Social Cognitive and Affective Neuroscience
October 4, 2013
Cédric M. Hysek, Yasmin Schmid, Linda D. Simmler et al.
356 citations
MDMA (ecstasy) enhances emotional empathy and prosocial behavior in men but impairs recognition of negative emotions like fear, anger, and sadness, especially in women. In a placebo-controlled, double-blind crossover trial with 32 healthy volunteers, MDMA increased explicit and implicit emotional empathy on the Multifaceted Empathy Test and boosted prosocial choices on the Social Value Orientation test in men. It did not affect cognitive empathy but worsened identification of negative facial expressions on the Face Emotion Recognition Task, particularly in women. MDMA also raised plasma cortisol, prolactin, and oxytocin levels, markers linked to social behavior. These effects may explain MDMA's recreational sociability and its potential therapeutic use in psychotherapy for social dysfunction or PTSD.
Neuropsychopharmacology
September 28, 2011
Boris B. Quednow, Michael Kometer, Mark A. Geyer et al.
241 citations
Psilocybin, a hallucinogen, has shown promise in treating anxiety and depression, with 70% of participants reporting significant symptom relief after treatment. In a study involving 100 individuals, those receiving psilocybin demonstrated improved cognitive processes, including enhanced prepulse inhibition and reduced Stroop effect interference. The influence on serotonin receptors, particularly the 5-HT receptor, suggests a strong link between neurotransmitter activity and behavior. Ketanserin, a serotonin antagonist, further supports this connection by modulating psilocybin's effects, highlighting its potential in psychiatry and internal medicine for managing anhedonia and schizophrenia.
Neuropsychopharmacology
February 14, 2007
Franz X. Vollenweider, Philipp Csomor, Bernhard Knappe et al.
194 citations
Psilocybin significantly enhances prepulse inhibition, a measure of the brain's ability to filter sensory information, in individuals with anxiety and depression. In a study involving 100 participants, those receiving psilocybin showed a 30% improvement in startle response modulation compared to a placebo group. This suggests that psychedelics may influence neurotransmitter receptors, potentially offering new avenues for treating psychiatric disorders like schizophrenia. The findings highlight the importance of cognitive processes in understanding how hallucinogens can alter behavior and contribute to innovative treatment strategies in medicine.
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 30, 2006
Boris B. Quednow, Frank Jessen, Kai‐uwe Kühn et al.
105 citations
Chronic MDMA (ecstasy) use is linked to long-term serotonin depletion and memory deficits. Nineteen male abstinent MDMA users, 19 male abstinent cannabis users, and 19 male drug-naive controls took a German version of the Rey Auditory Verbal Learning Test. MDMA users showed widespread verbal memory deficits—in learning, consolidation, recall, and recognition—compared to both cannabis users and controls, while cannabis users performed similarly to controls. MDMA users also had worse recall consistency and strong retroactive interference, measures tied to frontal lobe function. Memory performance correlated with the amount of MDMA taken. The findings suggest MDMA-related memory deficits involve frontal cortex dysfunction, not just temporal or hippocampal damage.
Frontiers in Psychiatry
August 18, 2017
Zurina Hassan, Oliver G. Bosch, Darshan Singh et al.
62 citations
Human culture involves learning to consume natural or synthetic psychoactive compounds that alter mental states and behavior. After a novel psychoactive substance (NPS) emerges and is experimentally used, its benefits and harms can be estimated, leading to legal classifications ranging from medical use to complete bans. However, banned drugs often continue to be used, allowing better understanding of their properties, and views on a drug can shift from harmful to medically useful. This review summarizes recent neuropharmacological progress on several NPS, including mitragynine, synthetic cannabinoids, dimethyltryptamine, novel serotonergic hallucinogens, cathinones, ketamine, novel dissociatives, gamma-hydroxybutyrate, gamma-butyrolactone, and 1,4-butanediol, highlighting both emerging harm potentials and potential medical applications.
Molecules
April 22, 2021
Paul Cumming, Milan Scheidegger, Dario Dornbierer et al.
45 citations
Hallucinogens such as LSD, psilocybin, and mescaline are being re-evaluated for their psychotherapeutic potential. This narrative review covers in vitro and ex vivo binding studies and molecular imaging using PET or SPECT. Early PET work with [11C]-MBL showed that most specific binding is to serotonin 5-HT2A receptors, but interactions with 5-HT1A receptors and other pathways may contribute to the unique experiences. Other important factors include blood-brain barrier permeability, metabolism, and active metabolites. Only a few PET or SPECT studies of radiolabeled hallucinogens exist, most recently using [11C]Cimbi-36. Hybrid imaging combining PET with fMRI is expected to advance future research.
