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.
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.
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.
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.
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.
Psychopharmacology
December 11, 2023
Haley Maria Dourron, Charles D Nichols, Otto Simonsson et al.
23 citations
5-MeO-DMT, a tryptamine being developed as an antidepressant, may work through a mechanism distinct from typical psychedelics. This review compares the acute and post-acute effects of 5-MeO-DMT to epileptiform activity, particularly in temporal lobe epileptogenic zones. The authors note that 5-MeO-DMT has notable 5-HT1A receptor agonist properties and that aberrant 5-HT1A receptor functioning occurs in epilepsy. They suggest that 5-MeO-DMT's therapeutic mechanism might be partly mediated by evoking temporary epileptiform activity, similar to electroconvulsive therapy. The phenomenon of 'reactivations'—sudden re-experiencing of drug effects common after 5-MeO-DMT but not typical psychedelics—may indicate recurrent epileptiform activity. The review concludes that further evaluation of 5-MeO-DMT's unique mechanisms is warranted.
JAMA psychiatry
January 1, 2023
Brian D Kiluk, Bethea A Kleykamp, Sandra D Comer et al.
22 citations
A review sponsored by a public-private partnership addresses clinical trial design for new opioid use disorder (OUD) treatments that target systems other than the μ-opioid receptor. The authors present consensus recommendations for evaluating novel therapies such as cannabinoids, psychedelics, sedative-hypnotics, and immunotherapeutics. Key design elements include specifying the treatment stage (e.g., early abstinence, long-term recovery), defining the treatment's role (adjunctive or independent), selecting patient-informed primary outcomes that assess opioid use patterns, retention, and quality of life, and monitoring adverse events like relapse or overdose, especially when patients are not on maintenance opioid agonist or antagonist medications. Incorporating input from people with lived experience is urged to accelerate development and uptake of effective therapeutics.
Psychopharmacology
January 1, 2025
Brian S Barnett, M Frances Vest, Marcus S Delatte et al.
20 citations
Establishing psychedelic research programs at academic medical centers in the United States faces unique obstacles because psychedelics are intensely psychoactive, carry sociopolitical baggage, and most are Schedule I drugs. This article reviews academic literature and draws on the authors' experiences with regulatory agencies and conducting basic science, investigator-initiated, and industry-sponsored psychedelic trials. It recommends that investigators cultivate broad institutional support early and anticipate challenges in securing funding, obtaining FDA Investigational New Drug approval, sourcing clinical-grade drug, getting DEA Schedule I researcher registration and any required state license, preparing treatment and storage spaces, managing controlled substance inventory, and engaging the local community. With planning, persistence, and expert assistance, these hurdles are likely surmountable.
Drug and alcohol dependence
October 1, 2022
Otto Simonsson, Simon B Goldberg, Richard Chambers et al.
16 citations
Among a US-representative sample of 2,822 adults, 613 reported lifetime classic psychedelic use, and 1.5% of those users reported having a seizure while using a classic psychedelic—a rate similar to epilepsy prevalence in the general population. Nearly half of those who had a seizure were also taking antidepressants, mood stabilizers, or opioid replacement therapies at the time. Seizures were more common among respondents with a personal or family history of epilepsy. The findings suggest that classic psychedelic use may elevate seizure risk in certain people, especially those with a personal or family history of epilepsy.
Psychological medicine
April 1, 2024
Otto Simonsson, Walter Osika, Cecilia U D Stenfors et al.
15 citations
People who used psychedelics during a two-month period reported a greater increase in days of mindfulness meditation per week than those who did not. Among psychedelic users, experiencing personal insight during the most intense psychedelic session was linked to larger increases in both mindfulness and loving-kindness or compassion meditation practice. Conversely, more frequent loving-kindness or compassion meditation at the start of the study was associated with less severe feelings of death or dying during the subsequent psychedelic experience. These findings suggest a bidirectional relationship: psychedelics may boost meditation engagement, while meditation may reduce challenging psychedelic experiences.
Mindfulness
April 1, 2023
Charlotta Simonsson, Richard Chambers, Peter S Hendricks et al.
15 citations
People who have used classic psychedelics report meditating more often, specifically mindfulness meditation, but not loving-kindness or compassion meditation. Among those who had a psychedelic experience, both psychological insight and ego dissolution were linked to more frequent practice of both types of meditation. However, when both factors were considered together, only psychological insight predicted higher meditation frequency. These findings, from a survey of 2,822 U.S. adults, suggest that psychedelic experiences—especially those that produce psychological insight—may encourage regular meditation, though causality cannot be established.
Pharmacological research
January 1, 2024
David B Yaden, Andrea P Berghella, Peter S Hendricks et al.
12 citations
Classic psychedelic-assisted therapies show initial promise for treating substance use disorders (SUDs) and may become legally available options. This article describes how these therapies could fit within current evidence-based SUD treatments, suggesting broad compatibility with most mainstream clinical approaches.
Journal of affective disorders
July 9, 2025
Otto Simonsson, Peter S Hendricks, Caroline M Swords et al.
8 citations
In a large observational study of US adults aged 18–50, naturalistic psychedelic use was modestly linked to increased depressive symptoms over time. Among 12,345 participants followed longitudinally, 505 reported psychedelic use. Those who used psychedelics in a 'risk context'—such as a negative mindset or lack of psychological support—showed a moderate increase in depressive symptoms compared to non-users and to users without such risks. This association was explained by more challenging psychedelic experiences in that context. The findings indicate that psychedelic use outside controlled therapeutic settings may not be generally beneficial and could worsen depressive symptoms under certain conditions.
