JAMA
August 31, 2023
Charles L Raison, Gerard Sanacora, Joshua Woolley et al.
493 citations
A single 25-mg dose of synthetic psilocybin, administered with psychological support, produced a clinically significant and sustained reduction in depressive symptoms and functional disability over 43 days in adults with major depressive disorder. In a phase 2 trial of 104 participants, those receiving psilocybin showed a mean 12.3-point greater improvement on the Montgomery-Asberg Depression Rating Scale at day 43 compared with those receiving a niacin placebo. Psilocybin also improved daily functioning and led to more sustained response, though not remission. No serious adverse events occurred, but psilocybin was associated with more overall and severe adverse events.
Journal of Psychopharmacology
February 1, 2022
Natalie Gukasyan, Alan K. Davis, Frederick S. Barrett et al.
419 citations
In patients with moderate to severe major depressive disorder, psilocybin-assisted therapy produced large and sustained decreases in depression severity through 12 months. Scores on the GRID-Hamilton Depression Rating Scale dropped substantially from baseline at 1, 3, 6, and 12 months (effect sizes of 2.3, 2.0, 2.6, and 2.4, respectively). At 12 months, 75% of participants showed a 50% or greater reduction in symptoms and 58% achieved remission. No serious adverse events linked to psilocybin occurred during long-term follow-up, and no participants used psilocybin outside the study. Ratings of personal meaning, spiritual experience, and mystical experience after sessions predicted greater well-being at 12 months but did not predict depression improvement.
Journal of Psychopharmacology
January 9, 2021
Alan K Davis, Frederick S Barrett, Sara So et al.
166 citations
A new questionnaire, the Psychological Insight Questionnaire, was developed to measure psychologically insightful experiences during psychedelic use. Among 1,661 psilocybin and LSD users, the 23-item measure showed two subscales: Avoidance and Maladaptive Patterns Insights and Goals and Adaptive Patterns Insights. Scores correlated strongly with an existing insight measure and moderately with mystical and challenging experience questionnaires. They also correlated with retrospectively reported increases in psychological flexibility, well-being, and life satisfaction attributed to a memorable psychedelic experience. The questionnaire predicted unique variance in these outcomes beyond mystical and challenging effects, suggesting it may help understand how psychological insight contributes to psychedelics' enduring effects.
Pharmacopsychiatry
August 4, 2021
Sandeep M Nayak, Natalie Gukasyan, Frederick S Barrett et al.
67 citations
Combining classic psychedelics like LSD or psilocybin with the mood stabilizer lithium carries a high risk of seizures. In an analysis of 62 online reports of such combinations, 47% involved seizures and 18% resulted in bad trips; 39% required medical attention. In contrast, none of 34 reports combining psychedelics with the mood stabilizer lamotrigine involved seizures, and most lamotrigine reports (65%) indicated no effect on the psychedelic experience. The findings suggest that lithium, but not lamotrigine, may pose a significant seizure danger when taken with psychedelics, though further research is needed.
PLoS ONE
March 14, 2024
Adam W Levin, Rafaelle Lancelotta, Nathan D Sepeda et al.
65 citations
In a small randomized trial of psilocybin-assisted therapy for adults with major depressive disorder, the therapeutic alliance between participants and facilitators strengthened from the final preparation session to one week after the intervention. A stronger alliance before the psilocybin sessions predicted lower depression scores at 4 weeks, 6 months, and 12 months afterward. Stronger alliance also correlated with more intense mystical experiences and psychological insight during the drug sessions, which in turn predicted better depression outcomes. The findings suggest the therapeutic relationship is important for treatment success.
Journal of Psychopharmacology
June 8, 2023
Natalie Gukasyan, Roland R. Griffiths, David B. Yaden et al.
60 citations
Psilocybin-containing mushrooms produce weaker drug effects in people taking SSRI or SNRI antidepressants, with a 47% probability of weaker-than-expected effects for SSRIs and 55% for SNRIs, compared to 29% for bupropion, a non-serotonergic antidepressant. This dampening effect persists for up to three months after discontinuing the antidepressant, based on retrospective survey data from over 2,000 reports. Removing responses involving fluoxetine, which has a long half-life, did not change the result. The findings suggest that serotonergic antidepressants may reduce psilocybin's effects both during use and for a period after stopping.
The International Journal of Neuropsychopharmacology
May 10, 2021
Natalie Gukasyan, David B. Yaden, Matthew W. Johnson et al.
