Journal of Psychopharmacology
May 30, 2022
Rebecca Smausz, Joanna C. Neill, John Gigg
60 citations
Psilocybin, a naturally occurring psychedelic compound, alters perception, emotion, and cognition and shows promise for treating brain disorders. This review outlines current understanding of its neurophysiology, focusing on its effects on brain regions within the default-mode network, especially the prefrontal cortex and hippocampus, which likely mediate its consciousness-altering properties. The authors describe specific receptor and cell types involved and note contradictory neuroimaging evidence regarding psilocybin's net effect on activity in these regions.
Journal of Psychopharmacology
January 1, 2022
Grant M Jones, Matthew K Nock
60 citations
Lifetime use of MDMA/ecstasy or psilocybin is linked to lower odds of suicidal thinking and psychological distress, while LSD use is linked to higher odds of suicidal thinking. Among 484,732 U.S. adults surveyed from 2008 to 2019, MDMA/ecstasy use was associated with 10% lower odds of past-year suicidal thinking and 12% lower odds of suicidal planning. Psilocybin use was associated with 22% lower odds of past-month psychological distress and 10% lower odds of past-year suicidal thinking. LSD use was associated with 7% higher odds of past-year suicidal thinking. These non-causal associations suggest potential therapeutic value but require experimental confirmation.
Journal of Psychopharmacology
May 29, 2018
Michelle S. Thiessen, Zach Walsh, Brian M. Bird et al.
58 citations
Men who had ever used LSD or psilocybin mushrooms were less likely to report having physically assaulted their current partner (odds ratio 0.42). This link was explained by better emotion regulation among male psychedelic users. The same pattern did not appear for women. The findings come from an online survey of 1,266 community members aged 16–70 and suggest that improved emotional control may be one reason psychedelic use is associated with lower intimate partner violence in men.
Journal of Psychopharmacology
January 21, 2008
Susana de Sola Llopis, Mónica Miguélez-Pan, Jordi Peña‐Casanova et al.
58 citations
Recreational ecstasy use, often alongside cannabis, is linked to lasting cognitive deficits. Over two years, regular ecstasy users performed worse than cannabis-only users and non-users on tests of verbal fluency, working memory, and processing speed. Heavier users (more than 100 tablets) also showed impairments in episodic memory. These deficits persisted across the study period. The findings suggest that ecstasy, possibly combined with cannabis, causes subtle but lasting cognitive harm, though pre-existing differences between groups cannot be ruled out.
Journal of Psychopharmacology
March 1, 2022
Max Wolff, Lea J. Mertens, Marie Walter et al.
57 citations
Psychedelic experiences can promote either acceptance or avoidance, and these two tendencies are relatively independent—they can alternate but do not occur simultaneously. A bilingual online survey of 997 English- and 836 German-speaking participants who used LSD, psilocybin, mescaline, or ayahuasca found that acceptance-related experiences and avoidance-related experiences were distinct and not strongly correlated. Subaspects within each type were closely linked. Therapeutic, escapist, and hedonic motives for use related differently to acceptance and avoidance, and these experiences were associated with later changes in psychological flexibility. The link between acceptance and increased flexibility was weaker when avoidance was high, suggesting an interplay between the two.
Journal of Psychopharmacology
October 8, 2020
Rotem Petranker, Thomas Anderson, Larissa J. Maier et al.
57 citations
In a large online survey of 6,753 people who had microdosed psychedelics in the past year, most reported enhanced mood, creativity, focus, and sociability, and the most common challenge was 'None'. Contrary to expectations, having an approach-intention—microdosing to achieve a specific goal—predicted fewer rather than more benefits. Most participants did not test their substances. The perceived benefits greatly outweighed the challenges, but double-blind, placebo-controlled experiments are needed to confirm these self-reported effects.
Journal of Psychopharmacology
February 21, 2019
Hina Akram, Claire Mokrysz, H. Valerie Curran
57 citations
Synthetic cannabinoids are more potent than natural cannabis because they fully activate the CB1 receptor, potentially causing more serious psychological effects. A review of 17 studies found that acute use impairs cognitive functioning and alters subjective psychological ratings compared to placebo. Non-intoxicated users show lower cognitive performance and elevated symptoms like paranoia compared to natural cannabis users and non-users. Methodological limitations across studies hinder conclusions about how dose, frequency, or type of synthetic cannabinoid influences outcomes. More research is urgently needed as use increases in at-risk populations.
