In this episode, I explore the history, science, and clinical promise of psychedelics. This was actually my Master's Thesis topic so very fun episode for me!

We cover everything from how the psychedelics actually work, by acting brain (serotonin) receptors to increase neuroplasticity (make your brain more malleable), disrupt rigid brain patterns, and increase brain "entropy"... and, more importantly, why those effects may help us treat conditions such as PTSD and treatment‑resistant depression.

The episode also discusses the current clinical evidence (including a critical appraisal of its robustness), logisitcal and ethical challenges, and the importance of use within therapeutic / research settings only.

As always, find a full bibliography below:

Carhart-Harris & Goodwin (2017), “The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future,” Neuropsychopharmacology - This one is a very good foundation if you only have time to read one paper, it should be this one!!

Yaden & Griffiths (2021), “The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic Effects,” ACS Pharmacology & Translational Science - This is great to read into the question of "is the trip actually necessary?"

Mitchell JM et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled Phase 3 study. Nature Medicine. 2021.

Mitchell JM et al. MDMA-assisted therapy for PTSD: results of a second Phase 3 randomized trial in a diverse cohort. Nature Medicine. 2023.

Carhart-Harris RL et al. Trial of psilocybin-assisted therapy versus escitalopram for major depressive disorder. New England Journal of Medicine. 2021.

Davis AK et al. Effects of psilocybin-assisted therapy on major depressive disorder: outcomes at 1 and 4 weeks. JAMA Psychiatry. 2020.

Raison CL et al. Psilocybin versus niacin placebo for major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2023.

Bogenschutz MP et al. Psilocybin-assisted treatment for alcohol use disorder: a randomized clinical trial. JAMA Psychiatry. 2022.

Griffiths RR et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer. Journal of Psychopharmacology. 2016.

Luoma JB et al. Meta-analysis of placebo-controlled trials of psychedelic-assisted therapy. Journal of Psychoactive Drugs. 2020.

Fang Y et al. Psilocybin for depressive and anxiety symptoms: systematic review and meta-analysis of randomized trials. Frontiers in Psychiatry. 2024.

Romeo B et al. Safety of psychedelic-assisted therapies: systematic review and meta-analysis. Psychiatry Research. 2024.

Hinkle JT et al. Adverse events in psychedelic-assisted therapy: a systematic review and pooled analysis. JAMA Psychiatry. 2024.

Siegel AN et al. Persistent decreases in hippocampus-default-mode connectivity following psilocybin correlate with mood improvement. Nature. 2024.

Ly C et al. Psychedelics promote structural and functional neural plasticity. Cell Reports. 2018.

Carhart-Harris RL, Friston KJ. REBUS and the anarchic brain: toward a unified model of the brain action of psychedelics. Pharmacological Reviews. 2019.

Griffiths RR et al. Psilocybin-occasioned mystical-type experience in humans: relationship to persisting positive effects. Psychopharmacology. 2019.

U.S. Food and Drug Administration. Guidance for Industry: Expedited Programs for Serious Conditions. Drugs and Biologics (Breakthrough Therapy Designation). FDA; 2014 (update).

Compass Pathways plc. Phase 3 program design of COMP360 (synthetic psilocybin) for treatment-resistant depression (TRD). Business Wire/Investor Press Release. 2024.

Johnson MW, Garcia-Romeu A, et al. Pilot study of psilocybin-facilitated smoking cessation treatment: long-term follow-up outcomes. Journal of Psychopharmacology. 2017.