Frontiers in Pharmacology
July 6, 2018
Elizabeth B. de Sousa Fernandes Perna, Eef L. Theunissen, Patrick C. Dolder et al.
18 citations
A single 100 mg dose of 4-fluoroamphetamine (4-FA), a phenethylamine novel psychoactive substance, produced strong elevation in blood pressure for 4-5 hours followed by sustained increased heart rate in healthy volunteers. Effects on mood and neurocognitive function peaked at 1 hour, including significant elevations of vigor, friendliness, elation, arousal, and positive mood, along with improvements in attention and motor performance. Negative affect also increased during the acute and subacute phases. The 150 mg dose was canceled after an interim safety review. The findings confirm clinical observations of acute toxicity and warrant warnings about health risks.
European Neuropsychopharmacology
February 3, 2022
Lilian Kloft, Henry Otgaar, Arjan Blokland et al.
17 citations
A double-blind, placebo-controlled trial with 60 healthy volunteers who had previously used MDMA examined the drug's effects on false memory. Participants received 75 mg of MDMA or a placebo and were tested using a word list task and two misinformation tasks involving a virtual reality crime scene. Memory was tested immediately and one week later. MDMA caused small impairments in true memory on the word list task at both time points. It increased false memory for related but non-critical lures immediately but decreased false memory for critical lures after a week. Episodic memory in the misinformation tasks was not consistently affected. The findings suggest no heightened vulnerability to external suggestion during MDMA intoxication.
Journal of Psychedelic Studies
August 26, 2021
Kim van Oorsouw, Malin V. Uthaug, Natasha L. Mason et al.
16 citations
A single ayahuasca ceremony reduced self-reported stress, anxiety, and somatization, and increased non-judging awareness four weeks later in 73 ceremony attendants. Satisfaction with life and awareness improved the day after the ceremony but returned to baseline after four weeks. No reduction in depression was found, contrary to earlier work. The intensity of ego dissolution during the ceremony predicted sub-acute mental health improvements. Effects were similar for first-time and experienced users. The authors call for placebo-controlled trials to confirm ayahuasca's therapeutic potential.
European Neuropsychopharmacology
February 25, 2021
Natasha L. Mason, Kim P. C. Kuypers, Johannes T. Reckweg et al.
16 citations
No Summary
Journal of Psychedelic Studies
December 15, 2021
Malin V. Uthaug, Natasha L. Mason, Martha N. Havenith et al.
15 citations
A naturalistic observational study of 58 Czech-speaking adults found that a single session of Holotropic Breathwork (a breathing technique intended to produce altered states of consciousness) was associated with lasting improvements in non-judgment, satisfaction with life, and reductions in stress-related symptoms. Although participants reported only low levels of psychedelic-like experience (averaging 0–34% on a 100% scale), the increase in non-judgment appeared sub-acutely and persisted for four weeks. Satisfaction with life increased and stress symptoms decreased at the four-week follow-up.
Biomedicine & Pharmacotherapy
March 24, 2022
Francisco Madrid-Gambin, Àlex Gomez‐gómez, Arnau Busquets-García et al.
14 citations
Consumption of ayahuasca increases N-acyl-ethanolamine endocannabinoids, decreases 2-acyl-glycerol endocannabinoids, and alters several large-neutral amino acids (LNAAs) in human plasma. Most LNAAs were inversely associated with nine of eleven subscales of the 5-Dimension Altered States of Consciousness Rating Scale, except tryptophan, which was positively associated. Several endocannabinoids and hexosylceramides were directly associated with ayahuasca alkaloids. Enrichment analysis confirmed dysregulation in pathways involved in serotonin and dopamine synthesis. A crosstalk between circulating LNAAs and subjective effects is suggested, independent of alkaloid concentrations, providing insights into the metabolic fingerprint and mechanism of action underlying ayahuasca experiences.
Frontiers in Psychology
June 23, 2021
Alexandre Augusto de Deus Pontual, Luís Fernando Tófoli, Carlos Fernando Collares et al.
14 citations
A new questionnaire, the Setting Questionnaire for the Ayahuasca Experience (SQAE), measures the physical and social context in which ayahuasca is consumed. Developed from a literature review, interviews with 19 users, and a survey of 2,994 participants, the scale's structure was tested using exploratory graph analysis and multidimensional item response theory. Six dimensions emerged—Leadership, Decoration, Infrastructure, Comfort, Instruction, and Social—though the original theoretical model fit the data better than the exploratory model. The instrument shows evidence of validity and can support future research on how setting influences the ayahuasca experience, with potential applications for studying psychedelic use more broadly.
