Journal of Psychopharmacology
November 30, 2016
Stephen Ross, Anthony Bossis, Jeffrey Guss et al.
1,699 citations
A single moderate dose of psilocybin (0.3 mg/kg), combined with psychotherapy, produced immediate and sustained improvements in anxiety and depression among 29 patients with cancer-related psychological distress. At the 6.5-month follow-up, approximately 60–80% of participants continued to show clinically significant reductions in depression or anxiety. Psilocybin also decreased demoralization and hopelessness, improved spiritual wellbeing, quality of life, and attitudes toward death. The therapeutic effects on anxiety and depression were mediated by the psilocybin-induced mystical experience.
Journal of Psychopharmacology
January 9, 2020
Gabrielle Agin-Liebes, Tara C. Malone, Matthew M. Yalch et al.
353 citations
A long-term follow-up of a randomized trial found that psilocybin-assisted psychotherapy produced lasting reductions in anxiety, depression, hopelessness, demoralization, and death anxiety in people with cancer-related psychiatric distress. At an average of 3.2 and 4.5 years after psilocybin administration, 60–80% of participants still showed clinically significant antidepressant or anxiolytic responses. Most participants (71–100%) attributed positive life changes to the therapy and rated it among the most personally meaningful and spiritually significant experiences of their lives. The study's conclusions are limited by the crossover design of the original trial, but the results suggest psilocybin-assisted therapy may promote long-term relief from cancer-related distress.
Journal of Humanistic Psychology
April 28, 2017
Alexander Belser, Gabrielle Agin-Liebes, Thomas Cody Swift et al.
305 citations
In psilocybin-assisted psychotherapy for cancer patients with anxiety, participants commonly reported feelings of interconnectedness, emotional range, meaningful visual phenomena, and revised life priorities. Most described exalted joy, bliss, love, and transient distress, while some experienced lasting identity changes, synesthesia, catharsis, improved relationships, and forgiveness. The findings suggest psilocybin-assisted psychotherapy may effectively treat psychological distress in cancer patients.
Journal of Humanistic Psychology
June 14, 2017
Thomas Cody Swift, Alexander Belser, Gabrielle Agin-Liebes et al.
187 citations
In psilocybin-assisted psychotherapy for cancer patients with anxiety, participants described reconciling with death, acknowledging cancer's place in life, and emotionally uncoupling from the disease. The immersive and sometimes distressing psilocybin session led to spiritual or religious interpretations, a felt reconnection to life, reclaiming presence, and greater confidence about cancer recurrence. Patients also reported anxiety and trauma related to cancer and a perceived lack of emotional support. The findings suggest psychological mechanisms—such as emotional uncoupling and reconciliation with death—that may underlie large reductions in anxiety and depression observed in recent trials.
ACS Pharmacology & Translational Science
March 18, 2021
Stephen Ross, Gabrielle Agin-Liebes, Sharon L. Lo et al.
133 citations
People with advanced cancer face elevated risks of desire for hastened death, suicidal ideation, and completed suicide. Loss of meaning, a component of demoralization, predicts these outcomes. In a randomized controlled trial, psilocybin-assisted psychotherapy produced rapid and sustained improvements in depression, demoralization, and hopelessness. Secondary analyses showed that among participants with elevated suicidal ideation at baseline, reductions in suicidal ideation appeared as early as 8 hours and persisted for 6.5 months. Large reductions in loss of meaning emerged 2 weeks after treatment and remained significant at 6.5 months and at 3.2 and 4.5 year follow-ups. The findings suggest psilocybin-assisted psychotherapy may be an effective antisuicidal intervention for cancer patients due to its positive impact on hopelessness and meaning-making.
Frontiers in Pharmacology
April 3, 2018
Tara C. Malone, Sarah E. Mennenga, Jeffrey Guss et al.