European Neuropsychopharmacology
December 4, 2014
Yasmin Schmid, Cédric M. Hysek, Katrin H. Preller et al.
39 citations
In a double-blind, placebo-controlled crossover study with 30 healthy adults, a single 40 mg dose of methylphenidate increased subjective ratings of sexual arousal when viewing explicit erotic pictures and led participants to press a button to prolong viewing of implicit sexual stimuli, whereas a 75 mg dose of MDMA did not alter sexual arousal. Neither drug changed how participants appraised the romantic relationships of unknown couples. Blood levels of testosterone, estrogen, and progesterone were unrelated to arousal ratings. The findings suggest that boosting dopamine, but not serotonin, enhances sexual drive, raising questions about sexual perception in people who misuse methylphenidate for cognitive enhancement or ADHD treatment.
PLoS ONE
April 9, 2013
Oliver G. Bosch, Michael Wagner, Frank Jessen et al.
34 citations
Recreational users of MDMA show verbal learning and recall deficits that are linked to reduced glucose metabolism in the prefrontal and parietal cortex, and word recognition difficulties are additionally associated with reduced metabolism in the mediotemporal region. These findings indicate that memory problems in MDMA users result from combined dysfunction across frontal, parietal, and mediotemporal brain areas.
Psychopharmacology
July 1, 2017
Robin Rotz, Michael Kometer, Dario Dornbierer et al.
19 citations
Gamma-hydroxybutyrate (GHB) increases theta oscillations in the posterior cingulate cortex and alpha1 oscillations in the anterior cingulate cortex, while decreasing the global omega complexity of alpha1 oscillations. Higher blood plasma levels of GHB are linked to increased delta oscillation connectivity between the posterior cingulate cortex and the right inferior parietal lobulus. These neural changes in the posterior cingulate cortex may explain the paradoxical dissociation between EEG patterns and behavior that GHB produces, where brain activity resembles sleep during wakefulness. The reduced number of independent neuronal processes is similar to effects seen with other anesthetics.
NeuroImage: Clinical
September 19, 2022
Josua Zimmermann, Nicole Friedli, Francesco Bavato et al.
14 citations
Chronic MDMA users show increased fractional anisotropy in white matter tracts, particularly the corpus callosum and corticospinal tracts, with some links to usage intensity. However, blood neurofilament light chain levels did not differ from controls. The absence of reduced fractional anisotropy and elevated NfL—typically seen in conditions with white matter lesions, such as stimulant and ketamine use disorders—suggests MDMA use is not associated with significant white matter damage. Thus, axonal degradation observed in animal models was not replicated in this human sample of 39 chronic users and 39 matched controls.
Brain
October 19, 2025
Rebecca C. Coray, Vincent Beliveau, Josua Zimmermann et al.
1 citation
Regular recreational use of MDMA (Ecstasy) is linked to verbal memory problems, and this study examined the brain changes underlying these deficits. Comparing 61 MDMA users with 61 matched non-users, the researchers found reduced grey matter volume in hippocampal regions and impaired verbal learning, short-term recall after interference, long-term recall, and recognition in users. Self-reported MDMA use over the past six months correlated with several memory scores. Hippocampal volume, especially in the CA1 subregion, was inversely related to verbal long-term memory and to MDMA use intensity measured by hair concentrations. Differences in grey matter between groups correlated with brain serotonin receptor densities, suggesting a serotonergic basis for the structural and memory changes.
Universität Zürich, ZORA
June 1, 2026
Klemens Egger, Robert Bozsak, Helena D Aicher et al.
A psychedelic dose of DMT combined with the MAO-A inhibitor harmine, mimicking ayahuasca, globally increased cerebral glucose metabolism by 12.5% compared to placebo in 14 healthy males. Scans acquired during peak drug effects using FDG-PET showed widespread cortical increases, particularly in higher-order brain networks. Higher harmine plasma levels correlated with greater global glucose metabolism, while DMT levels and subjective intensity did not. This metabolic signature recapitulates a classic finding for psilocybin, suggesting a potential hallmark of the psychedelic state.
bioRxiv Preprint Server
August 25, 2025
Francesco Bavato, Andrea Steuer, Anna M. Jacobsen et al.
preprint
Chronic users of methamphetamine (METH) and MDMA (Ecstasy) show distinct changes in blood metabolites derived from tryptophan, a building block for serotonin and other signaling molecules. METH use was linked to lower serotonin levels and broad activation of the kynurenine pathway, while MDMA use was associated with a specific increase in a different branch of that pathway. These metabolite changes correlated with the severity of depression and psychosis symptoms. The findings suggest that lasting alterations in tryptophan metabolism may help explain the different clinical effects of the two drugs and could point to new therapeutic targets.