Psilocybin and Other Classic Psychedelics in Depression.
D J Nutt, J M Peill, B Weiss, K Godfrey, R L Carhart-Harris, D Erritzoe
Current topics in behavioral neurosciences January 1, 2024 DOI: 10.1007/7854_2023_451 via PubMed
Summary
AI-generated from the abstractPsychedelic 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.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | Psilocybin DMT |
| Topics | Depression DMT Psilocybin Serotonin |
| Keywords | Antidepressants Dimethyltryptamine DMT Electroencephalograhy EEG Entropy |
| Citations | 30 |
| Key finding | Psychedelics targeting the 5-HT2A receptor can produce rapid and sustained mood improvement in depressed individuals, likely through mechanisms distinct from classical antidepressants. |
Abstract
Psychedelic drugs such as psilocybin and ketamine are returning to clinical research and intervention across several disorders including the treatment of depression. This chapter focusses on psychedelics that specifically target the 5-HT2A receptor such as psilocybin and DMT. These produce plasma-concentration related psychological effects such as hallucinations and out of body experiences, insightful and emotional breakthroughs as well as mystical-type experiences. When coupled with psychological support, effects can produce a rapid improvement in mood among people with depression that can last for months. In this chapter, we summarise the scientific studies to date that explore the use of psychedelics in depressed individuals, highlighting key clinical, psychological and neuroimaging features of psychedelics that may account for their therapeutic effects. These include alterations in brain entropy that disrupt fixed negative ruminations, a period of post-treatment increased cognitive flexibility, and changes in self-referential psychological processes. Finally, we propose that the brain mechanisms underlying the therapeutic effect of serotonergic psychedelics might be distinct from those underlying classical serotonin reuptake-blocking antidepressants.