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.
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 G J M 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.