Frontiers in Psychiatry
September 19, 2023
Hillary Jackson, Sara So, Abigail Yaffe et al.
87 citations
A large prospective survey of adults planning to take psilocybin outside clinical settings found that, on average, participants reported lasting reductions in anxiety, depression, and alcohol misuse, along with improvements in cognitive flexibility, emotion regulation, spiritual wellbeing, and extraversion, and decreases in neuroticism and burnout after use. However, a minority reported persisting negative effects: 11% at 2–4 weeks and 7% at 2–3 months after use, including mood fluctuations and depressive symptoms. The study included 2,833 respondents at baseline, 1,182 at 2–4 weeks, and 657 at 2–3 months post-use. Participants were primarily college-educated White men in the United States, mean age 40, who used dried psilocybin mushrooms (mean dose 3.1 grams) for self-exploration.
Frontiers in Psychology
March 25, 2022
David S. Mathai, Victoria Mora, Albert Garcia‐romeu
51 citations
Ketamine, a dissociative drug used as an anesthetic since the 1970s, also shows promise for psychiatric applications, especially when combined with psychological interventions. A review of historical and modern approaches discusses the clinical relevance of ketamine's acute psychoactive effects and proposes a unique model for using esketamine with Acceptance and Commitment Therapy (ACT). The authors suggest considerations for advancing medication-assisted psychotherapy as a field.
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.
Journal of Child and Adolescent Psychopharmacology
October 1, 2021
David S. Mathai, Alexis G. McCathern, Andrew G. Guzick et al.
14 citations
Parents of adolescents show high acceptability toward using ketamine to treat suicidality, major depressive disorder, and bipolar disorder, despite the drug not being FDA-approved for psychiatric use in children. In a survey of 283 English-speaking parents, primary concerns included potential side effects and lack of FDA approval. Parents preferred short-term applications and less invasive routes of administration. A parent's own history of mental illness, familiarity with psychological treatments, and comfort using other mental health interventions for their children predicted greater acceptability. The findings indicate parental interest in ketamine as a treatment for pediatric mood disorders, pointing to future research and clinical directions.
Journal of Psychoactive Drugs
February 7, 2025
Amy Lehrner, Heather Jackson, David S. Mathai et al.
11 citations
Among 679 adults using psilocybin in naturalistic settings, 68.2% reported acute feelings of shame or guilt during the experience, which were difficult to predict. The ability to constructively work through these feelings predicted wellbeing 2-4 weeks later. On average, psilocybin produced a small but significant decrease in trait shame maintained 2-3 months after use (Cohen's dz = 0.37), though trait shame increased in 29.8% of participants. The activation of self-conscious emotions with psychedelics warrants further attention as a challenging experience subcategory relevant to psychological outcomes, potentially creating a unique learning condition for shame-related memory reconsolidation.
Psychedelic Medicine
August 30, 2023
Samantha Hilbert, David S. Mathai, Nathan D. Sepeda et al.
10 citations
Dissociatives like dextromethorphan may have clinical applications when used in supportive settings similar to those in psychedelic research, which prioritize optimizing psychologically valuable drug experiences. The analysis suggests that such contexts could enhance therapeutic outcomes.
JAMA Netw Open
January 2, 2026
Amy L. Mcguire, Logan Neitzke-Spruill, Jill O. Robinson et al.
4 citations
Psychedelic retreat organizations vary widely in their safety precautions. All 49 organizations interviewed collected participant medical histories, and 73.5% excluded individuals with certain health conditions. Most required or recommended medication washout periods ranging from one day to over six weeks. While 69.4% worked with a licensed health care professional or someone with emergency response training, only 65.3% had such personnel in attendance at retreats at least some of the time. All organizations offered integration support. The variability in practices, particularly around medication washout and polysubstance use, may increase risks to participants. Best practice guidelines are needed and should be codeveloped with Indigenous and nonclinical communities.
International review of psychiatry (Abingdon, England)
December 1, 2024
David S. Mathai
3 citations
Dissociative therapies are increasingly studied for psychiatric use, but key clinical questions remain. This review identifies six areas: whether functional unblinding skews efficacy data; how therapeutic effects differ from recreational drug relief; how the concept of dissociation applies to these drugs; whether subjective drug effects predict outcomes; how dissociative and classic psychedelics compare; and the need for prescribing and deprescribing guidelines as these treatments become more common.
J Affect Disord
May 16, 2026
David S. Mathai, Madeleine Cluck, Amna M. Aslam et al.
1 citation
A panel of experts from the American Society of Ketamine Physicians, Psychotherapists, and Practitioners used a Delphi process to develop consensus guidelines for administering intravenous ketamine infusions to treat depressive disorders. The guidelines provide recommendations on patient selection, dosing, safety monitoring, and treatment protocols, aiming to standardize clinical practice and improve patient outcomes. The consensus reflects agreement among specialists on best practices for this off-label use of ketamine.
Brazilian Journal of Psychiatry
January 1, 2025
David S. Mathai, Jill O. Robinson, Kevin Wagner et al.
1 citation
Among 2,639 Hispanic and Latin American adults with obsessive-compulsive disorder (OCD) living across the Americas, 9% reported using psychedelics or related substances for treatment. Most (72%) had received traditional treatments like psychiatric medication or psychotherapy. Psilocybin, LSD, and MDMA were the most used psychedelics. Users were more likely to be male, have received non-ERP therapy, and have a comorbid psychiatric diagnosis. Outcomes for OCD symptoms varied widely by drug and were difficult to predict, but were most favorable for classic serotonergic psychedelics. Real-world evidence suggests Hispanic and Latin American adults are exploring psychedelics as a treatment for OCD, though further research is needed to establish safe and effective use.
October 14, 2023
David S. Mathai, Daniel E. Roberts, Sandeep M. Nayak et al.
preprint
A longitudinal study of 679 adults planning to use psilocybin in naturalistic settings found that while most users (89.7%) described the experience as positive, acute feelings of shame or guilt were commonly reported (68.2% of users) and difficult to predict. The ability to constructively work through these feelings predicted wellbeing 2-4 weeks after use. Psilocybin produced a small but significant average decrease in trait shame that lasted 2-3 months, but trait shame increased in a notable minority (29.8%) of participants. The activation of shame-related experiences with psychedelics may pose a unique learning condition for both therapeutic and detrimental forms of memory reconsolidation.