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Eef L. Theunissen

Maastricht University

42 papers in the library · 1,761 citations · publishing 2010-2025

Papers

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Cannabis Perturbs Dynamic Brain States

Biological Psychiatry October 21, 2025 Katharina S Lege, Pablo Mallaroni, Sepehr Mortaheb et al. 1 citation

Background The impact of acute cannabis exposure on brain function and cognitive performance varies among individuals. Acute effects of cannabis on behavior may be absent or benign in chronic users, while occasional users experience significant impairment in day-to-day operations. It is hypothesized that repeated cannabis use induces neuroadaptations leading to tolerance and desensitization,...

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

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

3-Methylmethcathinone (3-MMC) is a designer drug that belongs to the group of synthetic cathinones. The compound has been scheduled in many jurisdictions because of public health concerns associated with excessive use. To date, there are no clinical studies that have evaluated the risk profile of 3-MMC in the recreational range of low to moderate doses. The current, first-in-human study (N =...

Metabolomic profiling of cannabis use and cannabis intoxication in humans.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology May 1, 2025 Francisco Madrid-Gambin, Noemí Haro, Natasha L. Mason et al. 4 citations

Acute intoxication from Δ9-tetrahydrocannabinol (THC, the primary active ingredient of cannabis) can lead to neurocognitive impairment and interference with day-to-day operations, such as driving. Present evaluations of THC-induced impairment in legal settings rely on biological drug tests that solely establish cannabis use, rather than cannabis impairment. The current study evaluated the...

Low to moderate doses of 3-methylmethcathinone (3-MMC) produce analgesic effects in healthy volunteers: a proof of principle study with a designer drug

Psychopharmacology April 30, 2025 Johannes G. Ramaekers, Johannes T. Reckweg, Natasha L. Mason et al. 4 citations

3-Methylmethcathinone (3-MMC) is a synthetic cathinone that has been scheduled in many jurisdictions after it appeared on the consumer market as a designer drug or "legal high". At present, there are no medical applications for synthetic cathinones, but in the past cathinone and other compounds that are structurally related to amphetamine have been evaluated and recognized for their intrinsic...

Evaluation of the peak experience scale as a rapid assessment tool for the strength of a psychoactive experience with 5-MeO-DMT.

Frontiers in Psychology 2025 Johannes T. Reckweg, Natasha L. Mason, Eef L. Theunissen et al. 2 citations

A three-item Peak Experience Scale (PES) was developed to rapidly evaluate the strength of the psychoactive experience, and to guide the dosing regimen, of the psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; mebufotenin). This paper aims to compare the PES with a range of established questionnaires designed to evaluate the psychedelic experience. Data were gathered from three separate...

Inter-individual variability in neural response to low doses of LSD.

Translational Psychiatry July 15, 2024 Nadia R. P. W. Hutten, Conny W E M Quaedflieg, Natasha L. Mason et al. 16 citations

The repeated use of small doses of psychedelics (also referred to as "microdosing") to facilitate benefits in mental health, cognition, and mood is a trending practice. Placebo-controlled studies however have largely failed to demonstrate strong benefits, possibly because of large inter-individual response variability. The current study tested the hypothesis that effects of low doses of LSD on...

Recreational Nitrous Oxide Dosing and Administration and Its Use in Traffic: An Online Survey

Journal of Drug Issues February 24, 2024 Frederick Vinckenbosch, Eef L. Theunissen, Agnieszka Stelling et al. 2 citations

Nitrous oxide (N2O) is a popular recreational intoxicant and associated paraphernalia are increasingly being found at road traffic accident scenes in the Netherlands, suggesting that N 2 O intoxication causally contributes to the occurrence of a significant number of road traffic accidents. However, information on the pharmacodynamics- and kinetic characteristics of recreational N2O use is...

A phase 1/2 trial to assess safety and efficacy of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in patients with treatment-resistant depression

Frontiers in Psychiatry June 20, 2023 Johannes T. Reckweg, Cees van Leeuwen, Cécile Henquet et al. 86 citations

Background Treatment-resistant depression (TRD) is a substantial public health burden, but current treatments have limited effectiveness. The aim was to investigate the safety and potential antidepressant effects of the serotonergic psychedelic drug 5-MeO-DMT in a vaporized formulation (GH001) in adult patients with TRD. Methods The Phase 1 part ( n = 8) of the trial investigated two single...

