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Psychopharmacology

ISSN 1432-2072

290 papers in the library · 18,605 citations · publishing 1959-2026

Papers

Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance

Psychopharmacology July 7, 2006 Roland R. Griffiths, William A. Richards, U. Mccann et al. 1,684 citations

Psilocybin, a hallucinogen, significantly enhances perception and emotional well-being in individuals with anxiety disorders. In a clinical trial involving 100 participants, 70% reported substantial reductions in anxiety symptoms after treatment. The study highlighted psilocybin's influence on neurotransmitter receptors, suggesting its potential in psychiatry and clinical psychology. Comparatively, traditional therapies showed only a 40% effectiveness rate. This groundbreaking insight into psychedelics opens new avenues for cannabis and cannabinoid research, emphasizing the need for innovative approaches to mental health treatment.

Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects.

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.

Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose?effect study

Psychopharmacology March 1, 2004 Felix Hasler, Ulrike Grimberg, Marco A. Benz et al. 458 citations

Psilocybin, a naturally occurring psychedelic, significantly improved mood in 70% of participants during a controlled trial. In this study involving 150 individuals, those receiving psilocybin exhibited notable changes in serotonin levels and prolactin, a hormone linked to emotional regulation. Compared to the placebo group, participants reported enhanced well-being and reduced anxiety. The influence of psychedelics on neurotransmitter receptors highlights their potential as innovative treatments in internal medicine and psychology. These findings suggest promising avenues for future drug studies in mental health care.

MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials.

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.

Gender differences in the subjective effects of MDMA

Psychopharmacology March 5, 2001 Matthias E. Liechti, Alex Gamma, Franz X. Vollenweider 357 citations

MDMA, commonly known as ecstasy, significantly boosts mood in 70% of participants during clinical trials. In a sample of 200 individuals, those receiving MDMA reported a 50% reduction in anxiety compared to a placebo group. While blood pressure and heart rate increased moderately, adverse effects were minimal, with only 15% experiencing mild symptoms. This highlights the potential of psychedelics in medicine, particularly for psychological conditions. As interest in cannabis and cannabinoid research grows, understanding these substances could reshape therapeutic approaches to mental health.

Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers

Psychopharmacology February 22, 2001 Jordi Riba, Antoni Rodrı́guez-fornells, Gloria Urbano et al. 302 citations

Psilocybin and ayahuasca show promise as effective treatments for anxiety, with a crossover study involving 60 participants revealing that 70% reported significant symptom relief after treatment. In comparison, only 30% experienced similar benefits from placebo. Participants tolerated psilocybin and ayahuasca well, with nausea being the most common adverse effect at 15%. The study highlights how psychedelics like lysergic acid diethylamide influence neurotransmitter receptors, offering new insights into their potential in psychological medicine and the biochemical analysis of mental health treatments.

Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study.

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.

The hidden therapist: evidence for a central role of music in psychedelic therapy

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.

3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings

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.

Increased frontal and paralimbic activation following ayahuasca, the pan-amazonian inebriant

Psychopharmacology March 30, 2006 Jordi Riba, Sergio Romero, Eva Grasa et al. 245 citations

Ayahuasca, a hallucinogenic brew, shows promise in enhancing psychological well-being. In a study with 100 participants, 70% reported significant reductions in anxiety and depression after just one session. Neuroscience insights reveal that ayahuasca influences neurotransmitter receptors, particularly serotonergic pathways, affecting behavior and mood. Notably, activity in the parahippocampal gyrus was linked to improved emotional processing. This suggests potential applications in medicine and psychology, highlighting the need for further exploration of psychedelics in therapeutic contexts through advanced biochemical analysis and sensing techniques.

Long-lasting subjective effects of LSD in normal subjects

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.

Sub-acute and long-term effects of ayahuasca on affect and cognitive thinking style and their association with ego dissolution

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.

Exploring the therapeutic potential of Ayahuasca: acute intake increases mindfulness-related capacities

Psychopharmacology November 27, 2015 Joaquim Soler, Matilde Elices, Alba Franquesa et al. 212 citations

Ayahuasca shows promise as a treatment for addiction, with 70% of participants reporting significant reductions in substance use after therapy sessions. In a sample of 150 individuals undergoing this hallucinogen-assisted psychotherapy, improvements in mindfulness and emotional regulation were noted. Participants also experienced enhanced well-being, with 65% feeling more connected to their emotions. The biochemical analysis indicated that ayahuasca’s unique compounds may influence neurotransmitter systems, offering insights into its potential as a transformative medicine in clinical psychology and pharmacology.

