the last year data were available), over half (52%) of those who reported initiating use of a hallucinogen in the past year did so with psilocybin. Although psilocybin has very low physiological toxicity and is not associated with compulsive drug seeking, it sometimes produces acute and, more rarely, persisting adverse psychological reactions. Case reports document adverse effects of psilocybin in non-research settings, including short-term distressing psychological symptoms such as fear, individuals putting themselves at risk for physical harm, seeking medical help, and enduring negative psychological or psychiatric problems. However, the perceived risk of psilocybin-related harm was found to be very low when evaluated by drug expertsand by experienced drug users, and psilocybin was ranked as moderately beneficial by experienced drug users. Data-reporting systems from emergency rooms and poison centers also confirm that psilocybin is associated with seeking medical treatment. However, the incidence of psilocybin toxicity is extremely low relative to other drugs used non-medically. For instance, in 2011, emergency room mentions of problems with psilocybin alone (83 mentions) were only a very small fraction of mentions for heroin alone (10,309 mentions, 0.81%), cocaine alone (9828, 0.84%), and marijuana alone (9711, 0.85%). The present study was undertaken to characterize challenging experiences occasioned by psilocybin and the consequences of such experiences. An internet survey was conducted of a large international sample of individuals who reported having had a difficult or challenging experience with psilocybin. Detailed questions were asked about an individual's single worst "bad trip." Questions addressed demographics, the set and setting conditions in which psilocybin was ingested, as well as any negative and positive acute and enduring psychological and emotional consequences of the challenging psilocybin experience.

PARTICIPANT RECRUITMENT

Participants were recruited primarily via internet advertisements and email invitation. An internet link to the survey was posted on websites that attract individuals interested in hallucinogens (e.g.. Information about the survey was also shared by email with individuals knowledgeable about psychedelic drugs, and information about the survey spread through online social networks. Individuals were recruited who endorsed having had a difficult or challenging experience after ingesting psilocybin mushrooms (e.g. "Have you had a difficult or challenging experience (i.e., a "bad trip") with psilocybin mushrooms? If so, please take the Johns Hopkins online survey on psilocybin and bad trips"). The link directed participants to a webpage that described the aims of the study and provided basic information about study completion. Participants were informed that study participation was anonymous, they could choose to stop answering questions at any time, and if they did not complete the survey their specific responses would not be used. The Institutional Review Board of the Johns Hopkins University School of Medicine approved all study procedures.

SURVEY ADMINISTRATION

The survey was designed to take approximately 45 minutes to complete (not including an optional open-ended written response), and participants were required to complete the survey in one sitting. The survey was administered using SurveyMonkey (www.surveymonkey.com), an online survey and data-collection software tool with security and privacy features that make it suitable for clinical research.

INCLUSION CRITERIA

Participants were required to fulfill six inclusion criteria: (1) At least 18 years old; (2) Read, write, and speak English fluently; (3) Have taken a dose of psilocybin mushrooms that produced moderate to strong psychoactive effects; (4) After taking psilocybin mushrooms, "have you ever had a psychologically difficult or challenging experience (i.e., a bad trip)that is, have you experienced significant fear, anxiety, or distress or anything else that you found psychologically difficult?"; (5) The experience referred to above (#4) occurred when between 18 and 70 years old and did not occur in the context of a university or hospital study; (6) Have not completed this survey previously. Participants who met the inclusion criteria were directed to the remaining questions in the survey. In completing the survey, participants were instructed to complete the survey items in reference to their single most psychologically difficult or challenging session or experience (worst "bad trip"). Individuals who did not meet the inclusion criteria were linked to an alternate, shorter version of the survey and their data were not used in the analyses. It was reasoned that this approach would discourage such individuals from attempting to take the survey again and providing different answers because it would appear to them that they had completed the survey. Participants were excluded from analysis if the challenging experience was attributed to the co-consumption of a substance other than psilocybin or if the open-ended written comments raised concern about validity of their other responses.