Journal of Psychopharmacology
September 14, 2021
Robert F Leger, Ellen M. Unterwald
54 citations
Classical psychedelics such as psilocybin, ayahuasca, and LSD appear to be effective and relatively safe for rapidly and enduringly improving anxiety and depression. A meta-analysis of nine clinical trials found large positive effects on anxiety (Cohen's d = 1.26) and depression (Cohen's d = 1.38) overall, with benefits persisting beyond one week. No serious adverse drug reactions were reported. No significant differences in effectiveness emerged between the three psychedelic agents, but trials that used multiple dosing sessions showed significantly better outcomes than those using a single session.
Journal of Psychopharmacology
April 28, 2024
Xiangting Zhao, Yingjie Du, Yishan Yao et al.
53 citations
A single dose of psilocybin produces rapid and sustained antidepressant-like effects in both healthy mice and mice exposed to chronic corticosterone, a model of stress. Psilocybin reversed stress-induced reductions in neuroplasticity within the prefrontal cortex and hippocampus, increasing dendritic branching, spine density, and levels of synaptic proteins (p-GluA1, PSD95, synapsin-1) and activating the BDNF-mTOR signaling pathway. It also promoted neurogenesis, as indicated by more DCX-positive cells. These findings suggest that psilocybin's antidepressant action is linked to its ability to enhance structural and molecular neuroplasticity.
Journal of Psychopharmacology
February 15, 2022
Jessica L. Maples‐keller, Seth D. Norrholm, Mark Burton et al.
53 citations
A randomized placebo-controlled trial tested whether MDMA enhances fear extinction retention in healthy adults. Participants underwent fear conditioning, then received 100 mg MDMA or placebo before extinction training. Fear retention was tested 48 hours later. MDMA was well-tolerated with no serious adverse events. While the overall analysis showed no significant group difference in extinction retention between training and test sessions, a significantly larger proportion of the MDMA group retained extinction learning compared to the placebo group. The results provide a rationale for further research into MDMA's potential effects on fear extinction.
Journal of Psychopharmacology
April 15, 2010
Ben Sessa, Amanda Feilding, Robin Carhart‐Harris et al.
53 citations
Up to 2 mg of psilocybin administered as a slow intravenous injection to healthy, hallucinogen-experienced volunteers in a mock-MRI environment produces short-lived but typical drug effects that are psychologically and physiologically well tolerated. The pilot work supports the viability of using functional magnetic resonance imaging to investigate psilocybin's effects on cerebral blood flow and activity.
Journal of Psychopharmacology
July 17, 2008
Felix Hasler, Erich Studerus, Karl‐johan Lindner et al.
53 citations
MDMA primarily works by releasing serotonin in the primate brain, with additional contributions from dopamine release and stimulation of dopamine D2 and serotonin 5-HT2A receptors. The role of serotonin 5-HT1A receptors in MDMA's effects in humans was unclear. In a double-blind, placebo-controlled study, 15 healthy men received placebo, the 5-HT1A antagonist pindolol, MDMA alone, or MDMA after pindolol. MDMA impaired sustained attention and visual-spatial memory but not executive functions. Pre-treatment with pindolol did not significantly alter these cognitive impairments and only slightly affected two psychometric scales. The findings do not support animal studies suggesting MDMA's effects are mediated through 5-HT1A receptors.
Journal of Psychopharmacology
July 1, 2023
Oliver Rumle Hovmand, Emil Deleuran Poulsen, Sidse Arnfred et al.
52 citations
A systematic review of clinical trials on classical psychedelics (psilocybin, peyote, ayahuasca/DMT, and LSD) for psychiatric conditions found that all but one of the ten included trials were rated as high risk of bias. The trials predominantly enrolled white, highly educated participants, had small sample sizes, and experienced considerable dropout. Blinding was either unsuccessful or not reported regardless of the type of placebo used. Few trials published protocols, statistical analysis plans, or measures of psychotherapy fidelity. The authors suggest that future trials use parallel-group designs with active placebos in psychedelic-naïve populations, publish protocols and analysis plans, employ blinded clinician-rated outcomes, evaluate blinding, and measure expectancy and therapeutic fidelity.
