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.
JAMA Psychiatry
August 24, 2022
Michael P. Bogenschutz, Stephen Ross, Snehal Bhatt et al.
668 citations
Two doses of psilocybin, given alongside psychotherapy, substantially reduced heavy drinking in people with alcohol use disorder compared to an active placebo (diphenhydramine) plus psychotherapy. Over 32 weeks, heavy drinking days averaged 9.7% in the psilocybin group versus 23.6% in the placebo group—a mean difference of 13.9 percentage points. Daily alcohol consumption was also lower with psilocybin. No serious adverse events occurred in the psilocybin group. The findings support further research into psilocybin-assisted treatment for alcohol use disorder.
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
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.
Frontiers in Pharmacology
February 20, 2018
Michael P. Bogenschutz, Samantha K. Podrebarac, Jessie H. Duane et al.
125 citations
After a 40-year pause, clinical research on classic hallucinogens for addiction has resumed. An ongoing double-blind placebo-controlled trial tests psilocybin-assisted treatment for alcohol use disorder, building on a small open-label feasibility study. Descriptive case studies of three participants illustrate treatment trajectories. Pivotal moments during psilocybin sessions are individualized, vivid, and memorable, often extending beyond the clinical problem. Participants experienced lasting shifts in self-perception, consciousness, and relationship with alcohol. Experiences of catharsis, forgiveness, self-compassion, and love were as salient as mystical content. Feelings of increased mindfulness, spaciousness, and control over choices and behavior were reported. The treatment elicits highly variable experiences that appear to meet individual needs.
International Review of Psychiatry
July 4, 2018
Stephen Ross
103 citations
Cancer patients often experience severe psychological and existential distress, which worsens medical outcomes. Early studies from the 1960s-1970s suggested that psychedelic drugs like psilocybin and LSD might help treat this distress. After a long pause, research resumed in the last two decades. A systematic review of clinical trials from 1960-2018 identified 10 eligible trials with 445 participants, most with advanced or terminal cancer. Six open-label trials (1964-1980, n=341) suggested LSD therapy may improve depression, anxiety, and fear of death. Four randomized controlled trials (2011-2016, n=104), mostly using psilocybin (n=92), demonstrated that psychedelic-assisted treatment can produce rapid, robust, and sustained improvements in cancer-related psychological and existential distress.
Curr Top Behav Neurosci
January 1, 2018
Michael P. Bogenschutz, Stephen Ross
84 citations
This chapter reviews therapeutic uses of serotonergic hallucinogens like LSD and psilocybin, which act primarily on serotonin 2A receptors. After covering history and human use, it summarizes clinical data, including work on treating alcoholism and other addictions, using LSD and psilocybin to relieve death-related distress in advanced cancer patients, and limited data on mood and anxiety disorders. Safety of these drugs is well-established. Early-phase research from the 1950s to early 1970s strongly suggested clinically relevant effects, particularly for LSD in alcoholism, but was discontinued before firm conclusions. Recent trials have resumed, showing encouraging outcomes for existential distress in cancer and addictions, though not yet sufficient to establish efficacy. Mechanisms of persisting effects remain poorly understood.
The Psychiatric clinics of North America
June 1, 2012
Stephen Ross
54 citations
Serotonergic hallucinogen-assisted psychotherapy may prove safe and effective for treating substance use disorders in controlled trials, offering a novel treatment paradigm. These substances differ from other drugs of abuse by not producing dependence syndromes, with effects on the nucleus accumbens and dopamine ranging from inhibition to slight activation without causing addiction. Risks include adverse psychological events, manageable through careful screening, and low potential for misuse. Their ability to treat addictive, psychiatric, and existential disorders represents a potential paradigmatic shift in psychiatry.
European journal of psychotraumatology
January 1, 2024
Richard J Zeifman, Hannes Kettner, Stephen Ross et al.
34 citations
Therapeutic alliance—the quality of the relationship between therapist and client—predicts improvement in PTSD symptoms after MDMA-assisted psychotherapy. Among 22 adults with chronic PTSD who received MDMA during a clinical trial, stronger therapeutic alliance measured at sessions 4 and 9 (but not before the third session) was associated with lower clinician-assessed PTSD severity after treatment, even after accounting for initial symptom severity. Self-reported PTSD severity was also predicted by alliance at baseline, session 4, and session 9, though the baseline finding did not survive correction for multiple comparisons. These results provide initial evidence that common psychotherapeutic factors like alliance contribute to outcomes in MDMA-assisted therapy.