June 10, 2021
Drummond E-Wen Mcculloch, Gitte M. Knudsen, Frederick S. Barrett et al.
14 citations
preprint
Research into psychedelic drugs like psilocybin, LSD, and DMT is growing, with clinical trials showing promise for psychiatric conditions. Resting-state fMRI is a common method to study brain mechanisms in these contexts. A review of 42 articles from 17 datasets found high heterogeneity in methods and analyses; two datasets underlie over half the publications, and terms like "entropy" are used inconsistently. The authors suggest that the field needs greater methodological consistency and replicability to identify stable neural markers of psychedelic effects, and encourage development of new models and quantification methods.
Psychopharmacology
May 31, 2018
Kim P. C. Kuypers, E. B. de Sousa Fernandes Perna, Patrick C. Dolder et al.
14 citations
A single 100 mg dose of the new psychoactive substance 4-fluoroamphetamine (4-FA) increased self-reported drug liking, wanting, and good drug effect one hour after administration in 12 healthy poly-drug users, but these effects were absent 11 hours later. Impulsive behavior was not affected by 4-FA. The increase in liking and wanting suggests a potential for abuse, but the lack of effect on impulsivity and the small sample size limit the conclusions.
Journal of Psychoactive Drugs
January 24, 2019
Kim P. C. Kuypers, E. B. de Sousa Fernandes Perna, Eef L. Theunissen et al.
13 citations
4-Fluoroamphetamine (4-FA), a novel psychoactive substance with a chemical structure similar to amphetamine and MDMA, induces a mild psychedelic state. In a placebo-controlled crossover study of 12 healthy poly-drug users, the psychedelic state peaked one hour after administration, coinciding with highest serum concentrations, and declined over time as concentrations fell. No change in creative (flexible) thinking occurred. The intensity of the 4-FA-induced psychedelic state falls between that produced by amphetamine and MDMA, consistent with user reports. More research is needed to determine whether 4-FA can alter creative thinking.
Scientific Reports
January 12, 2018
Kim P. C. Kuypers, Rafael de la Torre, Magı́ Farré et al.
12 citations
MDMA's mood effects depend partly on a genetic variation in the serotonin transporter gene (5-HTTLPR). People with the short variant of this gene typically show more anxiety and negative mood, while those with two long alleles (l-group) tend to be less anxious. In a pooled analysis of four placebo-controlled studies with 63 polydrug ecstasy users, MDMA (75 mg) generally improved mood but also increased anxiety and confusion. Unexpectedly, the l-group reported higher anxiety regardless of MDMA or placebo. MDMA reduced depressive feelings only in females from the l-group, suggesting a sex- and genotype-dependent effect.
International Journal for the Psychology of Religion
December 5, 2022
Arne Bohn, Michiel H. H. Kiggen, Malin V. Uthaug et al.
10 citations
San Pedro, a cactus containing mescaline and used for millennia, is now popular in European ceremonial retreats. In a study of 42 participants at such retreats in the Netherlands, questionnaires measured 11 dimensions of altered consciousness, ego-dissolution, mystical experiences, and challenging experiences. Results indicate San Pedro produces deviations from normal waking consciousness on all 11 subscales, moderate ego-dissolution, and a complete mystical experience in two-thirds of participants. Spiritual experiences are strongly expressed, while disembodiment, anxiety, impaired control, and transcendence of space are low; physical distress and grief can occur during challenging experiences. Network analysis revealed two separate networks of positive and negative altered states.
Drug Testing and Analysis
March 26, 2019
Stefan W. Toennes, David J. Schneider, Werner Pogoda et al.
9 citations
The pharmacokinetics of 4-fluoroamphetamine (4-FA) in humans resemble those of amphetamine, with peak serum concentrations occurring about 2 hours after ingestion and an elimination half-life of roughly 8-9 hours, though this varies widely (5.5-16.8 hours). After a 100 mg dose, median maximum serum concentration was 195 ng/mL (range 155-316 ng/mL). Concentrations in oral fluid were higher than in serum, especially during the first 3 hours, likely due to oral contamination. Serum concentrations observed in forensic cases matched those in the study, suggesting recreational doses are similar, but such doses may already cause prominent adverse effects and life-threatening consequences.
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.
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.
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.
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.