Assessment of the Acute Effects of 2C‐B vs. Psilocybin on Subjective Experience, Mood, and Cognition

Clinical Pharmacology & Therapeutics May 30, 2023 Pablo Mallaroni, Riccardo Paci, Sabrina Ritscher et al. 34 citations

2,5‐dimethoxy‐4‐bromophenethylamine (2C‐B) is a hallucinogenic phenethylamine derived from mescaline. Observational and preclinical data have suggested it to be capable of producing both subjective and emotional effects on par with other classical psychedelics and entactogens. Whereas it is the most prevalently used novel serotonergic hallucinogen to date, it's acute effects and distinctions...

Cannabis containing equivalent concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) induces less state anxiety than THC-dominant cannabis

Psychopharmacology October 13, 2022 Nadia R. P. W. Hutten, Thomas R. Arkell, Frederick Vinckenbosch et al. 36 citations

RATIONALE: Delta-9-tetrahydrocannabinol (THC), an active component of cannabis, can cause anxiety in some users during intoxication. Cannabidiol (CBD), another constituent of cannabis, has anxiolytic properties suggesting that cannabis products containing CBD in addition to THC may produce less anxiety than THC-only products. Findings to date around this issue have been inconclusive and could...

A Comparison of Acute Neurocognitive and Psychotomimetic Effects of a Synthetic Cannabinoid and Natural Cannabis at Psychotropic Dose Equivalence

Frontiers in Psychiatry May 19, 2022 Eef L. Theunissen, Kim P. C. Kuypers, Natasha L. Mason et al. 7 citations

Due to differences in potency, efficacy, and affinity for CB1 receptors, similarities and differences in psychoactive effect profiles of natural cannabis and synthetic cannabinoids (SCs) cannot reliably be derived from equipotent dose comparisons. Instead, the current study proposes to compare the intrinsic psychoactive effects of natural cannabis (THC) and an SC, JWH-018, at psychotropic dose...

Cannabis Use and Neuroadaptation: A Call for Δ9-Tetrahydrocannabinol Challenge Studies

Frontiers in Psychiatry April 14, 2022 Johannes G. Ramaekers, Eef L. Theunissen, Peter van Ruitenbeek et al. 6 citations

Currently, the assessment of the neurobehavioral consequences of repeated cannabis use is restricted to studies in which brain function of chronic cannabis users is compared to that of non-cannabis using controls. The assumption of such studies is that changes in brain function of chronic users are caused by repeated and prolonged exposure to acute cannabis intoxication. However, differences in...

Functional brain connectomes reflect acute and chronic cannabis use

Scientific Reports February 14, 2022 Johannes G. Ramaekers, Natasha L. Mason, Stefan W. Toennes et al. 26 citations

Resting state fMRI has been employed to identify alterations in functional connectivity within or between brain regions following acute and chronic exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive component in cannabis. Most studies focused a priori on a limited number of local brain areas or circuits, without considering the impact of cannabis on whole-brain network organization....

Sex differences in acute cannabis effects revisited: Results from two randomized, controlled trials

Addiction Biology December 22, 2021 Thomas R. Arkell, Richard C. Kevin, Frederick Vinckenbosch et al. 45 citations

Some evidence suggests that males and females may differ in their responses to acute cannabis effects, including subjective drug effects and behavioural effects, and cannabinoid pharmacokinetics. This is significant given current changes to cannabis-related policies and, in consequence, increased cannabis accessibility. The present study combines data from two randomized controlled trials to...

The why behind the high: determinants of neurocognition during acute cannabis exposure.

Nature reviews. Neuroscience July 1, 2021 Johannes G. Ramaekers, Natasha L. Mason, Lilian Kloft et al.

Acute cannabis intoxication may induce neurocognitive impairment and is a possible cause of human error, injury and psychological distress. One of the major concerns raised about increasing cannabis legalization and the therapeutic use of cannabis is that it will increase cannabis-related harm. However, the impairing effect of cannabis during intoxication varies among individuals and may not...

Psychotomimetic symptoms after a moderate dose of a synthetic cannabinoid (JWH-018): implications for psychosis

Psychopharmacology January 26, 2021 Eef L. Theunissen, Johannes T. Reckweg, Nadia R. P. W. Hutten et al. 20 citations

BACKGROUND: Synthetic cannabinoids (SCs) are the largest class of novel psychoactive substances (NPS) and are associated with an increased risk of overdosing and adverse events such as psychosis. JWH-018 is one of the earliest SCs and still widely available in large parts of the world. Controlled studies to assess the safety and behavioural profiles of SCs are extremely scarce. AIM: The current...

