Social Neuroscience
June 25, 2009
Glenn Dumont, Fred C.g.j. Sweep, R. van der Steen et al.
238 citations
MDMA (ecstasy) causes a strong increase in blood oxytocin levels and enhances feelings of prosociality in healthy people. The changes in prosocial feelings are more closely tied to changes in oxytocin than to changes in MDMA concentration in the blood. This suggests that oxytocin release may be a key mechanism behind the drug's characteristic social effects.
Journal of Psychopharmacology
September 3, 2010
Gjh Dumont, J. G. Coen van Hasselt, M. de Kam et al.
38 citations
Combining MDMA and THC does not worsen cognitive impairment beyond that caused by THC alone, but it does increase the desired subjective drug effects and perceived drug strength, which may explain why many young people use them together. In a placebo-controlled crossover trial with 16 healthy volunteers aged 18–27, THC alone produced more robust cognitive impairment than MDMA alone, and co-administration did not exacerbate single-drug effects on cognitive function. However, the combination enhanced subjective experiences compared with MDMA alone.
Journal of Psychopharmacology
January 22, 2009
Gjh Dumont, Rik C. Schoemaker, Daan J Touw et al.
37 citations
Combining MDMA (ecstasy) with alcohol impairs psychomotor accuracy even though it increases feelings of arousal and psychomotor speed. In a double-blind, placebo-controlled crossover study with 16 healthy young adults, MDMA alone boosted speed without affecting accuracy and caused arousal, while alcohol alone slowed both speed and accuracy and induced sedation. When taken together, the combination reversed alcohol-induced sedation and improved speed, but accuracy remained significantly impaired. The effects peaked 90–150 minutes after MDMA administration and then declined, except for alcohol sedation, which emerged fully after the infusion stopped. This mismatch between perceived performance and actual impairment may affect neuropsychological functioning.
European Journal of Pharmacology
July 5, 2025
Jolien K E Veraart, Sanne Y Smith-Apeldoorn, Jeanine Kamphuis et al.
2 citations
Oral esketamine shows low and variable bioavailability, complicating its use as an antidepressant. In 17 patients with treatment-resistant depression given oral esketamine twice weekly for six weeks with a titration approach, esketamine and noresketamine serum levels were measured 30 and 60 minutes after administration. No association was found between changes in depressive symptoms and any pharmacokinetic outcomes, including serum levels of esketamine, noresketamine, their sum, or ratios. High inter-individual variability in pharmacokinetics was observed. The small sample and flexible-dose regimen limit conclusions. Clinical response may not correspond to esketamine pharmacokinetics, suggesting individually-based titration according to clinical effects is optimal.
Pharmaceuticals (Basel, Switzerland)
April 25, 2025
Jolien K E Veraart, Cornelis F Vos, Nieko C Punt et al.
2 citations
In patients with treatment-resistant depression receiving oral esketamine for six weeks, plasma concentrations of esketamine and noresketamine on day 39 were 59% and 35% lower than predicted by a pharmacokinetic model. This suggests that auto-induction of drug-metabolizing enzymes CYP3A4 and CYP2B6 occurs, which may explain the diminished therapeutic effects and side effects observed with long-term use. Identifying auto-induction as a mechanism of tolerance could have important clinical implications for maintaining efficacy.
The pharmacogenomics journal
April 24, 2026
Daniël T Coerts, Sanne Y Smith-Apeldoorn, Jérôme C Oude Nijhuis et al.
A genetic variation in the CYP2B6 enzyme, known as 516 G > T, is linked to higher blood levels of oral esketamine four hours after dosing in people with treatment-resistant depression. In a small sample of 18 participants from a placebo-controlled trial, carriers of the variant had median esketamine levels of 5.1 µg/L, compared to 2.1 µg/L in non-carriers. No significant associations were found for two other genetic variants, CYP3A4*22 and CYP3A5*3, but the numbers of carriers were very small. Larger studies are needed to clarify their effects.
Pharmacogenomics
December 12, 2025
Jérôme C Oude Nijhuis, Daniël T Coerts, Jens H van Dalfsen et al.
Oral esketamine is a promising treatment for depression that does not respond to other therapies, but how much of the drug reaches the bloodstream varies from person to person. This study tested whether common genetic variations in two drug-transport proteins, ABCB1 and ABCG2, affect esketamine levels in the blood. In 18 participants from a placebo-controlled trial, esketamine concentrations four hours after dosing did not differ significantly among people with different ABCB1 or ABCG2 genotypes. Metabolite levels also showed no association with these genetic variants. The findings suggest that these transporter polymorphisms do not influence oral esketamine pharmacokinetics, though the small sample size means the results are preliminary and need confirmation in larger studies.
BMC Psychiatry
November 29, 2019
Sanne Y Smith-Apeldoorn, Jolien K E Veraart, Jeanine Kamphuis et al.
A triple-blind randomized placebo-controlled trial investigates daily oral esketamine versus placebo as an add-on to regular antidepressants in patients with treatment-resistant depression over 6 weeks, followed by a 4-week follow-up. This is the first such trial to examine the efficacy, safety, tolerability, mechanisms of action, and economic impact of repeated oral esketamine administration. If effective and tolerated, oral esketamine offers practical advantages over intravenous administration. The study aims to address the urgent need for additional treatment strategies for treatment-resistant depression.