Rapid and prolonged antidepressant and antianxiety effects of psilocybin, lysergic acid diethylamide, ayahuasca, and 3, 4-methylenedioxy-methamphetamine. A systematic review and meta-analysis of randomized controlled trials

Abstract Background Hallucinogens attract research as alternatives to the commonly used medications to treat major depressive and anxiety disorders.

Aims: Assess hallucinogens’ efficacy for managing depressive and anxiety symptoms and evaluate their safety profiles.

Method: In five databases, we searched for randomized controlled trials of hallucinogens targeting depressive and anxiety symptoms. We performed a meta-analysis using a random effects model when data permitted it. The protocol of the review is registered in PROSPERO; CRD42022341325.

Results: Psilocybin produced a rapid and sustained reduction in depressive and anxiety symptoms in patients with major depressive disorder, severe, and in patients with life-threatening cancer. A decrease in depressive symptoms was observed with 3, 4-methylenedioxymethamphetamine (MDMA), primarily in patients with life-threatening cancer, autism spectrum disorder, and post-traumatic stress disorder. MDMA reduced social anxiety symptoms. However, MDMA’s effect size was either negligible or negative for anxiety symptoms overall. Ayahuasca reduced depressive symptoms in individuals with treatment-resistant major depressive and personality disorders. Lysergic acid diethylamide (LSD) reduced anxiety symptoms in individuals with life-threatening cancer. Psilocybin’s adverse effects were noticeable for elevated blood pressure, headaches, and panic attacks. For MDMA, elevated blood pressure, headaches, panic attacks, and feeling cold were noticeable.

Conclusions: Psilocybin, MDMA, ayahuasca, and LSD appear to have the potential to reduce depressive and anxiety symptoms. Adverse effects are noticed. Rigorous randomized controlled studies with larger sample sizes utilizing outcome measures instruments with better reliability and validity are warranted.