Psychiatry and Clinical Psychopharmacology
March 30, 2026
Kenji Hashimoto, Feyza Arıcıoğlu, Mesut Çetin
Classical serotonergic psychedelics—psilocybin, DMT, 5-methoxy-DMT, and LSD—can produce rapid and sometimes durable improvements in mood under supervised conditions. The review synthesizes clinical evidence for these compounds in depression and related disorders, noting challenges such as small sample sizes, expectancy effects, and limitations in maintaining blinding. Mechanistic frameworks extend beyond 5-HT2A receptor activity, involving multiple serotonergic subtypes, glutamatergic modulation, synaptic plasticity, and brain network reorganization. Preclinical and clinical evidence points to neurotrophic mechanisms, particularly BDNF-TrkB signaling, as contributors to sustained effects. Acute mystical-type experiences may enhance response but are not strictly required, suggesting plasticity-promoting mechanisms can be partially dissociated from hallucinogenic effects. Peripheral contributions, including gut-brain axis interactions, may influence treatment durability.
Psychiatry and Clinical Psychopharmacology
November 13, 2025
A 61-year-old woman with treatment-resistant depression, a history of poor response to electroconvulsive therapy, and structural brain damage from a traumatic brain injury received four doses of intranasal esketamine over two weeks. Her depression severity, measured by the Montgomery-Åsberg Depression Rating Scale, improved from severe to mild, suicidal thoughts resolved, anxiety decreased, and nightmares stopped. She experienced only transient dizziness after each dose, with no severe side effects. This single case suggests esketamine may help carefully selected patients with similar complex histories, but larger studies are needed to confirm.
Psychiatry and Clinical Psychopharmacology
August 14, 2025
Nadav Liam Modlin, Jessica L. Maples‐keller, Maria Sarang et al.
Among 873 people who reported trauma symptoms or a PTSD/CPTSD diagnosis, 94.8% had experienced psychological trauma and 73.4% had a formal diagnosis. Many had tried multiple medications and psychotherapies but were highly dissatisfied. Significant numbers used marijuana, psychedelics, or MDMA on their own to manage symptoms, with few physical or psychological complications. After learning about MDMA and psilocybin therapies, willingness to try them was high (0.81 and 0.83, respectively). Women and heterosexual individuals showed lower willingness, while younger and more educated respondents were more willing. The findings point to a need for further clinical research and public education about risks and harm reduction.