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

Classic psychedelics and MDMA are being revisited as potential psychiatric treatments. They work primarily by stimulating 5-HT2A receptors, inducing neuroplastic changes, and modifying functional brain networks, which may help shift entrenched cognitive and emotional patterns. Randomized trials with psilocybin show rapid and sustained reduction of depressive symptoms in treatment-resistant depression and cancer patients, as well as promise for alcohol use disorders. MDMA combined with psychotherapy shows substantial potential for PTSD. Caution is needed due to risks of adverse reactions and drug interactions, especially with serotonergic agents and MAOIs. Further multicenter studies with greater statistical power and longer follow-up are required before routine clinical use.

Study at a glance

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.