Psychopharmacology
July 7, 2006
Roland R. Griffiths, William A. Richards, U. Mccann et al.
1,684 citations
A high dose of psilocybin, given under supportive conditions to hallucinogen-naïve adults who regularly participate in religious or spiritual activities, produced acute perceptual changes, subjective experiences, and labile moods including anxiety. It also increased measures of mystical experience. Two months later, volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed sustained positive changes in attitudes and behavior to it, consistent with ratings by community observers. The ability to prospectively occasion such experiences allows rigorous scientific investigation of their causes and consequences.
Psychopharmacology
December 1, 2011
Roland R Griffiths, Matthew W Johnson, William A Richards et al.
938 citations
Psilocybin can produce mystical-type experiences that lead to lasting positive changes in attitudes, mood, and behavior. In a double-blind study, 18 adults (17 with no prior hallucinogen use) received 0, 5, 10, 20, or 30 mg/70 kg psilocybin in five sessions under supportive conditions. At the two highest doses, 72% of volunteers reported a mystical-type experience, and 39% experienced extreme anxiety or fear. One month later, participants rated these sessions as having substantial personal and spiritual significance, with the ascending dose sequence showing greater positive effects. At 14 months, these positive ratings remained undiminished and were consistent with observer reports. The effects generally increased with dose.
Psychopharmacology
March 1, 2004
Felix Hasler, Ulrike Grimberg, Marco A. Benz et al.
458 citations
Psilocybin, a serotonin 5-HT(2A) receptor agonist, dose-dependently altered consciousness, attention, and mood in eight healthy subjects. At medium and high doses (215 and 315 micrograms per kilogram body weight), performance on an attention test dropped by 50%, and participants reported increased emotional excitability, dreaminess, and general inactivation. Only one person experienced transient anxiety at the highest dose. Blood pressure rose modestly after the high dose, and levels of the hormones TSH, ACTH, cortisol, and prolactin increased during peak effects, with prolactin rising after both medium and high doses. No changes occurred in heart rhythm or body temperature. The authors conclude psilocybin affects core dimensions of consciousness and physiology in a dose-dependent manner and found no evidence of harm to physical health.
Psychopharmacology
September 1, 2019
Michael C Mithoefer, Allison A Feduccia, Lisa Jerome et al.
364 citations
A pooled analysis of six phase 2 trials found that MDMA-assisted psychotherapy significantly reduced PTSD symptoms in adults. Participants receiving active MDMA (75-125 mg) during manualized therapy sessions showed a large treatment effect (Cohen's d = 0.8) compared to those receiving placebo or low doses (0-40 mg). After two sessions, 54.2% of the active group no longer met PTSD diagnostic criteria versus 22.6% of the control group. Depression symptoms also improved more in the active group, though this difference was not statistically significant. MDMA was well tolerated with expected side effects. These findings supported advancement to phase 3 trials and FDA Breakthrough Therapy designation.
Psychopharmacology
March 5, 2001
Matthias E. Liechti, Alex Gamma, Franz X. Vollenweider
357 citations
Equal doses of MDMA per kilogram of body weight produce stronger subjective effects in women than in men. Women reported more intense perceptual changes, thought disturbances, and fear of losing body control, and they experienced more acute adverse effects and aftereffects. The dose of MDMA correlated with the intensity of perceptual changes in women. Men showed greater increases in blood pressure. These findings suggest women may be more susceptible to the serotonin-releasing effects of MDMA.
Psychopharmacology
February 22, 2001
Jordi Riba, Antoni Rodrı́guez-fornells, Gloria Urbano et al.
302 citations
Ayahuasca, a South American psychoactive beverage containing DMT, produced dose-dependent psychological effects in six healthy male volunteers with prior experience. Encapsulated freeze-dried ayahuasca at doses of 0.5, 0.75, and 1.0 mg DMT/kg body weight increased scores on hallucinogen rating scales, addiction research inventory scales, and visual analogue scales for liking, good effects, and high. Effects began within 30-60 minutes, peaked at 60-120 minutes, and resolved by 240 minutes. The tea was well tolerated cardiovascularly, though nausea and altered physical sensations were common. Five volunteers found the experience pleasant; one had an intensely dysphoric reaction with anxiety and withdrew. Ayahuasca induced perceptual, affective, cognitive, and somatic changes of longer duration and milder intensity than intravenous DMT.