56 citations
Psychedelic substances produce unusual changes in conscious experience, leading some to propose they offer unique insights into consciousness. However, psychedelics are unlikely to provide information relevant to the "hard problem of consciousness," which involves explaining how first-person experience emerges. Instead, they bear on multiple "easy problems of consciousness," involving relations between subjectivity, brain function, and behavior. This review discusses common meanings of "consciousness" regarding psychedelics and considers models of their effects on the brain linked to explanatory claims about consciousness. It calls for epistemic humility about psychedelic research's potential to explain the hard problem while noting ways psychedelics may advance study of specific aspects of consciousness.
Current topics in behavioral neurosciences
January 1, 2022
David B Yaden, Sandeep M Nayak, Natalie Gukasyan et al.
31 citations
End-of-life and palliative care have improved, but psychopharmacological options for depression, existential distress, and well-being remain limited. This review examines recent clinical research on psychedelics for patients with life-threatening diagnoses and proposes that psychedelics could offer clinicians an additional treatment option in end-of-life and palliative care settings.
Current psychiatry reports
December 1, 2022
Natalie Gukasyan, Colleen C Schreyer, Roland R Griffiths et al.
29 citations
Psychedelic-assisted therapy (PAT) may be safe and effective for various mental health conditions, including eating disorders such as anorexia nervosa. Classic psychedelics could have transdiagnostic benefits through mechanisms relevant to eating disorder pathology. Interest in and efforts to increase access to PAT are high, but early clinical trials are focused on safety and utility, with efficacy remaining unclear. High-quality published data supporting PAT for eating disorders is lacking, though recent studies suggest it may augment current interventions for these difficult-to-treat conditions.
JAMA Psychiatry
April 27, 2022
Mazdak M. Bradberry, Natalie Gukasyan, Charles L. Raison
20 citations
No Summary
Scientific reports
November 14, 2024
Erin Wang, David S Mathai, Natalie Gukasyan et al.
18 citations
Among 879 U.S. healthcare professionals surveyed online, most endorsed strong belief in the therapeutic promise of psychedelic-assisted therapy with psilocybin and MDMA, and showed moderate openness to clinical use and support for legal access, with higher ratings for psilocybin than MDMA. However, objective knowledge of therapeutic uses, risks, and pharmacology was low. Primary concerns included lack of trained providers, financial cost, and potential contraindications. Prior psychedelic use, self-rated knowledge, younger age, and professional role predicted greater openness, while physicians reported lower openness. Results indicate a pressing need for formal training to provide balanced, evidence-based information.
Med (New York, N.Y.)
January 13, 2023
Natalie Gukasyan
12 citations
A Phase II trial of psilocybin-assisted therapy for treatment-resistant depression showed modest effectiveness but also raised concerns about serious adverse effects. The findings underscore the importance of carefully evaluating whether blinding in such trials is maintained, accounting for participant expectations, and investigating factors that may increase risk in vulnerable groups.
February 24, 2021
Sandeep M. Nayak, Natalie Gukasyan, Frederick S. Barrett et al.
10 citations
preprint
Classic psychedelics such as LSD or psilocybin may pose a significant seizure risk for people taking the mood stabilizer lithium. Analysis of online reports found that 47% of 62 accounts of combining lithium with a psychedelic involved seizures, and an additional 18% resulted in bad trips; 39% required medical attention. In contrast, none of 34 reports of the mood stabilizer lamotrigine combined with a psychedelic involved seizures, and most lamotrigine reports (65%) indicated no effect on the psychedelic experience. The authors provisionally conclude that psychedelic use with lithium carries a seizure risk, warranting further research.
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.
Journal of Psychoactive Drugs
January 22, 2023
Natalie Gukasyan, Sasha K. Narayan
9 citations
Three women aged 27 to 34 reported distinct changes in menstrual function after using classic psychedelics: resumption of menses after amenorrhea, early onset of menses when psychedelics were used in the mid to late luteal phase, and improved menstrual regularity in a woman with irregular cycles later diagnosed with polycystic ovarian syndrome. The mechanisms remain unclear but may involve 5-HT2A receptor effects on the hypothalamic-pituitary-gonadal axis. These effects, largely overlooked in psychedelic research, may have therapeutic potential and need further investigation.
Journal of eating disorders
September 30, 2024
Adele Lafrance, Meg J Spriggs, Natalie Gukasyan et al.
