Journal of Psychopharmacology
October 8, 2020
Yasmin Schmid, Peter Gasser, Peter Oehen et al.
82 citations
Lysergic acid diethylamide (LSD) and 3,4-methylenedioxymethamphetamine (MDMA) are being reinvestigated as treatments for psychiatric disorders. In Switzerland, a compassionate use program allowed 18 patients (12 women, 6 men, aged 29–77) with posttraumatic stress disorder and major depression to receive LSD (100–200 µg) or MDMA (100–175 mg) in group settings from 2014–2018. Drug-assisted sessions occurred about every 3.5 months after 3–10 psychotherapy sessions. LSD produced pronounced alterations of consciousness and mystical-type experiences, with effects largely comparable to those in patients or healthy subjects treated alone in research settings. The data may inform further controlled studies of substance-assisted psychotherapy.
Journal of Psychopharmacology
October 8, 2020
Dea Siggaard Stenbæk, M. Madsen, Brice Ozenne et al.
81 citations
People with higher levels of serotonin 2A receptor (5-HT2AR) binding in the neocortex before taking psilocybin experienced shorter peak psychedelic intensity and a longer time to return to normal consciousness. Higher pre-drug 5-HT2AR binding also predicted lower scores on a measure of mystical-type experiences. The findings reinforce that individual differences in brain 5-HT2AR levels shape the temporal and subjective features of the psilocybin experience.
Journal of Psychopharmacology
June 30, 2021
Drummond E-Wen Mcculloch, Martin Bruun Madsen, Dea Siggaard Stenbæk et al.
79 citations
A single dose of psilocybin in 10 healthy volunteers who had never used psychedelics produced a significant decrease in resting-state functional connectivity within the executive control network (ECN) one week later, an effect that was no longer present at three months. No other changes in brain connectivity were observed at either time point. Exploratory analyses suggested that the decreased ECN connectivity at one week predicted increased mindfulness at three months. The findings point to modulation of the ECN during the psychedelic 'afterglow' period as a possible neural pathway for lasting positive effects on well-being, though the neural basis of personality changes seen at three months remains unknown.
Journal of Psychopharmacology
December 14, 2022
Emma Morton, Kimberly Sakai, Amir Ashtari et al.
75 citations
A web-based survey of 541 people with bipolar disorder who had used psilocybin found that one-third reported new or worsening symptoms afterward, especially manic symptoms, insomnia, and anxiety. No difference in adverse event rates emerged between bipolar I and bipolar II. Emergency medical care was rare (3.3%). Despite adverse effects, respondents rated psilocybin use as more helpful than harmful. The findings suggest psilocybin may offer subjective mental health benefits for some people with bipolar disorder, but clinical trials should closely monitor symptoms because they may emerge or intensify.
Journal of Psychopharmacology
March 9, 2021
Otto Simonsson, James Sexton, Peter S. Hendricks
75 citations
People who have used a classic psychedelic at least once in their lifetime report better overall health and are less likely to be overweight or obese, based on data from over 171,000 U.S. adults. The study also found a trend toward lower odds of having a heart condition or cancer in the past year among those who had used a classic psychedelic. The findings suggest that classic psychedelics may be linked to better physical health, but the authors note that further research is needed to determine whether the relationship is causal and to explore possible mechanisms.
Journal of Psychopharmacology
February 28, 2020
Daniel Rosenbaum, Cory R. Weissman, Thomas Anderson et al.
75 citations
People who microdose psychedelics—taking small, non-hallucinogenic amounts of LSD or psilocybin—are less likely to report a history of substance use disorders or anxiety disorders than non-microdosers, but more likely to report recent recreational substance use. Among 909 participants recruited from Reddit, most microdosers used LSD (59.3%) or psilocybin (25.9%) on a one-day-on, two-days-off schedule. The findings suggest that microdosers differ from non-microdosers in psychiatric and substance-use profiles, and well-designed randomized controlled trials are needed to evaluate safety and potential benefits in clinical populations.
Journal of Psychopharmacology
April 30, 2014
T. Buchborn, H. Schröder, V. Höllt et al.
71 citations
Repeated low doses of lysergic acid diethylamide (LSD) reverse depression-like behavioral deficits in bulbectomised rats, an animal model of depression that responds only to antidepressants. Bulbectomised rats showed marked impairments in active avoidance learning, which were largely reversed by 11 days of LSD treatment (0.13 mg/kg/day). LSD also normalized a specific hippocampal decrease in 5-HT2 receptor signaling, but did not improve behavior in sham-operated rats and instead reduced their hippocampal 5-HT2 signaling. The findings suggest LSD may have antidepressant-like effects through re-balancing hippocampal 5-HT2 and 5-HT1A receptor signaling.
Journal of Psychopharmacology
December 17, 2021
Josephine Marschall, George Fejer, Pascal Lempe et al.
