Psychopharmacology
November 16, 2017
Eline Haijen, Magı́ Farré, Rafael de la Torre et al.
9 citations
MDMA impaired verbal memory 90 minutes after administration in a word learning task, replicating earlier findings with the same dose (75 mg). Contrary to expectations, MDMA did not affect endocannabinoid concentrations (anandamide and 2-AG) in blood, and the 5-HT2 receptor blocker ketanserin did not block MDMA-induced memory impairment. Ketanserin alone increased AEA concentrations 180 minutes after administration. The findings suggest that peripherally measured endocannabinoids are not involved in the verbal memory deficit during MDMA intoxication.
Nature Medicine
April 1, 2026
Manesh Girn, Manoj K. Doss, Leor Roseman et al.
8 citations
Psychedelic drugs are being studied again for their therapeutic potential, but how they change brain function is not well understood. By combining 11 brain-scanning datasets from five different psychedelics (psilocybin, LSD, mescaline, DMT, and ayahuasca) across three continents, researchers found a common pattern: increased communication between brain networks that handle high-level thinking (default, frontoparietal, and limbic) and those that handle sensory input (visual and somatomotor). Key deep-brain regions (thalamus, caudate, putamen) and the cerebellum also changed how they connect with sensorimotor networks. Contrary to some earlier studies, reductions in within-network connectivity were weak to moderate and varied by drug. These findings help resolve previous inconsistencies and provide a comprehensive map of how psychedelics alter large-scale brain organization.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
June 1, 2025
Johannes G. Ramaekers, Johannes T. Reckweg, Natasha L. Mason et al.
8 citations
In a first-in-human trial, low to moderate doses of the synthetic cathinone 3-MMC were well tolerated and safe, with potential health risks only at high or excessive doses. 3-MMC caused dose-dependent increases in heart rate and blood pressure that were not clinically significant, along with feelings of subjective high. It also enhanced performance on several neurocognitive tasks, including processing speed, cognitive flexibility, psychomotor function, attention, and memory, while impulse control was unaffected. Participants reported mild dissociative and psychedelic effects, decreased appetite, and transient liking and wanting for the drug. The cardiovascular, psychostimulant, and psychotomimetic profile resembles that of amphetamine-related compounds.
Frontiers in Neuroscience
October 5, 2023
Pablo Mallaroni, Lilian Kloft, Natasha L. Mason et al.
8 citations
Repeated ayahuasca use is associated with a spatially distributed pattern of brain structural changes: sensorimotor areas become more distinct from surrounding regions while transmodal areas become less distinct. These changes correlate with the expression of genes for 5-HT2A receptors and other targets of ayahuasca, as well as with genes for transcription factors and immediate early genes previously linked to psychedelic-induced neuroplasticity in animal studies. The findings suggest that molecular mechanisms of psychedelic action may scale up to large-scale brain organization in living humans, potentially helping to explain behavioral differences in experienced users.
Biological psychiatry. Cognitive neuroscience and neuroimaging
October 1, 2024
Manoj K. Doss, Pablo Mallaroni, Natasha L. Mason et al.
7 citations
Two psychedelics, psilocybin and 2C-B, impair the encoding of detailed recollections and distort feelings of familiarity for emotional memories. In a double-blind, placebo-controlled study with 20 participants, both drugs reduced estimates of recollection and familiarity the next day, but increased false alarms based on familiarity, especially for negative and positive images. The drugs also tended to impair metamemory for negative and neutral memories while enhancing it for positive ones, though these effects were less reliable. The similar pattern across both substances suggests a shared neurocognitive mechanism among psychedelics that may underlie other phenomena.
bioRxiv (Cold Spring Harbor Laboratory)
September 18, 2023
Sepehr Mortaheb, Larry D. Fort, Natasha L. Mason et al.
7 citations
preprint
Psilocybin increases functional connectivity across the brain and induces a recurrent hyperconnected pattern with low BOLD signal amplitude, suggesting heightened cortical arousal. These brain dynamics are linked to feelings of oceanic boundlessness and visionary restructuralization, as measured by the 5-Dimensional Altered States of Consciousness Rating Scale. The brain's tendency to enter this hyperconnected-hyperarousal pattern under psilocybin may enable variant mental associations. For the first time, these findings connect brain dynamics with phenomenological alterations, offering new insights into the neurophenomenology and neurophysiology of the psychedelic state.
Frontiers in Psychiatry
May 19, 2022
Eef L. Theunissen, Kim P. C. Kuypers, Natasha L. Mason et al.
