Pharmacology & Therapeutics
May 1, 2019
Matthew W Johnson, Peter S. Hendricks, Frederick S. Barrett et al.
520 citations
Classic psychedelics like LSD, mescaline, and psilocybin are serotonin 2A receptor agonists with a long history of sacramental use and a resurgence in research. Epidemiological studies suggest naturalistic nonmedical use may be linked to positive mental health and prosocial outcomes, though some individuals are harmed in unsupervised settings. Recent therapeutic studies indicate efficacy in treating psychological distress from life-threatening diseases, depression, and nicotine and alcohol addictions. These compounds fairly reliably occasion mystical experiences, which are associated with improved psychological outcomes in healthy volunteers and patients. Neuroimaging studies reveal neurobiological mechanisms, broadening understanding of the brain, serotonin system, and consciousness. Overall, classic psychedelics show strong therapeutic potential and as tools for investigating mystical experiences and brain function.
Journal of psychopharmacology (Oxford, England)
March 1, 2015
Peter S. Hendricks, Christopher B Thorne, C Brendan Clark et al.
377 citations
Among over 190,000 US adults surveyed from 2008 to 2012, those who had ever used classic psychedelics (such as LSD or psilocybin) showed lower odds of past-month psychological distress, past-year suicidal thinking, past-year suicidal planning, and past-year suicide attempt compared with those who had not. The reduced odds ranged from 14% lower for suicidal thinking to 36% lower for suicide attempt. In contrast, use of other illicit drugs was generally linked to higher odds of these outcomes. The findings suggest that classic psychedelics might help prevent suicide and that their strict legal status should be reconsidered to allow more research.
Neuropharmacology
June 5, 2018
Matthew W. Johnson, Roland R. Griffiths, Peter S. Hendricks et al.
348 citations
Psilocybin, like other classic psychedelics that activate 5-HT2A receptors, has limited reinforcing effects and only marginal, transient non-human self-administration, indicating low abuse potential. Illicit use of psilocybin-containing mushrooms is occasional, with a few lifetime uses being typical. Potential harms include dangerous behavior in unprepared, unsupervised users and exacerbation of mental illness in those predisposed to psychotic disorders, but the scope of use and associated harms are low compared to prototypical abused drugs. The medical model mitigates these risks through dose control, patient screening, preparation, follow-up, and session supervision. If approved as a medicine, the review suggests that Schedule IV placement under the US Controlled Substances Act may be appropriate.
International Review of Psychiatry
July 4, 2018
Peter S. Hendricks
181 citations
A psychological model proposes that the mystical experience induced by classic psychedelics in therapy is characterized by profound awe—a response to a vast stimulus that forces mental structures to accommodate. Awe promotes a 'small self,' which at its extreme resembles ego dissolution or unitive experience. This small self is central to understanding the therapeutic effects that follow. Based on this framework, clinical recommendations are offered to advance psychedelic-assisted psychotherapy.
Journal of Affective Disorders
April 1, 2023
Otto Simonsson, Peter S. Hendricks, Richard Chambers et al.
124 citations
Using nationally representative US adult data (N = 2822), most people who have used classic psychedelics (59.1%) never had a challenging, difficult, or distressing experience. However, 8.9% reported functional impairment lasting more than one day from such an experience, and 2.6% sought medical, psychiatric, or psychological help afterward. Co-use of lithium or other mood stabilizers, and certain set and setting factors—including no preparation, disagreeable physical environment, negative mindset, no psychological support, a dose perceived as too large, and a major life event prior—were associated with greater difficulty. Negative mindset, no psychological support, and a major life event prior were also linked to overall risk of harm.
Journal of Psychopharmacology
September 1, 2015
Peter S. Hendricks, Matthew W Johnson, Roland R. Griffiths
107 citations
Adults in the United States who had ever used psilocybin alone showed lower odds of past-month psychological distress (weighted OR = .81) and past-year suicidal thinking, planning, and attempt compared with those who had never used any classic psychedelic. Those who used psilocybin without other psychedelics also had reduced odds of psychological distress relative to users of other classic psychedelics. The findings suggest psilocybin may have therapeutic potential and a favorable safety profile, but do not directly address clinical applications or risk.
