OPEN Foundation

M. Johnson

An online survey of tobacco smoking cessation associated with naturalistic psychedelic use

Data suggest psychedelics such as psilocybin and lysergic acid diethylamide (LSD) may hold therapeutic potential in the treatment of addictions, including tobacco dependence. This retrospective cross-sectional anonymous online survey characterized 358 individuals (52 females) who reported having quit or reduced smoking after ingesting a psychedelic in a non-laboratory setting ⩾1 year ago. On average, participants smoked 14 cigarettes/day for 8 years, and had five previous quit attempts before their psychedelic experience. Of the 358 participants, 38% reported continuous smoking cessation after psychedelic use (quitters). Among quitters, 74% reported >2 years’ abstinence. Of the 358 participants, 28% reported a persisting reduction in smoking (reducers), from a mode of 300 cigarettes/month before, to a mode of 1 cigarette/month after the experience. Among reducers, 62% reported >2 years of reduced smoking. Finally, 34% of the 358 participants (relapsers) reported a temporary smoking reduction before returning to baseline smoking levels, with a mode time range to relapse of 3–6 months. Relapsers rated their psychedelic experience significantly lower in personal meaning and spiritual significance than both other groups. Participants across all groups reported less severe affective withdrawal symptoms (e.g. depression, craving) after psychedelic use compared with previous quit attempts, suggesting a potential mechanism of action for psychedelic-associated smoking cessation/reduction. Changes in life priorities/values were endorsed as the most important psychological factor associated with smoking cessation/reduction. Results suggest psychedelics may hold promise in treating tobacco addiction as potentially mediated by spiritual experience, changed priorities/values, and improved emotional regulation.

Johnson, M. W., Garcia-Romeu, A., Johnson, P. S., & Griffiths, R. R. (2017). An online survey of tobacco smoking cessation associated with naturalistic psychedelic use. Journal of Psychopharmacology, 0269881116684335. 10.1177/0269881116684335
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Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial

Abstract

Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes.

Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., … & Klinedinst, M. A. (2016). Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of Psychopharmacology, 30(12), 1181-1197. 10.1177/0269881116675513
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The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms

Abstract

Acute adverse psychological reactions to classic hallucinogens (“bad trips” or “challenging experiences”), while usually benign with proper screening, preparation, and support in controlled settings, remain a safety concern in uncontrolled settings (such as illicit use contexts). Anecdotal and case reports suggest potential adverse acute symptoms including affective (panic, depressed mood), cognitive (confusion, feelings of losing sanity), and somatic (nausea, heart palpitation) symptoms. Responses to items from several hallucinogen-sensitive questionnaires (Hallucinogen Rating Scale, the States of Consciousness Questionnaire, and the Five-Dimensional Altered States of Consciousness questionnaire) in an Internet survey of challenging experiences with the classic hallucinogen psilocybin were used to construct and validate a Challenging Experience Questionnaire. The stand-alone Challenging Experience Questionnaire was then validated in a separate sample. Seven Challenging Experience Questionnaire factors (grief, fear, death, insanity, isolation, physical distress, and paranoia) provide a phenomenological profile of challenging aspects of experiences with psilocybin. Factor scores were associated with difficulty, meaningfulness, spiritual significance, and change in well-being attributed to the challenging experiences. The factor structure did not differ based on gender or prior struggle with anxiety or depression. The Challenging Experience Questionnaire provides a basis for future investigation of predictors and outcomes of challenging experiences with classic hallucinogens.

Barrett, F. S., Bradstreet, M. P., Leoutsakos, J. M. S., Johnson, M. W., & Griffiths, R. R. (2016). The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms. Journal of Psychopharmacology, 0269881116678781.
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Psychedelics as Medicines: An emerging new paradigm

Abstract

Scientific interest in serotonergic psychedelics (e.g., psilocybin and LSD; 5-HT2Areceptor agonists) has dramatically increased within the last decade. Clinical studies administering psychedelics with psychotherapy have shown preliminary evidence of robust efficacy in treating anxiety and depression, as well as addiction to tobacco and alcohol. Moreover, recent research has suggested that these compounds have potential efficacy against inflammatory diseases through novel mechanisms, with potential advantages over existing anti-inflammatory agents. We propose that psychedelics exert therapeutic effects for psychiatric disorders by acutely destabilizing local brain network hubs and global network connectivity via amplification of neuronal avalanches, providing the occasion for brain network “resetting” after acute effects have resolved. Anti-inflammatory effects may hold promise for efficacy in treatment of inflammation-related non-psychiatric as well as potentially for psychiatric disorders. Serotonergic psychedelics operate through unique mechanisms that show promising effects for a variety of intractable, debilitating, and lethal disorders, and should be rigorously researched.

Nichols, D. E., Johnson, M. W., & Nichols, C. D. (2016). Psychedelics as Medicines: An emerging new paradigm. Clinical Pharmacology & Therapeutics. 10.1002/cpt.557
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Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences

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.

