J Psychopharmacol
February 2, 2022
Anne K. Schlag, Jacob S. Aday, Iram Salam et al.
319 citations
Classic psychedelics carry minimal medical risks such as toxicity and overdose, and many persistent negative perceptions of psychological risks—including abuse liability and dependence—are unsupported by current scientific evidence when use occurs in regulated or medical contexts. Most reported adverse effects are not observed under these conditions. The review underscores the need for clinicians and therapists to maintain high safety and ethical standards and for balanced media reporting to avoid future controversies and allow continued research.
Neuroscience & Biobehavioral Reviews
March 16, 2020
Jacob S. Aday, Cayla M. Mitzkovitz, Emily K. Bloesch et al.
260 citations
A systematic review of 34 experimental studies on classic psychedelics with follow-up periods of at least two weeks found lasting changes in personality, attitudes, depression, spirituality, anxiety, wellbeing, substance misuse, meditative practices, and mindfulness. Psilocybin was the most commonly administered drug. Mystical experiences, connectedness, emotional breakthrough, and increased neural entropy were linked to these long-term psychological changes. With proper screening, preparation, supervision, and integration, participants reported few aversive side effects. The review calls for larger, more diverse samples, longer longitudinal designs, stronger control conditions, and standardized dosages in future research.
ACS Pharmacol Transl Sci
March 5, 2021
Jacob S. Aday, Alan K. Davis, Cayla M. Mitzkovitz et al.
228 citations
People who are more open, accepting, and prone to absorption, as well as those who enter a psychedelic session with a mindset of surrender, are more likely to have positive, mystical-type experiences. Conversely, individuals who are low in openness or surrender, or who arrive in a preoccupied, apprehensive, or confused state, are more likely to experience adverse reactions. A systematic review of 14 studies found that sex is not a robust predictor of drug effects, but certain brain-based measures—such as 5-HT2AR binding potential, executive network node diversity, and rACC volume—may serve as biomarkers. Older age and prior experience with psychedelics are linked to less intense effects, suggesting users may become slightly less sensitive after repeated use.
Psychopharmacology
April 1, 2022
Jacob S. Aday, Boris D. Heifets, Steven D. Pratscher et al.
214 citations
Psychedelic research faces unique methodological challenges beyond those typical of psychotherapy and pharmacology trials. The pronounced subjective effects of high-dose psychedelics make it difficult to mask participants to their treatment condition. Positive media coverage inflates participants' expectations for benefit, and unmasking combined with expectations can produce large placebo and nocebo effects. Recommendations to improve masking and reduce expectancy bias include careful study development, participant recruitment and selection, incomplete disclosure of study design, choice of active placebo, and measurement of expectations and masking efficacy. Incorporating these design elements aims to reduce bias and improve the ability to discern treatment-specific effects.
Drug Science Policy and Law
January 1, 2020
Jacob S. Aday, Emily K. Bloesch, Christopher C. Davoli
59 citations
Public and scientific interest in psychedelic drugs increased steadily over two decades and then grew exponentially in recent years, with 2019 bringing notable changes in science, industry, and deregulation. The article synthesizes these developments, including the establishment of psychedelic research centers, novel drug applications, and international expansion that solidified the field's place in science. Business and pharmaceutical industries stimulated considerable investment and innovation in psychedelics for the first time. In the US, successful decriminalization efforts and endorsements by political figures like Alexandria Ocasio-Cortez, Andrew Yang, and heads of the NIH and FDA represented unprecedented regulatory changes. The article serves as a summary of emerging research themes, industrial innovations, and attitude shifts in 2019.
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.
Ther Adv Psychopharmacol
August 14, 2020
Jacob S. Aday, Christopher C. Davoli, Emily K. Bloesch
50 citations
Psychedelic drugs and virtual reality (VR) both disrupt the rigidity of typical conscious experience. They alter sensory experience and evoke awe, and each is used alongside traditional therapies to treat mood disorders by transiently shifting perspective and disrupting rigid mental patterns. Recreational users already combine psychedelics and VR to enhance their experience. The authors propose VR could prepare hallucinogen-naïve clinical trial participants for the sensory distortions of psychedelic states and optimize the environment in psychedelic sessions. The article outlines connections between psychedelics and VR, reflecting growing scientific interest in technology, psychopharmacology, and mental health.
