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.
Journal of Psychopharmacology
March 1, 2022
Neiloufar Family, Peter S. Hendricks, Luke T. J. Williams et al.
23 citations
LSD doses of 50, 75, and 100 micrograms are tolerable and safe in healthy adults when administered in a novel group-based intervention paradigm with one attendant per participant. Thirty-two adults (mean age 28.8 years) received LSD or placebo across open-label and double-blind designs. No serious adverse events occurred; 28% of participants reported at least one mild expected adverse event and one moderate event. Peak blood plasma levels appeared 1.2 to 2 hours after administration, with an apparent half-life of 2.8 to 4.3 hours. LSD produced greater subjective effects than placebo, including mystical-type experiences. Further research is needed in clinical populations.
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.
Psychiatr Res Clin Pract
February 11, 2025
Jules Evans, Marc Aixalà, Brian T Anderson et al.
18 citations
Thirty psychedelic researchers identified critical gaps in knowledge about harms from psychedelic use, including how to define those harms, predict them, and treat them effectively. They recommend better online information, peer support groups, affordable therapy, and psychiatric consultation for people experiencing post-psychedelic difficulties. The researchers also call for improved funding for a psychedelic safety net, suggesting that psychedelic philanthropists, investors, and companies commit 1% of their investment to support safety measures such as research and support services. The article outlines practical steps to make the field of psychedelic medicine safer.
Psychol Med
March 31, 2025
Otto Simonsson, Simon B. Goldberg, Walter Osika et al.
16 citations
In a large online survey of over 12,000 participants followed for two months, people who used psychedelics outside of medical supervision reported increases in psychotic and manic symptoms. These increases occurred only among those who used psychedelics in an illegal context. The severity of psychotic symptoms rose with more frequent use and more intense challenging experiences, while manic symptoms increased more in individuals with a history of schizophrenia or bipolar I disorder and those who reported a strong sense of insight during their psychedelic experience. The findings suggest that naturalistic psychedelic use in illegal settings may pose risks for certain individuals.
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.
Journal of Psychopharmacology
November 30, 2016
Richard C. Shelton, Peter S. Hendricks
14 citations
No Summary
Journal of Drug Issues
August 30, 2019
Blake Beaton, Heith Copes, Megan Webb et al.
13 citations
People who microdose classic psychedelics such as LSD and psilocybin do not excuse their practice but instead justify it using six main strategies: denying that it causes harm, claiming it helps sustain themselves, pursuing self-fulfillment, appealing to normality, citing loyalty to valued groups, and emphasizing their knowledgeable. These justifications help align their actions with societal expectations. The findings come from interviews with 30 individuals who had microdosed.
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.
Psychedelic Med (New Rochelle)
December 13, 2023
Nicholas A. Carlisle, Haley Maria Dourron, Sarah Maccarthy et al.
12 citations
Chronic shame, often stemming from internalized stigma, disproportionately affects sexual and gender minority (SGM) adults and undermines mental health. This theoretical and philosophical paper argues that psychedelic-assisted therapy holds unique potential to reduce such shame by disrupting rigid self-narratives and fostering self-compassion. The authors suggest that the pharmacological and contextual features of psychedelic experiences—particularly enhanced emotional openness and mystical-type experiences—may directly target shame-related neural and psychological processes. They propose that psychedelic therapy could offer SGM individuals a reparative pathway toward healing and psychological wellness, distinct from conventional treatments. The paper calls for further empirical investigation into psychedelics as a tailored intervention for chronic shame in this population.
Nature Mental Health
May 1, 2025
Daniel H. Grossman, Kevin R. Madden, Nicky J. Mehtani et al.
10 citations
Socioeconomic status (SES) strongly affects mental health outcomes and treatment access, but its reporting in psychedelic-assisted therapy trials is inadequate. A systematic review of 98 articles (49 primary trials and 49 secondary analyses) from 2006 to 2024 found that only 12% of primary trials reported participant income data, and 31% reported educational attainment. In US-based trials, participants had markedly higher SES than the general population: 93% had some college education (versus 62% nationally), and median incomes in major trials substantially exceeded the national median for all workers. Non-US trials showed variable patterns. This underreporting and evidence of socioeconomic disparities highlights an urgent need for standardized SES reporting and strategies to improve socioeconomic diversity in psychedelic-assisted therapy research.
JAMA Health Forum
November 1, 2024
Otto Simonsson, Matthew W. Johnson, Peter S. Hendricks
10 citations
Psychedelic and MDMA therapies carry potential risks that must be better understood to ensure safe and ethical practice. This viewpoint identifies four key research goals: characterizing adverse effects, understanding how context influences outcomes, developing risk mitigation strategies, and establishing guidelines for safe administration. The authors argue that rigorous investigation of these risks is essential before widespread clinical adoption, emphasizing that safety concerns should be addressed proactively rather than reactively.
