Translational psychiatry
September 30, 2024
Aaron Klaiber, Yasmin Schmid, Anna M Becker et al.
27 citations
Mescaline produces dose-dependent subjective and physiological effects in healthy people, with doses above 100 mg increasing blood pressure and heart rate. Subjective effects lasted from 6.4 hours at 100 mg to 14 hours at 800 mg, and the drug reached peak concentration in blood after about 2 hours with a half-life of 3.5 hours. Nausea and vomiting were common at the highest dose. Blocking serotonin 5-HT2A receptors with ketanserin reduced the effects of 800 mg mescaline to levels similar to lower doses, indicating that mescaline's acute effects are primarily mediated by these receptors.
Clinical Pharmacology & Therapeutics
February 28, 2025
Lorenz Mueller, Alen Jelusic, Avram Tolev et al.
15 citations
In a double-blind, placebo-controlled crossover study with 23 healthy participants, daily paroxetine (an SSRI antidepressant) did not reduce the pleasant subjective effects of a single 100 μg dose of LSD, but it significantly lessened negative effects such as 'bad drug effect,' anxiety, and nausea. Paroxetine increased LSD's peak concentration and total exposure by 40% and 50%, respectively, by inhibiting the CYP2D6 enzyme, indicating this enzyme is involved in LSD metabolism. The interaction was strongest in normal CYP2D6 metabolizers and weakest in poor metabolizers. The findings suggest LSD can be safely added to SSRI treatment without dose adjustment when the SSRI inhibits CYP2D6, but no definitive recommendation can be made for other SSRIs.
Journal of psychopharmacology (Oxford, England)
August 16, 2025
Dila Suay, Helena D Aicher, Berit Singer et al.
A psychedelic formulation combining DMT and harmine, but not harmine alone, impaired convergent thinking—the ability to find a single correct solution—in 30 healthy men, especially those with higher baseline reasoning. Divergent thinking, the generation of many ideas, showed no overall effect but trended toward reduced fluency and elaboration. In a real-world painting task, both DMT/HAR and harmine reduced transitions associated with incubation, and DMT/HAR uniquely decreased the shift from incubation to illumination, indicating altered pathways to insight. Subjective experiences like altered meaning and insightfulness predicted divergent but not convergent thinking. The effects of DMT/HAR on creativity are not uniform, affecting both cognitive performance and the dynamic creative process.
Universität Zürich, ZORA
August 16, 2025
Dila Suay, Helena Dorothea Aicher, Berit Singer et al.
A psychedelic formulation combining DMT and harmine impaired convergent thinking, especially in people with higher baseline reasoning, while harmine alone had no such effect. Divergent thinking showed no overall change, though there were trend-level reductions in fluency and elaboration under the combined formulation. In a real-world painting task, both the combined formulation and harmine alone reduced incubation-related transitions, and the combined formulation uniquely decreased transitions from incubation to illumination, suggesting altered pathways to insight. Subjective experiences like altered meaning perception and increased insightfulness predicted divergent, but not convergent, thinking outcomes. The effects of psychedelics on creativity are not uniform and depend on the cognitive stage and individual differences.