Psychedelic Medicine
February 16, 2023
Zachary Skiles, Noa Eaton, Lisa Fredenburg et al.
49 citations
Most psychedelic therapists in a Usona Institute trial for psilocybin and major depressive disorder had personal experience with psychedelics: 88% had used at least one serotonergic psychedelic, most commonly psilocybin (81%), with a median of 2–10 uses and last use 6–12 months before the survey. The sample was predominantly white, female, and held doctoral degrees. All endorsed favorable views of psilocybin therapy. Experiential learning is common in psychotherapy but not psychiatry, placing psychedelic therapy between two traditions. The study was limited by a low response rate (22%) and lack of diversity. These first data on professionals' personal use inform the debate on whether such experience aids competency or introduces bias.
JAMA Psychiatry
June 1, 2023
Jacob S. Aday, Robin Carhart-Harris, Joshua Woolley
48 citations
The abstract discusses emerging challenges for psychedelic therapy, highlighting obstacles such as regulatory hurdles, accessibility issues, equity concerns, and the need for practitioner training. It underscores difficulties in integrating psychedelic treatments into mainstream healthcare, including governance, legal frameworks, and developing accessible and equitable treatment models. The text suggests that responsible integration requires addressing these barriers to ensure safe and effective mental health care.
Psychopharmacology
August 1, 2024
Jacob S. Aday, David Horton, Gisele Fernandes-Osterhold et al.
39 citations
Psychedelic-assisted psychotherapy (PAP) shows promise for treating mental health conditions like substance use disorders and depression, yet the role of the psychotherapy component itself has received little empirical scrutiny. This review examines current debates over whether PAP involves full psychotherapy or merely psychological support, and summarizes existing clinical trial models and theoretical frameworks. It draws lessons from traditional psychotherapy research, advocating for standardized treatment manuals, clear provider eligibility criteria, measurement of established mechanisms of change, and optimized trial designs such as dismantling studies and comparative efficacy trials. The authors argue that PAP is a distinct, integrative, transdisciplinary intervention requiring further research into its psychotherapeutic components to inform best practices and federal guidelines.
Drug Science Policy and Law
January 1, 2019
Jacob S. Aday, Christopher C. Davoli, Emily K. Bloesch
30 citations
Interest in psychedelic drug research grew over the last decade, but 2018 marked a true turning point for the field, especially in the United States. That year saw substantive advances in scientific, public, and regulatory communities. Scientific progress came from impactful research applications and acknowledgment in top journals. Michael Pollan's book "How to Change Your Mind" became a commercial hit and spurred positive media coverage. Unprecedented psychedelic ballot initiatives reflected shifting public interest. Regulatory bodies began acknowledging psychedelic science in earnest, highlighted by the FDA granting psilocybin-assisted psychotherapy "breakthrough therapy" status for treatment-resistant depression. 2018 was a seminal year for psychedelic science.
Nature Medicine
June 3, 2025
Chloé Pronovost-Morgan, Kyle T. Greenway, Leor Roseman et al.
26 citations
A Delphi consensus study with 89 experts from 17 countries identified 30 extra-pharmacological variables that are important or very important for reporting the setting in psychedelic clinical trials. These variables, forming the ReSPCT guidelines, cover physical environment, dosing session procedure, therapeutic framework and protocol, and subjective experiences. The findings reveal significant ambiguities in current conceptualizations of set and setting. The guidelines provide a new standard for designing and documenting contextual factors in psychedelic research.
Int J Neuropsychopharmacol
April 1, 2025
Jacob S. Aday, Otto Simonsson, Emmanuelle A. D. Schindler et al.
25 citations
Classic psychedelics show promise for treating neuropsychiatric disorders, but weak blinding integrity in clinical trials limits the interpretability of therapeutic effects, making alternative active placebos necessary. This review describes drawbacks of current placebos, proposes criteria for suitable active placebos—including acute psychoactive and physiological effects, matched onset and duration, safety, and lack of therapeutic effects for the target disease—and identifies several pharmacological agents that may serve as active placebos for moderate-to-high doses of short- and long-acting psychedelics, as well as low-dose and microdosing regimens. Future research should apply a thoughtful selection process and ancillary strategies to improve blinding.
December 1, 2021
Jacob S. Aday, Boris D. Heifets, Steven D. Pratscher et al.
