Journal of Psychopharmacology
January 1, 1998
A. C. Parrott, A. J. Lees, N. J. Garnham et al.
226 citations
Regular and novice users of MDMA (ecstasy) showed similar performance to non-users on tests of reaction time and vigilance, but both user groups recalled significantly fewer words than controls on immediate and delayed word recall tasks. The study involved 10 regular users (10+ lifetime uses), 10 novice users (1-9 uses), and 10 never-users. These memory deficits align with animal research suggesting MDMA may cause serotonergic damage in brain regions critical for memory, such as the hippocampus and frontal cortex.
Journal of Psychopharmacology
September 8, 2010
Tibor M. Brunt, Anneke Poortman, Raymond J.m. Niesink et al.
217 citations
The ecstasy market in the Netherlands became unstable in 2009, with more than a 50% drop in tablets containing MDMA. A new substance, mephedrone, partially replaced MDMA in tablets sold as ecstasy, at doses between 96 and 155 mg. Based on reports from 70 regular ecstasy users, mephedrone produced enjoyable effects similar to other amphetamine-type stimulants, including MDMA, but unlike MDMA it induced strong cravings in most users. If the unstable market continues, mephedrone may substantially substitute for MDMA, raising health concerns.
Journal of Psychopharmacology
December 8, 2010
Liselore Koedood, Adam L. Halberstadt, Susan B. Powell et al.
212 citations
Psilocin, the active metabolite of psilocybin, acts as an agonist at 5-HT1A, 5-HT2A, and 5-HT2C receptors. In mice, psilocin induced head twitch response (HTR) via 5-HT2A receptors, as effects were absent in mice lacking that gene. In the behavioral pattern monitor (BPM), psilocin decreased locomotor activity, holepoking, and time in the chamber center; these effects were blocked by the 5-HT1A antagonist WAY-100635 but not by 5-HT2C antagonism or 5-HT2A gene deletion. 5-MeO-DMT produced similar BPM effects attenuated by WAY-100635. Psilocin and 5-MeO-DMT decreased path linearity via 5-HT2C and 5-HT1A receptors, respectively. 1-methylpsilocin induced HTR via 5-HT2A but was inactive in the BPM, suggesting greater pharmacological selectivity and potential as a therapeutic alternative to psilocybin.
Journal of Psychopharmacology
January 16, 2020
Lea J. Mertens, Matthew B. Wall, Leor Roseman et al.
211 citations
After a single 25 mg dose of psilocybin, patients with treatment-resistant depression showed decreased functional connectivity between the ventromedial prefrontal cortex and the right amygdala while viewing faces, particularly fearful and neutral ones. This decrease was linked to lower rumination levels one week later. Increased connectivity between these regions and occipital-parietal cortices also emerged. The findings suggest psilocybin therapy may revive emotional responsiveness at both neural and psychological levels, offering a potential treatment mechanism. Placebo-controlled studies are needed to confirm these results.
Journal of Psychopharmacology
November 18, 2016
James Rucker, Luke A. Jelen, Sarah Kalen Flynn et al.
187 citations
Unipolar mood disorders such as major depressive disorder and dysthymia cause high disability, mortality, and socioeconomic burden, with current treatments often suboptimal and little new pharmaceutical development. Psychedelic drugs like psilocybin were used extensively before prohibition in the late 1960s and are relatively safe in medically controlled environments with no dependence risk. A systematic review of 19 clinical treatment studies found that of 423 individuals, 335 (79.2%) showed clinician-judged improvement after psychedelic treatment. A recent UK pilot study supports psilocybin with psychological support for treatment-resistant depression. The evidence strongly suggests psychedelics should be re-examined in modern clinical trials for unipolar mood disorders.
Journal of Psychopharmacology
March 1, 2006
Euphrosyne Gouzoulis‐mayfrank, Jörg Daumann
179 citations
The popular dance drug ecstasy (MDMA) is neurotoxic to central serotonergic neurons in laboratory animals and possibly in humans. Studies have reported alterations in serotonergic transmission and neuropsychiatric abnormalities in ecstasy users that may relate to MDMA-induced neurotoxic brain damage. The most consistent findings associate subtle cognitive, particularly memory, deficits with heavy ecstasy use. However, most studies have important methodological problems, especially the widespread pattern of polydrug use—commonly alcohol, cannabis, and stimulants (amphetamines and cocaine)—which makes it difficult to link findings to MDMA alone. Stimulants are also neurotoxic and may act synergistically with MDMA, while cannabis has complex interactions, including neuroprotective actions that can partially block MDMA-induced neurotoxicity in animals. Future longitudinal research should clarify these relationships.