Journal of Psychopharmacology
October 17, 2017
Peter S. Hendricks, Michael S Crawford, Karen L. Cropsey et al.
91 citations
Lifetime use of classic psychedelics, including psilocybin, is associated with lower odds of recent larceny/theft, assault, and arrests for property or violent crimes among over 480,000 U.S. adults surveyed from 2002 to 2014. In contrast, illicit use of other drugs generally increased the odds of these criminal behaviors. Lifetime classic psychedelic use was linked to higher odds of drug distribution, similar to other substances. The findings suggest a potential protective effect of psilocybin against antisocial criminal behavior and support further clinical research in forensic settings.
Journal of Psychopharmacology
January 1, 2014
Peter S. Hendricks, Christopher Clark, Matthew W. Johnson et al.
88 citations
Hallucinogen use among individuals under community corrections supervision with a history of substance involvement was associated with a reduced likelihood of supervision failure, such as noncompliance with legal requirements including alcohol and other drug use. In a longitudinal study of 25,622 people, those who used hallucinogens had 40% lower odds of supervision failure after controlling for confounding factors. The findings suggest hallucinogens may promote abstinence and prosocial behavior in a population with high rates of recidivism.
Journal of Psychopharmacology
March 9, 2021
Otto Simonsson, James D. Sexton, Peter S. Hendricks
75 citations
People who have used a classic psychedelic at least once in their lifetime report better overall health and are less likely to be overweight or obese, based on data from over 171,000 U.S. adults. The study also found a trend toward lower odds of having a heart condition or cancer in the past year among those who had used a classic psychedelic. The findings suggest that classic psychedelics may be linked to better physical health, but the authors note that further research is needed to determine whether the relationship is causal and to explore possible mechanisms.
International Journal of Drug Policy
May 8, 2019
Megan Webb, Heith Copes, Peter S. Hendricks
75 citations
People who microdose classic psychedelics such as LSD and psilocybin describe themselves as conventional citizens who use the drugs for rational, practical reasons. Through interviews with 30 microdosers, the study found that participants emphasized the rationality of their practice by discussing practical procurement and administration, a connection to general health and wellness awareness, and the benefits of microdosing. They framed their microdosing as embracing traditional middle-class values, which created social distance between themselves and recreational drug users. Unlike recreational users who distance themselves from stigmatized groups, microdosers instead emphasize their connection to conventional citizens, which helps normalize their drug use and supports persistence.
Journal of Psychopharmacology
April 19, 2016
Zach Walsh, Peter S. Hendricks, Stephanie D. Smith et al.
63 citations
Hallucinogen use among inmates at a US county jail was associated with a reduced likelihood of arrest for intimate partner violence (IPV). In a prospective study of 302 inmates, those who used hallucinogens were about 40% less likely to be arrested for IPV, both before and after accounting for other factors. The findings add to evidence that hallucinogens may help reduce problematic behaviors linked to externalizing psychopathology, such as substance misuse and criminality.
Psychedelic Med (New Rochelle)
September 13, 2023
Jacob S. Aday, Brian S. Barnett, Dan Grossman et al.
56 citations
The psychedelic industry has grown into a multibillion dollar sector, with hundreds of companies formed in recent years to commercialize psychedelic-assisted therapies. Investment surged in the late 2010s and early 2020s, focusing on drug discovery, novel formulations, manufacturing, treatment centers, consumer goods, and adjunct technologies. Key challenges include regulatory barriers, high treatment costs, and intellectual property issues. Ethical concerns involve potential adverse effects, cost-cutting, ensuring access for marginalized communities, and reciprocity with Indigenous peoples. Lessons from the ketamine and cannabis industries offer guidance on regulatory approval, clinical implementation, and insurance reimbursement.
Scientific Reports
July 13, 2021
Otto Simonsson, Walter Osika, Robin Carhart-Harris et al.