8 citations
Psychedelic medicine, including psychedelic-assisted therapy (PAT), may offer a valuable adjunct to existing treatments for eating disorders, particularly anorexia nervosa, by addressing underlying psychological and transpersonal factors and improving treatment engagement. Preliminary findings from multiple studies suggest promise, though risks remain. This commentary, informed by lived experience and authors' field experience, provides a rationale and multi-dimensional perspective for applying these models as they become more accessible in naturalistic, research, and clinical settings.
Journal of psychoactive drugs
June 18, 2025
Rafaelle Lancelotta, Meghan DellaCrosse, Diana Quinn et al.
7 citations
Among 346 LGBTQIA+ individuals, mostly White and in their early 30s, those who used psychedelics reported improvements in mental health and shifts in gender and sexual identity. Retrospective reports showed large reductions in traumatic stress, depression, and anxiety, along with increased psychological flexibility. A significant link emerged between the intensity of the psychedelic experience and greater self-acceptance and sexual identity exploration. Most participants (77%) saw therapeutic potential in psychedelics for gender dysphoria, and 65% reported changes in gender identity attitudes after use. The findings suggest psychedelics may support identity exploration and mental health in this population, warranting further research.
Current topics in behavioral neurosciences
December 31, 2024
Mazdak M Bradberry, Paul S Appelbaum, Natalie Gukasyan
7 citations
Informed consent in psychedelic therapy requires clear communication of risks and potential benefits, as classical serotonergic psychedelics like psilocybin and entactogens like MDMA are increasingly used in Western clinical settings. Rigorous informed consent standards are essential for quality care and risk mitigation, especially in research and for vulnerable individuals. This chapter outlines practical elements of informed consent for these treatments based on current understanding.
American Journal of Bioethics
January 1, 2025
Zachary J Verne, Natalie Gukasyan, Jeffrey S Zabinski
2 citations
Psychedelics raise ethical concerns similar to those in other areas of medicine and psychology, not unique ones. The authors argue that treating psychedelics as ethically exceptional distorts risk assessment and policy. They identify several shared ethical considerations—such as informed consent, vulnerability, and adverse effects—that apply to psychedelic therapy just as they do to other treatments. The paper concludes that psychedelics should be integrated into existing medical and ethical frameworks rather than governed by special rules.
JAMA Psychiatry
December 6, 2023
David B. Yaden, Natalie Gukasyan, Sandeep M. Nayak
2 citations
No Summary
Psychiatry Research
February 13, 2026
Sean P. Goldy, Nathan D. Sepeda, Samantha Hilbert et al.
1 citation
Psilocybin has shown remarkable potential in reducing depressive symptoms, with a clinical trial involving 216 participants revealing a 60% reduction in these symptoms after treatment. In this randomized controlled trial, varying doses were administered, demonstrating significant improvements in mood and well-being. Additionally, participants reported lasting effects beyond the initial sessions, highlighting psilocybin's promise as a transformative medicine. These findings could reshape approaches in clinical psychology and pain management, offering new avenues for therapy and enhancing the understanding of psychedelics in mental health.
October 28, 2022
Natalie Gukasyan, Roland R. Griffiths, David B. Yaden et al.
1 citation
preprint
Serotonergic antidepressants, such as SSRIs and SNRIs, weaken psilocybin's effects, while the non-serotonergic antidepressant bupropion has less of a dampening effect. In 595 reports of taking psilocybin with an antidepressant, the probability of weaker than expected effects was 0.48 for SSRIs, 0.56 for SNRIs, and 0.29 for bupropion. After discontinuing a serotonergic antidepressant, reduced psilocybin effects persisted for up to 3 months, with odds of reduced effects not significantly different from the first week until 3–6 months post-discontinuation. The findings suggest that serotonergic antidepressants diminish psilocybin's effects both concurrently and for months after stopping.
Current psychiatry reports
May 14, 2026
Jamarie A Geller, Rachel Pacilio, Amanda E Downey et al.
Psilocybin-assisted therapy may hold promise for anorexia nervosa, a serious and often treatment-resistant illness. Although research has focused on adults, anorexia frequently begins in adolescence, and early onset is linked to more severe illness, greater psychiatric comorbidity, and more life difficulties. The authors argue that exploring the theoretical potential of this therapy for adolescents is warranted, considering biological implications, developmental stage, and consent. They propose adaptations to adult treatment models and discuss emerging models that address the unique challenges of adolescent patients.
Drug and Alcohol Dependence
July 1, 2024
Alan K. Davis, Adam W. Levin, Rafael Lancelotta et al.
No Summary