Journal of Psychopharmacology
January 17, 2018
Taylor Lyons, Robin Carhart‐Harris
176 citations
In patients with moderate to severe treatment-resistant depression, psilocybin given in two oral doses (10 mg and 25 mg one week apart) was associated with increased nature relatedness and decreased authoritarianism one week after dosing. Nature relatedness remained significantly higher 7–12 months later, while the reduction in authoritarianism persisted only at a trend level. No changes occurred in healthy control subjects. The findings suggest that psilocybin combined with psychological support may produce lasting shifts in attitudes and beliefs, though the small sample size precludes causal conclusions.
Journal of Psychopharmacology
August 26, 2022
Joost J. Breeksema, Bouwe Kuin, Jeanine Kamphuis et al.
171 citations
A systematic review of 44 clinical studies (34 quantitative, 10 qualitative) involving 598 patients treated with MDMA or serotonergic psychedelics (psilocybin, LSD, ayahuasca) found that treatments were generally well tolerated, though adverse events were often not systematically assessed. Common acute adverse events across diagnoses and compounds included nausea, headaches, and anxiety. Late adverse events included headaches (psilocybin, MDMA), fatigue, low mood, and anxiety (MDMA). One serious adverse event occurred during MDMA administration (increased premature ventricular contractions requiring brief hospitalization); no other events required medical intervention. Qualitative studies suggested that psychologically challenging experiences may be therapeutically beneficial. The authors conclude that adverse events are poorly defined and likely underreported due to study design and sample selection.
Journal of Psychopharmacology
January 9, 2021
Alan K Davis, Frederick S Barrett, Sara So et al.
166 citations
A new questionnaire, the Psychological Insight Questionnaire, was developed to measure psychologically insightful experiences during psychedelic use. Among 1,661 psilocybin and LSD users, the 23-item measure showed two subscales: Avoidance and Maladaptive Patterns Insights and Goals and Adaptive Patterns Insights. Scores correlated strongly with an existing insight measure and moderately with mystical and challenging experience questionnaires. They also correlated with retrospectively reported increases in psychological flexibility, well-being, and life satisfaction attributed to a memorable psychedelic experience. The questionnaire predicted unique variance in these outcomes beyond mystical and challenging effects, suggesting it may help understand how psychological insight contributes to psychedelics' enduring effects.
Journal of Psychopharmacology
March 1, 2006
Rainer Thomasius, P. Zapletalova, Kay Uwe Petersen et al.
158 citations
Heavy ecstasy (MDMA) use is associated with lasting verbal memory deficits and elevated psychological symptoms even after more than 2.5 years of abstinence, while reduced serotonin transporter availability in the brain may partially recover when use stops. In a longitudinal study comparing current ecstasy users, ex-users, polydrug controls, and drug-naive controls over two years, ex-users showed the worst verbal memory and highest symptom scores, with no improvement over time. Current users' memory and symptoms did not worsen during continued use. Serotonin transporter availability in the midbrain recovered as current users reduced MDMA use, but this recovery may not reflect neuronal integrity. Pre-existing differences cannot be ruled out as an alternative explanation.
Journal of Psychopharmacology
July 22, 2014
Yasmin Schmid, Cédric M. Hysek, Linda D. Simmler et al.
154 citations
A low dose of MDMA (75 mg) enhanced emotional empathy for positive emotional situations and reduced recognition of sad faces, but did not affect cognitive empathy, social cognitive inferences, or moral judgment. Methylphenidate (40 mg) had no effects on emotional processing, empathy, or mental perspective-taking. MDMA increased subjective feelings of closeness, openness, and trust, along with plasma oxytocin and prolactin levels. These social-cognitive effects likely contribute to MDMA's popularity as a party drug.
Journal of Psychopharmacology
March 20, 2023
Jordan Sloshower, Hamideh Safi-Aghdam, Surbhi Pathania et al.
153 citations
In a small exploratory study, 19 adults with moderate-to-severe major depression received placebo first, then 4 weeks later a single dose of psilocybin (0.3 mg/kg), both embedded in psychotherapy. Depression and anxiety improved after both placebo and psilocybin, with no statistically significant difference between the two conditions. However, antidepressant effect sizes were larger after psilocybin (d′ = 1.02–2.27) than after placebo (d′ = 0.65–0.99), and 66.7% of participants responded and 46.7% remitted following psilocybin. Improvements lasted about 2 months on average. The intensity of mystical-type experience during psilocybin did not correlate with antidepressant effects. The authors conclude that expectancy and therapy effects complicate interpretation but support further study of psilocybin for depression.