MEASURES

Demographics-Participants provided basic demographic information as described in the results section. Lifetime hallucinogen use-Participants reported the total number of different occasions on which they had ingested any of the following hallucinogens: psilocybin mushrooms, LSD, morning glory seeds, mescaline, peyote cactus, San Pedro cactus, DMT, or ayahuasca. They also provided the total number of occasions they used only psilocybin mushrooms. Both questions were answered on an 8-point categorical scale; and more than 300 times). Participants also reported how old they were when they first and last used psilocybin mushrooms. Questions about the session experience-After participants had chosen their session (i.e. their worst "bad trip"), they were asked questions about the estimated dose of psilocybin consumed, the set and setting conditions in which the session occurred, the duration of the difficult experience, strategies attempted and that helped to stop the experience, and acute negative consequences of the experience. As with laboratory studies of psilocybin, the phenomenology of the psilocybin experience was assessed using three questionnaires: Hallucinogen Rating Scale (HRS); Mystical Experience Questionnaire -30 item version (MEQ30) which is part of the States of Consciousness Questionnaire; and selected subscales from the 5D-ASC. Data analyzed for this report were the six subscales of the HRS (expressed as raw scores) and the total and four subscales of the MEQ30 (expressed as percentages of maximum possible scores). A participant was designated as having had a "complete" mystical experience if scores on each of the four subscales of the MEQ30 were 60% or higher. The results from other questions and subscales will be reported elsewhere. Qualitative ratings of the psilocybin experience-Participants were instructed to answer four questions according to "how you feel now about your chosen psilocybin session" and to "retrospectively evaluate your experiences during your psilocybin session in the context of your full life experience." The questions were as follows: (1) How psychologically difficult or challenging was the experience? (2) How personally meaningful was the experience? (3) Indicate the degree to which the experience was spiritually significant to you; and (4) Do you believe that the experience and your contemplation of that experience have led to a change in your current sense of personal well-being or life satisfaction? The response options for all four questions are shown in Figure. Negative psychological or emotional experiences before and after the experience-Participants answered questions about the occurrence, duration, and severity of the negative psychological or emotional experiences of fear, paranoia, anxiety, depression, and "other" that they may have experienced at any time before the challenging experience occurred. Participants also answered a similar set of questions about these same types of negative psychological experiences if they occurred after the challenging experience and were attributed to the challenging psilocybin experience. Open-ended written comments-Participants were offered an optional opportunity to provide a written description of their psilocybin experience.

STATISTICAL ANALYSIS

Descriptive statistics (percentages, mean, median, range, and standard error of the mean) were used to characterize the responses to questions and the subscale scores of the questionnaires. Pearson correlations were used to analyze the associations among participant ratings of the degree of difficulty of the challenging experience, the duration of the challenging experience, personal meaning, spiritual significance, and enduring change in well-being. Multiple regression analysis was used to further explore the relative roles of duration of difficult experience and the degree of difficulty of the experience on the ratings of personal meaning, spiritual significance, and enduring change in well-being. Pearson correlations were also used to analyze the association of difficulty and duration of difficulty of the psilocybin experience to dose (weight of dried mushrooms consumed and HRS item referring to approximate dose), setting conditions, age at time of the psilocybin experience, past hallucinogen experience, use of cannabis and use of another mood-altering drug (including cannabis, but excluding nicotine) immediately before or during the session, and endorsement of putting self or others at risk for physical harm. Binary logistic regression (odds ratios) were used to analyze the associations of setting conditions, use of cannabis and the use of another mood-altering drug (including cannabis, but excluding nicotine) immediately before or during the session to endorsement of putting self or others at risk for physical harm. The percentage of participants reporting negative psychological and emotional symptoms as well as the percentage seeking treatment for such symptoms before and after the chosen psilocybin session was assessed. Rates of endorsing these experiences were analyzed by z-tests to compare independent proportions.