69 citations
In a double-blind, placebo-controlled, within-subject crossover study, psilocybin microdosing (a sub-hallucinogenic dose taken every third day) did not alter emotion processing, symptoms of anxiety or depression, or self-reported interoceptive awareness compared with placebo. Exploratory analyses showed that symptoms of depression and stress were significantly reduced in the first block compared with baseline, but participants broke blind in the second block, and there was no effect of expectations. The authors call for further research in a substance-naïve population with clinical-range anxiety and depressive symptoms to substantiate potential beneficial effects.
Journal of Psychopharmacology
April 29, 2015
Matthew J. Baggott, Matthew G. Kirkpatrick, Gillinder Bedi et al.
69 citations
MDMA increases the use of social, sexual, and emotional words during conversation. In a double-blind, within-subjects study, 35 healthy volunteers who had previously used MDMA received either 1.5 mg/kg oral MDMA or a placebo and then discussed a close personal relationship for five minutes. Both a standard dictionary method and a machine learning analysis showed that MDMA altered speech content: it boosted social and sexual words, and also increased words related to both positive and negative emotions. These changes in speech content may help explain how MDMA enhances sociability and emotional connection during social interactions.
Journal of Psychopharmacology
January 1, 2018
David E Nichols
68 citations
The pineal gland has been mythologized across cultures as the seat of the soul or third eye, with modern claims that it secretes the psychedelic compound N,N-dimethyltryptamine (DMT) during birth, dreaming, and near death to cause out-of-body experiences. Scientific evidence contradicts these ideas. The adult pineal gland weighs less than 0.2 g and primarily produces about 30 µg per day of melatonin, a hormone regulating circadian rhythm. Minute concentrations of DMT have been detected in the brain, but they are insufficient for psychoactive effects. Alternative explanations are offered for how stress and near-death states produce altered consciousness without DMT.
Journal of Psychopharmacology
September 1, 2004
Verónica Sánchez, Esther O’shea, Kathryn S. Saadat et al.
66 citations
Repeated doses of MDMA (ecstasy) given to rats in a single session cause a dose-dependent increase in body temperature and long-term damage to serotonin neurons in the brain, but not to dopamine neurons. A dosing schedule of three injections of 4 mg/kg led to about a 50% loss of serotonin in the hippocampus, cortex, and striatum, while three injections of 6 mg/kg led to about a 65% loss. When rats were housed in a hot environment (30 °C), the same dose produced a larger temperature increase (up to 2.6 °C) and a 65% loss of serotonin in the cortex and hippocampus, with no loss of dopamine in the striatum.
Journal of Psychopharmacology
April 7, 2022
Emma I Kopra, Jason Ferris, Adam Winstock et al.
65 citations
Among 9,233 people who used magic mushrooms in the past year, only 19 (0.2%) sought emergency medical treatment, corresponding to a per-event risk of 0.06%. Younger age was the only factor linked to a higher chance of needing emergency care. The most common symptoms were psychological—anxiety, panic, paranoia, and suspiciousness. Poor mindset, poor setting, and mixing substances were the most frequently cited reasons for the incidents. All but one person returned to normal within 24 hours. The findings confirm that psilocybin mushrooms are relatively safe, with serious adverse reactions being rare and short-lived.
Journal of Psychopharmacology
March 30, 2006
Kirstie Soar, John Turner, A. C. Parrott
65 citations
People who report problems from their ecstasy use show higher levels of psychiatric symptoms such as depression, anxiety, and somatization compared to those who use ecstasy without problems, polydrug users, and people who have never used illegal drugs. In contrast, non-problematic ecstasy users do not differ from controls on these measures. Problematic users also report greater lifetime consumption, average dosage, and binge use, and are more likely to have personal and family psychiatric histories. The findings suggest that ecstasy-related psychological problems are linked to dosage and pre-existing mental health vulnerabilities, not ecstasy use alone.
Journal of Psychopharmacology
March 6, 2023
Emma I Kopra, Jason Ferris, Adam Winstock et al.
62 citations
A large international survey of 3364 people who used LSD or psilocybin mushrooms for self-treatment of mental health conditions or life worries found positive changes across all 17 measured outcomes, with the strongest benefits for insight and mood. However, 22.5% of respondents reported negative effects. Higher intensity of the psychedelic experience, seeking advice beforehand, using psilocybin mushrooms, and treating post-traumatic stress disorder were linked to better outcomes. Younger age, high experience intensity, and using LSD were associated with more negative effects. The findings suggest self-treatment outcomes are generally favorable but carry more frequent negative effects than clinical settings.
Journal of Psychopharmacology
June 8, 2023
Natalie Gukasyan, Roland R. Griffiths, David B. Yaden et al.
60 citations
Psilocybin-containing mushrooms produce weaker drug effects in people taking SSRI or SNRI antidepressants, with a 47% probability of weaker-than-expected effects for SSRIs and 55% for SNRIs, compared to 29% for bupropion, a non-serotonergic antidepressant. This dampening effect persists for up to three months after discontinuing the antidepressant, based on retrospective survey data from over 2,000 reports. Removing responses involving fluoxetine, which has a long half-life, did not change the result. The findings suggest that serotonergic antidepressants may reduce psilocybin's effects both during use and for a period after stopping.
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
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
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.