20 citations
preprint
Clinical trials of psychedelic therapy face unique methodological challenges that threaten the interpretability of results. The intense subjective effects of high-dose psychedelics make it difficult to mask participants to their treatment condition, and widespread positive media coverage inflates participants' expectations for benefit. Participant unmasking and treatment expectations can interact, making psychedelic therapy highly susceptible to large placebo and nocebo effects. Recommendations to improve rigor include careful study development, participant recruitment and selection, incomplete disclosure of the study design, choice of active placebo condition, and measurement of participant expectations and masking efficacy. Incorporating these design elements is intended to reduce bias and increase the ability to discern treatment-specific effects.
Psychedelic medicine (New Rochelle, N.Y.)
March 1, 2025
Daniel J. Kruger, Jacob S. Aday, Christopher W Fields et al.
19 citations
In an anonymous online survey of 1,221 people who reported past psychedelic use, most described adverse experiences: 74.3% felt frightened, 58.6% sadness, 54.3% body shaking or trembling, and 51.6% loneliness. About half reported some other adverse experience, and one in ten had adverse physical reactions. One-third knew someone arrested for possession or use of psychedelics; 8% reported that they or someone they know was the victim of inappropriate sexual contact by a psychedelic sitter, guide, or practitioner; and one-quarter knew someone who experienced a severe adverse event other than inappropriate sexual contact or arrest. The findings indicate that despite beneficial effects, psychedelic experiences can be challenging, distressing, or harmful, highlighting the need to prevent, identify, manage, and treat adverse events.
Journal of Psychoactive Drugs
March 6, 2019
Jacob S. Aday, Emily K. Bloesch, Christopher C. Davoli
19 citations
The surge in psychedelic research during the 1950s and 1960s is often attributed primarily to the discovery of LSD's psychoactive effects in 1943. This article argues that such a 'Great Person' or 'Great Chemical' historiographical lens overlooks other crucial factors. Mescaline was already being studied for psychotherapy and as a psychosis model before LSD. Psilocybin and other psychedelics were also discovered by Western researchers around the same time. Furthermore, dominant zeitgeists in psychology—pharmacological, psychoanalytic, and humanistic—were congruent with psychedelic research. While LSD's discovery may have been a catalyst, a broader psychedelic zeitgeist deserves recognition for setting the stage.
Frontiers in Pain Research
March 18, 2025
Jenna McAfee, Avinash Hosanagar, Vijay Tarnal et al.
18 citations
In a small open-label pilot trial, five people with fibromyalgia received two doses of psilocybin (15 mg and 25 mg) along with psychotherapy. The treatment was well-tolerated: there were temporary increases in blood pressure or heart rate during dosing that returned to normal, no serious adverse events, and four of five participants had short-lived headaches. One month after the second dose, participants reported large reductions in pain severity, pain interference, and sleep disturbance. One participant rated their symptoms as very much improved, two as much improved, and two as minimally improved. Recruitment stopped early due to generalizability concerns and changing FDA guidance, but the results suggest psilocybin-assisted therapy is safe for fibromyalgia and warrants larger trials.
J Psychopharmacol
December 13, 2021
Ben Sessa, Jacob S. Aday, Steve O’Brien et al.
18 citations
An open-label study of 14 participants found that mood remained positive during the week after receiving MDMA in a clinical setting, contrary to the 'Blue Monday' crash reported by recreational users. Self-reported sleep quality improved at 3- and 6-month follow-ups compared to baseline. No participants used or desired to use illicit MDMA, and anecdotal reports were favorable. The findings suggest that negative after-effects previously associated with MDMA may stem from confounds such as illicit drug sourcing and recreational settings, rather than the drug itself.
Journal of Psychoactive Drugs
January 1, 2025
Jacob S. Aday, Emily K. Bloesch, Alan K. Davis et al.
16 citations
People who attended an ayahuasca retreat reported lasting increases in gratitude, feeling connected to nature, and appreciating nature. Surveys of 54 participants taken one week before, one week after, and one month after the retreat showed significant improvements at both follow-ups compared to baseline. The intensity of mystical-type experiences and awe during ayahuasca sessions weakly to moderately correlated with these increases, while the number of ceremonies attended did not. Older participants reported less intense mystical and awe experiences. The findings suggest that the quality of psychedelic experiences, particularly mystical and awe states, may foster prosocial changes in gratitude and nature connection.