SURVEY COMPLETION

During recruitment (January-July, 2013), 5850 individuals began the survey. Of these, 1074 were excluded because they did not meet the inclusion criteria; 92 were excluded because participants reported that the experience was attributed to the co-consumption of a substance other than psilocybin or because the open-ended written comments raised concern about validity of their other responses. Some 2691 were excluded because they did not complete the survey, with 91% of these failing to complete half of the survey questions. Thus 1993 individuals provided useable data. Of these, 70% found the survey link on a website, 7% received the survey link as a part of an email distribution list, and 13% heard of the survey by word of mouth. The median time to complete the survey was 59 minutes. A written response in the open-ended comment section was provided by 83% of participants.

PARTICIPANT CHARACTERISTICS

Tablepresents participants' reported characteristics. Participants were, on average 29.8 years of age. The majority were male (78%), White (89%), had a college or graduate degree (51%). Most participants (93%) had used psilocybin more than two times in their life (median = 6-10 times) and had used hallucinogens more than 10 times in their life (59%) (median = 11-20 times). At the time of the survey, daily use of cannabis, tobacco, and alcohol were reported by 38%, 27%, and 11% of the group, respectively. Participants were, on average 23.3 years of age at the time of their chosen session (Table), which occurred on average 6.5 years before completing the survey. Median number of uses of psilocybin before their chosen session was 2-5 times. Of the respondents, 16% had not used psilocybin at all before their chosen session and for 10% of the total sample, the chosen session was the first time they had used any hallucinogen.

THE CHALLENGING PSILOCYBIN SESSION

Some 84% and 16% of participants, respectively, reported taking dried and fresh mushrooms. Of those who reported knowing the weight of the mushrooms consumed, the median reported weight of dried psilocybin mushrooms was 4 g (n = 1203 respondents), and the median weight of fresh mushrooms was 21-30 g (n = 148). Of the participants, 68% endorsed having taken a moderately high or high dose of psilocybin; 36% reported that they were attempting to take a larger than usual dose of psilocybin for the session. During the session, participants reported being alone (25%) or in the company of one person (24%), with a few people (39%), in a small to medium size group (9%), or a large gathering (4%). The majority of participants indicated that their emotional state before taking psilocybin (76%), the physical comfort and safety of the surroundings (76%), and the social support and trust for others during the session (65%) were conducive to having a positive experience. Only 25% had a "guide" or "sitter" present during the session and only 2.7% had a trusted and sober guide present who was experienced in supporting psychedelic sessions. Some 53% and 19%, respectively, reported using cannabis or alcohol immediately before or during their chosen challenging psilocybin session. Fifty-nine percent reported having had a serious intention (psychological or spiritual exploration) for their session; 73% covered or closed their eyes for some length of time during the session (median = 10-30 minutes). Figureshows the distribution of durations of the psychologically difficult portion of the experience; 31% percent reported the duration to be 1 hour or less, with 25% and 40% reporting the duration to be 1 to 2 hours and 2 hours or longer, respectively.