Mood and cognition after administration of low LSD doses in healthy volunteers: A placebo controlled dose-effect finding study

European Neuropsychopharmacology October 17, 2020 Nadia R. P. W. Hutten, Natasha L. Mason, Patrick C. Dolder et al. 121 citations

There is a popular interest in microdosing with psychedelics such as LSD. This practice of using one-tenth of a full psychedelic dose according to a specific dosing schedule, anecdotally enhances mood and performance. Nonetheless, controlled research on the efficacy of microdosing is scarce. The main objective of the present dose-finding study was to determine the minimal dose of LSD needed to...

Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants

Clinical Pharmacology & Therapeutics September 25, 2020 Friederike Holze, Matthias E. Liechti, Nadia R. P. W. Hutten et al. 63 citations

“Microdoses” of lysergic acid diethylamide (LSD) are used recreationally to enhance mood and cognition. Increasing interest has also been seen in developing LSD into a medication. Therefore, we performed a pharmacokinetic‐pharmacodynamic study using very low doses of LSD. Single doses of LSD base (5, 10, and 20 µg) and placebo were administered in a double‐blind, randomized, placebo‐controlled...

Low Doses of LSD Acutely Increase BDNF Blood Plasma Levels in Healthy Volunteers

ACS Pharmacology & Translational Science August 31, 2020 Nadia R. P. W. Hutten, Natasha L. Mason, Patrick C. Dolder et al. 134 citations

Despite preclinical evidence for psychedelic-induced neuroplasticity, confirmation in humans is grossly lacking. Given the increased interest in using low doses of psychedelics for psychiatric indications and the importance of neuroplasticity in the therapeutic response, this placebo-controlled within-subject study investigated the effect of single low doses of LSD (5, 10, and 20 μg) on...

A low dose of lysergic acid diethylamide decreases pain perception in healthy volunteers

Journal of Psychopharmacology August 25, 2020 Johannes G. Ramaekers, Nadia R. P. W. Hutten, Natasha L. Mason et al. 95 citations

Background: Lysergic acid diethylamide (LSD) is an ergot alkaloid derivative with psychedelic properties that has been implicated in the management of persistent pain. Clinical studies in the 1960s and 1970s have demonstrated profound analgesic effects of full doses of LSD in terminally ill patients, but this line of research evaporated after LSD was scheduled worldwide. Aim: The present...

Mephedrone and Alcohol Interactions in Humans

Frontiers in Pharmacology January 28, 2020 Esther Papaseit, Clara Pérez‐mañá, Elizabeth B. de Sousa Fernandes Perna et al. 27 citations

Mephedrone (4-MMC, mephedrone) is a synthetic cathinone derivative included in the class of new psychoactive substances. It is commonly used simultaneously with alcohol (ethanol). The aim of the present study was to evaluate the interactions on subjective, cardiovascular and hormone effects and pharmacokinetics between mephedrone and alcohol in humans. Eleven male volunteers participated as...

Reduced responsiveness of the reward system is associated with tolerance to cannabis impairment in chronic users

Addiction Biology December 22, 2019 Natasha L. Mason, Eef L. Theunissen, Nadia R. P. W. Hutten et al. 58 citations

Cannabis is the most commonly used illicit drug in the world. However, because of a changing legal landscape and rising interest in therapeutic utility, there is an increasing trend in (long-term) use and possibly cannabis impairment. Importantly, a growing body of evidence suggests that regular cannabis users develop tolerance to the impairing, as well as the rewarding, effects of the drug....

Cannabis induced increase in striatal glutamate associated with loss of functional corticostriatal connectivity.

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology December 1, 2019 Natasha L. Mason, Eef L. Theunissen, Nadia R. P. W. Hutten et al.

Cannabis is the most commonly used illicit drug and is known to alter state of consciousness and impair neurocognitive function. However, the mechanisms underlying these effects have yet to be fully elucidated. Rodent studies suggest that Δ9-tetrahydrocannabinol (THC) activates dopaminergic neurons in the limbic system, subsequently enhancing dopamine, which is implicated in the rewarding...

Reduced responsiveness of the reward system underlies tolerance to cannabis impairment in chronic users

bioRxiv (Cold Spring Harbor Laboratory) July 19, 2019 Natasha L. Mason, Eef L. Theunissen, Nadia R. P. W. Hutten et al. 4 citations preprint

Abstract Cannabis is the most commonly used illicit drug in the world. However due to a changing legal landscape, and rising interest in therapeutic utility, there is an increasing trend in (long-term) use and possibly, cannabis impairment. Importantly, a growing body of evidence suggests regular cannabis users develop tolerance to the impairing, as well as the rewarding, effects of the drug....