Scientific Reports
August 22, 2023
Hannes Kettner, Stephen Ross, Richard J. Zeifman et al.
31 citations
Co-using a low dose of MDMA with psilocybin or LSD is associated with less intense challenging experiences—such as grief and fear—and increased feelings of self-compassion, love, and gratitude, compared to using psilocybin or LSD alone. In a survey of 698 people planning to use these substances, the 27 who also took a low dose of MDMA reported these benefits without a reduction in mystical-type experiences or compassion. Medium-to-high MDMA doses did not show the same effects. The findings suggest MDMA may buffer against some difficult aspects of psychedelic experiences, but the study's small, non-experimental convenience sample limits certainty.
Neuropharmacology
April 2, 2023
Farah Z Zia, Michael H Baumann, Sean J Belouin et al.
28 citations
Chronic pain is a leading cause of disability and opioid overdose in the United States. While many people manage pain with existing medicines and psychosocial treatments, others find these options ineffective or unacceptable due to side effects and risks. Preliminary evidence suggests psychedelics may improve quality of life, functionality, and reduce disability and distress for people whose pain may never be completely relieved. This commentary calls for more basic research and clinical trials to explore psychedelics' potential in chronic pain management, and to determine whether effects stem from direct antinociceptive or anti-inflammatory mechanisms, or from increased tolerability, acceptance, and spirituality that mediate therapeutic effects seen in psychiatric disorders.
Contemporary clinical trials
December 1, 2022
Kelley C O'Donnell, Sarah E Mennenga, Lindsey T Owens et al.
24 citations
Classic psychedelics like psilocybin may help people change their behavior in substance use disorders. This paper describes the protocol for a multi-site, double-blind, randomized controlled trial that tested psilocybin-assisted psychotherapy in 96 alcohol-dependent volunteers. Participants received either psilocybin or an active placebo (diphenhydramine) during two dosing sessions, alongside a structured 12-week psychotherapy platform. The primary outcome was the proportion of heavy drinking days over 32 weeks after the first dose. Secondary outcomes included safety, abstinence, craving, and self-efficacy. The primary results are reported elsewhere; this paper focuses on the rationale and design decisions.
American Journal of Psychiatry
January 1, 2025
Noam Goldway, Snehal Bhatt, Stephen Ross et al.
23 citations
Psilocybin-assisted therapy (PAT) produced lasting changes in personality, indicating a normalization of abnormal personality trait expression in people with alcohol use disorder. The findings suggest that PAT may reduce impulsiveness, or that impulsive individuals may inherently respond better to the therapy. Further research is needed to clarify the mechanism.
Journal of Psychopharmacology
January 1, 2024
Lisa Bouchet, Zachary Sager, Antoine Yrondi et al.
22 citations
Older adults (65+) account for less than 1.4% of participants in psychedelic clinical trials, despite these compounds showing potential for conditions common in this age group, such as depression, anxiety, and existential distress. A systematic review of 36 trials involving 1,400 patients found only 19 were aged 65 or older. Safety data for 10 of these older adults showed no serious adverse events; only transient mild-to-moderate effects like anxiety, gastrointestinal upset, and hypertension occurred during dosing sessions. The authors conclude that psychedelic-assisted psychotherapy appears safe and well tolerated in older adults and warrants more rigorous investigation for psychiatric treatment in this population.
The journal of pain
October 1, 2022
Robert H Dworkin, Brian T Anderson, Nick Andrews et al.
22 citations
Psychedelic substances have been used historically for spiritual and mystical experiences, and recent interest focuses on their potential to treat chronic pain. Clinical trials support psychedelics' effectiveness for psychiatric conditions, but studies on chronic pain—such as cancer pain, phantom limb pain, migraine, and cluster headache—are few and mostly uncontrolled. Risks are relatively rare with careful patient screening and supervision. Key challenges include identifying mechanisms of action, selecting appropriate pain conditions, designing rigorous trials with proper control groups, minimizing unblinding bias, and accounting for patient mindset and setting. Evidence-based recommendations are needed for future research to yield informative results.