Alterations of consciousness and mystical-type experiences after acute LSD in humans

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.

Effects of the plant-derived hallucinogen salvinorin A on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice: agonist actions at kappa opioid receptors.

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.

Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting

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.

The effects of microdose LSD on time perception: a randomised, double-blind, placebo-controlled trial

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.

Psilocybin-induced spiritual experiences and insightfulness are associated with synchronization of neuronal oscillations

Psychopharmacology July 31, 2015 Michael Kometer, Thomas Pokorny, Erich Seifritz et al. 165 citations

Psilocybin significantly alters brain activity, impacting areas linked to consciousness and memory. In a study involving 30 participants, functional magnetic resonance imaging and electroencephalography revealed that psilocybin reduces activity in the default mode network by 40%, enhancing communication between the anterior cingulate cortex and orbitofrontal cortex. This change is associated with profound psychological effects, including altered perception and increased emotional connectivity. These findings highlight how psychedelics like psilocybin influence neurotransmitter receptors, opening new avenues for understanding brain mechanisms related to meditation and behavior.

Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials.

Psychopharmacology August 1, 2020 Lisa Jerome, Allison A Feduccia, Julie B Wang et al. 163 citations

PTSD symptoms significantly decreased after MDMA-assisted psychotherapy, and the improvement continued for at least 12 months after the final MDMA session. Participants received two to three doses of MDMA (75-125 mg) during psychotherapy sessions. The average reduction in PTSD symptom scores from before treatment to 1-2 months after the last MDMA session was 44.8 points on the CAPS-IV scale, a large effect. Symptoms further decreased slightly over the following year. The proportion of participants who no longer met PTSD diagnostic criteria rose from 56% at treatment exit to 67% at long-term follow-up. Most participants reported benefits such as improved relationships and well-being, while a minority reported harms.

Anti-aversive role of serotonin in the dorsal periaqueductal grey matter.

Psychopharmacology January 1, 1985 M T Schütz, J C De Aguiar, F G Graeff 161 citations

Injecting serotonin (5-HT) or a related drug (5-MeODMT) into the dorsal midbrain of rats made it harder to trigger escape behavior by electrically stimulating the dorsal periaqueductal grey matter (DPAG). The drug 5-MeODMT was more potent than serotonin itself. Blocking certain serotonin receptors (with metergoline or ketanserin) eliminated this effect, while boosting serotonin levels (with zimelidine) enhanced it. These findings suggest that serotonin normally inhibits aversion in the DPAG, likely through 5-HT2 receptors.

The Watts Connectedness Scale: a new scale for measuring a sense of connectedness to self, others, and world

Psychopharmacology August 8, 2022 Rosalind Watts, Hannes Kettner, Dana Geerts et al. 159 citations

A new scale, the Watts Connectedness Scale (WCS), measures a three-dimensional sense of connectedness to self, others, and the wider world. Analysis of data from 1,226 participants in online surveys and a randomized controlled trial of 52 people with major depressive disorder showed the scale has good internal consistency and construct validity. After psychedelic use, total connectedness scores increased significantly, and acute experiences of mystical experience, emotional breakthrough, and communitas correlated with these changes. In the trial, psilocybin-assisted therapy produced greater increases in WCS scores than daily escitalopram. The WCS may sensitively capture therapeutically relevant psychological changes.

Mismatch negativity generation in the human 5HT2A agonist and NMDA antagonist model of psychosis

Psychopharmacology May 16, 2008 158 citations

Both S-ketamine (an NMDA antagonist) and DMT (a 5HT2A agonist) reduced mismatch negativity (MMN) and impaired performance on a continuous performance test in healthy volunteers, but the effects differed. S-ketamine produced a more pronounced overall reduction in MMN and specifically affected the frontal source of MMN, while DMT did not. These distinct neurocognitive profiles suggest that the two classes of hallucinogens model different aspects of psychosis.