European Neuropsychopharmacology
April 10, 2026
Deborah Rudin, Jan Valenta, Helene Rolli et al.
2 citations
Serotonergic psychedelics primarily activate the serotonin 2A receptor, but their full effects involve multiple receptor subtypes and signaling pathways. Using stable cell lines and bioassays measuring phospholipase C activation via inositol monophosphate formation, phospholipase A2 activation, β-arrestin2 recruitment, and Gαi-protein dissociation across 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT1A receptors, the study found that inositol monophosphate formation provides the most robust measure of 5-HT2 receptor activation and correlates strongly with known psychoactive doses. Most psychedelics showed signaling bias toward the PLC-IP1 or PLA2-AA pathway at the 5-HT2A receptor. The 5-HT2A/5-HT1A activation ratio may indicate seizure risk and therapeutic potential. Low activation at the 5-HT2B receptor suggests reduced cardiac risk with intermittent use, while strong 5-HT2C receptor activation aligns with low abuse potential.
Translational Psychiatry
June 4, 2026
Mélusine Humbert‐droz, Anna M. Becker, Jan Valenta et al.
A booster dose of MDMA prolongs the acute subjective drug effects compared with a single dose, without increasing peak effects. In a double-blind, randomized, placebo-controlled crossover study with 23 healthy volunteers, a 120 mg dose of MDMA followed by a 60 mg booster after 2 hours extended the duration of subjective effects to an average of 5.6 hours, versus 4.6 hours with a single dose. Adverse effects were more common after both MDMA conditions than placebo. Whether the prolonged effect translates into clinical benefit for MDMA-assisted psychotherapy remains unknown.
Translational Psychiatry
March 27, 2026
Livio Erne, Lorenz Mueller, Isabelle Straumann et al.
Bolus injections of DMT produce very strong subjective effects that peak within 2 minutes and subside completely within 12–30 minutes, consistent with a short elimination half-life of about 6–7 minutes. A ceiling effect for peak subjective effects occurred at the 15 mg dose, and no tolerance developed to the acute effects. Tolerability markedly improved when doses were escalated openly rather than given double-blind, and at equivalent doses the subjective effects were rated as less intense. These results indicate that blinding and expectancy influence the subjective experience and that individual dose-escalation may improve tolerability and guide dose selection in future DMT studies.