QUALITATIVE RATINGS OF THE PSILOCYBIN EXPERIENCE

As shown in Figure, the majority of participants (62%) considered the experience to be among the top 10 most psychologically difficult or challenging experiences of their lives (Figure, sum of among top 10, among top five and single most), with 39% rating it as among the top five including single most and 11% rating to be the single most. Despite this psychological challenge, 34% and 31% rated this same session to be among the top five including single most personally meaningful and spiritually significant, respectively (Figure), experiences of their lives, with 6.2% and 8.6%, respectively, rating it to be the single most personally meaningful and spiritually significant of their lives. Although most of the participants (76%) reported that experiences during the psilocybin session led to increases in current well-being and life satisfaction, 8% reported that the chosen challenging experience resulted in a decrease in their sense of well-being or life satisfaction (slightly or greater) (Figure). A substantial majority of participants (84%) rated that they benefited from the challenging portions of their sessions. Almost half (46%) endorsed that they would want to repeat their chosen session and all that had happened in it, including the difficult or challenging portions of the session. Tableshows correlations among the four measures of qualitative effects described above and the duration of difficult experience. The duration correlated positively (r = 0.30) with the overall degree of difficulty of the experience, but negatively or less robustly with the meaningfulness, spiritual significance, or enduring changes in well-being. Interestingly, the degree of difficulty of the experience correlated positively with the degree of personal meaning (r = 0.41), with less robust but significant correlations with spiritual significance and enduring well-being. Finally, spiritual significance correlated robustly with personal meaning, and enduring change in well-being correlated robustly with both personal meaning and spiritual significance. Tableshows the results of multiple regression analysis regressing participant ratings of personal meaning, spiritual significance, and enduring change in well-being on degree of difficulty and the duration of the psychologically challenging experience after taking psilocybin. These data show a consistent pattern of effects, with personal meaning, spiritual significance, and increases in well-being all positively and significantly related to difficulty of experience. In contrast, all three of these outcome measures are significantly negatively related to the duration of the difficulty of the experience.

DIFFICULTY AND DURATION OF DIFFICULTY OF THE PSILOCYBIN EXPERIENCE: RELATIONSHIP OF DOSE, SETTING CONDITIONS, USE OF ANOTHER MOOD-ALTERING DRUG, AGE, AND PAST HALLUCINOGEN EXPERIENCE

As shown in Table, dose assessed by weight of dried mushrooms consumed, and estimated dose (from a question on the HRS), both significantly positively correlated with degree of difficulty and duration of difficult experience. Emotional state before ingesting psilocybin mushrooms, physical comfort of setting, and social support present during the session were significantly negatively correlated with degree of difficulty and duration of difficult experience. Having a guide present was significantly negatively correlated with duration of difficult experience, but not with degree of difficulty. The use of cannabis and/or another mood-altering drug (excluding nicotine) immediately before or during the session, age at the time of the experience, and past hallucinogen experience were significantly negatively correlated with difficulty of experience, but not with duration of difficult experience. Endorsement of putting self or others at risk of physical harm: Relationship of dose, setting conditions, difficulty and duration of difficulty of experience, use of another moodaltering drug, age, and past hallucinogen experience Endorsement of putting self or others at risk for physical harm was positively correlated with estimated dose (from a question on the HRS) (r = 0.071, p < 0.01), degree of difficulty of experience (r = 0.154, p < 0.001), and duration of difficult experience (r = 0.157, p < 0.001). Furthermore, endorsement of putting self or others at risk for physical harm was less likely in those who also endorsed that the physical comfort of the setting (odds ratio = 0.562, p < 0.001, 95% CI [0.416, 0.760]) and the social support during the session (odds ratio = 0.657, p = 0.004, 95% CI [0.493-0.875]). Endorsement of risk of physical harm was not significantly associated with the weight of dried mushrooms, age, past hallucinogen experience, emotional state before ingestion, use of cannabis, or use of a mood-altering drug (excluding nicotine).

HALLUCINOGEN RATING SCALE AND MYSTICAL EXPERIENCE QUESTIONNAIRE 30

The mean (SEM) for all 1993 participants for the six subscales of the HRS were: Intensity, 2.62 (0.01); Somaesthesia, 1.64 (0.02), Affect, 1.89 (0.01), Perception, 2.54 (0.02), Cognition, 2.30 (0.02), Volition, 2.02 (0.02). The means (SEM) for the subscales and total scores on the MEQ30 were: Mystical 45.35 (0.65), Positive Mood 50.74 (0.61), Transcendence of Time and Space 52.56 (0.53), Ineffability 69.24 (0.58), and Total Score 50.26 (0.54). The percentage of participants who fulfilled criteria for having had a "complete" mystical experience on the MEQ30 was 20.5%.

