The International Journal of Neuropsychopharmacology
October 21, 2022
James J Gattuso, Daniel Perkins, Simon Ruffell et al.
233 citations
Classical psychedelics like LSD, psilocybin, and ayahuasca consistently disrupt resting-state connectivity within the Default Mode Network (DMN) and increase functional connectivity between canonical resting-state networks. The DMN, a set of brain regions active during self-referencing and mind wandering, is altered in various neuropsychiatric conditions. While DMN modulation is central to some cognitive models of psychedelics, its role in their therapeutic potential remains unclear. This systematic review provides a comprehensive overview to guide future research on the neurocognitive mechanisms of these agents.
Australian & New Zealand Journal of Psychiatry
March 21, 2021
Daniel Perkins, Jerome Sarris, Susan L. Rossell et al.
53 citations
Psychedelic substances such as psilocybin, ayahuasca, LSD, and MDMA are gaining renewed medical interest due to the need for new psychiatric treatments and promising study results. This viewpoint reflects on the Royal Australian and New Zealand College of Psychiatrists' Clinical Memorandum on Psychedelics and notes regulatory developments, including applications for down-scheduling and access approvals. The authors argue that rigorous research is needed to assess benefits, safety, and therapeutic mechanisms. They summarize recent findings on mechanisms of action and the psychedelic-assisted psychotherapy model, suggesting medicinal psychedelics could become a new class of psychiatric treatments when used under medical supervision with psychotherapeutic support. However, sufficiently powered trials and safety protocols are required before clinical use, and untrained practitioner access could be harmful.
British Journal of Pharmacology
June 15, 2025
Daniël Hoyer
9 citations
Psychedelics like psilocybin, LSD, and ayahuasca, along with non-hallucinogenic entactogens such as MDMA, are being investigated as rapidly acting treatments for major depressive disorder, treatment-resistant depression, PTSD, and generalized anxiety disorder. Late-stage clinical trials support their use in assisted psychotherapy. These drugs primarily target serotonin and monoamine systems, with classical psychedelics acting as 5-HT2A receptor agonists. Advanced imaging shows that depression involves reduced brain serotonin levels and impaired neural networks, which psychedelics and entactogens can correct. They promote neuroplasticity and synaptogenesis through monoamine or glutamate receptors and pathways like BDNF and mTORC1, supporting a biological basis for these disorders.
May 23, 2024
Daniël Hoyer
The serotonin (5-HT) system plays an essential but not unique role in major depressive disorder and related conditions. Classical antidepressants targeting 5-HT are not universally effective, and treatment-resistant depression remains a major issue. The newest class of potential rapid-acting treatments—psychedelics like psilocybin, LSD, and DMT, and entactogens like MDMA—all target the 5-HT system, primarily as 5-HT2A receptor agonists. Phase II/III clinical trials support psychedelic- and MDMA-assisted psychotherapy for generalized anxiety disorder, major depressive disorder, treatment-resistant depression, and PTSD. These drugs produce rapid and long-lasting antidepressant effects after one or two administrations, promote synaptogenesis and synaptic plasticity, and have anti-neuroinflammatory effects. Depression may be considered a biochemical, neurological, and immune condition.