Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function
This comprehensive review (2019) by some of the leading researchers in psychedelics looks at both the epidemiological & clinical studies and the positive (and negative) effect that psychedelics can have.
Authors
- Peter Hendricks
- Roland Griffiths
- Matthew Johnson
Published
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.
Research Summary of 'Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function'
Introduction
Classic psychedelics are compounds that primarily act as agonists at the serotonin 2A receptor (5-HT2A R) and include substances such as LSD, mescaline, psilocybin, and naturally occurring DMT in ayahuasca. Earlier preclinical and human work implicates 5-HT2A R as central to the characteristic subjective and behavioural effects of these drugs, although other receptor actions (e.g. 5-HT2C, 5-HT1A, dopaminergic effects at high LSD doses, and TAAR1 activation) and downstream gene expression changes are also reported. Historically, these compounds were used sacramentally in a range of indigenous contexts and attracted major scientific interest in the 1950s–1960s for both basic neuroscience and psychiatry, with early clinical signals for cancer-related psychological distress and addiction; research largely halted in the early 1970s and re-emerged from the 1990s onward. Johnson and colleagues set out to provide an integrative review across four domains: epidemiology of classic psychedelic use, contemporary therapeutic clinical research, the construct and measurement of mystical-type experiences occasioned by psychedelics, and neuroimaging/brain network findings that might explain acute and persisting effects. The review aims to synthesise modern findings on safety, population-level associations, experimental and pilot therapeutic trials, the role of mystical-type experiences as predictors or mediators of benefit, and systems-level neural mechanisms that could underlie both altered conscious states and therapeutic outcomes.
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Johnson, M. W., Hendricks, P. S., Barrett, F. S., & Griffiths, R. R. (2019). Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. Pharmacology & Therapeutics, 197, 83-102. https://doi.org/10.1016/j.pharmthera.2018.11.010
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