54 citations
Lifetime use of classic psychedelics is associated with lower odds of heart disease and diabetes. Analyzing data from the National Survey on Drug Use and Health (2005–2014), people who had ever tried a classic psychedelic had 23% lower odds of past-year heart disease and 12% lower odds of past-year diabetes. The associations persisted after adjusting for other factors. The authors suggest classic psychedelic use might benefit cardiometabolic health but call for more research on causal pathways.
Journal of Psychoactive Drugs
October 8, 2016
Noah W Sweat, Larry W. Bates, Peter S. Hendricks
48 citations
People who have used classic psychedelics and also had a mystical experience solved a creative problem-solving task faster than those who had not, with a large effect. However, the amount of lifetime mystical experience did not predict task performance, indicating that mystical experience does not explain the link between psychedelic use and creativity. The findings suggest that classic psychedelics may enhance creativity through mechanisms separate from those that produce mystical experiences, and that inducing mystical experiences may not be necessary for creativity-boosting interventions.
Frontiers in Psychiatry
February 11, 2020
James D. Sexton, Charles D. Nichols, Peter S. Hendricks
45 citations
Lifetime use of classic tryptamine psychedelics is linked to lower odds of past-month psychological distress and past-year suicidal thinking, while lifetime use of novel phenethylamines is linked to higher odds of past-year suicidal thinking and planning. These findings, from a large nationally representative U.S. survey, suggest that classic tryptamines may hold greater therapeutic potential than novel phenethylamines, which may pose risks for harm. No significant associations were found for other psychedelic classes.
Journal of Affective Disorders
January 26, 2024
Ludwig Honk, Cecilia U.D. Stenfors, Simon B. Goldberg et al.
41 citations
Using data from nearly 10,000 adults in the US and UK, psychedelic use over a two-month period was not linked to changes in psychotic symptoms overall. However, among people with a personal or family history of bipolar disorder, psychedelic use was associated with an increase in symptoms. Conversely, those with a personal history of psychotic disorders experienced a decrease in symptoms. These findings suggest that the effects of psychedelics on psychotic symptoms depend on an individual's psychiatric history.
Psychedelic Med (New Rochelle)
March 13, 2023
David E. Nichols, Charles D. Nichols, Peter S. Hendricks
39 citations
A proposed consensus statement defines psychedelic drugs as substances that reliably produce profound alterations in consciousness, perception, and mood through agonist activity at the serotonin 2A receptor. The definition emphasizes pharmacological mechanism over subjective effects, distinguishing psychedelics from other psychoactive compounds. The authors argue that a standardized definition is essential for advancing medical research, drug development, and clinical applications by providing a clear framework for classification and nomenclature. This consensus aims to reduce ambiguity in scientific and therapeutic contexts, supporting more precise communication and regulatory clarity in psychedelic research.
Hypertension
March 8, 2021
Otto Simonsson, Peter S. Hendricks, Robin Carhart-Harris et al.
36 citations
Adults who had used a classic psychedelic at least once in their lifetime had 14% lower odds of hypertension in the past year, after adjusting for confounders. The association was strongest for tryptamine psychedelics (DMT, ayahuasca, psilocybin), which were linked to 20% lower odds of hypertension. No significant association was found for LSD or mescaline. The authors note these findings are correlational and call for randomized controlled trials to test causal effects.
Neuropharmacology
August 17, 2022
Jack E Henningfield, Marion A Coe, Roland R. Griffiths et al.
34 citations
New medicines containing classic hallucinogenic and entactogenic psychedelics like psilocybin, LSD, and MDMA are being developed for psychiatric and neurological disorders. These substances are currently Schedule I under the US Controlled Substances Act (CSA) and similarly controlled globally. The CSA framework governs research, drug approval, and rescheduling; upon FDA approval, a drug containing a Schedule I substance must be rescheduled. Abuse potential research informs the eight CSA factors used for rescheduling, as well as product labeling and required risk evaluation and mitigation strategies (REMS). Standard human abuse potential studies are problematic for strong hallucinogens like psilocybin, so alternative strategies are discussed. Abuse-related research may also illuminate mechanisms of action, therapeutic effects, and effects on brain, behavior, mood, spirituality, and consciousness.
