Journal of Psychopharmacology
November 30, 2016
Annie Umbricht, Mary P Cosimano, Roland R. Griffiths et al.
2,174 citations
In cancer patients with life-threatening diagnoses and symptoms of depression or anxiety, a high dose of psilocybin (22 or 30 mg/70 kg) produced large decreases in depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety, compared with a very low placebo-like dose (1 or 3 mg/70 kg). At 6-month follow-up, about 80% of participants continued to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life, mood, relationships, and spirituality to the high-dose experience, with over 80% endorsing moderately or greater increased well-being or life satisfaction. The mystical-type experience during the session mediated the effect of dose on therapeutic outcomes.
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 13, 2015
Michael P. Bogenschutz, Alyssa A. Forcehimes, Jessica A. Pommy et al.
1,164 citations
In a small proof-of-concept study, ten volunteers with alcohol dependence received one or two supervised doses of psilocybin alongside therapy. Abstinence did not increase during the first four weeks of treatment but increased significantly after psilocybin administration, with gains largely maintained up to 36 weeks. The intensity of effects during the first psilocybin session strongly predicted reduced drinking and craving and increased abstinence self-efficacy in the following weeks. No serious adverse events occurred. These preliminary findings support larger controlled trials to test efficacy and mechanisms.
Journal of Psychopharmacology
September 11, 2014
Mary P Cosimano, Matthew W. Johnson, Albert Garcia‐romeu et al.
910 citations
In an open-label pilot study, 15 nicotine-dependent smokers received moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin as part of a structured 15-week smoking cessation program. At 6-month follow-up, 12 of 15 participants (80%) showed seven-day point prevalence abstinence, a rate substantially exceeding the typical 35% or less reported for other behavioral or pharmacological therapies. The authors note the open-label design prevents definitive conclusions about efficacy, but the findings suggest psilocybin may be a potentially useful adjunct to smoking cessation treatment.
Journal of Psychopharmacology
September 28, 2011
Katherine A Maclean, Matthew W Johnson, Roland R Griffiths
907 citations
Core personality traits are generally stable after age 30, but a high dose of the hallucinogen psilocybin can increase Openness to experience in healthy adults. In a double-blind controlled study, participants who had a mystical experience during their psilocybin session showed significantly higher Openness than baseline, and this increase persisted for more than a year. The findings suggest that psilocybin and mystical-type experiences can produce lasting personality change in adults.
Journal of Psychopharmacology
May 30, 2008
R. R. Griffiths, Wa Richards, Mw Johnson et al.
883 citations
A double-blind study of 36 hallucinogen-naïve adults who regularly participated in religious or spiritual activities found that a single high dose of psilocybin (30 mg/70 kg) produced experiences that, at a 14-month follow-up, were rated among the five most personally meaningful (58%) and spiritually significant (67%) experiences of their lives. 64% reported increased well-being or life satisfaction, and 58% met criteria for a complete mystical experience. The mystical experience assessed on the session day was central to the high ratings of personal meaning and spiritual significance at follow-up. Only a scale measuring mystical experience showed a difference from screening among measures of personality, affect, quality of life, and spirituality.
Journal of Psychopharmacology
October 6, 2015
Frederick S Barrett, Matthew W Johnson, Roland R Griffiths
634 citations
The 30-item revised Mystical Experience Questionnaire (MEQ30) is validated using data from five controlled laboratory experiments with psilocybin. Participants (n=184) received a moderate to high oral dose of psilocybin (at least 20 mg/70 kg). Confirmatory factor analysis shows the MEQ30 is reliable and internally valid. Structural equation models demonstrate external and convergent validity: latent variable scores on the MEQ30 positively predict persisting changes in attitudes, behavior, and well-being attributed to psilocybin experiences, beyond the participant-rated intensity of drug effects. The findings support the MEQ30 as an efficient measure of individual mystical experiences. A method to score a "complete mystical experience" from previous versions is validated, and a stand-alone MEQ30 is provided.
