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Kim P. C. Kuypers

Maastricht University

88 papers in the library · 3,825 citations · publishing 2005-2026

Papers

Subjective and neurocognitive profiling of clinical doses of 3,4-methylenedioxymethamphetamine (MDMA) in healthy volunteers: implications for therapeutic use

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.

Safety and cognitive pharmacodynamics following dose escalations with 3-methylmethcathinone (3-MMC): a first in human, designer drug study

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.

Ayahuasca enhances creative divergent thinking

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.

Sex Differences in Acute Responses to Psychedelics: Evidence for Greater Subjective Intensity and Impairment in Female Participants

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.

Trajectories of psychedelic-assisted change: An observational study of a psilocybin retreat program followed by psychotherapeutic interventions

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.

Daily self-assessment within a regimen of microdosing indicates enhanced psychological functioning on microdosing days relative to non-microdosing days.

Psychopharmacology October 11, 2025 Michelle St Pierre, Elena Argento, Jordyn Cates et al.

On days when adults microdose psychedelics, they report higher levels of wellbeing, productivity, creativity, connectedness, contemplation, and focus compared to days they do not microdose. The increase in creativity is especially pronounced among people who have previously used larger doses of psychedelics. These findings come from a large international survey of 1,435 adults who microdose, using daily-level self-reports that reduce reliance on memory. Because the study is observational and exploratory, the results should be interpreted cautiously.

Comparative effects of ayahuasca and breathwork on self-reported cognitive flexibility, emotion regulation, positive affect, and sleep quality

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.

A randomised placebo-controlled study of the effects of lysergic acid diethylamide microdosing (15 μg) on pain perception in healthy volunteers.

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.

Applications of psychedelics in small doses and alternative treatments in psychiatry

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.

Potential therapeutic effects of psychedelics in small doses: Is there a role for microdosing in psychiatry?

International review of neurobiology January 1, 2025 Iva Totomanova, Eline Haijen, Petra P M Hurks et al.

Small doses of LSD and psilocybin produce subtle acute effects on neural connectivity, brain electrophysiology, blood pressure, sleep duration, pain perception, temporal processing, and mood, and reduce symptoms of depression and obsessive-compulsive behavior in patient samples. Extra-pharmacological factors such as baseline subjective state, expectations, and individual differences in drug metabolism influence treatment outcomes. Controlled microdosing studies suggest potential therapeutic applications, but large-scale clinical trials are still needed.

Klassieke psychedelica: veiligheid, neveneffecten en medicatie-interacties

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.

Persisting decreases in state and trait anxiety post-psilocybin: A naturalistic, observational study among retreat attendees

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.

Microdosing psychedelics: More questions than answers? An overview and suggestions for future research

Journal of Psychopharmacology July 14, 2019 Livia Ng, Luca Pani, Anaïs Soula et al.

Claims about the positive effects of microdosing psychedelics on mood and cognition have entered public discussion, but scientific studies are scarce and no consensus on what microdosing means exists. This critique identifies questions future research must answer and offers guidelines, focusing on psilocybin due to its potential clinical approval and short-lasting effects. While anecdotal reports emphasize benefits, the paper concludes that future studies should also investigate potential risks of repeated low-dose administrations. Preclinical and clinical research examining biological measures like heart rate and receptor turnover, as well as cognitive parameters such as memory and attention, is needed to uncover possible negative consequences.