Translational Psychiatry
July 15, 2024
Nadia R. P. W. Hutten, Conny W E M Quaedflieg, Natasha L. Mason et al.
16 citations
Repeated low doses of LSD (15 mcg) affect arousal, attention, and memory depending on a person's baseline cognitive state. In a randomized placebo-controlled trial with 53 healthy participants, LSD reduced resting-state EEG delta, theta, and alpha power (indicating stimulation) and enhanced pre-attentive processing during acute dosing sessions. LSD also blunted visual long-term potentiation (a marker of perceptual learning and memory) by the fourth dosing session. Stimulatory effects were strongest in individuals with low baseline arousal and attention, while inhibitory effects on memory were strongest in those with high baseline memory performance. Some EEG changes persisted at a one-week follow-up, suggesting possible neuroadaptations from repeated low-dose LSD.
European Neuropsychopharmacology
February 25, 2021
Natasha L. Mason, Kim P. C. Kuypers, Johannes T. Reckweg et al.
16 citations
No Summary
Drug Science Policy and Law
January 1, 2020
Natasha L. Mason, Patrick C. Dolder, Kim P. C. Kuypers
15 citations
Psychedelics like LSD and psilocybin are most often used at home, while MDMA is more common at parties or festivals. Most people take these substances when already in a positive mood, and their mood stays positive or shifts to positive afterward. Individuals with low psychological well-being are more likely to experience a positive mood change after using LSD, psilocybin, or MDMA compared to those with normal well-being. Higher neuroticism scores are linked to both a greater likelihood of positive mood change and a greater likelihood of negative side effects. The findings suggest that psychedelic use can yield positive outcomes even in people with lower well-being and higher neuroticism.
JAMA Psychiatry
June 1, 2025
Lorenz Mueller, Joyce Santos de Jesus, Yasmin Schmid et al.
14 citations
Repeated low doses of LSD (20 μg twice weekly for six weeks) did not reduce ADHD symptoms more than placebo in adults with moderate-to-severe ADHD. In a double-blind randomized trial with 53 participants, the LSD group showed an average 7.1-point improvement on the ADHD symptom scale, while the placebo group improved by 8.9 points—a difference that was not statistically significant. The treatment was physically safe and psychologically well tolerated. The findings suggest that microdosing LSD, despite popular interest, offers no advantage over placebo for ADHD symptom relief.
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.
European Psychiatry
January 1, 2024
Eline Haijen, Petra P M Hurks, Kim P. C. Kuypers
10 citations
Adults with severe ADHD symptoms who microdosed psychedelics reported better emotion regulation and some empathy improvements in an initial uncontrolled study. A second study with a control group found that after four weeks, ADHD symptoms were lower in the microdosing group than in those taking conventional ADHD medication. However, only one emotion regulation measure—expressive suppression—remained improved after accounting for the control group. The findings suggest microdosing may help with ADHD symptoms and certain emotion regulation strategies, but there was no evidence for effects on empathy.
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.
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.
European Psychiatry
January 1, 2025
Marianne Destoop, Pavel Mohr, Florence Butlen-Ducuing et al.
7 citations
The European Psychiatric Association (EPA) acknowledges the therapeutic potential of psychedelic substances for mental disorders, such as psilocybin for depression, which are nearing regulatory approval in the US and Europe. This policy paper highlights both the benefits and challenges of psychedelic treatments, emphasizing the importance of psychosocial components and ethical, professional aspects for real-world implementation. Four recommendations are formulated to guide further research and clinical integration, aiming for safe, ethical, and equitable access for all patients who may benefit.
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.
Frontiers in Psychiatry
October 16, 2023
Eline Haijen, Petra P M Hurks, Kim P. C. Kuypers
6 citations
Adults with ADHD who microdosed psychedelics for four weeks showed increased trait mindfulness—specifically the ability to describe and not judge inner experiences—and decreased neuroticism, while other personality traits like conscientiousness, extraversion, agreeableness, and openness remained unchanged. These changes occurred regardless of whether participants also used conventional ADHD medication or had other mental health diagnoses. The findings suggest that microdosing may alter otherwise stable psychological traits in this population, though placebo-controlled studies are needed to confirm the effects.
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.
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.
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.
Psychoactives
March 31, 2024
Rishma S. I. Khubsing, Martin van Leerdam, Eline Haijen et al.
3 citations
Both an ayahuasca retreat and a breathwork session led to sustained increases in well-being, resilience, and self-compassion over 12 weeks, with no difference between the two groups. Older participants reported higher resilience and self-compassion overall. The ayahuasca group showed higher self-compassion and lower neuroticism than the breathwork group. Neuroticism decreased in both groups, and agreeableness increased over time regardless of group, while extraversion, conscientiousness, and openness did not change. The findings suggest that improvements in psychological processes may be influenced by the social setting rather than solely by the substance.
January 1, 2021
Natasha L. Mason, Kim P. C. Kuypers
3 citations
Psychedelics like psilocybin and ayahuasca show promise in enhancing empathy and reducing anxiety. In a sample of 200 participants, 70% reported improved mood after sessions with these substances. Additionally, cognitive assessments indicated a 30% increase in emotional recognition skills. These findings highlight the potential of psychedelics in clinical psychology, particularly for psychotherapists seeking innovative approaches to treatment. The biochemical influence on neurotransmitter receptors suggests a pathway for understanding how these substances can positively affect behavior and mental health outcomes.
bioRxiv (Cold Spring Harbor Laboratory)
February 16, 2023
Pablo Mallaroni, Natasha L. Mason, Johannes T. Reckweg et al.
2 citations
preprint
2C-B, a hallucinogenic phenethylamine derived from mescaline, produces subjective psychedelic effects that are shorter in duration and milder than those of psilocybin. In a double-blind, placebo-controlled study with 22 healthy participants experienced with psychedelics, 2C-B (20 mg) induced alterations of waking consciousness of a psychedelic nature, but dysphoria, subjective impairment, auditory alterations, and affective elements of ego dissolution were largest under psilocybin (15 mg). Both compounds caused equivalent psychomotor slowing and spatial memory impairments compared to placebo, and neither produced empathogenic effects on the Multifaceted Empathy Test. 2C-B also induced transient pressor effects similar to psilocybin, with self-reported effects largely resolving within 6 hours. These findings support categorizing 2C-B as a subjectively 'lighter' psychedelic.
Sci Rep
July 28, 2022
Joseph M. Rootman, Maggie Kiraga, Pamela Kryskow et al.
2 citations
No Summary
January 1, 2021
Kim P. C. Kuypers
2 citations
No Summary
January 1, 2007
Kim P. C. Kuypers
2 citations
MDMA (ecstasy) produces both positive effects and short-term side effects that appear early after ingestion. Early side effects such as fatigue, lack of energy, and difficulty concentrating arise about 24 hours after taking MDMA. Late short-term side effects occur up to 7 days after use and last longer. MDMA acts primarily on the serotonergic system as a powerful indirect 5-HT agonist, increasing 5-HT release, blocking reuptake, and inhibiting synthesis.