Psychopharmacology
November 1, 2018
Alicia L Danforth, Charles S Grob, Christopher Struble et al.
284 citations
Autistic adults with severe social anxiety who received MDMA-assisted psychotherapy showed significantly greater improvement in social anxiety symptoms compared to those given an inactive placebo. The improvement was rapid and durable, with effects still present at a six-month follow-up. The study used two eight-hour psychotherapy sessions with either MDMA (75–125 mg) or placebo, plus three non-drug sessions after each. The effect size was very large at the primary endpoint and remained large at follow-up. Social anxiety stayed the same or continued to improve for most in the MDMA group after treatment ended. Initial safety and efficacy support larger studies.
Psychopharmacology
February 1, 2018
Mendel Kaelen, Bruna Giribaldi, Jordan Raine et al.
274 citations
Music plays a central therapeutic role in psychedelic therapy with psilocybin for treatment-resistant depression. In interviews with 19 patients, music had both welcome influences—evoking meaningful emotion, mental imagery, guidance, openness, calm, and safety—and unwelcome influences, such as unpleasant emotion, imagery, and resistance. Patients' experience of the music correlated with mystical experiences and insightfulness. Critically, the nature of the music experience significantly predicted reductions in depression one week after psilocybin, whereas general drug intensity did not.
Psychopharmacology
March 15, 2006
Michael H. Baumann, Xiaoying Wang, Richard B. Rothman
269 citations
High doses of MDMA (ecstasy) reduce serotonin levels in the brains of rats, but this reduction does not necessarily indicate that neurons have been damaged. The drug works by stimulating the release of serotonin, norepinephrine, and dopamine. At doses that cause long-term serotonin depletion (10-20 mg/kg), markers of actual neuronal damage such as cell death or gliosis are not reliably increased. Even moderate doses that do not deplete serotonin can produce lasting anxiety-like behaviors in rats, suggesting potential risks from the drug beyond neurotoxicity.
Psychopharmacology
August 9, 2017
Robin Carhart‐Harris, David Erritzøe, Eline Haijen et al.
268 citations
Psychedelic drugs show therapeutic potential in psychiatry, but how they work is unclear. The authors propose that a sense of connectedness is key to their effectiveness, provide preliminary evidence supporting this idea, and outline a roadmap for further testing.
Psychopharmacology
March 30, 2006
Jordi Riba, Sergio Romero, Eva Grasa et al.
245 citations
A single oral dose of ayahuasca, equivalent to 1.0 mg DMT per kilogram of body weight, increased blood flow in frontal and paralimbic brain regions of fifteen male volunteers with prior psychedelic experience. Greater perfusion was observed bilaterally in the anterior insula, with stronger effects in the right hemisphere, and in the right anterior cingulate/frontomedial cortex—areas linked to somatic awareness, subjective feeling states, and emotional arousal. Additional increases occurred in the left amygdala/parahippocampal gyrus, a structure involved in emotional processing. These findings indicate that ayahuasca interacts with neural systems central to interoception and emotional processing, suggesting a modulatory role for serotonergic neurotransmission.
Psychopharmacology
September 16, 2017
Yasmin Schmid, Matthias E. Liechti
234 citations
A single 200 microgram dose of LSD, given to 16 healthy volunteers in a controlled lab setting, produced long-lasting positive effects. Participants reported increased positive attitudes, mood, altruistic behavior, and well-being one month and twelve months later. These benefits were subjectively attributed to the LSD experience. The strength of the acute altered state and mystical-type experience correlated with improved well-being after twelve months. No negative effects were reported. Ten of fourteen participants rated the experience among the ten most meaningful in their lives, and five rated it among the five most spiritually meaningful. Mystical and death transcendence scores increased at one and twelve months, while personality traits did not change.
Psychopharmacology
April 1, 2022
Jacob S. Aday, Boris D. Heifets, Steven D. Pratscher et al.
