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.
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.
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.
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 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.
Journal of psychoactive drugs
April 22, 2025
Nicolas G Glynos, Mallet R Reid, Jacob S Aday et al.
4 citations
People of Color have been underrepresented in psychedelic-assisted therapy (PAT) research, and some have suggested that systemic harms like the War on Drugs and discrimination in healthcare might reduce their willingness to participate. A large-scale survey of people using psychedelics in North America compared 3,547 White people, 448 People of Color, and 377 Multiracial people. A lower proportion of People of Color used psychedelics with a trained provider, but equal proportions had disclosed psychedelic use to primary care providers, were equally motivated to use psychedelics with a trained provider, used psychedelics for similar issues, and reported similar effectiveness. The findings suggest that lack of trust may not fully explain underrepresentation, and other barriers should be investigated.
Research square
April 8, 2026
Oliver C Robinson, David Luke, Jules Evans et al.
1 citation
In a large global online survey of 6,476 people who have used psychedelics, nearly half (48.3%) reported at least one difficulty lasting 24 hours or more, and 9.9% experienced difficulties for over a year. The most common difficulties were existential struggle (36.6%), depression (34%), and derealization (29.4%). Existential struggle was rated as the most severe difficulty but also the one most linked to healing. Clinically relevant disruptive difficulties lasting at least a month and disrupting daily life were reported by 8% of participants and were associated with younger age, lower income, lack of family support, lower emotional stability, higher pre-existing anxiety or depression, and using psychedelics to treat mental health conditions. The findings highlight the need for education on risks and benefits, safety guidelines, and support services.
PsyArXiv
September 4, 2025
Jacob S Aday, Robin Carhart-Harris, Kevin F. Boehnke
1 citation
preprint
Classic psychedelic drugs such as psilocybin, LSD, and ayahuasca are being explored as treatments for many health conditions, but predicting how individuals will respond is difficult. Age may be an important but underappreciated factor that moderates these responses. Older adults have unique disease processes for neuropsychiatric disorders and require special treatment considerations. Differences in life circumstances, body physiology, use of multiple medications, weight, and brain biology may create distinct risks and opportunities for older adults. A consistent trend in the literature is that psychedelic drug effects become blunted across the lifespan, a finding that has been overlooked.
Journal of psychopharmacology (Oxford, England)
May 1, 2025
Niloufar Pouyan, Jacob S Aday, Steven E Harte et al.
1 citation
People with treatment-resistant conditions often see their illness as part of their identity. The pictorial representation of illness and self measure (PRISM) gauges this self-condition enmeshment. In a survey of 297 individuals who used psychedelics therapeutically on their own, most reported symptom improvement: 95.4% with depression, 98.36% with posttraumatic stress disorder, and 94.87% with anxiety. PRISM scores dropped significantly after the most salient psychedelic experience, indicating reduced identification with the condition. The decrease in PRISM scores correlated with symptom improvement across all conditions. PRISM appears useful for tracking how psychedelics affect self-perception across diagnoses, though limitations include convenience sampling, potential positive bias, and retrospective reporting.
Drugs
June 4, 2026
Kevin F Boehnke, Niloufar Pouyan, Jacob S Aday
Chronic pain is common, costly, and often poorly treated by existing therapies. Classic serotonergic psychedelics—psilocybin, LSD, ayahuasca, DMT, and mescaline—have re-emerged as potential tools for chronic pain, administered alone or within psychedelic-assisted therapy. This review examines mechanisms relevant to pain, including effects on neuroplasticity, inflammation, brain network dynamics, and psychological processes like pain acceptance and cognitive flexibility. Observational studies and early-phase clinical trials show preliminary signals of benefit for fibromyalgia, migraine, cluster headache, and other chronic pain syndromes. The field is limited by small sample sizes, functional unblinding, and a lack of large, well-controlled randomized trials. The authors outline methodological priorities and future research directions needed to rigorously evaluate these compounds for chronic pain.
Neuroscience and biobehavioral reviews
February 1, 2026
Mallet R Reid, Jonathan Song, Kevin F Boehnke et al.
People of color have been significantly underincluded in psychedelic-assisted therapy (PAT) research, despite facing challenges commonly addressed in PAT and often more severe symptoms. A systematic review of the past 10 years of psilocybin, MDMA, and LSD clinical trials in the United States (N = 27) found that only 3 out of 27 studies (11.11%) incorporated community-engaged research (CEnR) practices. In the rare instances CEnR was integrated, researchers used community consultation, which involves relatively little engagement with community members. The authors recommend incorporating five CEnR principles to improve representation in PAT trials: mapping and engaging local stakeholders, leveraging existing university-hospital infrastructures, co-designing research and outreach initiatives, securing dedicated CEnR resources, and establishing mechanisms for ongoing evaluation.
Drug science, policy and law
January 1, 2026
Jacob S Aday, Zoe Zong, Jonathan Song et al.
A Mandarin version of the Five Dimensional Altered States of Consciousness (5D-ASC) Rating Scale was developed to improve language accessibility for Mandarin-speaking individuals in psychedelic research. The translation followed the ISPOR Task Force guidelines, involving forward translation by two professionals, review by a native Mandarin speaker, back-translation, and comparison with the original. The scale includes 11 facets such as experience of unity, spiritual experience, and anxiety, and can also be analyzed using the original 5-factor structure. The full survey is provided in the appendix. Further research is needed to evaluate its reliability and validity in Mandarin-speaking populations.