Current topics in behavioral neurosciences
January 1, 2024
D J Nutt, J M Peill, B Weiss et al.
30 citations
Psychedelic drugs that activate the 5-HT2A receptor, such as psilocybin and DMT, produce dose-related psychological effects including hallucinations, out-of-body experiences, emotional breakthroughs, and mystical-type experiences. When combined with psychological support, these substances can rapidly improve mood in people with depression, with benefits lasting months. The therapeutic effects may stem from increased brain entropy that disrupts fixed negative thinking, enhanced cognitive flexibility after treatment, and changes in self-referential psychological processes. The brain mechanisms underlying serotonergic psychedelics likely differ from those of classical serotonin reuptake-blocking antidepressants.
Nature communications
May 5, 2026
T Lyons, M Spriggs, L Kerkelä et al.
19 citations
A single high dose of psilocybin (25 mg) in 28 healthy, psychedelic-naive participants produced anatomical and functional brain changes lasting from one hour to one month. At one month, participants showed increased cognitive flexibility, psychological insight, and well-being. Diffusion tensor imaging revealed decreased axial diffusivity in prefrontal-subcortical tracts, correlating with reduced brain network modularity. Decreased modularity negatively correlated with increased well-being, consistent with depression findings. Increased cortical signal entropy one to two hours after dosing predicted improved well-being at one month, mediated by next-day psychological insight. No effects occurred with a 1 mg placebo dose.
International review of neurobiology
January 1, 2025
A M Wingert, C Agnorelli, J Peill et al.
1 citation
Depressive disorders remain a major global challenge, especially with rising treatment-resistant cases. Recent research highlights the antidepressant potential of psilocybin and other 5-HT₂A receptor agonists for major depressive disorder and treatment-resistant depression. Phase I and II clinical trials show that even a single administration can produce rapid and sustained symptom reduction, with effects comparable to conventional treatments like SSRIs and ketamine. Serotonergic psychedelics have a distinctive pharmacological profile and robust safety data, making them promising for patients unresponsive to standard therapies. However, integration into routine practice is hindered by the resource-intensive nature of psychedelic-assisted therapy, requiring specialized training and controlled settings. Some countries, including Australia, Switzerland, and Canada, have begun allowing psilocybin use for treatment-resistant depression.