Title & Introduction

  • Paper Title: Psychedelics and Suicide-Related Outcomes: A Systematic Review
  • Published In: Journal of Clinical Medicine
  • Publish Date: February 20, 2025
  • Authors: Shakila Meshkat, Taha Malik, Richard Zeifman, Jennifer Swainson, Yanbo Zhang, Lisa Burback, Olga Winkler, Andrew J. Greenshaw, Amy Claire Reichelt, Eric Vermetten, David Erritzoe, Manish K. Jha, Walter Dunn, Rakesh Jetly, Muhammad Ishrat Husain, Venkat Bhat
  • Objective: To systematically evaluate the impact of psychedelic therapies on suicide-related outcomes.
  • Importance: Suicide accounts for 1.4% of global deaths, and current treatments often act too slowly to prevent acute suicide risk. Psychedelics may offer rapid-acting effects in reducing suicidal ideation and behaviors.

Summary & Takeaways

Key Takeaway:
Preliminary evidence suggests that psilocybin and MDMA-assisted therapy may reduce suicidal ideation in specific clinical populations, but findings on LSD and other psychedelics are mixed, highlighting the need for further research.

Practical Application:
Psychedelic therapies could serve as adjunct treatments for individuals at risk of suicide, particularly in cases where rapid-acting interventions are needed. However, regulatory and clinical frameworks must ensure safety and efficacy before widespread implementation.

Key Background Information

  • Context: Suicide risk is a major public health issue, with current treatments often requiring weeks to take effect. Psychedelics have shown potential for rapid therapeutic benefits in psychiatric conditions such as PTSD, depression, and substance use disorders.
  • Hypothesis: Psychedelic therapies may reduce suicidal ideation by promoting emotional processing, neuroplasticity, and interconnectedness. However, certain substances, such as LSD, may be associated with increased suicide risk in some populations.

Methodology

  • Study Design: Systematic review of randomized controlled trials (RCTs), non-randomized studies, and population-based research.
  • Participants: 1,671,773 individuals across 39 studies, including RCT participants, observational study subjects, and general population samples.
  • Intervention/Exposure: Various psychedelics, including psilocybin, MDMA, LSD, DMT, ayahuasca, and ibogaine.
  • Controls: Placebo or active comparator groups in RCTs; non-users in population studies.
  • Duration: Data collected from inception to November 2024.

Key Findings

Primary Outcomes:

  • Four RCTs reported significant reductions in suicidal ideation with psilocybin (three studies) and MDMA-assisted therapy (one study), with effect sizes ranging from d = 0.52 to 1.25 (p = 0.01 to 0.005).
  • Five additional RCTs assessing suicidality as a safety measure showed similar reductions (p = 0.02 to 0.04).
  • Non-randomized studies on psilocybin (three studies) reported reductions in suicidal ideation, with odds ratios (OR) ranging from 0.40 to 0.75.
  • MDMA-assisted therapy in PTSD patients (five studies) showed a pooled effect size of d = 0.61 (95% CI: 0.32–0.89).
  • LSD studies (six studies) suggested increased odds of suicidality (OR = 1.15–2.08).
  • DMT studies (two studies) found no significant effects on suicidality.
  • Studies involving multiple psychedelics (three studies) showed mixed results, with some reporting reductions in suicidal ideation and others showing no significant change.

Secondary Outcomes:

  • Population-based studies suggested that lifetime psychedelic use (excluding LSD) was associated with lower odds of suicide attempts.
  • Two studies on ibogaine and 5-MeO-DMT in military veterans reported reductions in suicidal ideation post-treatment.
  • One study on ayahuasca found reductions in suicidal ideation lasting up to 21 days post-treatment.
  • Some cross-sectional studies reported increased suicide risk with LSD use, particularly among adolescents and individuals with pre-existing psychiatric conditions.

Interpretation & Implications

  • Conclusion: Psychedelic therapies, particularly psilocybin and MDMA-assisted therapy, may have potential in reducing suicidal ideation. However, the effects of other psychedelics, such as LSD, remain inconclusive.
  • Implications: Future clinical trials should include suicidality as a primary outcome and examine long-term effects. Regulatory agencies should carefully assess risks and benefits before integrating psychedelics into suicide prevention strategies.
  • Limitations: Many studies assessed suicidality as a secondary outcome. The lack of long-term follow-up and the exclusion of high-risk populations from trials limit generalizability.

Researchers & Publication

  • Researchers: Shakila Meshkat, Taha Malik, Richard Zeifman, Jennifer Swainson, Yanbo Zhang, Lisa Burback, Olga Winkler, Andrew J. Greenshaw, Amy Claire Reichelt, Eric Vermetten, David Erritzoe, Manish K. Jha, Walter Dunn, Rakesh Jetly, Muhammad Ishrat Husain, Venkat Bhat
  • Publication Name: Journal of Clinical Medicine
  • Study URL: https://doi.org/10.3390/jcm14051416
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