Psychedelics as a Therapeutic Opportunity or Threat: A Narrative Review.

Abstract

Classic psychedelics and related substances, such as 3,4-methylenedioxymethamphetamine (MDMA), have again become a focus of interest in psychiatry as potential therapeutic tools. The aim of this paper is to review current data on their mechanisms of action, clinical applications in the treatment of mood and anxiety disorders, addictions and post-traumatic stress disorder (PTSD), as well as to assess safety, drug interactions and long-term complications. Studies indicate that psychedelics act mainly through stimulation of 5-hydroxytryptamine 2A (5-HT2A) receptors, induction of neuroplastic changes and modification of functional brain networks, which may facilitate changes in entrenched cognitive and emotional patterns. Randomized clinical trials with psilocybin have shown a rapid and sustained reduction of depressive symptoms, including in populations with treatment-resistant depression and cancer patients, as well as promising results in the treatment of alcohol use disorders. MDMA, when combined with psychotherapy, has demonstrated substantial therapeutic potential in the treatment of PTSD. The literature indicates that particular caution is required when using these substances in therapy because of the risk of acute and chronic adverse reactions and potential drug interactions, including with serotonergic agents and monoamine oxidase inhibitors (MAOIs). The available findings confirm a substantial, though still only partly explored, therapeutic potential of classic psychedelics and MDMA. At the same time, they emphasize the need for strict control of "set and setting", careful patient selection, further multicentre studies with greater statistical power and longer follow-up before these interventions can be incorporated into routine clinical practice.

In the evidence

This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.

• State of the evidence: Psilocybin for PTSD ↑Supports

  Reports that psilocybin and MDMA show therapeutic potential for depression, alcohol use disorders, and PTSD, but require careful patient selection and further research due to risks of adverse reactions and drug interactions.

  Synthesized September 21, 2026

Comparable studies

Other narrative reviews on psilocybin for PTSD, most cited first.