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Gabriël E. Jacobs

13 papers in the library · 53 citations · publishing 2022-2026

Papers

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Safety, pharmacokinetics, and pharmacodynamics of intravenously administered deuterated N,N-dimethyltryptamine (CYB004) in healthy volunteers.

Journal of psychopharmacology (Oxford, England) September 3, 2026 Katelijne V Van der Heijden, Gabriel E Jacobs, Ellen H James et al.

Serotonergic psychedelics, such as N,N-dimethyltryptamine (DMT), have shown therapeutic potential in various psychiatric disorders. However, DMT demonstrates pharmacokinetic (PK) variability and a short half-life. This exploratory study investigated the PK, pharmacodynamic (PD), and safety profile of CYB004, a deuterated DMT analogue, following intravenous administration in healthy volunteers....

Pharmacokinetics, pharmacodynamics and safety of N,N -dimethyltryptamine administered intravenously in healthy smoking and non-smoking volunteers

Journal of Psychopharmacology August 31, 2026 Katelijne V. van der Heijden, Soma Makai‐bölöni, Amir Inamdar et al.

BACKGROUND: -dimethyltryptamine (DMT) might have therapeutic effects in various psychiatric disorders. AIMS: Prior to exploring this clinical potential, it is essential to determine an optimal administration regimen for DMT, explore the relationship between its pharmacokinetics (PK) and pharmacodynamics and identify potential sources of pharmacokinetic variability. METHODS: Therefore, DMT was...

Pharmacokinetics and pharmacodynamics of intravenous and oral (S)-ketamine: Investigating metabolite contribution to subjective effects.

British Journal of Clinical Pharmacology July 1, 2026 Marije E. Otto, Gabriël E. Jacobs, Joost C Van Mechelen et al.

Oral administration of (S)-ketamine for treatment-resistant depression (TRD), as alternative to the registered intranasal or off-label intravenous administrations, has high potential. However, it is characterized by an extensive first-pass metabolism, resulting in low (S)-ketamine exposure and high levels of active metabolites, including (S)-norketamine and (S)-hydroxynorketamine. The relative...

Pharmacokinetics and pharmacodynamics of orally administered S-ketamine in healthy participants.

Journal of psychopharmacology (Oxford, England) June 25, 2026 Joost C Van Mechelen, Tobias A Wieles, Laura Borghans et al.

Oral S-ketamine (S-KETPO) is being explored as an alternative to intravenous maintenance treatment (S-KETIV) in treatment-resistant depression (TRD). However, the first-pass effect with S-KETPO significantly alters S-ketamine's bioavailability and the systemic exposure of its active metabolites, raising potential safety and efficacy concerns. This study characterized the pharmacodynamic and...

Sustained pharmacodynamic effects of S-ketamine on cortical excitability and resting-state brain activity: A randomized, placebo-controlled trial.

British Journal of Clinical Pharmacology June 24, 2026 Catherine M K E De Cuba, Annika A De Goede, Joost C Van Mechelen et al.

This study aimed to investigate a set of pharmacodynamic biomarkers reflecting acute, delayed and sustained central nervous system effects of S-ketamine, used as a tool compound for rapid-acting antidepressant activity, with the goal of informing biomarker strategies for delayed antidepressant effects. In this randomized, double-blind, double-dummy, placebo-controlled, 4-way crossover study in...

A novel psychedelic 5-HT 2A receptor agonist GM-2505: The pharmacokinetic, safety, and pharmacodynamic profile from a randomized trial healthy volunteer

Journal of Psychopharmacology October 16, 2025 Gerard J. Marek, Soma Makai‐bölöni, Daniel Umbricht et al. 2 citations

Background: The treatment of major depressive disorder (MDD) with available antidepressant drugs is characterized by considerable ineffectiveness. Classical psychedelics such as psilocybin and N,N-dimethyltryptamine (DMT), which act primarily as 5-hydroxytryptamine 2A (5-HT 2A ) receptor agonists, have shown preliminary efficacy for inducing long-term remission in MDD after one or two doses....

