OPEN Foundation

C. Weissman

On the Relationship between Classic Psychedelics and Suicidality: A Systematic Review

Abstract

Use of classic psychedelics (e.g., psilocybin, ayahuasca, and lysergic acid diethylamide) is increasing, and psychedelic therapy is receiving growing attention as a novel mental health intervention. Suicidality remains a potential safety concern associated with classic psychedelics and is, concurrently, a mental health concern that psychedelic therapy may show promise in targeting. Accordingly, further understanding of the relationship between classic psychedelics and suicidality is needed. Therefore, we conducted a systematic review of the relationship between classic psychedelics (both non-clinical psychedelic use and psychedelic therapy) and suicidality. We identified a total of 64 articles, including 41 articles on the association between non-clinical classic psychedelic use and suicidality and 23 articles on the effects of psychedelic therapy on suicidality. Findings on the association between lifetime classic psychedelic use and suicidality were mixed, with studies finding positive, negative, and no significant association. A small number of reports of suicide and decreased suicidality following non-clinical classic psychedelic use were identified. Several cases of suicide in early psychedelic therapy were identified; however, it was unclear whether this was due to psychedelic therapy itself. In recent psychedelic therapy clinical trials, we found no reports of increased suicidality and preliminary evidence for acute and sustained decreases in suicidality following treatment. We identify some remaining questions and provide suggestions for future research on the association between classic psychedelics and suicidality.

Zeifman, R. J., Singhal, N., Breslow, L., & Weissman, C. R. (2021). On the Relationship between Classic Psychedelics and Suicidality: A Systematic Review. ACS pharmacology & translational science, 4(2), 436–451. https://doi.org/10.1021/acsptsci.1c00024

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Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial

Abstract

Rationale: Suicidality is a major public health concern with limited treatment options. Accordingly, there is a need for innovative interventions for suicidality. Preliminary evidence indicates that treatment with the psychedelic ayahuasca may lead to decreases in depressive symptoms among individuals with major depressive disorder (MDD). However, there remains limited understanding of whether ayahuasca also leads to reductions in suicidality.

Objective: To examine the acute and post-acute effect of ayahuasca on suicidality among individuals with MDD.

Methods: We conducted a secondary analysis of an open-label trial in which individuals with recurrent MDD received a single dose of ayahuasca (N = 17). Suicidality was assessed at baseline; during the intervention; and 1, 7, 14, and 21 days after the intervention.

Results: Among individuals with suicidality at baseline (n = 15), there were significant acute (i.e., 40, 80, 140, and 180 min after administration) and post-acute (1, 7, 14, and 21 days after administration) decreases in suicidality following administration of ayahuasca. Post-acute effect sizes for decreases in suicidality were large (Hedges’ g = 1.31-1.75), with the largest effect size 21 days after the intervention (g = 1.75).

Conclusions: When administered in the appropriate context, ayahuasca may lead to rapid and sustained reductions in suicidality among individuals with MDD. Randomized, double-blind studies with larger sample sizes are needed to confirm this early finding.

Zeifman, R. J., Singhal, N., Dos Santos, R. G., Sanches, R. F., de Lima Osório, F., Hallak, J., & Weissman, C. R. (2021). Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial. Psychopharmacology, 238(2), 453–459. https://doi.org/10.1007/s00213-020-05692-9

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Microdosing psychedelics: Demographics, practices, and psychiatric comorbidities.

Abstract

RATIONALE:
Microdosing psychedelics – the practice of consuming small, sub-hallucinogenic doses of substances such as LSD or psilocybin – is gaining attention in popular media but remains poorly characterized. Contemporary studies of psychedelic microdosing have yet to report the basic psychiatric descriptors of psychedelic microdosers.
OBJECTIVES:
To examine the practices and demographics of a population of psychedelic microdosers – including their psychiatric diagnoses, prescription medications, and recreational substance use patterns – to develop a foundation on which to conduct future clinical research.
METHODS:
Participants (n = 909; Mage = 26.9, SD = 8.6; male = 83.2%; White/European = 79.1%) recruited primarily from the online forum Reddit completed an anonymous online survey. Respondents who reported using LSD, psilocybin, or both for microdosing were grouped and compared with non-microdosing respondents using exploratory odds ratio testing on demographic variables, rates of psychiatric diagnoses, and past-year recreational substance use.
RESULTS:
Of microdosers, most reported using LSD (59.3%; Mdose = 13 mcg, or 11.3% of one tab) or psilocybin (25.9%; Mdose = 0.3 g of dried psilocybin mushrooms) on a one-day-on, two-days-off schedule. Compared with non-microdosers, microdosers were significantly less likely to report a history of substance use disorders (SUDs; OR = 0.17 (95% CI: 0.05-0.56)) or anxiety disorders (OR = 0.61 (95% CI: 0.41-0.91)). Microdosers were also more likely to report recent recreational substance use compared with non-microdosers (OR = 5.2 (95% CI: 2.7-10.8)).
CONCLUSIONS:
Well-designed randomized controlled trials are needed to evaluate the safety and tolerability of this practice in clinical populations and to test claims about potential benefits.
Rosenbaum, D., Weissman, C., Anderson, T., Petranker, R., Dinh-Williams, L. A., Hui, K., & Hapke, E. (2020). Microdosing psychedelics: Demographics, practices, and psychiatric comorbidities. Journal of Psychopharmacology, 0269881120908004., https://doi.org/10.1177/0269881120908004
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Psychedelic microdosing benefits and challenges: an empirical codebook.