214 citations
Psychedelic research faces unique methodological challenges beyond those typical of psychotherapy and pharmacology trials. The pronounced subjective effects of high-dose psychedelics make it difficult to mask participants to their treatment condition. Positive media coverage inflates participants' expectations for benefit, and unmasking combined with expectations can produce large placebo and nocebo effects. Recommendations to improve masking and reduce expectancy bias include careful study development, participant recruitment and selection, incomplete disclosure of study design, choice of active placebo, and measurement of expectations and masking efficacy. Incorporating these design elements aims to reduce bias and improve the ability to discern treatment-specific effects.
Psychopharmacology
August 13, 2018
Malin V. Uthaug, Kim van Oorsouw, Kim P. C. Kuypers et al.
213 citations
Ayahuasca, a psychotropic plant tea used ceremonially in South America, produces sub-acute and long-term improvements in affect and cognitive thinking style. In 57 ceremony attendees in the Netherlands and Colombia, ratings of depression and stress significantly decreased the day after the ceremony and these changes persisted for 4 weeks. Convergent thinking also improved post-ceremony and was maintained at 4 weeks. Satisfaction with life and several aspects of mindfulness increased the day after but were not significantly different from baseline at 4 weeks. Changes in affect, satisfaction with life, and mindfulness correlated with the degree of ego dissolution experienced during the ceremony, not with prior ayahuasca experience. These findings highlight ayahuasca's therapeutic potential for mental health disorders like depression.
Psychopharmacology
November 27, 2015
Joaquim Soler, Matilde Elices, Alba Franquesa et al.
212 citations
Ayahuasca, a psychotropic plant tea containing DMT and β-carboline alkaloids, increases mindfulness capacities within 24 hours of a single session. In 25 individuals, ayahuasca significantly reduced judgmental processing of experiences and inner reactivity, as measured by the Five Facets Mindfulness Questionnaire, and increased decentering ability, as measured by the Experiences Questionnaire. These changes match those seen after extensive mindfulness practice and support the tea's therapeutic potential, particularly for addiction and depression.
Psychopharmacology
July 19, 2016
Kim P. C. Kuypers, Jordi Riba, Mario de la Fuente Revenga et al.
204 citations
Ayahuasca, a psychedelic plant tea used in Amazonian shamanism, may enhance creative divergent thinking—the ability to generate new ideas and strategies—while decreasing convergent thinking, which focuses on a single correct answer. In a study of 26 participants at two spiritual workshops, creativity tests before and during the acute effects of ayahuasca showed that the tea significantly increased divergent thinking and decreased convergent thinking, as measured by the picture concept test. No significant effects were found on the pattern/line meanings test. These results suggest ayahuasca increases psychological flexibility, potentially aiding psychotherapeutic interventions.
Psychopharmacology
October 7, 2016
Matthias E. Liechti, Patrick C. Dolder, Yasmin Schmid
203 citations
Mystical-type experiences were uncommon after LSD, likely due to the set and setting of the study. LSD at 200 μg, a dose used in psychotherapy in Switzerland, may cause greater or different alterations of consciousness compared with 100 μg, a dose used in imaging studies. Ego dissolution may correspond to plasma levels of LSD, whereas more strongly induced effects of the drug may not show such relationships.
Psychopharmacology
May 1, 2005
Yong Zhang, Eduardo R Butelman, Stefan D Schlussman et al.
198 citations
Salvinorin A, a hallucinogen from Salvia divinorum, is a potent kappa opioid receptor agonist. In mice, higher doses (1.0 and 3.2 mg/kg) significantly decreased dopamine levels in the caudate putamen but not in the nucleus accumbens, an effect blocked by a kappa opioid receptor antagonist. These same doses caused conditioned place aversion and reduced locomotor activity. The findings suggest that salvinorin A's reduction of striatal dopamine may contribute to its aversive and motor-suppressing effects, consistent with its in vitro characterization as a kappa opioid receptor agonist.
Psychopharmacology
October 24, 2018
Luisa Prochazkova, Dominique P. Lippelt, Lorenza S. Colzato et al.