Journal of Psychopharmacology
May 13, 2012
Michael E. Ballard, Gillinder Bedi, Harriet de Wit
52 citations
Acute oral doses of Δ⁹-tetrahydrocannabinol (THC) impair recognition of fearful and angry facial expressions but have only marginal effects on recognition of sadness and happiness. THC does not consistently alter ratings of emotional scenes, nor does its effect on emotional evaluation relate to its mood-altering properties. The findings indicate that THC specifically reduces perception of facial threat without positively biasing the evaluation of emotional stimuli more broadly.
Journal of Psychopharmacology
March 1, 2022
Gabrielle Agin-Liebes, Richard J. Zeifman, Jason B. Luoma et al.
51 citations
People who participated in ayahuasca retreats in Central and South America reported reduced negative mood and increased positive mood and psychological flexibility three months later. Acute experiences of cognitive reappraisal during the ceremony were the strongest predictor of improvements in positive mood and flexibility. Increases in psychological flexibility statistically accounted for the link between acute psychological factors, including reappraisal, and later mood improvements. The findings suggest that acute reappraisal and subsequent gains in psychological flexibility are key mechanisms behind psychedelic-assisted therapy's benefits, supporting the integration of mindfulness-based and third-wave therapy approaches with such interventions.
Journal of Psychopharmacology
March 30, 2021
Erich Studerus, Patrick Vizeli, Samuel Harder et al.
51 citations
The acute response to MDMA (ecstasy) is shaped by both drug concentration in the blood and personal characteristics. Pooling data from 10 placebo-controlled studies with 194 healthy adults, the strongest predictor of effects was MDMA plasma level. After adjusting for dose by body weight, higher activity of the enzyme CYP2D6 predicted lower MDMA concentrations. People scoring high in openness to experience reported more closeness, less general inactivation, and stronger altered states of consciousness. Those with high neuroticism or trait anxiety were more likely to have unpleasant or anxious reactions. These findings highlight that both pharmacological and non-pharmacological factors influence MDMA's effects, which may inform its therapeutic use.
Journal of Psychopharmacology
March 19, 2021
Rafael G. Dos Santos, Jaime Ec Hallak, Glen B. Baker et al.
51 citations
Major depressive disorder affects many people worldwide and current antidepressants often work slowly, have side effects, and fail about a third of patients. Psychedelics such as LSD, psilocybin, and ayahuasca are among the few compounds with recent human evidence of fast-acting antidepressant effects. Studies from the 1950s to 1970s reported antidepressive and anxiolytic effects, which modern trials are confirming (LSD, one trial; psilocybin, five trials; ayahuasca, two trials). These drugs appear to work primarily by activating serotonin receptors, especially the 5-HT2A receptor. The promising but limited evidence of safety and efficacy has encouraged further research into psychedelics for depression.
Journal of Psychopharmacology
May 1, 2007
Karsten Heekeren, Anna Neukirch, Jörg Daumann et al.
49 citations
Schizophrenia patients show reduced prepulse inhibition (PPI) of the startle reflex, but hallucinogen models of psychosis in healthy volunteers do not replicate this effect. In a double-blind crossover study with 15 healthy volunteers, the serotonergic hallucinogen DMT had no significant effect on PPI, while the NMDA antagonist S-ketamine increased PPI and decreased startle magnitude. Neither drug affected the attentional modulation of PPI. These results highlight differences between human hallucinogen models and both animal models and schizophrenia itself.
Journal of Psychopharmacology
June 30, 2023
Jordan Sloshower, Hamideh Safi-Aghdam, Surbhi Pathania et al.
47 citations
A single dose of psilocybin (0.3 mg/kg) doubled electroencephalographic theta power—a marker of neuroplasticity—in the auditory cortex of people with major depressive disorder two weeks later, while placebo produced no such change. Greater increases in theta power correlated with greater reductions in depression symptoms measured by the GRID-HAM-D-17 scale. These results provide evidence that psilocybin can induce sustained changes in human brain plasticity, and the theta-power increase may serve as an EEG biomarker for its antidepressant effects.