International review of psychiatry (Abingdon, England)
December 1, 2024
Sean P Goldy, Peter S Hendricks, Dacher Keltner et al.
8 citations
This review discusses how psychedelics produce acute subjective effects, including positive emotions such as awe and joy, and outlines the science of positive emotions. Despite a rich literature on distinct emotions and their different correlates and consequences, distinct emotions in psychedelic science remain understudied. Understanding the role of specific positive emotions in psychedelic experiences could help clarify the connection between the acute subjective effects of psychedelics and their therapeutic outcomes, such as decreased depression, anxiety, and substance misuse.
Psychedelic medicine (New Rochelle, N.Y.)
June 1, 2025
Haley Maria Dourron, Melissa Bradley, Otto Simonsson et al.
7 citations
Greater lifetime psychedelic use was not associated with psychotic symptoms in a cross-sectional survey of 548 adults, even among those with a personal or family history of psychotic or bipolar disorders. In unadjusted analyses, more psychedelic use was linked to less referential thinking, but this association disappeared after adjusting for covariates. A personal history of psychotic disorders was tied to moderately greater magical ideation, referential thinking, and auditory hallucinations, while family history of psychotic disorders related to slightly greater negative symptoms. Notably, among individuals with a personal history of psychotic disorder, auditory hallucinations were less severe as psychedelic use increased, with no such relationship in those without that history. Naturalistic psychedelic use may not heighten psychosis risks.
Irish Journal of Psychological Medicine
November 7, 2024
Andrew Gribben, Tara Burke, Colm Harrington et al.
5 citations
A survey of 151 psychiatrists in Ireland found that most hold positive attitudes toward psilocybin therapy: 81.5% agreed it shows promise for treating psychiatric disorders, 86.8% supported funding research, 86.8% would refer a patient if licensed, and 78.1% would consider it for themselves. However, only 40.0% felt knowledgeable and just 9.9% felt adequately prepared to participate. A minority expressed concerns: 6.6% thought it unsafe under medical supervision, 21.9% considered it potentially addictive, and 15.9% reported at least one concern about evidence, effectiveness, safety, cost, or impartiality. Consultant psychiatrists were less optimistic than trainees about its role in bipolar depression and emotionally unstable personality disorder.
Frontiers in psychology
January 1, 2023
Otto Simonsson, Cecilia U D Stenfors, Simon B Goldberg et al.
4 citations
Mindfulness meditation and psychedelic use are both associated with positive impacts on leadership, though through different mechanisms. In a representative sample of 3,150 managers in the US and UK, more lifetime hours of mindfulness meditation and greater psychological insight during the most intense psychedelic experience each independently predicted a positive leadership impact (odds ratios 2.33 and 3.49, respectively). Both practices shared subthemes such as improved focus, creativity, patience, empathy, and compassion. Unique to mindfulness were better sleep, stress reduction, and calming effects; unique to psychedelics were greater self-understanding, less hierarchical attitudes, and positive interpersonal changes. The cross-sectional design precludes causal conclusions, but the findings suggest complementary benefits for leadership development.
The Journal of rural health : official journal of the American Rural Health Association and the National Rural Health Care Association
January 1, 2025
Melissa Bradley, Daniel Grossman, Otto Simonsson et al.
1 citation
Rural residents in the United States are 1.2 to 1.4 times more likely than urban residents to perceive using LSD once or twice as of great risk, based on national survey data from 2015 to 2021. The perception of monthly cannabis use as having great risk was slightly higher among rural residents only until 2019, with no significant differences in 2020 and 2021. These rural-urban differences in risk perception could influence policymaking on psychedelic therapies and highlight the need for equitable policies.
Research square
May 19, 2026
Sunjuri Sun, Claudia Hanson, Peter S Hendricks et al.
The evidence on child and maternal outcomes after exposure to classic psychedelics during pregnancy is very sparse and of very low certainty. A systematic review of 42 studies, mostly case reports from high-income countries, found that LSD was the most commonly reported substance. Outcomes reported included spontaneous abortions (2 studies), stillbirth (1 study), neonatal mortality (16 studies), preterm birth (17 studies), birthweight (15 studies), and congenital malformations (26 studies). No maternal deaths were reported. Because of small sample sizes and varied study designs, no meta-analysis was possible. The authors conclude that methodologically rigorous research on psychedelic use during pregnancy is urgently needed.
Drug and alcohol dependence
July 1, 2025
Dilara Bahceci, Krista Siefried, Maureen Steele et al.
Among 268 people who used methamphetamine, nearly half had a diagnosed mental illness and were at risk of suicide, and most had taken other substances besides methamphetamine and psychedelics. Most psychedelic experiences were unplanned, recreational, and combined with other drugs. After the experience, about 59% reported improved mood, 50% improved social functioning, and 34% reduced methamphetamine use. Planning the experience and having less challenging experiences were linked to better outcomes. The findings suggest that psychedelic use may improve mood and social function and reduce substance use in this population, but highlight the importance of context and setting.
Journal of psychopharmacology (Oxford, England)
January 1, 2024
Otto Simonsson, Peter S Hendricks, Cecilia Ud Stenfors et al.
A longitudinal study with nearly 10,000 US and UK adults found that people who used psychedelics during a two-month period reported greater increases in unusual visual experiences compared to those who did not. The effect was strongest among first-time users. These visual experiences occurred after the acute drug effects had worn off. The findings support earlier case reports and cross-sectional studies suggesting that naturalistic psychedelic use may be linked to persistent visual phenomena, though further longitudinal research is needed to clarify cause-and-effect relationships.