Journal of Psychopharmacology
March 8, 2012
Teri Suzanne Krebs, Pål-ørjan Johansen
580 citations
A meta-analysis of six randomized controlled trials involving 536 participants found that a single dose of LSD, given alongside various alcoholism treatment programs, was associated with a decrease in alcohol misuse. The odds ratio for a beneficial effect was 1.96 (95% confidence interval 1.36–2.84), indicating a statistically significant reduction in alcohol misuse. Heterogeneity between trials was negligible. The analysis discusses secondary outcomes, risk of bias, and limitations of the included studies.
Journal of Psychopharmacology
August 31, 2016
Theresa M. Carbonaro, Matthew P. Bradstreet, Frederick S. Barrett et al.
541 citations
In a survey of 1,993 people who recalled their worst 'bad trip' after taking psilocybin mushrooms, 39% ranked it among the top five most challenging experiences of their lives. Eleven percent put themselves or others at risk of physical harm, with factors such as higher dose, longer duration, and lack of physical comfort or social support increasing that risk. About 2.6% acted aggressively and 2.7% needed medical help. Among those whose experience was more than a year prior, 7.6% sought treatment for lasting psychological symptoms, with three cases linked to enduring psychotic symptoms and three to attempted suicide. Despite difficulties, 84% reported benefiting from the experience. The incidence of risky behavior or lasting distress is very low when psilocybin is given in controlled laboratory settings.
Journal of Psychopharmacology
September 20, 2010
Erich Studerus, Michael Kometer, Felix Hasler et al.
529 citations
Psilocybin, a hallucinogenic compound, dose-dependently induced profound changes in mood, perception, thought, and self-experience, but most subjects described the experience as pleasurable, enriching, and non-threatening. Acute adverse drug reactions—strong dysphoria or anxiety—occurred only at the two highest doses in a small proportion of subjects, and were managed with interpersonal support without medication. Follow-up showed no subsequent drug abuse, persisting perception disorders, prolonged psychosis, or long-term impairment. The findings suggest that moderate doses given to healthy, high-functioning, well-prepared subjects in a carefully monitored research setting carry an acceptable level of risk.
Journal of Psychopharmacology
October 11, 2017
Roland R. Griffiths, Matthew W. Johnson, William A. Richards et al.
528 citations
A double-blind trial compared a high dose of psilocybin (20 and 30 mg/70 kg) with a very low dose (1 mg/70 kg) in healthy adults who also undertook a program of meditation and spiritual practices. At six months, the high-dose groups, compared with the low-dose group, showed large, significant positive changes in interpersonal closeness, gratitude, life meaning, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings. The enduring trait-level increases in prosocial attitudes and healthy psychological functioning were linked to the mystical-type experience occasioned by psilocybin and the rate of meditation or spiritual practices.
Journal of Psychopharmacology
November 16, 2016
469 citations
Placebo response theory and set and setting theory both explore how non-biological factors—such as expectancy, preparation, and beliefs—influence responses to therapy, but they differ in scope and purpose. Set and setting theory applies only to psychoactive drugs and is prescriptive, guiding users and therapists to optimize drug effects. Placebo theory applies to all therapeutic interventions and is descriptive, explaining how placebo effects occur. This paper examines how the two theories can complement each other, broadening understanding of how non-biological factors shape responses to drugs and other treatments.
Journal of Psychopharmacology
November 11, 2014
Peter Gasser, Katharina Kirchner, Torsten Passie
458 citations
In patients with anxiety linked to life-threatening diseases, LSD-assisted psychotherapy produced lasting benefits. Twelve months after treatment, none of the ten participants reported adverse reactions, and significant reductions in anxiety (measured by the STAI) were sustained. Qualitative interviews revealed that most participants experienced insightful, cathartic, and interpersonal encounters; 77.8% reported reduced anxiety and 66.7% reported improved quality of life. Subjective accounts pointed to facilitated access to emotions, confrontation of unknown anxieties and resources, and intense peak experiences as key psychological mechanisms. These experiences helped restructure emotional trust, situational understanding, habits, and worldview. The findings suggest that medically supervised LSD therapy can be safe and yield enduring benefits.