STRATEGIES FOR ALLEVIATING THE CHALLENGING EXPERIENCE

The majority of participants reported that the social support and trust for others physically present (65%), physical comfort and safety of surroundings (75%), and emotional state (76%) before taking psilocybin was conducive to having a positive experience. Most participants (91%) reported trying to stop the challenging experience. As shown with the gray bars in Figure, participants tried a wide range of different strategies to attempt to stop the experience. Most participants reported trying to calm their mind (69%) or change location (63%). Some 33-40% tried to stop the experience by shifting their body, changing the music or social environment, or asking for help from a friend. About 25% smoked cannabis or changed their environment in other ways, with a minority reporting drinking alcohol (5%) or taking another drug (3%). The striped bars in Figureshow the percentage of participants who indicated that the specific strategy helped to substantially stop the challenging experience. Comparison of the gray and striped bars indicates that all strategies were only modestly effective (i.e. on average, striped bars are 57% as long as gray bars).

RISKS AND PROBLEMS DURING THE EXPERIENCE

Of the 1993 respondents, 10.7% reported putting themselves or others at risk of physical harm, 2.6% reported behaving in a physically aggressive or violent manner towards themselves or others, and 2.7% reported getting help at a hospital or emergency department during the chosen occasion.

SUICIDALITY

Two research staff members independently reviewed all open-ended textual responses to identify instances in which changes in suicidal thoughts or behavior were attributed to acute or enduring effects of the challenging experience. This review provided evidence of both increased suicidality (five cases) and decreased suicidality (six cases). More specifically, one individual, who had pre-existing anxiety, depression and suicidal planning, reported purposely attempting suicide by overdosing with benzodiazepines and, subsequently, awakening in an intensive care medical unit. Another respondent reported unsuccessfully trying to shoot himself in the head. A third respondent reported that pre-existing serious depression was exacerbated by the psilocybin experience and later resulted in a suicide attempt. Two other individuals reported salient suicidal thoughts during their psilocybin experience. In contrast, six respondents reported that pre-existing suicidal thoughts (including depression in five cases) fully remitted after their psilocybin experience.

ENDURING NEGATIVE PSYCHOLOGICAL AND EMOTIONAL EXPERIENCES

To meaningfully assess enduring effects, data from participants whose session occurred at least 1 year before completing the survey were analyzed (n = 1339). Of the participants, 19.3% endorsed that they had sought treatment for at least one of five negative psychological symptoms: fear (F), anxiety (A), depression (D), paranoia (P), and "other" (O) before their chosen session and which they did not attribute to having taken psilocybin or some other hallucinogen. After the challenging session, 24% of these 1339 participants reported experiencing one or more of these symptoms that lasted 1 week or longer and that the participant attributed to the chosen psilocybin session (F = 13%, A = 16%, D = 12%, P = 9%, O = 12%). The majority of those reporting symptoms (65%) reported more than one symptom. Some 10% of the 1339 participants reported psychological symptom(s) lasting ⩾12 months after the challenging session, and 7.6% sought professional treatment for the symptom(s) after the chosen session (F = 3.4%, A = 4.6%, D = 4.8%, P = 1.8%, O = 3%). Of those who sought professional treatment after the session, 28 (2.1% of the 1339) reported no previous symptoms or treatment. Those that sought treatment before the challenging experience were significantly more likely to seek treatment afterwards (14.3% with vs. 6% without prior treatment histories; p < 0.001; z = 4.37). All of these findings based on the subset of 1339 participants were similar to those that occurred in the total participant sample. Inspection of data and review of open-ended comments documented three cases in which the challenging experience with psilocybin was reported to be associated with the onset of enduring and impairing psychotic symptoms. All three were White males who were 18 to 21 years old at the time of the experience, which had occurred 3 to 20 years before the survey. None of the three reported having psychotic symptoms before the experience. In their openended written comments about their symptoms the first individual described auditory hallucinations (hearing voices) and paranoia. The second described severe depersonalization, very disturbing visual hallucinations, and extreme confusion. This individual subsequently started taking unspecified antipsychotic drugs and later received a diagnosis of schizophrenia. The third individual reported paranoia, agoraphobia, severe social withdrawal, mental confusion, and also reported that he had received diagnoses of bipolar disorder and post-traumatic stress disorder.