128 citations
Cancer patients who receive psilocybin-assisted psychotherapy often have personalized experiences that extend beyond their diagnosis, centering on self-compassion, love, acceptance of death, and past trauma. In a double-blind trial, 29 patients with cancer-related anxiety and depression received either psilocybin or niacin with psychotherapy. Psilocybin produced rapid and lasting reductions in anxiety and depression. Detailed accounts of four participants show that while the content of each psilocybin session was unique, common themes emerged. The findings highlight how the subjective effects of psilocybin can address individual spiritual and psychological needs.
Journal of Psychedelic Studies
October 5, 2018
Elizabeth M. Nielson, Jeffrey Guss
104 citations
Clinical research on psychedelic-assisted psychotherapy is advancing in the USA, with psilocybin and MDMA in FDA-approved trials. In the 1950s and 1960s, researchers' and clinicians' personal use of psychedelics was considered a potential confound, contributing to a 20-year research hiatus. Currently, no empirical research exists on personal use by current academic researchers and clinicians; its influence is undocumented and undertheorized. This paper explores the history of personal use, its potential impact on therapy and research, and argues that training for psychedelic-assisted therapy cannot fit neatly into modern psychopharmacology or psychotherapy frameworks. It contends that scientific exploration of therapists' firsthand psychedelic experience on therapy outcomes is feasible, timely, and necessary.
August 13, 2020
Jeffrey Guss, Robert Krause, Jordan Sloshower
86 citations
preprint
The Yale Manual for Psilocybin-Assisted Therapy of Depression offers researchers and therapists a detailed guide on methods, structure, and considerations for using psychedelic-assisted therapy to treat Major Depressive Disorder. It specifically demonstrates how Acceptance and Commitment Therapy (ACT) can serve as a therapeutic framework for psilocybin-assisted depression treatment.
Frontiers in Psychiatry
December 2, 2022
Torsten Passie, Jeffrey Guss, Rainer Krähenmann
71 citations
Lysergic acid diethylamide (LSD) and similar psychoactive drugs have been used in psychotherapy since 1949, when the first clinical study with lower-dose LSD showed therapeutically relevant effects. Psycholytic therapy, named in 1960, involved serial lower-dose LSD or psilocybin sessions within a psychoanalytical framework, conducted in clinical settings on both inpatient and outpatient bases. Over 15 years, it was established at 30 clinical treatment centers and by more than 100 outpatient psychotherapists in Europe, while North America favored high-dose psychedelic therapy. Professor Hanscarl Leuner in Germany was the leading figure, providing a detailed analysis of the LSD reaction in a 1962 monograph. The article reviews evidence for psycholytic therapy's efficacy and argues for its inclusion in substance-assisted psychotherapy.
Scientific reports
April 17, 2024
Jordan Sloshower, Richard J Zeifman, Jeffrey Guss et al.
56 citations
Psilocybin-assisted therapy improves psychological flexibility, mindfulness, and values-congruent living in people with moderate to severe major depressive disorder, and these improvements are strongly linked to reductions in depression severity. In an exploratory placebo-controlled study, participants received placebo then psilocybin (0.3 mg/kg) four weeks later, with dosing sessions embedded in Acceptance and Commitment Therapy. Psychological flexibility, several facets of mindfulness, and values-congruent living significantly improved after psilocybin and were maintained through week 16. The findings suggest that increasing psychological flexibility may be a key mechanism underlying psilocybin's therapeutic effects.
Journal of palliative medicine
August 1, 2022
William E Rosa, Zachary Sager, Megan Miller et al.
49 citations
Psychedelic-assisted therapy (PAT) is a promising treatment for conditions like treatment-resistant depression, substance use disorder, and PTSD. In palliative care, a single PAT session can produce lasting reductions in anxiety, depression, and demoralization—symptoms that harm quality of life for seriously ill and end-of-life patients. Although interest in psychedelics has revived, few resources exist for applying PAT in hospice and palliative care. This article provides 10 evidence-informed tips for palliative care clinicians, developed with international experts, to help familiarize teams with PAT, address legal and logistical barriers, discuss therapeutic competencies, and highlight approaches to maximize safety and benefits for patients and caregivers.
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.
Frontiers in Psychiatry
December 6, 2024
Jonathan Brett, Elizabeth Knock, Kathy Watson et al.
