Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function.
Matthew W Johnson, Peter S. Hendricks, Frederick S. Barrett, Roland R. Griffiths
Pharmacology & Therapeutics May 1, 2019 DOI: 10.1016/j.pharmthera.2018.11.010 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Integrative review Peer reviewed |
|---|---|
| Population | General population |
| Topics | Addiction Depression LSD Psilocybin Mystical experience |
| Keywords | Cancer Classic psychedelics Treatment Efficacy in treating These compounds Psychological distress |
| Citations | 520 |
| Key findings | Classic psychedelics show strong potential as therapeutics for psychological distress, depression, and addiction, and as tools for studying mystical experiences and brain function. |
Abstract
The purpose of this paper is to provide an integrative review and offer novel insights regarding human research with classic psychedelics (classic hallucinogens), which are serotonin 2A receptor (5-HT2AR) agonists such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Classic psychedelics have been administered as sacraments since ancient times. They were of prominent interest within psychiatry and neuroscience in the 1950s to 1960s, and during this time contributed to the emergence of the field of molecular neuroscience. Promising results were reported for treatment of both end-of-life psychological distress and addiction, and classic psychedelics served as tools for studying the neurobiological bases of psychological disorders. Moreover, classic psychedelics were shown to occasion mystical experiences, which are subjective experiences reported throughout different cultures and religions involving a strong sense of unity, among other characteristics. However, the recreational use of classic psychedelics and their association with the counterculture prompted an end to human research with classic psychedelics in the early 1970s. We provide the most comprehensive review of epidemiological studies of classic psychedelics to date. Notable among these are a number of studies that have suggested the possibility that nonmedical naturalistic (non-laboratory) use of classic psychedelics is associated with positive mental health and prosocial outcomes, although it is clear that some individuals are harmed by classic psychedelics in non-supervised settings. We then review recent therapeutic studies suggesting efficacy in treating psychological distress associated with life-threatening diseases, treating depression, and treating nicotine and alcohol addictions. We also describe the construct of mystical experience, and provide a comprehensive review of modern studies investigating classic psychedelic-occasioned mystical experiences and their consequences. These studies have shown classic psychedelics to fairly reliably occasion mystical experiences. Moreover, classic-psychedelic-occasioned mystical experiences are associated with improved psychological outcomes in both healthy volunteer and patient populations. Finally, we review neuroimaging studies that suggest neurobiological mechanisms of classic psychedelics. These studies have also broadened our understanding of the brain, the serotonin system, and the neurobiological basis of consciousness. Overall, these various lines of research suggest that classic psychedelics might hold strong potential as therapeutics, and as tools for experimentally investigating mystical experiences and behavioral-brain function more generally.
In the evidence
This study is part of the evidence base for 4 syntheses in the library. Here is how each one recorded it.
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Classic psychedelics show strong potential as therapeutics for psychological distress, depression, and addiction.
Synthesized
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Classic psychedelics show strong potential as therapeutics for psychological distress, depression, and addiction.
Synthesized
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Reviews report promising results for classic psychedelics in treating addiction and end-of-life distress, and note epidemiological associations between naturalistic use and positive mental health outcomes.
Synthesized
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Classic psychedelics show strong potential as therapeutics for psychological distress, depression, and addiction, and as tools for studying mystical experiences and brain function.
Synthesized
Comparable studies
Other narrative reviews on LSD 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 |
| Top Ten Tips Palliative Care Clinicians Should Know About Psychedelic-Assisted Therapy in the Context of Serious Illness. Palliative care clinicians and patients | 2022 | Review | |
| Serotonergic psychedelics for depression: What do we know about neurobiological mechanisms of action? | 2023 | Narrative review | |
| Role of psilocybin in the treatment of depression | 2016 | Review | |
| Psilocybin in Treatment-Resistant Depression Adults with major depressive disorder | 2022 | Review |