Psychopharmacology
July 1, 2025
Otto Simonsson, Simon B. Goldberg, Richard Chambers et al.
33 citations
In a US-representative sample of 2,822 adults, lifetime naturalistic psychedelic use was associated with more unusual visual experiences but not with psychotic symptoms in the past two weeks. Among those who had used psychedelics, 1.3% reported a diagnosis of hallucinogen persisting perception disorder. An interaction emerged: individuals with a family history of psychotic or bipolar disorders who used psychedelics reported more psychotic symptoms, while those without such a family history reported fewer. The findings suggest that family history may modify the association between psychedelic use and psychotic symptoms.
Journal of psychopharmacology (Oxford, England)
September 1, 2019
James D. Sexton, Michael S Crawford, Noah W Sweat et al.
33 citations
Novel psychedelics, such as 2C-B, 2C-I, and 2C-E, are used by a very small fraction of the U.S. adult population (0.12%). Users tend to be younger, male, White, more educated but with lower income, and almost all have also used classic psychedelics. Compared to those who have used only classic psychedelics, people who have used novel psychedelics are more likely to report past-year suicidal thinking and planning, though novel psychedelic use alone is not associated with psychological distress or suicidality. The findings suggest novel psychedelics may differ from classic psychedelics in their mental health associations, but more research is needed.
Am J Psychiatry
January 1, 2024
Kelley C. O’donnell, Brian T Anderson, Frederick S. Barrett et al.
31 citations
This critical response addresses misinterpretations and omissions in a commentary by Goodwin and colleagues on psilocybin-assisted therapy, arguing that the commentary misrepresents existing evidence and overlooks key methodological issues. The authors contend that the commentary fails to adequately discuss safety concerns, including adverse events and the potential for psychological distress, and omits important data on long-term outcomes. They emphasize the need for rigorous, balanced evaluation of psilocybin-assisted therapy's risks and benefits, cautioning against overstating positive outcomes while underreporting negative findings. The response calls for more transparent reporting and careful interpretation of clinical trial results.
Neuropharmacology
April 2, 2023
Farah Z Zia, Michael H. Baumann, Sean J Belouin et al.
28 citations
Chronic pain is a leading cause of disability and opioid overdose in the United States. While many people manage pain with existing medicines and psychosocial treatments, others find these options ineffective or unacceptable due to side effects and risks. Preliminary evidence suggests psychedelics may improve quality of life, functionality, and reduce disability and distress for people whose pain may never be completely relieved. This commentary calls for more basic research and clinical trials to explore psychedelics' potential in chronic pain management, and to determine whether effects stem from direct antinociceptive or anti-inflammatory mechanisms, or from increased tolerability, acceptance, and spirituality that mediate therapeutic effects seen in psychiatric disorders.
Neuropharmacology
May 13, 2022
Cynthia E. Ortiz, Haley Maria Dourron, Noah W Sweat et al.
26 citations
Psilocybin-facilitated psychotherapy may be effective across many mental health conditions, but vulnerable populations, who carry a disproportionate mental health burden, have been largely excluded from clinical research. This report highlights the need to include these groups in studies, considering their problematic historical context and differential experiences with psychedelics. It offers actionable recommendations for future research, such as improved recruitment strategies, careful communication of subjective effects, building therapeutic alliance, multicultural competence, and flexible study designs. The authors call for expanded and improved research in this rapidly advancing field.
Therapeutic Advances in Psychopharmacology
January 1, 2022
Otto Simonsson, Peter S. Hendricks, Richard Chambers et al.
26 citations
In a US-representative sample of 2822 adults, lifetime use of classic psychedelics was linked to healthier tobacco-related and diet-related behaviors. Among the 613 who had used psychedelics, greater psychological insight during their most insightful experience was associated with healthier exercise habits, a healthy body mass index, and diet improvements. Psychological insight was also tied to self-reported health behavior improvements attributed to the psychedelic experience, including alcohol-related changes. The findings suggest that psychological insight during a classic psychedelic experience may promote positive health behavior change and better physical health, especially in weight management, though causality cannot be established.