Psilocybin and Other Classic Psychedelics in Depression.
D J Nutt, Joseph Peill, B Weiss, Kate Godfrey, R L Carhart-Harris, David Erritzøe
Current Topics in Behavioral Neurosciences 2024 DOI: 10.1007/7854_2023_451 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | Psilocybin DMT |
| Topics | Depression DMT Psilocybin Serotonin |
| Keywords | Antidepressants Dimethyltryptamine DMT Electroencephalograhy EEG Entropy Modularity Neuroimaging Psychedelics hallucinogens Entheogens Neuroscience brain connectivity Mood disorder Depressive symptoms |
| Citations | 30 |
| Key findings | 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.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Psychedelics targeting the 5-HT2A receptor, including DMT, can produce rapid mood improvement in depressed individuals that can last for months when coupled with psychological support.
Synthesized
Comparable studies
Other narrative reviews on DMT for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Registered clinical studies investigating psychedelic drugs for psychiatric disorders. Registered clinical trials on clinicaltrials.gov evaluating psychedelics for... | 2021 | Review | n = 70 |
| Role of Psychedelics in Treatment-Resistant Depression. | 2023 | Review | |
| Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression | 2025 | Review | |
| Ayahuasca for the Treatment of Depression. | 2022 | Review | |
| A Brief Review on the Potential of Psychedelics for Treating Alzheimer’s Disease and Related Depression | 2023 | Review |