DISCUSSION

This survey documents that psychologically difficult experiences after taking psilocybin mushrooms can be associated with acute adverse effects and enduring psychological problems as well as enduring benefits. Almost 2000 participants, who were on average 30 years old when they took the survey, met inclusion criteria and completed the survey on the basis of their single most psychologically difficult or challenging experience (worst "bad trip") after taking psilocybin mushrooms. Of these respondents, 39% rated the experience as among the top five (including single most) most challenging experiences of their lifetime, 11% reported putting themselves or others at risk of physical harm, 2.6% reported behaving in a physically aggressive or violent manner, and 2.7% reported getting medical help during the occasion. Of those whose session occurred at least 1 year earlier, 7.6% reported that they sought treatment for one or more psychological symptom they attributed to the challenging psilocybin experience. Three cases appeared associated with onset of enduring and impairing psychotic symptoms and three cases with attempted suicide. Despite these difficulties, it is notable that 84% of respondents reported having benefited from the experience, with 76% reporting increased well-being or life satisfaction attributed to the experience. Some 60% of respondents considered their experience to be among the top 10 most psychologically personally meaningful experiences of their lives, while 34% and 31% reported the experience in the top five most personally meaningful and spiritually significant, respectively. The distributions of the degree of difficulty and the degree of personal meaningfulness (Figure, top row) were strikingly similar. Furthermore, correlation and multiple regression analyses showed that the degree of difficulty of the experience was positively and significantly related to the attribution of enduring personal meaning, spiritual significance, and increased life satisfaction. These counterintuitive findings are consistent with clinical observations of psychedelic psychotherapists who have reported that, during a psychedelic session, the resolution of psychologically challenging experiences may result in attribution of meaning, spiritual significance, and increased life satisfaction, sometimes described as catharsis. Challenging experiences are not necessary for positive therapeutic outcomes. Whether some challenging experiences can have facilitative or detrimental effects on therapeutic outcome has not been scientifically explored. The duration of the challenging experience was positively related to the degree of difficulty of the experience and negatively related to personal meaning, spiritual significance, and enduring increased well-being. From the perspective of maximizing meaning, spiritual significance, and enduring well-being, this finding suggests that therapeutic interventions during a challenging experience should be preferentially aimed at reducing the duration rather than the peak difficulty of the challenging experience. Dose assessed by weight of dried mushrooms consumed and estimated dose (from a question on the HRS) positively correlated with degree of difficulty (r = 0.11 and 0.18). This finding is consistent with laboratory studies showing that the frequency of challenging experiences increase at higher psilocybin doses. In the present study, respondents who reported having been treated for psychological symptoms before their challenging session were more than twice as likely than those with no treatment history to subsequently seek treatment for psychological symptoms that they attributed to the session (14.3% vs. 6%). This finding suggests alternative interpretations. First, those with treatment histories may be less reluctant to seek out professional treatment or may have better access to treatment services. Second, it is possible that those with treatment histories are more vulnerable to enduring adverse effects of psilocybin. The present survey documents nontrivial rates of both acute problems (e.g. 11% putting themselves or others at risk for physical harm during the session) and enduring problems (e.g. 7.6% seeking professional help for negative psychological symptoms lasting >1 year). These rates are likely much higher than the expected population rates of problems with a single exposure to psilocybin because survey participants completed the survey based on their worst "bad trip", with participants reporting a median of 6-10 prior psilocybin experiences. More relevant to understanding associations between psilocybin use and treatment-seeking for psychological problems, a population survey has indicated protective effects of lifetime psilocybin exposure and psychological distress and suicidality. The rates and severity of both acute and enduring problems