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
October 31, 2012
Peter Oehen, Rafael Traber, Verena Widmer et al.
407 citations
MDMA-assisted psychotherapy for treatment-resistant PTSD can be safely administered in a clinical setting. In a randomized, double-blind, active-placebo controlled pilot trial, 12 patients received either a low dose (25 mg plus 12.5 mg supplemental) or a full dose (125 mg plus 62.5 mg supplemental) of MDMA during three experimental sessions, combined with weekly non-drug psychotherapy. No serious drug-related adverse events occurred. While clinician-rated PTSD symptoms (CAPS) did not show statistically significant reductions (p = 0.066), self-reported improvement (PDS) was clinically and statistically significant (p = 0.014). CAPS scores further improved at one-year follow-up, and three MDMA sessions were more effective than two (p = 0.016).
Journal of Psychopharmacology
November 18, 2016
Frederick S. Barrett, Matthew P. Bradstreet, Jeannie‐marie Leoutsakos et al.
364 citations
A questionnaire was developed and validated to measure challenging psychological reactions to the hallucinogen psilocybin, often called 'bad trips.' Seven factors emerged: grief, fear, death, insanity, isolation, physical distress, and paranoia. These factors were linked to how difficult, meaningful, spiritually significant, and impactful on well-being participants rated their experiences. The factor structure was consistent regardless of gender or prior struggles with anxiety or depression. The questionnaire offers a tool for studying predictors and outcomes of such challenging experiences.
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 Psychopharmacology
November 20, 2013
310 citations
The glutamate hypothesis of schizophrenia, which arose from observations that NMDAR antagonists like ketamine and PCP induce schizophrenia-like symptoms, may explain negative and cognitive symptoms better than the dopamine hypothesis and even account for dopamine dysfunction itself. Ketamine primarily acts at the NMDAR, and genetic and molecular evidence points to NMDAR hypofunction in schizophrenia. This hypofunction can explain connectional and oscillatory abnormalities through weakened excitation of GABAergic interneurons and disinhibition of principal cells. Individuals with prenatal NMDAR aberrations might experience symptom onset in adolescence when synaptic pruning reduces network connectivity below a critical threshold. Ketamine challenge is useful for studying multiple aspects of acute schizophrenia.
Journal of Psychopharmacology
March 1, 2015
Pål-ørjan Johansen, Teri Suzanne Krebs
300 citations
A large study of 135,095 randomly selected US adults, including 19,299 who had used psychedelics such as LSD, psilocybin, or mescaline, found no link between lifetime psychedelic use and mental health problems. After adjusting for sociodemographics, other drug use, and childhood depression, there were no significant associations with past-year serious psychological distress, mental health treatment, suicidal thoughts, plans, or attempts, depression, or anxiety. Psychedelic use was not an independent risk factor for mental health issues. Serious adverse events are extremely rare, and psychedelics are not known to harm organs or cause addiction. The authors argue that prohibiting psychedelics as a public health measure is difficult to justify.
Journal of Psychopharmacology
May 14, 2019
Albert Garcia-Romeu, Alan K Davis, Fire Erowid et al.
286 citations
In a survey of 343 people who had problematic alcohol use for an average of seven years and then used psychedelics in non-clinical settings, 83% no longer met criteria for alcohol use disorder after the experience. Most respondents were White males in the USA who took moderate or high doses of LSD or psilocybin. They rated the experience as highly meaningful and insightful, and 28% said changes in life priorities or values helped reduce alcohol misuse. Greater dose, insight, mystical-type effects, and personal meaning were linked to larger reductions in drinking. The results suggest naturalistic psychedelic use may reduce problematic alcohol use, supporting further research into psychedelic-assisted treatment.