7 citations
A daily methamphetamine user, a 36-year-old transwoman, achieved sustained abstinence and improved mental health after a single session of psilocybin-assisted psychotherapy following inpatient withdrawal management. She reported increased self-esteem, mindfulness, and distress tolerance over three months. The case suggests that psilocybin-assisted therapy may offer a scalable, safe, and effective approach for treating methamphetamine dependence, though further research is needed to confirm generalizability.
Journal of psychopharmacology (Oxford, England)
June 10, 2025
Torsten Passie, Anja Loizaga-Velder, Alicia Danforth et al.
4 citations
A consensus-based model curriculum for education and training in substance-assisted psychotherapy (SAP) covers theoretical topics and practical components including apprenticeship observation, ongoing clinical supervision, and self-experience for trainees. The model, developed by authors with extensive SAP experience, also addresses peer and conventional supervision, respect for intercultural differences, and teachings about indigenous use of related substances. It is largely adapted to western industrialized countries with established graduate-level psychotherapy training. The curriculum may be valuable for psychedelic researchers, those training therapists for research studies, and those preparing for clinical work outside research settings.
Drugs Education Prevention and Policy
June 4, 2024
Eli Kraiem, Marc J. Diener, Jeffrey Guss et al.
4 citations
Psychoanalysts are cautiously supportive of psychedelic-assisted therapy (PAT) and open to their clients engaging in it, but they believe PAT would be ineffective for substance use disorders. Those who had personally used psychedelics held significantly more positive attitudes. The findings suggest misinformation and cultural stigma about psychedelics persist among psychoanalysts, indicating a need for education on risks, benefits, and evidence limitations.
Psychodynamic psychiatry
June 1, 2026
Nadav Liam Modlin, Zsofia Elek, Carolina Maggio et al.
Psychedelic therapy may help people access unconscious mental content—preverbal, dissociated, or developmentally buried material—that emerges through bodily sensations, symbolic images, and intense emotions. A psychodynamic framework, drawing on psychoanalytic theory, can guide clinicians in working with this material across four phases: screening, preparation, the treatment session, and follow-up integration. Although neurobiological mechanisms like 5-HT2A receptor activation are well studied, unconscious processes remain underexplored. The authors argue that psychoanalytic models, though currently underrepresented, can deepen understanding of therapeutic change beyond symptom reduction and should inform future research, training, and individualized care as psychedelic treatments move toward broader clinical use.
Journal of Psychedelic Studies
April 2, 2025
Hope Kronman, Alison Locker, Abdi Assadi et al.
A person experienced persistent insomnia, anxiety, and tinnitus for months after MDMA therapy, symptoms that did not resolve with Western medical approaches. Her symptoms eventually improved when treated within a Traditional Chinese Medicine framework. The authors argue that psychedelic treatment, particularly during the integration phase, may benefit from techniques that address energies not recognized by Western medicine.
November 4, 2024
Jacob S. Aday, Jenna McAfee, Deirdre A. Conroy et al.
preprint
In a small open-label proof-of-concept trial, five adults with fibromyalgia received two doses of psilocybin (15 mg and 25 mg) two weeks apart, along with psychotherapy sessions. No serious adverse events occurred; transient blood pressure or heart rate elevations during dosing resolved by the end of treatment, and four of five participants had temporary headaches. One month after the second dose, participants reported clinically meaningful improvements 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. Improvements were also seen in fibromyalgia symptoms, anxiety, and fatigue. The findings suggest psilocybin-assisted therapy is well-tolerated and warrants larger randomized controlled trials.
November 15, 2022
Jeffrey Guss, Robert Krause, Jordan Sloshower
preprint
This document is the French translation of the Yale Manual for Psilocybin-Assisted Therapy of Depression. It provides researchers and therapists with methods, structure, and considerations for using psychedelic-assisted therapy to treat major depressive disorder. Specifically, the manual illustrates how Acceptance and Commitment Therapy (ACT) can serve as the therapeutic framework for psilocybin-assisted depression treatment.