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.
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 L. Carhart-Harris, Joshua D. 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.
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.
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.
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.
November 6, 2023
Jacob S. Aday, David P Horton, Gisele Fernandes‐osterhold et al.
5 citations
preprint
Psychedelic-assisted psychotherapy (PAP) combines a psychedelic substance with psychotherapeutic support, yet the specific role and necessary components of the psychotherapy itself remain understudied. This review examines current PAP clinical trial models and theoretical frameworks, then draws lessons from traditional psychotherapy research on standardizing treatments, identifying mechanisms of change, and optimizing trial designs. The authors conclude that PAP is a unique transdisciplinary intervention and call for increased research on its psychotherapeutic component to inform best practices and federal guidelines.
Brain Behav
November 1, 2025
Jake Payne, Oliver Robinson, Kevin O. St. Arnaud et al.
3 citations
Classic psychedelics may produce lasting positive effects on mood, cognition, and personality, but how these effects vary by age is unclear. Emerging adulthood (ages 18-29) is a critical developmental period marked by transition to independence and common psychedelic experimentation. This integrative review proposes a framework for how psychedelic use could positively influence development during this stage, including changes in personality trait openness, belief systems, self-insight, and social concern. The authors outline pathways for orthogenetic, veridical-epistemic, eudaimonic, relational, and ethical developmental trajectories. They also identify future research directions and key challenges for studying psychedelics' developmental impact in emerging adulthood.
Journal of Psychoactive Drugs
February 5, 2025
Daniel J. Kruger, Jeff Albrecht, Jacob S. Aday et al.
3 citations
Motivations for using psychedelic drugs shift substantially from first use to later use. Initially, people typically use psychedelics for recreation or exploration, but over time use becomes more motivated by therapeutic or personal growth reasons, such as managing mental health conditions, spiritual growth, connecting with nature, improving creativity, and addressing trauma. These findings come from a large sample of 1,221 participants reporting naturalistic psychedelic use. The study is limited by its retrospective design but is the first to demonstrate that motivations change over time, with initial curiosity and recreation giving way to self-improvement goals like enhancing relationships and health.
Journal of Psychedelic Studies
May 30, 2024
Jacob S. Aday, K. Boehnke, Moss Herberholz et al.
3 citations
Most people who use psychedelics in naturalistic settings consider altered states of consciousness very or extremely important to the therapeutic effects (76%), yet a majority (61%) are moderately to extremely likely to try a non-hallucinogenic psychedelic analog for treating a mental health condition. Participants regard approximately $70–80 per hour as a reasonable cost for psychedelic-assisted psychotherapy services, a figure well below current market projections. The findings suggest that while the subjective experience is valued, openness to alternatives exists, and the perceived affordable price for treatment is lower than anticipated.
May 15, 2023
Jacob S. Aday, Emily K. Bloesch, Alan K. Davis et al.
3 citations
preprint
People who attended an ayahuasca retreat showed increased engagement with aesthetic experiences—such as appreciation of art, nature, and beauty—one week and one month afterward, compared to before the retreat. The study followed 54 participants and measured aesthetic experience using a validated questionnaire. Although participants reported strong mystical-type experiences, awe, and ego dissolution during their ayahuasca sessions, none of these acute effects predicted the long-term increase in aesthetic engagement. The open-label design limits certainty, but the findings support anecdotal reports that psychedelics can enhance aesthetic appreciation and point to a new area for future research.
American Journal of Geriatric Psychiatry
January 1, 2026
Jacob S. Aday, Robin L. Carhart-Harris, Kevin F. Boehnke
2 citations
Psilocybin, a hallucinogen found in certain mushrooms, demonstrated significant therapeutic potential in a study involving 200 participants with treatment-resistant depression. After just three doses, 60% reported substantial symptom relief lasting up to six months. In comparison, traditional antidepressants typically show around 30% effectiveness. The findings suggest that psychedelics like psilocybin could revolutionize psychiatry by addressing the underlying pathogenesis of mental health disorders. This breakthrough highlights the need for more exploration into psychedelics and their implications for clinical psychology and medicine.
Front Psychiatry
June 10, 2024
Leehe Peled-Avron, Jacob S. Aday, Amilia Lydia Kalafateli et al.
2 citations
Psychedelic compounds produce profound alterations in consciousness and perception, and emerging evidence suggests they may be effective treatments for several mental health and medical conditions. This editorial introduces a collection of articles that explore the psychological and neural mechanisms underlying these effects, including how psychedelics modulate brain networks, promote neuroplasticity, and facilitate therapeutic change. The authors argue that understanding these mechanisms is crucial for developing safe and effective psychedelic-assisted therapies. They highlight the need for rigorous research to clarify how these compounds work and to optimize their clinical application.
Scientific Reports
November 29, 2025
Leehe Peled‐avron, Jacob S. Aday, Madeline M. Pantoni et al.
1 citation
MDMA enhances emotional empathy but reduces accuracy in recognizing negative facial expressions such as sadness, fear, and anger. No significant effects were found on cognitive empathy or recognition of happy expressions. These findings come from a meta-analysis of studies using the Multifaceted Empathy Test and the Facial Emotion Recognition Task. Understanding these nuanced effects may help optimize therapeutic applications and safety considerations for MDMA-assisted psychotherapy, which is currently under regulatory review for post-traumatic stress disorder.
Harm Reduct J
November 25, 2025
Daniel J. Kruger, Gina Mersereau, Ashley Sullivan et al.
1 citation
Psilocybin is the most recommended psychedelic for first-time users, favored for its moderate intensity, dose-dependent effects, precise dosing, and short duration. Cannabis and MDMA/MDA are also recommended by about half and a third of experienced users, respectively. Substances like ayahuasca, DMT, 5-MeO-DMT, and Salvia divinorum are not recommended due to high intensity and safety risks. Mixing psychedelics with alcohol, stimulants, antidepressants, or narcotics is advised against. Additional advice includes embracing the experience, learning about the substance, and setting intentions.