shown in the survey are notably higher than those we and others have observed in laboratory research studies involving administration of high doses of psilocybin to carefully screened, well-prepared, and closely monitored volunteers (e.g.. At Johns Hopkins, we adhere to our published guidelines for safe administration of classic hallucinogens. Since initiating psilocybin research in 2000, we have administered psilocybin doses of 20 mg/70 kg or higher to about 250 volunteers in more than 380 sessions (as of May 2016). Although no volunteer has been physically harmed during sessions, there were three instances (0.9%) in which a participant's disorientation during a session might have put them or staff members at risk if appropriate supervision had not been provided: (1) a volunteer decided to stand up and engage in expressive movements; (2) a volunteer moved from the couch to the floor while vigorously moving legs and arms in an erratic fashion; and (3) a volunteer became confused and disoriented when in the restroom. In response to these instances, we changed our session management procedures to strongly emphasize to both volunteers and session staff the instruction and intention that volunteers remain on the couch throughout the session when not engaged in a specific task or using the restroom. When volunteers need to go to the restroom, they walk to the restroom with the staff member at their side. When in the restroom, the door remains unlocked and slightly ajar with a staff member of the same gender remaining immediately outside of the door and in intermittent (about 1 minute intervals) verbal contact with the volunteer. With regard to post-session negative symptoms, we have had three cases (0.9%) in which volunteers reported physical or psychological symptoms within several days to a week after a psilocybin session. In the first case, 1 week after a session the volunteer reported feeling anxious after experiencing physical symptoms consistent with a heart attack. An evaluation at an emergency department found no abnormal signs. The volunteer was offered a further medical consultation that the volunteer declined as unnecessary. In the second case, the volunteer reported a range of symptoms that were ultimately diagnosed as hyperthyroidism. In the third case, the volunteer reported that the psilocybin session experience was dominated by negative emotions such as sadness and fear. After the session, the volunteer reported periods of intermittent depressed mood. The volunteer declined our offer to meet with a psychologist, but, instead, sought out a spiritual counselor. At a 5-month follow-up visit, the volunteer reported that the symptoms had resolved. This low rate of enduring psychological symptoms in laboratory studies is also consistent with a summary of such effects from 110 psilocybin research participants from another laboratory. In that report, seven participants endorsed negative changes in psychological well-being, but only one participant (0.9%) reported a level of distress sufficient for him to contact the researchers. Those symptoms resolved after a few sessions with an experienced psychotherapist. Many factors likely contribute to the higher rates of acute and enduring problems reported in the survey compared with the controlled laboratory studies. In addition to the probable absence of psychological screening and unknown psychological preparation for psilocybin ingestion, only 2.1% of survey respondents reported taking psilocybin under conditions that are usually achieved in laboratory settings (i.e. a conducive emotional state before administration, physical comfort and safety, social support and trust of others, and the presence of a sober, trusted guide who is experienced in supporting psychedelic experiences). Some 36% of survey respondents indicated they took a larger than usual dose of psilocybin and 53% reported using cannabis before or during the session. Cannabis use before or during the session was slightly negatively correlated with difficulty of experience, but had no effect on the duration of the difficult experience or the likelihood of putting themselves or others at risk of physical harm. Twenty-six percent of participants who tried to stop the challenging aspect of the psilocybin session reported using cannabis to try to do so. Of those, 50% reported that it helped substantially. It is noteworthy, however, that in optional open-ended textual responses at the end of the survey several volunteers spontaneously commented that the use of cannabis significantly exacerbated their challenging experience. Several limitations of the current survey should be noted. As an anonymous internet survey, we cannot know if respondents were truthful in completing the survey. Furthermore, the rate of non-completion was high. However, respondents were not paid for their participation