Psychedelic Medicine
January 20, 2025
Marianna Graziosi, Gabrielle Agin-Liebes, Mary P Cosimano et al.
9 citations
Psilocybin and other serotonergic psychedelics are used in research settings with safety measures including controlled environments, staff presence, screening, and psychoeducation. An analysis of study materials from psilocybin trials over the past two decades found that psychoeducation documents varied but commonly emphasized biological and physical safety, psychological safety and well-being, aspects of setting, and the potential for expectancies. The materials prioritized biological and psychological safety across all sites. The authors also identified elements unrelated to safety that may contribute to participant expectancies and suggest these extrapharmacological factors be studied systematically to maximize safety while minimizing extraneous expectancies.
Scientific Reports
August 2, 2024
Jennifer Mitchell, Nicky J. Mehtani, Mallory O. Johnson et al.
9 citations
HIV-related shame predicts substance use and poor antiretroviral adherence among people with HIV, hindering national epidemic-ending goals. In a pilot clinical trial with 12 participants, psilocybin-assisted group therapy produced a large decrease in HIV-related shame, with a median reduction of 5.5 points on the HIV and Abuse Related Shame Inventory from baseline to 3-month follow-up. However, two participants experienced a paradoxical worsening of sexual abuse-related shame after psilocybin, raising concerns about its use in patients with trauma. These preliminary results suggest potential for addressing HIV-related shame but highlight cautions.
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.
Journal of Psychopharmacology
March 1, 2022
Peter S. Hendricks, Heith Copes, Neiloufar Family et al.
8 citations
In a proof-of-concept study with 31 healthy participants given 50 to 100 µg of LSD, most felt safe throughout the experiment, attributing their comfort to the study structure and support from attendants, which allowed them to let go and immerse themselves. A minority initially worried about having a challenging experience, but those concerns lessened over time. Participants reported transcendent, mystical-type experiences typical of classic psychedelics, with nearly half noting the important role of music during the drug's acute effects. They endorsed the clinical utility of LSD in controlled environments, believing it is safe and could help others. Findings suggest this scalable intervention paradigm is feasible and warrants further research with clinical populations.
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.
Psychedelic Med (New Rochelle)
March 13, 2023
Peter S. Hendricks, Charles D. Nichols, Kathryn A. Cunningham et al.
7 citations
A roundtable discussion among experts traces the history, current state, and future directions of psychedelic medicine. Participants review the early research era of the mid-20th century, the subsequent decades of prohibition, and the recent resurgence of clinical trials exploring psychedelics for mental health conditions. The conversation highlights therapeutic applications of substances such as psilocybin and MDMA, emphasizing their potential to treat depression, PTSD, and addiction. Experts also address challenges including regulatory hurdles, the need for trained therapists, and the importance of integrating these treatments into mainstream healthcare. The discussion concludes with cautious optimism about the field's trajectory.
Journal of Psychopharmacology
October 1, 2022
Grant Jones, Jocelyn A. Ricard, Peter S. Hendricks et al.
7 citations
Lifetime use of MDMA (ecstasy) is associated with better self-reported physical health, including lower risks of overweight/obesity, heart conditions, cancer, hypertension, and diabetes, along with higher odds of reporting good overall health. These associations emerged from a large, nationally representative U.S. sample, controlling for potential confounders. The findings suggest protective links between ecstasy use and various physical health markers, but the authors call for longitudinal studies and clinical trials to confirm causality.
JAMA Network Open
March 10, 2026
Mw Johnson, Gideon P. Naudé, Peter S. Hendricks et al.
6 citations
A single high dose of psilocybin combined with cognitive behavioral therapy (CBT) led to significantly higher long-term smoking abstinence rates than nicotine patch treatment plus CBT. At six months, 40.5% of participants who received psilocybin had biochemically verified prolonged abstinence, compared to 10.0% of those using the nicotine patch. No serious adverse events were attributed to either treatment. The pilot trial randomized 82 psychiatrically healthy adult smokers and used an intention-to-treat analysis. The findings suggest psilocybin-assisted therapy may be a promising intervention for tobacco smoking cessation.
Journal of Psychoactive Drugs
February 10, 2024
Alyssa F. Harlow, Peter S. Hendricks, Adam M. Leventhal et al.
6 citations
Among 2,396 young adults aged 18-22 in Southern California surveyed in 2018-2019, 12% had heard of microdosing psychedelics and 3% had ever tried it. Of those aware of microdosing, 79% correctly defined it as taking a much lower than standard dose, but 15% mistakenly thought it meant a standard dose. Psilocybin was the most commonly microdosed drug (70%), followed by LSD (57%). About 18% of those who microdosed reported using doses far higher than a typical microdose. Factors associated with having ever microdosed included white race, male/masculine gender identity, bisexual identity, past 6-month other drug use, greater ADHD symptoms, mindfulness, and sensation-seeking. The findings suggest microdosing merits attention to prevent misperceptions and potential harms while exploring therapeutic uses.