Journal of Psychopharmacology
June 20, 2017
Matthias Forstmann, Christina Sagioglou
153 citations
People who have used classic psychedelics like LSD, psilocybin, or mescaline report more pro-environmental behaviors such as recycling and saving water. This relationship is explained by a stronger self-identification with nature, even after controlling for other drug use and personality traits like openness and conscientiousness. The findings suggest that lifetime psychedelic experience may contribute to environmental behavior by incorporating the natural world into one's self-concept, pointing to a possible societal benefit of these substances.
Journal of Psychopharmacology
March 1, 2006
G. J. H. Dumont, R. J. Verkes
148 citations
A review of the literature on MDMA (ecstasy) in healthy volunteers found that the drug produces robust effects on subjective experiences and physiological measures, but evidence for cognitive effects is limited. Cardiovascular effects showed a clear dose-response relationship: doses below 1.0 mg/kg caused no change compared to placebo, while higher doses consistently increased heart rate and blood pressure. MDMA also reliably increased pupil size, plasma cortisol, and plasma prolactin levels. Subjective effects matched an entactogenic profile. The authors recommend further research, especially into cognitive effects and potential therapeutic uses.
Journal of Psychopharmacology
April 1, 2021
Ari Brouwer, Robin Lester Carhart-Harris
147 citations
A new construct called the 'pivotal mental state' is defined as a hyper-plastic state that enables rapid and deep learning, potentially mediating psychological transformation. These states are argued to serve an evolutionary function, aiding adaptation when environmental pressures demand change. Chronic stress and neurotic traits are identified as primers, while acute stress can trigger the state. Activity at the serotonin 2A receptor, as seen with psychedelics, can robustly induce pivotal mental states, but the capacity for such states is proposed as an inherent property of the human brain. The model links increased serotonin 2A receptor signaling to a hyper-plastic brain state, enhanced associative learning, and psychological transformation.
Journal of Psychopharmacology
May 1, 2000
Matthias E. Liechti, Franz X. Vollenweider
144 citations
MDMA (Ecstasy) moderately increases blood pressure and heart rate, slightly elevates body temperature, and produces a range of short-term side effects in humans. Pretreatment with the serotonin uptake inhibitor citalopram (40 mg i.v.) reduced all these physiological changes except for body temperature, in a double-blind placebo-controlled study of 16 healthy volunteers. These findings suggest that MDMA's physiological effects in humans are partially due to its interaction with the serotonin carrier and subsequent release of serotonin.
Journal of Psychopharmacology
February 21, 2017
Patrick Vizeli, Matthias E. Liechti
142 citations
In nine double-blind, placebo-controlled studies with 166 healthy subjects, single doses of MDMA (75 or 125 mg) produced acute positive subjective effects lasting about 4 hours, with the higher dose yielding stronger 'good drug effect' ratings. Moderate and transient 'bad drug effects' were greater in women than men. MDMA raised systolic blood pressure above 160 mmHg in 33% of subjects, heart rate above 100 beats/min in 29%, and body temperature above 38°C in 19%; these effects were more frequent with the 125 mg dose. Adverse effects were dose-dependent and more common in females. No serious adverse events occurred, and liver or kidney function was unaffected about a month later. MDMA was safe in healthy subjects in a medical setting, but risks are likely higher in patients with cardiovascular disease.
Journal of Psychopharmacology
March 1, 2006
Andy C. Parrott
139 citations
Recreational ecstasy/MDMA users show a range of neuropsychobiological deficits, but not all users are affected. Heavy use, especially intensive sessions, is linked to memory, attention, and executive function problems, as well as disturbed sleep, sexual dysfunction, reduced immune function, and oxidative stress. Around 90–95% of users also take cannabis, which independently contributes to adverse effects, though acute co-use may sometimes be interactive rather than additive. Alcohol, nicotine, and amphetamine further complicate outcomes. Pure MDMA users are rare but still show significant neurocognitive deficits.
Journal of Psychopharmacology
January 18, 2017
Matthew W. Johnson, Albert Garcia‐romeu, Patrick S. Johnson et al.
129 citations
A survey of 358 people who quit or reduced smoking after using a psychedelic (like psilocybin or LSD) in a non-laboratory setting at least one year earlier found that 38% reported continuous smoking cessation, with 74% of those abstinent for over two years. Another 28% reported a lasting reduction in smoking, from a median of 300 cigarettes per month before to 1 per month after. The remaining 34% temporarily reduced smoking but relapsed, typically within 3–6 months. Those who relapsed rated their psychedelic experience as less personally meaningful and spiritually significant than the other groups. Across all groups, participants reported less severe withdrawal symptoms like depression and craving after psychedelic use compared with past quit attempts. Changes in life priorities and values were cited as the most important psychological factor.