Frontiers in Psychiatry
January 1, 2024
Nicolas G. Glynos, Jacob S. Aday, Daniel J. Kruger et al.
15 citations
A large global survey of 5,268 adults who had used psychedelics found that nearly three-quarters (70.9%) reported ceasing or decreasing use of at least one non-psychedelic substance afterward. Among those who had previously used specific substances, 60.6% decreased alcohol use, 55.7% decreased antidepressant use, and 54.2% decreased cocaine or crack use. Over a quarter said the decrease lasted 26 weeks or longer. However, 19.8% reported increased or initiated use of other substances, most commonly illicit opioids (14.7%) and cannabis (13.3%). Factors linked to decreased use included motivation to reduce substance use or self-treat a medical condition; increased use was associated with higher income and residing in Canada or the US.
Drug Science Policy and Law
September 1, 2025
David Nutt, David Erritzøe, Anne Katrin Schlag et al.
9 citations
The field of psychedelic research lacks standardized terminology for clinical development, dosing, safety monitoring, and regulatory classification. A comprehensive framework is proposed that classifies psychedelics by pharmacology (serotonergic, glutamatergic, kappaergic, GABAergic, and atypical), introduces dose-dependent categories (microdose, minidose, mididose, macrodose), and standardizes terms like “short-acting” with specific pharmacokinetic parameters. Safety considerations include cardiovascular and psychological effects, with risk mitigation protocols for higher-risk compounds like ibogaine. A three-phase treatment model—preparation, dosing, and integration—is recommended as a minimum standard. The lack of comparative research on psychotherapy modalities is identified as a critical gap.
Journal of Psychoactive Drugs
September 19, 2024
Anne Baker, Niloufar Pouyan, Julie Barron et al.
9 citations
A survey of 107 people who provide psychedelic support services outside clinical trials found that 40.2% held a full or in-progress license and 44.9% lacked a relevant graduate degree. Almost all practitioners pre-screened clients, offered preparation, integration, and trip-sitting, and used primarily non-directive approaches. Clients most often consumed psilocybin for conditions similar to those in clinical research. Practitioners perceived mostly positive symptom changes, though a small proportion reported worsened personality disorder symptoms. Further research on naturalistic psychedelic-assisted therapy is needed.
The Journal of Sex Research
March 28, 2025
Daniel J. Kruger, Eirini K. Argyri, Justin K. Mogilski et al.
7 citations
A survey of 581 participants found that most (70.2%) reported psychedelic experiences affected their sexuality or sexual experiences, with 65.4% noting short-term effects and 52.8% reporting long-term effects. Psychedelic experiences were more often associated with enhanced relationship quality, attraction to partners, and sexual activities than with diminished ones. About 10% reported influences on gender identity or expression, citing increased authenticity and openness. One-quarter of women and one-eighth of men reported heightened same-sex attraction after use. More participants reported being polyamorous or in open relationships after psychedelic experiences than before. Effects were linked to larger doses, more frequent use, younger age, and identifying as a woman or gender diverse.
British Journal of Pain
February 11, 2025
Anne Baker, Stephanie Lake, Philippe Lucas et al.
7 citations
Most people with chronic pain who use psychedelics to self-treat report ceasing or decreasing their use of other substances, especially alcohol and prescription opioids. In a survey of 466 adults, 86.3% said they stopped or reduced at least one non-psychedelic substance because of psychedelic use, with 21.2% reporting the decrease lasted over 26 weeks. Alcohol (71.1%) and prescription opioids (64.1%) were most often decreased or stopped. Illicit opioids (27.8%) and cannabis (21.5%) were more likely to be increased or initiated. Psilocybin was rated the most effective psychedelic for physical and mental health symptoms. Findings suggest potential benefits and risks of naturalistic psychedelic use for chronic pain.
Journal of Humanistic Psychology
February 27, 2024
Jacob S. Aday, Emily K. Bloesch, Alan K. Davis et al.
5 citations
People who attended an ayahuasca retreat showed increased appreciation of art and beauty one week and one month later, according to a survey of 54 participants. Contrary to expectations, intense drug effects such as mystical experiences, awe, or ego dissolution did not predict these changes. The open-label design limits certainty, but the findings align with anecdotal reports of lasting shifts in aesthetic attitudes after psychedelic use. Further research is needed to identify the mechanisms behind these changes.