Journal of Psychopharmacology
June 25, 2018
Tehseen Noorani, Albert Garcia‐romeu, Thomas Cody Swift et al.
285 citations
In a follow-up study of a psilocybin-facilitated smoking cessation pilot, 12 of 15 original participants were interviewed about 30 months after their psilocybin sessions. Participants described gaining vivid insights into their self-identity and reasons for smoking, and reported that experiences of interconnectedness, awe, and curiosity persisted long after the drug's acute effects. The content of the psilocybin experience overshadowed short-term withdrawal symptoms. Participants also emphasized the importance of preparatory counseling, strong rapport with the study team, and a sense of momentum from being engaged in the treatment. Beyond quitting smoking, many reported lasting positive changes such as increased aesthetic appreciation, altruism, and pro-social behavior.
Journal of Psychopharmacology
February 9, 2015
267 citations
Interest in using psychedelic substances therapeutically has revived. Early research suggested they could help with various conditions, and recent clinical applications include cluster headaches, obsessive-compulsive disorder, addiction, and fear and anxiety in terminal illness, pointing to possibly different therapeutic mechanisms. Psychotherapeutic approaches emphasize subjective experiences like peak experiences or afterglow phenomena as key to therapeutic action. This review re-evaluates older and newer concepts of how psychedelics may produce benefits, discussing neurophenomenological aspects and different psychotherapeutic uses. Evidence shows that while pharmacological and psychological actions are not clearly separable, they appear to contribute differently depending on the pathology.
Journal of Psychopharmacology
May 20, 2006
Marc Wittmann, Olivia Carter, Felix Hasler et al.
245 citations
Psilocybin impairs the ability to reproduce time intervals longer than 2.5 seconds, to synchronize movements to beats longer than 2 seconds, and slows preferred tapping rate. These objective timing deficits are accompanied by working-memory impairments and subjective changes including depersonalization and derealization. The findings indicate the serotonin system is selectively involved in processing durations longer than 2–3 seconds and in voluntary movement speed control. The disruption of longer intervals likely results from interactions with cognitive dimensions of temporal processing via 5-HT2A receptor stimulation.
Journal of Psychopharmacology
November 6, 2020
Luke A. Jelen, Allan H. Young, James Stone
244 citations
The discovery that the dissociative anaesthetic ketamine produces rapid antidepressant effects is considered the most important breakthrough in depression research in the last 50 years. Ketamine, a racemic mixture of (S)-ketamine and (R)-ketamine, remains an off-label treatment for treatment-resistant depression, limited by dissociative effects and abuse potential. An (S)-ketamine nasal spray is approved in the United States and Europe, though concerns about efficacy and side effects persist. Preclinical evidence suggests (R)-ketamine may have more potent and longer-lasting antidepressant effects than (S)-ketamine with fewer side effects, and a pilot trial showed rapid-acting and sustained antidepressant effects in individuals with treatment-resistant depression. Research continues on the cellular and molecular mechanisms underlying these effects.
Journal of Psychopharmacology
January 1, 2005
A. C. Parrott
241 citations
Chronic tolerance to MDMA (Ecstasy) is well-documented: novice users typically take one tablet per session, regular users two to three, and experienced users may take ten to twenty-five tablets. Users often report reduced subjective effects with repeated use, leading to dose escalation and binge patterns such as stacking multiple tablets or boosting successive doses. Some experienced users snort or inject MDMA. Chronic tolerance and bingeing are statistically linked to higher rates of drug-related psychobiological problems. Neuroadaptive processes are involved, but evidence on hepatic and behavioral mechanisms is lacking. Animal research suggests serotonergic neurotoxicity from intensive dosing may contribute, potentially explaining parallel declines in efficacy, dose escalation, and rising problems. The underlying mechanisms remain unclear, with serotonergic neurotoxicity as a possible novel cause.