7 citations
At equal levels of subjective intoxication, natural cannabis (THC) and the synthetic cannabinoid JWH-018 both impair psychomotor function, divided attention, and impulse control to a similar degree. Both drugs also produce psychotomimetic effects, but JWH-018 causes considerably more pronounced dissociative effects than THC. The study matched participants from two placebo-controlled experiments by their subjective high to compare the drugs' neurocognitive and psychotomimetic profiles, concluding that psychotropic dose equivalence offers a uniform method for comparing CB1 receptor agonists.
medRxiv
November 1, 2022
Natasha L. Mason, Attila Szabo, Kim P. C. Kuypers et al.
6 citations
preprint
Psilocybin immediately reduced concentrations of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), while other inflammatory markers (interleukin-1α, IL-1β, IL-6, and C-reactive protein) remained unchanged. Seven days later, TNF-α returned to baseline, but IL-6 and CRP were persistently reduced in the psilocybin group. Changes in immune profile were linked to acute neurometabolic activity: reductions in TNF-α were associated with lower hippocampal glutamate concentrations. Greater reductions in IL-6 and CRP at seven days correlated with persisting positive mood and social effects. Psilocybin also blunted the cortisol response to a psychosocial stressor compared to placebo.
Frontiers in Psychiatry
April 14, 2022
Johannes G. Ramaekers, Eef L. Theunissen, Peter van Ruitenbeek et al.
6 citations
Comparing brain function between chronic cannabis users and non-users may be confounded by factors like polydrug use, alcohol, withdrawal, or lifestyle. A proposed methodology uses acute Δ9-tetrahydrocannabinol (THC) dosing studies to directly assess neuroadaptations in chronic users. This approach quantifies neurochemical, receptor, and functional brain network changes in response to an acute cannabis challenge and stratifies users from occasional to dependent. It enables evaluation of THC-induced neuroadaptive and neurocognitive changes across cannabis use history, informing neurobiological models of reward-driven, compulsive cannabis use.
Human Psychopharmacology Clinical and Experimental
October 25, 2018
Patrick C. Dolder, Elizabeth B. de Sousa Fernandes Perna, Natasha L. Mason et al.
6 citations
4-Fluoroamphetamine (4-FA), a novel psychoactive substance with effects between MDMA and amphetamine, reduced cognitive empathy while leaving emotional empathy unaffected in healthy poly-drug users. Plasma oxytocin levels increased one hour after a 100 mg dose compared with placebo, but this hormonal change was unrelated to the behavioral effects on empathy. The findings indicate that 4-FA affects empathy differently from MDMA and amphetamine, and confirm that drug-induced changes in peripheral oxytocin are not associated with empathy.
Current Opinion in Psychology
August 6, 2025
Iva Totomanova, Eline Haijen, Petra P M Hurks et al.
5 citations
Regular use of low doses of LSD or psilocybin, known as microdosing, has been studied in 57 human studies. Reported benefits include improved mood, enhanced cognition, social functioning, and mental health, but findings are inconsistent and largely based on self-reports. Adverse effects such as anxiety, physical discomfort, and cognitive disruption are also common. Outcomes vary greatly by individual and are shaped by expectations, context, and baseline state. Experimental studies of single doses often yield null findings, while observational studies of repeated use report more benefits. The evidence remains inconclusive and warrants caution.
Journal of psychopharmacology (Oxford, England)
April 1, 2025
Manoj K. Doss, Lilian Kloft, Natasha L. Mason et al.
5 citations
In experienced users, ayahuasca acutely enhances recollection-based memory—the ability to recall specific details—without increasing false memories or affecting familiarity-based memory, a feeling of knowing. In an observational study of 24 Santo Daime members who had consumed ayahuasca over 500 times on average, participants completed a false memory task before and after taking a self-selected church dose. After ayahuasca, hit rates, memory accuracy, and recollection improved, while familiarity and false memory remained unchanged. The authors suggest that β-carboline activity in the brew may account for this recollection enhancement, which contrasts with past psychedelic research showing impaired recollection. Practice effects could not be ruled out, but multiple measures of false memory and metamemory did not improve across sessions.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
August 1, 2024
Zeus Tipado, Kim P. C. Kuypers, Bettina Sorger et al.
5 citations
Psychedelics like LSD and psilocybin alter perception by activating serotonin receptors in cortical and subcortical brain regions, often causing visual disturbances or hallucinations. While current theories focus on disrupted communication between these brain areas, rare conditions like Charles Bonnet syndrome suggest the retinofugal pathway may also play a key role. Interneurons in the retina called amacrine cells could be the first site of psychedelic modulation, disrupting how visual information is hierarchically processed. This paper presents a new theory of psychedelic modulation in the retinofugal pathway, drawing parallels with clinical conditions to explain visual perceptual changes.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
May 1, 2025
Francisco Madrid-Gambin, Noemí Haro, Natasha L. Mason et al.
