9 papers in the library · 46 citations · publishing 2022-2026
Clinical Pharmacokinetics January 1, 2025 Marije E. Otto, Katelijne V. van der Heijden, Jan W. Schoones et al. 20 citations
The pharmacokinetic parameters of psilocin are consistent across different studies. This finding may help guide the further clinical development of psilocybin-based therapies.
Journal of Psychopharmacology February 25, 2022 Francis M. Dijkstra, Aurora JAE van de Loo, Smedra Abdulahad et al. 16 citations
A single 84 mg dose of intranasal esketamine did not impair next-morning driving performance in patients with mild-to-moderate major depressive disorder or persistent depressive disorder, and same-day driving was not impaired after twice-weekly administration over three weeks. Alcohol, used as a positive control, significantly worsened driving (increased weaving by 1.83 cm), while esketamine showed no such effect. Twenty-seven patients completed on-road driving tests on a public highway. The findings suggest that esketamine, at this dose, does not compromise driving ability the morning after or on the same day of repeated use.
Clinical and Translational Science May 1, 2025 Katelijne V. van der Heijden, Rob G J A Zuiker, Marije E. Otto et al. 7 citations
Intravenous DMT administered as a 30-second bolus followed by a 6-hour infusion, reaching peak blood concentrations around 35 ng/mL, is safe in healthy volunteers. No serious adverse events occurred; all side effects were mild and self-limiting. Vital signs, electrocardiography, and measures of suicidality or psychopathology showed no significant abnormalities. Mild psychedelic effects were accompanied by temporary decreases in sustained attention, postural stability, and occipital alpha brain wave power at the highest dose. Moderate variability in drug levels between individuals was observed. These findings support further testing of prolonged DMT infusion as a potential treatment to promote neuroplasticity in stroke recovery.
Journal of Psychopharmacology October 16, 2025 Gerard J. Marek, Soma Makai‐bölöni, Daniel Umbricht et al. 2 citations
A single intravenous dose of GM-2505, a novel 5-HT2A receptor agonist, was safe and well tolerated in 48 healthy volunteers at doses up to 20 mg. The drug produced mild, transient increases in blood pressure and pulse, no significant electrocardiograph changes, and a half-life of 40–50 minutes. Dose-dependent effects appeared on neuroendocrine hormones, neuropsychological and neurophysiological measures, subjective drug effects, and resting-state electroencephalography, with decreased theta and alpha power and increased slow and fast gamma power. These pharmacodynamic effects resembled those of other 5-HT2A agonists, but GM-2505's shorter duration of cardiovascular and subjective effects than psilocybin and longer than DMT suggests a more practical temporal profile for supervised clinical use, with an optimal dose range of 10–15 mg IV.
Frontiers in Neuroscience January 1, 2025 Kasper Recourt, Joop van Gerven, Nadieh Drenth et al. 1 citation
Ketamine, given intravenously at 0.5 mg/kg, rapidly reduces depression symptoms in patients with non-treatment-resistant major depressive disorder. In a randomized, double-blind, placebo-controlled crossover study with 16 patients, ketamine lowered mean MADRS scores from 21.2 before dosing to 10.3 at 24 hours, compared with placebo. Resting-state fMRI showed that ketamine altered functional connectivity only in brain circuits previously linked to depression—the corticolimbic-insular-striatal-pallidal-thalamic (CLIPST) network—at both acute (50–165 minutes) and delayed (24 hours) time points. No connectivity changes occurred outside this depression-related circuitry. The results indicate that ketamine specifically targets depression-associated neural pathways, supporting model-based analysis in future pharmaco-fMRI studies.
British Journal of Clinical Pharmacology July 1, 2026 Marije E. Otto, Gabriël E. Jacobs, Joost C Van Mechelen et al.
Oral (S)-ketamine for treatment-resistant depression undergoes extensive first-pass metabolism, yielding low parent drug but high levels of active metabolites like (S)-norketamine. Using data from 17 healthy participants in a crossover trial, researchers developed a population PK model linking (S)-ketamine and (S)-norketamine concentrations to subjective 'Feeling High' scores. A significant relationship was found for (S)-norketamine alongside (S)-ketamine, though model variance was high. The analysis suggests that (S)-norketamine, not (S)-ketamine itself, primarily drives subjective effects after oral administration and may contribute to antidepressant effects in patients.
Journal of psychopharmacology (Oxford, England) June 25, 2026 Joost C Van Mechelen, Tobias A Wieles, Laura Borghans et al.
Oral S-ketamine (S-KETPO) has poor bioavailability (9-12%) and produces much lower peak concentrations of S-ketamine but higher levels of its active metabolites norketamine and hydroxynorketamine compared to intravenous S-ketamine (S-KETIV). In 16 healthy participants, S-KETIV caused sedative, psychomotor, and psychotomimetic effects along with reductions in brain electrical activity, while the higher oral dose (0.45 mg/kg) showed limited psychotomimetic effects and smaller brain activity reductions, and the lower oral dose (0.20 mg/kg) had no effects. Safety was similar across treatments. These pharmacokinetic and pharmacodynamic differences may affect dose selection and therapeutic outcomes in treatment-resistant depression.
British Journal of Clinical Pharmacology June 24, 2026 Catherine M K E De Cuba, Annika A De Goede, Joost C Van Mechelen et al.
A single intravenous dose of S-ketamine produced acute and delayed effects on brain activity and motor cortex excitability that lasted up to seven days in 16 healthy adults. Intravenous S-ketamine reduced motor-evoked potential amplitude acutely and caused a sustained weakening of long-interval intracortical inhibition, which followed a linear relationship with drug concentration. Transcranial magnetic stimulation combined with electroencephalography showed acute changes in brain electrical activity across all treatments, but delayed changes only after intravenous and high-dose oral S-ketamine. Electroencephalography revealed acute decreases in alpha, beta, and delta power with eyes closed, and sustained increases in delta power with eyes open, the latter also showing a linear concentration-effect relationship. These delayed pharmacodynamic effects are distinct from acute effects and may help explain S-ketamine's antidepressant action.
Clinical Pharmacokinetics February 21, 2025 Marije E. Otto, Katelijne V. van der Heijden, Jan W. Schoones et al. correction
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