Psychedelic-Assisted Therapies for Depression and PTSD: Current Evidence and Clinical Considerations

Interest in psychedelic-assisted therapies has increased substantially, and primary care clinicians are increasingly fielding questions from patients about self-directed use outside medical supervision.¹ In this segment, Gus Alva, MD, emphasizes that most investigational psychedelic therapies are being studied within tightly controlled clinical research protocols that include structured dosing, psychological preparation, and monitored integration sessions.^2,3 He underscores that unsupervised use—particularly microdosing or recreational experimentation—carries clinical risks, including exacerbation of anxiety, precipitation of psychosis in vulnerable individuals, and unpredictable drug interactions.^4,5 Current research in depression, posttraumatic stress disorder, and anxiety disorders suggests that potential benefits are closely tied to the therapeutic setting rather than the pharmacologic agent alone.^2,6 For primary care physicians, this distinction is critical when counseling patients who may conflate emerging research findings with real-world safety or regulatory approval. Alva highlights the importance of framing these therapies as investigational and not yet ready for routine clinical use, while acknowledging that patient interest reflects unmet needs in treatment-resistant mental health conditions.^1,7 He also notes that primary care clinicians play an essential role in harm reduction by setting expectations, screening for psychiatric risk factors, and guiding patients away from unsafe self-experimentation. As research evolves, PCPs should be prepared to discuss what is known, what remains uncertain, and why participation in regulated clinical trials differs fundamentally from nonmedical use, according to Alva. This approach allows clinicians to maintain trust, reinforce evidence-based care, and support patient safety while the field continues to develop.

References:

1. Rucker JJH, Iliff J, Nutt DJ. Psychiatry & the psychedelic drugs. Past, present & future. Neuropharmacology. 2018;142:200-218. doi:10.1016/j.neuropharm.2017.12.040
2. Carhart-Harris RL, Bolstridge M, Rucker J, et al. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. 2016;3:619–627.
3. Davis AK, Barrett FS, May DG, et al. Effects of psilocybin-assisted therapy on major depressive disorder. JAMA Psychiatry. 2021;78:481–489.
4. Johnson MW, Richards WA, Griffiths RR. Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008;22:603–620.
5. Andersen KAA, Carhart-Harris R, Nutt DJ, Erritzoe D. Therapeutic effects of classic serotonergic psychedelics: a systematic review. Ther Adv Psychopharmacol. 2021;11:20451253211003414.
6. Yaden DB, Griffiths RR. The subjective effects of psychedelics are necessary for their enduring therapeutic effects. ACS Pharmacol Transl Sci. 2021;4:568–572.
7. Reiff CM, Richman EE, Nemeroff CB, et al. Psychedelics and psychedelic-assisted psychotherapy. Am J Psychiatry. 2020;177:391–410.