Safety, Pharmacokinetics, and Pharmacodynamics of a 6-h N,N-Dimethyltryptamine (DMT) Infusion in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Trial.

Clinical and Translational Science May 1, 2025 Katelijne V. van der Heijden, Rob G J A Zuiker, Marije E. Otto et al. 7 citations

The serotonergic psychedelic N,N-dimethyltryptamine (DMT) presumably stimulates neuroplasticity in vitro and in vivo, by which it may exert neuroprotective effects during acute ischemic stroke. Since neuroplasticity has been implicated in the mechanism of action of rehabilitative therapy in stroke recovery, a pharmacological augmentation strategy facilitating neuroplasticity could be...

Correction: Clinical Pharmacokinetics of Psilocin After Psilocybin Administration: A Systematic Review and Post‑Hoc Analysis

Clinical Pharmacokinetics February 21, 2025 Marije E. Otto, Katelijne V. van der Heijden, Jan W. Schoones et al. correction

Correction to: Clinical Pharmacokinetics (2025) 64:53–66 https://doi.org/10.1007/s40262-024-01454-4 In the original version of this article, the given and family names of J. G. Coen van Hasselt were incorrectly structured as Coen J.G. van Hasselt. The correct name should read as given name: J. G. Coen and family name: van Hasselt.

Clinical Pharmacokinetics of N,N-Dimethyltryptamine (DMT): A Systematic Review and Post-hoc Analysis.

Clinical Pharmacokinetics February 1, 2025 Katelijne V. van der Heijden, Marije E. Otto, Jan W. Schoones et al. 7 citations

N,N-Dimethyltryptamine (DMT) is currently being studied for its therapeutic potential in various psychiatric disorders. An understanding of its pharmacokinetics (PK) is essential to determine appropriate dose ranges in future clinical studies. We conducted a systematic literature review on the PK of DMT. Clinical studies that administered known amounts of DMT and reported PK data and/or...

Clinical Pharmacokinetics of Psilocin After Psilocybin Administration: A Systematic Review and Post-Hoc Analysis

Clinical Pharmacokinetics 2025 Marije E. Otto, Katelijne V. van der Heijden, Jan W. Schoones et al. 20 citations

Overall, we found the pharmacokinetic parameters of psilocin to be consistent between studies. This review may guide the further clinical development of psilocybin-based therapies.

Ketamine effects on resting state functional brain connectivity in major depressive disorder patients: a hypothesis-driven analysis based on a network model of depression.

Frontiers in Neuroscience 2025 Kasper Recourt, Joop van Gerven, Nadieh Drenth et al. 1 citation

Ketamine demonstrates robust and rapidly occurring antidepressant effects in patients with difficult-to-treat major depressive disorder. Ketamine's antidepressant effects and its impact on functional networks in non-resistant forms of major depressive disorder are expected to provide valuable insight into ketamine's mechanism of action related to depression. This study employs an existing...

Clinical pharmacokinetics of N,N-dimethyltryptamine (DMT): a systematic review and post-hoc analysis

Leiden Repository (Leiden University) 2025 Katelijne V. van der Heijden, Marije E. Otto, Jan W. Schoones et al.

BACKGROUND AND OBJECTIVE\nMETHODS\nRESULTS\nCONCLUSION\nN,N-Dimethyltryptamine (DMT) is currently being studied for its therapeutic potential in various psychiatric disorders. An understanding of its pharmacokinetics (PK) is essential to determine appropriate dose ranges in future clinical studies. We conducted a systematic literature review on the PK of DMT.\nClinical studies that administered...

The effects of intranasal esketamine on on-road driving performance in patients with major depressive disorder or persistent depressive disorder

Journal of Psychopharmacology February 25, 2022 Francis M. Dijkstra, Aurora JAE van de Loo, Smedra Abdulahad et al. 16 citations

Background: Intranasal esketamine demonstrates rapid improvement of depressive symptoms. However, transient adverse effects (dissociation, sedation and dizziness) may occur, which could impact driving performance. Aims: To evaluate the effects of 84 mg intranasal esketamine on driving performance in unipolar major depressive disorder (MDD) or persistent depressive disorder (PDD) patients....