Carbonaro, T. M., Bradstreet, M. P., Barrett, F. S., MacLean, K. A., Jesse, R., Johnson, M. W., & Griffiths, R. R. (2016). Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. Journal of Psychopharmacology, 0269881116662634.
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Long-term follow up of psilocybin-assisted smoking cessation

Abstract

Background: A recent open-label pilot study (N = 15) found that two to three moderate to high doses (20 and 30 mg/70 kg) of the serotonin 2A receptor agonist, psilocybin, in combination with cognitive behavioral therapy (CBT) for smoking cessation, resulted in substantially higher 6-month smoking abstinence rates than are typically observed with other medications or CBT alone. Objectives: To assess long-term effects of a psilocybin-facilitated smoking cessation program at ≥12 months after psilocybin administration.
Methods: The present report describes biologically verified smoking abstinence outcomes of the previous pilot study at ≥12 months, and related data on subjective effects of psilocybin.
Results: All 15 participants completed a 12-month follow-up, and 12 (80%) returned for a long-term (≥16 months) follow-up, with a mean interval of 30 months (range = 16–57 months) between target-quit date (i.e., first psilocybin session) and long-term follow-up. At 12-month follow-up, 10 participants (67%) were confirmed as smoking abstinent. At long-term follow-up, nine participants (60%) were confirmed as smoking abstinent. At 12-month follow-up 13 participants (86.7%) rated their psilocybin experiences among the five most personally meaningful and spiritually significant experiences of their lives.
Conclusion: These results suggest that in the context of a structured treatment program, psilocybin holds considerable promise in promoting long-term smoking abstinence. The present study adds to recent and historical evidence suggesting high success rates when using classic psychedelics in the treatment of addiction. Further research investigating psilocybin-facilitated treatment of substance use disorders is warranted.

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Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans.

Abstract

Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the Salvia divinorum plant, which has been used for hallucinogenic effects. Previous research on salvinorin A pharmacokinetics likely underestimated plasma levels typically resulting from the doses administered due to inefficient vaporization and not collecting samples during peak drug effects. Six healthy adults inhaled a single high dose of vaporized salvinorin A (n = 4, 21 mcg/kg; n = 2, 18 mcg/kg). Participant- and monitor-rated effects were assessed every 2 min for 60 min post-inhalation. Blood samples were collected at 13 time points up to 90 min post-inhalation. Drug levels peaked at 2 min and then rapidly decreased. Drug levels were significantly, positively correlated with participant and monitor drug effect ratings. Significant elevations in prolactin were observed beginning 5 min post-inhalation and peaking at 15 min post-inhalation. Cortisol showed inconsistent increases across participants. Hormonal responses were not well correlated with drug levels. This is the first study to demonstrate a direct relationship between changes in plasma levels of salvinorin A and drug effects in humans. The results confirm the efficacy of an inhalation technique for salvinorin A.

Johnson, M. W., MacLean, K. A., Caspers, M. J., Prisinzano, T. E., & Griffiths, R. R. (2016). Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans. Journal of psychopharmacology (Oxford, England). http://dx.doi.org/10.1177/0269881116629125

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Comparative phenomenology of psilocybin experiences in research and non-research settings

Abstract

This study sought to compare questionnaire ratings of subjective experiences after psilocybin when administered in controlled research settings vs. uncontrolled, non-research settings.

Carbonaro, T. M., Klinedinst, M., Johnson, M. W., & Griffiths, R. R. (2015). Comparative phenomenology of psilocybin experiences in research and non-research settings. Drug and Alcohol Dependence, 156, e36-e37.  http://dx.doi.org/10.1016/j.drugalcdep.2015.07.1017
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Long-term follow-up of psilocybin-facilitated smoking cessation: Abstinence outcomes and qualitative analysis of participant accounts

Abstract

We assessed long-term (>12 months) outcomes of psilocybin-facilitated smoking cessation, and qualitatively analyzed participants’ accounts to inform potential psychological mechanisms of treatment efficacy.

Garcia-Romeu, A. P., Noorani, T., Griffiths, R. R., Johnson, M. W., Garey, L., Zvolensky, M. J., & Schmidt, N. B. (2015). Long-term follow-up of psilocybin-facilitated smoking cessation: Abstinence outcomes and qualitative analysis of participant accounts. Drug and Alcohol Dependence, 156, e78.  http://dx.doi.org/10.1016/j.drugalcdep.2015.07.1130
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Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin

Abstract

The 30-item revised Mystical Experience Questionnaire (MEQ30) was previously developed within an online survey of mystical-type experiences occasioned by psilocybin-containing mushrooms. The rated experiences occurred on average eight years before completion of the questionnaire. The current paper validates the MEQ30 using data from experimental studies with controlled doses of psilocybin. Data were pooled and analyzed from five laboratory experiments in which participants (n=184) received a moderate to high oral dose of psilocybin (at least 20 mg/70 kg). Results of confirmatory factor analysis demonstrate the reliability and internal validity of the MEQ30. Structural equation models demonstrate the external and convergent validity of the MEQ30 by showing that latent variable scores on the MEQ30 positively predict persisting change in attitudes, behavior, and well-being attributed to experiences with psilocybin while controlling for the contribution of the participant-rated intensity of drug effects. These findings support the use of the MEQ30 as an efficient measure of individual mystical experiences. A method to score a “complete mystical experience” that was used in previous versions of the mystical experience questionnaire is validated in the MEQ30, and a stand-alone version of the MEQ30 is provided for use in future research.

Barrett, F. S., Johnson, M. W., & Griffiths, R. R. (2015). Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin. Journal of psychopharmacology (Oxford, England). http://dx.doi.org/10.1177/0269881115609019
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7 May - Psychedelics, Nature & Mental Health with Sam Gandy

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