4 citations
The metabolome—the collection of small molecules in blood—differs between occasional and chronic cannabis users both when sober and after acute THC intoxication. Fourteen metabolites, mainly involved in endocannabinoid and amino acid metabolism, distinguished the two groups with 80% accuracy. During intoxication, occasional users showed attentional impairment and elevated subjective high, accompanied by increases in organic acids, β-hydroxybutyrate, and ceramides; chronic users did not show these changes. The findings demonstrate that metabolomic profiling can identify metabolic alterations specific to the neurocognitive state of cannabis intoxication and to cannabis use frequency.
Psychopharmacology
April 30, 2025
Johannes G. Ramaekers, Johannes T. Reckweg, Natasha L. Mason et al.
4 citations
Low to moderate doses of 3-methylmethcathinone (3-MMC) produce prolonged, dose-related analgesic effects in healthy volunteers. In a cross-over, placebo-controlled study with 14 participants, doses of 25, 50, and 100 mg elevated pressure pain threshold and reduced subjective painfulness and unpleasantness in both pressure pain threshold and cold pressor test paradigms. The analgesic effects were most prominent after 50 and 100 mg and persisted for up to 5 hours after dosing. 3-MMC also produced dose-related mood improvements at 1 hour but not at 5 hours. The findings suggest that doses low enough to avoid challenging subjective experiences and associated with a benign side effect profile may be sufficient for analgesia.
bioRxiv (Cold Spring Harbor Laboratory)
October 11, 2022
Pablo Mallaroni, Natasha L. Mason, Lilian Kloft et al.
4 citations
preprint
Brain functional connectomes are unique and reliable identifiers of individuals, but it was unknown whether these 'fingerprints' persist during altered states of consciousness. Ayahuasca, a serotonergic psychedelic, disrupts functional connectivity. In a within-subject study using 7T fMRI, 21 members of the Santo Daime church were scanned after collective ayahuasca intake. Connectome fingerprinting revealed a shared functional space and a spatiotemporal reallocation of key edges. Differences in higher-order functional connectivity motifs predicted perceptual drug effects, showing that individualized connectivity markers can trace a subject's functional connectome across altered states.
Drugs Education Prevention and Policy
September 10, 2020
Jan Van Amsterdam, Johannes G. Ramaekers, Ton Nabben et al.
4 citations
Ecstasy (MDMA) is a popular recreational drug with low abuse and dependence liability compared to several other illicit drugs and alcohol, and there is little evidence of long-term harm. A potential health risk is acute hyperthermia, which occurs at an unknown incidence rate and is more prevalent when ecstasy is consumed with heavy exercise at high ambient temperatures or with other substances including alcohol. However, illegal production and trade in the Netherlands have developed into a serious public order and ecological problem, with organized crime related to production and trafficking growing. This review provides a science-based summary to assist debate on future Dutch ecstasy policy to reduce organized crime while maintaining harm reduction.
bioRxiv (Cold Spring Harbor Laboratory)
July 19, 2019
Natasha L. Mason, Eef L. Theunissen, Nadia R. P. W. Hutten et al.
4 citations
preprint
Regular cannabis users develop tolerance to the drug's impairing and rewarding effects, but the underlying brain changes are unclear. In a double-blind, randomized, placebo-controlled crossover study, 12 occasional and 12 chronic cannabis users received acute doses of cannabis (300 μg/kg THC) and placebo, then underwent ultra-high field fMRI and magnetic resonance spectroscopy. In occasional users, cannabis caused decreased functional connectivity and increased striatal glutamate concentrations in reward circuitry, linked to greater subjective high and worse sustained attention. These changes were absent in chronic users, suggesting reduced responsiveness of reward circuitry to cannabis intoxication and a pharmacodynamic mechanism for tolerance development.
JAMA Psychiatry
March 25, 2026
Wiesław Jerzy Cubała, Malek Bajbouj, Michael Bauer et al.
3 citations
A single day of treatment with an inhaled synthetic formulation of mebufotenin (GH001) significantly reduced depression symptoms in adults with treatment-resistant depression compared to placebo. In a randomized, double-blind trial of 81 patients, those receiving up to three escalating doses of GH001 showed an average 15.5-point greater improvement on the Montgomery-Åsberg Depression Rating Scale by day 8 than those on placebo. Remission rates were 57.5% for GH001 and 0% for placebo. No severe or serious adverse events occurred. The findings suggest GH001 may be a rapid-acting, well-tolerated treatment option for treatment-resistant depression.
bioRxiv (Cold Spring Harbor Laboratory)
August 19, 2024
Naji Alnagger, Paolo Cardone, Charlotte Martial et al.