and completing the survey took about an hour on average. Furthermore, 83% of respondents took the time to write open-ended comments about their challenging experience at the end of the survey, and many spontaneously expressed their interest in and gratitude for having had the opportunity to complete the survey. Another limitation is that respondent population was not diverse: 78% were male, 89% were White, and 87% had at least some college education. On the other hand, this lack of diversity may accurately reflect the population of psychedelic users. Two additional factors limit the generalizability of the findings. First, only people who endorsed having had a challenging experience after psilocybin completed the survey. Therefore it is not possible to estimate the prevalence of such experiences after a single psilocybin exposure or after multiple psilocybin exposures. Second, because recruiting for the survey was primarily conducted via psychedelic-focused internet media, the participant sample was likely biased toward individuals with current favorable interest in psychedelic drugs. As such, the survey may have underestimated the severity of negative effects because individuals who had severe negative effects would be less likely to have heard about the survey. The current study did not address hallucinogen persisting perception disorder, which is an uncommon DSM-5 psychiatric disorder characterized by clinically significant distress in response to the re-experiencing of hallucinogen-like perceptual symptoms after a period of normalcy following a psychedelic drug experience. The median reported dose of dried psilocybin mushrooms taken in the survey was 4 g, with most respondents (84%) reporting having taken dried mushrooms rather than fresh. Although there is wide variation in psilocybin and psilocin content both within and across different species of psilocybin-containing mushrooms, we estimate that 4 g of typically available dried mushrooms (P. cubensis) delivers the approximate psychoactive equivalent to 25 mg of psilocybin. A 25 mg dose of psilocybin is in the moderate to high range of doses we have administered in our previous laboratory studies. In the survey, the mean score on the HRS Intensity subscale was 2.62 (out of a maximum possible of 4.25), which is quite similar to the mean score of 2.64 at 20 mg/70 kg in a laboratory study. The mean total score from the MEQ30 in the survey was 50.3, with 21% of participants fulfilling criteria for a "complete" mystical experience. Comparable values in a laboratory study of 20 mg/70 kg were considerably higher (mean total score 70.0 and 61% complete mystical experience), which is consistent with the fact that survey participants were reporting on the most challenging psilocybin experience of their life. In conclusion, this survey of almost 2000 people showed that psychologically difficult experiences after taking psilocybin mushrooms can include acute psychological distress, dangerous behavior, and enduring psychological problems. Factors contributing to the increased likelihood of putting self or others at risk of physical harm included the magnitude of the estimated psilocybin dose, the degree of difficulty of the experience, the duration of the difficult experience, and the absence of physical comfort and social support during the experience. Epidemiological data indicate that rates of adverse effects after psilocybin are very low relative to adverse effects after other psychoactive drugs. However, the findings from this survey affirm concerns about taking psilocybin in uncontrolled environments. With increasing research exploring possible therapeutic uses of psilocybin, it is important to note that risks of dangerous behavior or enduring psychological problems are extremely low in laboratory studies of psilocybin with carefully screened, well-prepared participants who are supported during and after psilocybin administration. Percentage of participants endorsing specific strategies that they reported using to attempt to stop the challenging experience (gray bars) (N = 1993) and that they reported having helped substantially to stop the challenging experience (striped bars) (N = 1993). Of the participants 9.1% reported doing nothing to try to stop the experience. The bars sum to more than 100% because most participants (52%) endorsed trying more than one strategy. Pearson correlations (r) examining the relationship of dose, setting conditions, use of another mood-altering drug, age, and past hallucinogen experience to difficulty and duration of difficulty of the psilocybin session. 4 Estimated dose was rated on a scale from 1 (low) to 4 (high) in the Hallucinogen Rating Scale (HRS). 5 Use of another mood-altering drug (excluding nicotine) immediately before or during the session.

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