Journal of Psychopharmacology
December 20, 2020
Benjamin Illingworth, Declan J Lewis, Andrew T Lambarth et al.
47 citations
A meta-analysis of four randomized controlled trials found that MDMA-assisted psychotherapy can reduce symptoms of treatment-resistant post-traumatic stress disorder (PTSD), as measured by the Clinician Administered PTSD Scale (CAPS-IV). Doses of 75 mg and 125 mg of MDMA, but not 100 mg, produced significant decreases in CAPS-IV scores compared to active placebo. A significant reduction in Beck's Depression Inventory scores was only seen with the 75 mg dose. Participants reported more episodes of low mood, nausea, jaw-clenching during sessions, and lack of appetite within seven days. The authors conclude there is potential therapeutic benefit with minimal physical and neurocognitive risk, though better-powered trials are needed.
Journal of Psychopharmacology
August 22, 2007
Rüssel S. Falck, Jichuan Wang, Robert G. Carlson
45 citations
Among 402 young adult MDMA users followed for two years, depressive symptoms measured by the Beck Depression Inventory (BDI-II) declined from an average score of 9.8 at baseline to 7.7 at 24 months, decreasing by 0.36 points every six months. People with higher initial scores showed greater declines. Men and white participants had lower scores than women and non-whites; those with some university education had lower scores than those without. Current benzodiazepine or opioid users and people who had used MDMA more than 50 times had higher scores. The low and declining average scores suggest that for most people, MDMA use does not lead to long-term depressive symptoms.
Journal of Psychopharmacology
February 28, 2007
Ben Sessa
44 citations
While much has been written about the dangers of recreational MDMA/ecstasy use, the history of its apparently safe and effective therapeutic use in psychotherapy is less known. This paper explores that history and describes the recent re-emergence of scientific interest in MDMA and other psychedelic drugs, with several new double-blind randomized controlled trials underway. The author calls for the medical profession to engage in a dispassionate, open-minded debate about whether MDMA might have a legitimate place as an adjunct to psychotherapy, while acknowledging the limitations of new research and emphasizing appropriate but realistic caution.
Journal of Psychopharmacology
February 1, 2022
Isabel Wießner, Marcelo Falchi-Carvalho, Lucas Oliveira Maia et al.
43 citations
A randomized, double-blind, placebo-controlled crossover study gave 24 healthy volunteers 50 micrograms of LSD or an inactive placebo and tested creativity near the drug's peak using multiple tasks. LSD changed creativity in three ways: it increased novelty, surprise, originality, and semantic distances (pattern break); decreased utility, convergent thinking, and marginally elaboration (disorganization); and increased symbolic thinking and ambiguity (meaning). The findings suggest LSD shifts cognitive resources away from normal patterns toward new ones, and that LSD-induced symbolic thinking might aid psychedelic-assisted therapy.
Journal of Psychopharmacology
May 18, 2015
Sunjeev K. Kamboj, Emma J. Kilford, Stephanie Minchin et al.
43 citations
MDMA (ecstasy) and compassionate imagery both increase self-compassion and reduce self-criticism in recreational users. In a non-blind experiment, participants who consumed ecstasy showed similar pro-social effects to those produced by a contemplative compassion exercise, particularly in those with higher attachment-related avoidance. The findings suggest MDMA may enhance psychotherapy by fostering compassionate attitudes toward oneself. However, because the study was not blinded and drug purity was unknown, controlled trials with pharmaceutical-grade MDMA are needed to confirm these effects.
Journal of Psychopharmacology
June 19, 2013
Rl Carhart-Harris, Stefan Brugger, Dj Nutt et al.
43 citations
Five drugs—cannabis, psilocybin, amphetamine, ketamine, and alcohol—were compared for how well they model psychiatric symptoms. Mental health professionals rated how specific certain experiences were to symptom clusters like depression or psychosis. People with personal drug experience then reported how reliably each drug produced those experiences. No experiences were specific to negative or cognitive psychotic symptoms over depression. Psilocybin best modeled positive psychotic symptoms, while acute alcohol and amphetamine best modeled mania. These findings challenge current assumptions about drug models and point to an understudied area needing more research.