Journal of Psychopharmacology
June 11, 2016
Rafael G. Dos Santos, Fermanda M Balthazar, José Carlos Bouso et al.
126 citations
A systematic review of 28 human studies found that acute ayahuasca administration is well tolerated, increases introspection and positive mood, alters visual perceptions, activates frontal and paralimbic brain regions, and decreases default mode network activity. It improves planning and inhibitory control but impairs working memory, and shows antidepressive and antiaddictive potentials. Long-term use is associated with increased cortical thickness of the anterior cingulate cortex and cortical thinning of the posterior cingulate cortex, inversely correlated to age of onset, intensity of prior use, and spirituality. Subacute and long-term use is not linked to increased psychopathology or cognitive deficits but to enhanced mood, cognition, spirituality, and reduced impulsivity. Overall toxicity appears low, though therapeutic effects need replication.
Journal of Psychopharmacology
July 10, 2020
Nicole Leite Galvão‐coelho, Ana Cecília de Menezes Galvão, Raíssa Nóbrega de Almeida et al.
124 citations
In a double-blind placebo-controlled trial, people with treatment-resistant depression had higher baseline levels of C-reactive protein than healthy controls, and a negative correlation between C-reactive protein and cortisol was observed. Ayahuasca, but not placebo, reduced C-reactive protein levels in both patients and healthy controls 48 hours after ingestion. Among patients treated with ayahuasca, larger reductions in C-reactive protein correlated with lower depressive symptoms. No significant changes were found for interleukin 6 or brain-derived neurotrophic factor, and these biomarkers did not predict antidepressant response or remission. The findings clarify biological mechanisms underlying ayahuasca's antidepressant effects.
Journal of Psychopharmacology
November 4, 2020
Oskar Hougaard Jefsen, Betina Elfving, Gregers Wegener et al.
123 citations
Psilocybin, the psychoactive compound in magic mushrooms, rapidly alters the activity of genes linked to neuroplasticity, with stronger effects in the prefrontal cortex than in the hippocampus. In rats given a single dose of 0.5–20 mg/kg, psilocybin increased expression of ten genes in the prefrontal cortex (including c-Fos, Fosb, and Nr4a1) and decreased one. In the hippocampus, it increased four genes (e.g., Sgk1, Dusp1) and decreased four others (e.g., Arc, Egr2). Protein levels for three key genes only partly matched the gene activity changes, indicating that measuring gene expression alone may not fully capture the drug's effects. These findings support psilocybin's potential to rapidly promote brain plasticity.
Journal of Psychopharmacology
May 1, 2001
Nicholas Macinnes, Sheila L. Handley, G. F. A. Harding
120 citations
Former chronic users of MDMA (ecstasy) who now lead relatively drug-free lives report higher levels of depression than matched non-drug users. In a group of 29 respondents who had consumed an average of 527 tablets over their lifetime and none in the past 14 days, depression scores on the Beck Depression Inventory were significantly elevated compared to controls. Within the user group, depression levels were not related to current use of alcohol, cannabis, or amphetamine, but were positively correlated with an external locus of control and life stress. The strongest predictors of depression were frequent but mild life stress and the quantity of ecstasy tablets consumed over a 12-hour period.
Journal of Psychopharmacology
January 1, 2016
Jana Speth, Clemens Speth, Mendel Kaelen et al.
119 citations
A single dose of LSD (75 μg) reduced how often people spontaneously thought about the past, while thoughts about the present or future remained unchanged. In a placebo-controlled crossover study with 20 healthy volunteers, fewer references to past mental spaces appeared in reports collected about 2.5 hours after intravenous administration. This reduction correlated with the drug's subjective intensity and with decreased resting-state functional connectivity within the default-mode network, a brain system involved in autobiographical memory and rumination. The findings suggest LSD may reduce past-focused thinking, which could be relevant for treating conditions like depression where excessive reflection on the past is common.
Journal of Psychopharmacology
May 25, 2020
115 citations
A meta-analysis of eight studies found that psychedelic drugs produce a rapid and sustained reduction in depressive symptoms, with effects appearing as early as day one and lasting up to six months. No serious adverse effects were reported, though transient increases in heart rate and blood pressure occurred compared to placebo. The analysis included studies published through April 2019.