3 citations
preprint
Disorders of consciousness, such as unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), have few treatments. Using whole-brain computational models built from individual patients' fMRI and diffusion-weighted imaging data, this virtual clinical trial simulated the effects of LSD and psilocybin. The psychedelics shifted the brains of patients with disorders of consciousness closer to a critical dynamical state, with a larger effect in MCS patients. In UWS patients, the treatment response depended on structural connectivity, whereas in MCS patients it aligned with baseline functional connectivity. These results provide a computational foundation for considering psychedelics in treating disorders of consciousness and highlight the role of computational modeling in drug discovery and personalized medicine.
Drug and Alcohol Dependence
August 11, 2023
Teuntje A. D. Pelgrim, Johannes G. Ramaekers, Matthew B. Wall et al.
3 citations
THC, the main psychoactive component of cannabis, reduces functional connectivity in the salience network—a brain system involved in processing awareness and salient information—specifically weakening connections from the right insula to the left insula and anterior cingulate cortex. A trend toward decreased connectivity was also observed in the hippocampus-midbrain-striatum network, which may relate to acute psychotic-like effects. The COMT Val158Met genotype modulated subjective responses: individuals with the Met/Met genotype experienced the strongest dysphoric reactions and showed reduced connectivity in the hippocampus-midbrain-striatum network after THC. These findings suggest that prefrontal dopamine levels influence the acute effects of cannabis.
Advanced Science
November 20, 2025
Paolo Cardone, Charlotte Martial, Yonatan Sanz Perl et al.
2 citations
Simulated administration of LSD and psilocybin in computational models of patients with disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), shifted brain activity closer to criticality—the phase transition between order and chaos. The effect was greater in MCS patients. In UWS patients, the treatment response correlated with structural connectivity, while in MCS patients it aligned with baseline functional connectivity. These results provide a computational foundation for using psychedelics in DoC treatment and highlight the potential role of computational modeling in drug discovery and personalized medicine.
Frontiers in Psychology
January 1, 2025
Johannes T. Reckweg, Natasha L. Mason, Eef L. Theunissen et al.
2 citations
A three-item Peak Experience Scale (PES) was developed to quickly gauge the intensity of the psychoactive experience with the psychedelic 5-MeO-DMT and to guide dosing. Data came from three studies involving 84 healthy volunteers and patients with treatment-resistant depression who inhaled a 5-MeO-DMT formulation at doses of 0 (placebo), 2, 6, 12, or 18 mg, or an incremental individualized dosing regimen. PES ratings increased significantly with dose, peaking after the individualized regimen. The scale showed strong internal consistency and high correlation with other psychedelic assessment tools like the Mystical Experience Questionnaire and Ego Dissolution Inventory, but not with the Challenging Experience Questionnaire. The PES is an effective, simple tool for rapidly assessing psychedelic experience strength and may help guide dosing of rapid-acting psychedelics.
bioRxiv (Cold Spring Harbor Laboratory)
October 22, 2024
Pablo Mallaroni, S. Parker Singleton, Natasha L. Mason et al.
2 citations
preprint
A double-blind, placebo-controlled crossover study with 22 healthy volunteers compared the acute brain effects of the psychedelic phenethylamine 2C-B (20 mg) and the tryptamine psilocybin (15 mg) using 7T resting-state functional MRI. Both compounds reduced connectivity within brain networks and broadly increased connections between networks and between subcortical and cortical regions. Compared to psilocybin, 2C-B caused less reduction in between-network connectivity but increased connectivity in transmodal regions. Both drugs similarly increased brain complexity. The neural effects aligned with differences in monoaminergic and serotonergic receptor binding beyond 5-HT2A, suggesting 2C-B's distinct pharmacology shapes its functional brain dynamics.
Journal of Drug Issues
February 24, 2024
Frederick Vinckenbosch, Eef L. Theunissen, Agnieszka Stelling et al.
2 citations
A survey of 511 nitrous oxide users in the Netherlands found that most inhale the gas from party balloons filled with 4–14 liters, using a repetitive rebreathing technique for about 12 cycles with or without short breaks. 10.3% of respondents reported having inhaled N2O while driving, and many drove within an hour of inhalation. The findings establish a representative dosing method and a relevant timeframe for future research on the drug's psychomotor effects, which may inform policy and enforcement regarding N2O-related road traffic accidents.