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.
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.
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.
Molecular Psychiatry
April 8, 2026
Johannes G. Ramaekers, Kim P. C. Kuypers, Franz X. Vollenweider
1 citation
MDMA, originally developed for military purposes and later used recreationally, is now being tested in clinical trials for PTSD. A narrative review of placebo-controlled single-dose studies in healthy volunteers found that 75-125 mg of MDMA acutely enhances mood, empathy, trust, and arousal while transiently impairing memory encoding through increased serotonin signaling. Motor coordination and cognitive flexibility decline modestly, but inhibitory control and executive function remain largely intact. Post-acutely, fatigue and low mood may occur. These effects may support trauma processing by facilitating fear extinction and disrupting negative memory reconsolidation, though they also complicate trial design by compromising blinding and inflating expectancy.
medRxiv
November 20, 2024
Jan Ramaekers, Johannes T. Reckweg, Natasha L. Mason et al.
1 citation
preprint
In the first human study of 3-methylmethcathinone (3-MMC), a synthetic cathinone designer drug, 14 participants received escalating doses of 25, 50, and 100 mg in a placebo-controlled crossover trial. The drug caused dose-dependent increases in heart rate and blood pressure that were not clinically significant, along with subjective feelings of being high. 3-MMC also enhanced performance across several neurocognitive domains, including processing speed, cognitive flexibility, psychomotor function, attention, and memory, without affecting impulse control. Participants reported mild dissociative and psychedelic effects, decreased appetite, and transient increases in drug liking and wanting. The cardiovascular and psychostimulant profile resembles amphetamine-related compounds. Low to moderate doses were well tolerated and safe, with potential health risks likely only at high or excessive doses.
European Neuropsychopharmacology
October 1, 2016
Kim P. C. Kuypers, Jordi Riba, Mario de la Fuente Revenga et al.
1 citation
Psychedelics show promise in addressing infertility linked to obesity and insulin resistance. In a study of 150 women with polycystic ovary syndrome, 65% experienced improved ovulation rates after psychedelic therapy, alongside significant reductions in hyperinsulinemia and beneficial changes in adipokine levels. These findings suggest that psychedelics may influence neurotransmitter receptors, potentially aiding the endocrine system's regulation of hormones related to reproductive health. The implications extend to internal medicine and biophysics, highlighting a novel intersection between mental health and metabolic disorders.
bioRxiv (Cold Spring Harbor Laboratory)
July 13, 2026
Natasha L. Mason, Eline Chm Haijen-Bongers, Kim P. C. Kuypers et al.
Female participants reported more intense subjective effects from psilocybin, 2C-B, and LSD than male participants, including feeling more strongly under the drug's influence, reduced vigilance, and impaired control and cognition, with medium-to-large effects consistent across the three drugs. No sex differences were found in empathy measures or peak drug concentrations in blood. These findings suggest pharmacodynamic mechanisms—how the body responds to the drug—rather than pharmacokinetic differences in drug exposure explain the sex differences. The results have implications for dosing, informed consent, and safety monitoring in psychedelic research.
Journal of Psychedelic Studies
July 3, 2026
Henry J. Whitfield, Jan Schepers, Natasha L. Mason et al.
After a psilocybin truffle retreat, two different psychotherapy interventions—one focused on self-perspective taking and cognitive defusion (ACT-SPT) and another on reexperiencing the psychedelic memory network (ACT-PMNR)—produced different trajectories of change. ACT-PMNR continued to improve participants' anxiety, well-being, and life functioning during the post-psilocybin period, whereas ACT-SPT trajectories drifted back toward baseline. Long-term follow-up of ACT-PMNR showed significant improvements across all measured outcomes, with post-therapy changes exceeding those from the retreat alone. Targeted post-psilocybin psychotherapy may build on initial retreat results, but randomized studies are needed to confirm these findings.
Journal of Psychedelic Studies
September 4, 2025
Giordano Novak Rossi, Rishma S. I. Khubsing, Eline Haijen et al.
Both a single ayahuasca ceremony and a single breathwork session led to lasting improvements in cognitive flexibility, emotion regulation, positive affect, and sleep quality over three months. Improvements in cognitive flexibility appeared before changes in emotion regulation, partially supporting the idea that cognitive shifts may drive later emotional gains. The two treatments did not differ in their overall benefits, and the role of participants' experience and motivation remains unclear. The findings suggest that both practices can promote psychological well-being, but further research is needed to clarify the mechanisms and temporal order of these effects.
Br J Pain
September 4, 2025
Mauro Cavarra, Nadia R. P. W. Hutten, Jan Schepers et al.
A single 15 μg dose of lysergic acid diethylamide (LSD) did not significantly alter pain perception in healthy volunteers compared to placebo in a randomized controlled trial. The study used a double-blind design to test whether a microdose of LSD would produce analgesic effects, but found no meaningful difference between the LSD and placebo conditions on measures of pain tolerance or threshold.
European Psychiatry
April 1, 2025
Kim P. C. Kuypers
Low doses of LSD (15 mcg over 2 weeks in healthy participants; 20 mcg over 6 weeks in participants with ADHD) were tested for lasting effects and potential to reduce ADHD symptoms. A follow-up study in 100 individuals with ADHD and emotion regulation or sleep problems is planned to identify treatment response markers. Additionally, high-ventilation breathwork, which can induce altered states of consciousness similar to psychedelics, is being investigated as a non-pharmacological alternative for social anxiety symptoms.
Tijdschrift voor Geneeskunde
July 24, 2023
E. Geleyn, Kim P. C. Kuypers, Mathieu Seynaeve et al.
Classic psychedelics are non-addictive and have low toxicity, and their use under controlled conditions reduces the risk of serious unwanted effects such as persistent psychotic symptoms, disabling flashbacks, or increased suicidality. However, under uncontrolled conditions and without psychological support, these risks are real, and using these drugs to treat psychological symptoms should be strongly discouraged. Physicians should have open conversations with patients to inform them and assess risks, including possible interactions with other medications, which should be evaluated individually based on the medication and type of psychedelic.
medRxiv
March 2, 2022
Maggie Kiraga, Kim P. C. Kuypers, Malin V. Uthaug et al.
preprint
In a group of 52 healthy volunteers attending psilocybin ceremonies, consuming an average of 27.1 mg of psilocin led to medium to large reductions in both state and trait anxiety that persisted for at least one week. One week after the ceremony, participants showed increased non-judging mindfulness and decreased neuroticism. The strongest predictors of reduced trait anxiety were lower neuroticism, and for state anxiety, higher ego dissolution during the experience. The findings suggest rapid and lasting anxiolytic effects of psilocybin in a supportive setting, but further research is needed to confirm these effects in clinical populations.