181 citations
Microdosing psychedelics may enhance cognitive performance by improving the balance between cognitive persistence and flexibility, according to preliminary quantitative findings. The authors speculate that psychedelics affect cognitive metacontrol policies, optimizing this balance. However, they emphasize that future research with rigorous placebo-controlled designs is needed to confirm these initial results. The study provides support for cognitive-enhancing properties but remains preliminary.
Psychopharmacology
May 1, 2019
Thomas R. Arkell, Nicholas Lintzeris, Richard C. Kevin et al.
177 citations
Both THC-dominant and THC/CBD equivalent cannabis increased lane weaving during simulated driving but had little effect on other driving measures. Impairment on the Digit Symbol Substitution Task, Divided Attention Task, and Paced Auditory Serial Addition Task occurred with both active cannabis types, with worse performance on the latter two tasks after THC/CBD equivalent cannabis. Subjective feelings of being "stoned" and confidence in driving ability did not differ by CBD content. Peak plasma THC concentrations were higher after THC/CBD equivalent cannabis, suggesting a possible pharmacokinetic interaction. Cannabis with equivalent CBD and THC appears no less impairing than THC-dominant cannabis, and CBD may exacerbate THC-induced impairment in some circumstances.
Psychopharmacology
September 2, 2016
Will Lawn, Tom P. Freeman, Rebecca Pope et al.
177 citations
Cannabis containing only THC reduced the likelihood of choosing high-effort rewards compared to placebo, indicating a transient amotivational state, while adding CBD altered the effect of THC on expected value. Cannabis-dependent individuals showed preserved motivation but impaired reward learning compared to non-dependent controls, though depression may have influenced results.
Psychopharmacology
January 2, 2019
Thomas Anderson, Rotem Petranker, Daniel Rosenbaum et al.
171 citations
People who currently or formerly microdosed psychedelics like LSD or psilocybin reported lower dysfunctional attitudes and negative emotionality, and higher wisdom, open-mindedness, and creativity compared to non-microdosers. These differences were observed in an online observational study using self-report questionnaires and a creativity task. The findings suggest potential benefits of microdosing, but controlled experiments are needed to confirm safety and clinical efficacy.
Psychopharmacology
November 26, 2018
Steliana Yanakieva, Naya Polychroni, Neiloufar Family et al.
169 citations
Microdoses of LSD (5, 10, and 20 μg) caused older adults to over-reproduce time intervals of 2000 milliseconds and longer, with the strongest effect at 10 μg. This temporal dilation occurred without noticeable changes in perception, mentation, or concentration, and was independent of any subjective drug effects. The findings suggest that LSD can directly alter interval timing at doses too low to produce conscious psychedelic effects, indicating a dissociation between neurochemical influences on time perception and altered states of consciousness.
Psychopharmacology
October 30, 2010
Johannes G. Ramaekers, Eef L. Theunissen, Marjolein de Brouwer et al.
168 citations
Heavy cannabis users develop tolerance to the impairing effects of THC on neurocognitive tasks, but they do not develop cross-tolerance to the impairing effects of alcohol. In a double-blind study, 21 heavy cannabis users received alcohol at three levels (targeting blood alcohol concentrations of 0, 0.5, and 0.7 mg/ml) and smoked a THC cigarette (400 μg/kg) 3 hours after drinking began. Alcohol alone impaired performance on tests of perceptual motor control, divided attention, and motor inhibition, while THC alone generally did not affect performance. However, combining THC and alcohol produced greater impairments in divided attention than alcohol alone, indicating that alcohol can potentiate THC effects in tolerant users.
Psychopharmacology
July 31, 2015
Michael Kometer, Thomas Pokorny, Erich Seifritz et al.
165 citations
A moderate dose of psilocybin, a naturally occurring hallucinogen, decreased brain electrical activity at 1.5-20 Hz in a network involving the anterior and posterior cingulate cortices and parahippocampal regions. The intensity of spiritual experience and insightfulness correlated with the synchronization of delta oscillations (1.5-4 Hz) between the retrosplenial cortex, parahippocampus, and lateral orbitofrontal area. These findings directly link a specific spatiotemporal neuronal mechanism to spiritual experiences and enhanced insight into life, suggesting a pathway for modulating mental health and promoting well-being.