Am J Addict
January 1, 2015
James X. Liu, Erin Zerbo, Stephen Ross
17 citations
A patient with bipolar I disorder and a long history of substance dependence used large daily doses of ketamine (1-3 g) for five years. He reported acute antidepressant effects and reduced cravings for alcohol. Although his use was unsustainable and led to inpatient admission, he experienced no withdrawal syndrome and showed no observable cognitive deficits after stopping. This unique profile suggests that further research into ketamine's risks and therapeutic potential for mood and addiction disorders is warranted.
Psychedelic Medicine
May 16, 2025
Roland R. Griffiths, William A. Richards, Robert L. Jesse et al.
14 citations
In clergy from various world religions who had never used psychedelics, two supported psilocybin sessions (20 mg/70 kg, then 20 or 30 mg/70 kg) led to sustained positive changes in religious practices, attitudes about their religion, and effectiveness as a religious leader, as well as in non-religious attitudes, moods, and behavior, compared with a waitlist control group. At 16‑month follow‑up, 96% rated at least one experience among the top five most spiritually significant of their lives, 42% rated it the single most profound, and 79% reported positive effects on daily sense of the sacred. No serious adverse events occurred, though 46% rated an experience among the top five most psychologically challenging of their lives.
Focus (American Psychiatric Publishing)
October 1, 2022
Jenna M Traynor, Daniel E Roberts, Stephen Ross et al.
14 citations
Borderline personality disorder is a complex psychiatric condition with limited and often ineffective treatment options, high variability in patient response, and frequent dropout from therapy. This review considers the potential of MDMA-assisted psychotherapy (MDMA-AP) as a new or complementary treatment. Based on MDMA-AP's promise in treating overlapping disorders like posttraumatic stress disorder, the authors propose initial treatment targets and hypothesized mechanisms of change grounded in prior literature and theory. They also outline considerations for designing clinical trials to investigate the safety, feasibility, and preliminary effects of MDMA-AP for borderline personality disorder.
Psychedelic Med (New Rochelle)
December 13, 2023
Kelley C. O'Donnell, Daniel E. Roberts, Terence H.W. Ching et al.
13 citations
The term 'psychedelic' carries multiple, sometimes conflicting, meanings across different contexts—scientific, cultural, legal, and historical. This ambiguity can hinder clear communication and slow research progress by creating misunderstandings among researchers, clinicians, policymakers, and the public. The authors argue that recognizing and clarifying these varied definitions is essential for advancing the field, as precise language helps align expectations, improve study reproducibility, and inform policy decisions. Without shared understanding, efforts to study and apply psychedelics therapeutically risk confusion and fragmentation.
Annals of Palliative Medicine
August 22, 2024
Arum Kim, Barley Halton, Akash Shah et al.
11 citations
Existential distress, a distinct condition from depression or anxiety, is common among patients with life-threatening illnesses and is linked to worse quality of life, suicidal ideation, and requests for hastened death. Traditional medications and psychotherapy show limited effectiveness for this condition. Psychedelic drugs, such as psilocybin and LSD, combined with psychotherapy, have produced rapid and sustained reductions in existential and psychiatric distress, offering a promising treatment for palliative care patients. This narrative review covers the history of psychedelic medicine, including early studies and modern clinical trials, and outlines practical considerations for psilocybin-assisted therapy, such as pharmacokinetics, patient selection, dosing, protocol design, and safety measures. The review aims to help palliative care providers become familiar with the current science and potential of this treatment.
Nature Mental Health
October 7, 2024
Petros Petridis, Jack Grinband, Gabrielle Agin-Liebes et al.
10 citations
Psilocybin-assisted psychotherapy (PAP) may treat a wider range of psychiatric symptoms in cancer patients than previously recognized. Pooled data from two phase II randomized placebo-controlled crossover trials involving 79 participants with cancer-related distress showed that PAP significantly improved anxiety, depression, interpersonal sensitivity, hostility, obsession-compulsion, and somatization. No lasting phobia, paranoia, or psychosis was induced. Improvements were consistent across both trials, suggesting PAP could serve as a comprehensive mental health treatment for this population.