Abstract

BACKGROUND:
Microdosing psychedelics is the practice of consuming very low, sub-hallucinogenic doses of a psychedelic substance, such as lysergic acid diethylamide (LSD) or psilocybin-containing mushrooms. According to media reports, microdosing has grown in popularity, yet the scientific literature contains minimal research on this practice. There has been limited reporting on adverse events associated with microdosing, and the experiences of microdosers in community samples have not been categorized.
METHODS:
In the present study, we develop a codebook of microdosing benefits and challenges (MDBC) based on the qualitative reports of a real-world sample of 278 microdosers.
RESULTS:
We describe novel findings, both in terms of beneficial outcomes, such as improved mood (26.6%) and focus (14.8%), and in terms of challenging outcomes, such as physiological discomfort (18.0%) and increased anxiety (6.7%). We also show parallels between benefits and drawbacks and discuss the implications of these results. We probe for substance-dependent differences, finding that psilocybin-only users report the benefits of microdosing were more important than other users report.
CONCLUSIONS:
These mixed-methods results help summarize and frame the experiences reported by an active microdosing community as high-potential avenues for future scientific research. The MDBC taxonomy reported here informs future research, leveraging participant reports to distil the highest-potential intervention targets so research funding can be efficiently allocated. Microdosing research complements the full-dose literature as clinical treatments are developed and neuropharmacological mechanisms are sought. This framework aims to inform researchers and clinicians as experimental microdosing research begins in earnest in the years to come.
Anderson, T., Petranker, R., Christopher, A., Rosenbaum, D., Weissman, C., Dinh-Williams, L. A., … & Hapke, E. (2019). Psychedelic microdosing benefits and challenges: an empirical codebook. Harm reduction journal16(1), 43., https://doi.org/10.1186/s12954-019-0308-4
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Microdosing psychedelics: personality, mental health, and creativity differences in microdosers

Abstract

RATIONALE:

Microdosing psychedelics-the regular consumption of small amounts of psychedelic substances such as LSD or psilocybin-is a growing trend in popular culture. Recent studies on full-dose psychedelic psychotherapy reveal promising benefits for mental well-being, especially for depression and end-of-life anxiety. While full-dose therapies include perception-distorting properties, microdosing mayprovide complementary clinical benefits using lower-risk, non-hallucinogenic doses.

OBJECTIVES:

This pre-registered study aimed to investigate whether microdosing psychedelics is related to differences in personality, mental health, and creativity.

METHODS:

In this observational study, respondents recruited from online forums self-reported their microdosing behaviors and completed questionnaires concerning dysfunctional attitudes, wisdom, negative emotionality, open-mindedness, and mood. Respondents also performed the Unusual Uses Task to assess their creativity.

RESULTS:

Current and former microdosers scored lower on measures of dysfunctional attitudes (p < 0.001, r = – 0.92) and negative emotionality (p = 0.009, r = – 0.85) and higher on wisdom (p < 0.001, r = 0.88), openmindedness(p = 0.027, r = 0.67), and creativity (p < 0.001, r = 0.15) when compared to non-microdosing controls.

CONCLUSIONS:

These findings provide promising initial evidence that warrants controlled experimental research to directly test safety and clinical efficacy. As microdoses are easier to administer than full-doses, this new paradigm has the exciting potential to shape future psychedelic research.

Anderson, T., Petranker, R., Rosenbaum, D., Weissman, C. R., Dinh-Williams, L. A., Hui, K., … & Farb, N. A. (2018). Microdosing Psychedelics: Personality, mental health, and creativity differences in microdosers. Psychopharmacology, 1-10., 10.1007/s00213-018-5106-2
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Microdosing psychedelics: personality, mental health, and creativity differences in microdosers.

Abstract

RATIONALE:
Microdosing psychedelics-the regular consumption of small amounts of psychedelic substances such as LSD or psilocybin-is a growing trend in popular culture. Recent studies on full-dose psychedelic psychotherapy reveal promising benefits for mental well-being, especially for depression and end-of-life anxiety. While full-dose therapies include perception-distorting properties, microdosing mayprovide complementary clinical benefits using lower-risk, non-hallucinogenic doses.
OBJECTIVES:
This pre-registered study aimed to investigate whether microdosing psychedelics is related to differences in personality, mental health, and creativity.
METHODS:
In this observational study, respondents recruited from online forums self-reported their microdosing behaviors and completed questionnaires concerning dysfunctional attitudes, wisdom, negative emotionality, open-mindedness, and mood. Respondents also performed the Unusual Uses Task to assess their creativity.
RESULTS:
Current and former microdosers scored lower on measures of dysfunctional attitudes (p < 0.001, r = – 0.92) and negative emotionality (p = 0.009, r = – 0.85) and higher on wisdom (p < 0.001, r = 0.88), openmindedness(p = 0.027, r = 0.67), and creativity (p < 0.001, r = 0.15) when compared to non-microdosing controls.
CONCLUSIONS:
These findings provide promising initial evidence that warrants controlled experimental research to directly test safety and clinical efficacy. As microdoses are easier to administer than full-doses, this new paradigm has the exciting potential to shape future psychedelic research.

Anderson, T., Petranker, R., Rosenbaum, D., Weissman, C. R., Dinh-Williams, L. A., Hui, K., … & Farb, N. A. (2019). Microdosing Psychedelics: Personality, mental health, and creativity differences in microdosers. Psychopharmacology236(2), 731-740., https://doi.org/10.1007/s00213-018-5106-2
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21 March - Ketamine Discussion with Celia Morgan, Filip Tylš & Will Barone

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