OPEN Foundation

Day: 15 October 2020

Psilocybin exerts distinct effects on resting state networks associated with serotonin and dopamine in mice

November 26, 2021 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychopharmacology / Leave a Comment / By / , , , , , , ,

Abstract

Hallucinogenic agents have been proposed as potent antidepressants; this includes the serotonin (5-HT) receptor 2A agonist psilocybin. In human subjects, psilocybin alters functional connectivity (FC) within the default-mode network (DMN), a constellation of inter-connected regions that displays altered FC in depressive disorders. In this study, we investigated the effects of psilocybin on FC across the entire brain with a view to investigate underlying mechanisms. Psilocybin effects were investigated in lightly-anaesthetized mice using resting-state fMRI. Dual-regression analysis identified reduced FC within the ventral striatum in psilocybin- relative to vehicle-treated mice. Refinement of the analysis using spatial references derived from both gene expression maps and viral tracer projection fields revealed two distinct effects of psilocybin: it increased FC between 5-HT-associated networks and cortical areas, including elements of the murine DMN, thalamus, and midbrain; it decreased FC within dopamine (DA)-associated striatal networks. These results suggest that interactions between 5-HT- and DA-regulated neural networks contribute to the neural and therefore psychological effects of psilocybin. Furthermore, they highlight how information on molecular expression patterns and structural connectivity can assist in the interpretation of pharmaco-fMRI findings.

Grandjean, J., Buehlmann, D., Buerge, M., Sigrist, H., Seifritz, E., Vollenweider, F. X., Pryce, C. R., & Rudin, M. (2021). Psilocybin exerts distinct effects on resting state networks associated with serotonin and dopamine in mice. NeuroImage, 225, 117456. https://doi.org/10.1016/j.neuroimage.2020.117456

Link to full text

Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects

November 26, 2021 / LSD, Papers, Phenomenology, Psychopharmacology / Leave a Comment / By / , , , , , , , , , ,

Abstract

Growing interest has been seen in using lysergic acid diethylamide (LSD) in psychiatric research and therapy. However, no modern studies have evaluated subjective and autonomic effects of different and pharmaceutically well-defined doses of LSD. We used a double-blind, randomized, placebo-controlled, crossover design in 16 healthy subjects (eight women, eight men) who underwent six 25 h sessions and received placebo, LSD (25, 50, 100, and 200 µg), and 200 µg LSD 1 h after administration of the serotonin 5-hydroxytryptamine-2A (5-HT2A) receptor antagonist ketanserin (40 mg). Test days were separated by at least 10 days. Outcome measures included self-rating scales that evaluated subjective effects, autonomic effects, adverse effects, plasma brain-derived neurotrophic factor levels, and pharmacokinetics up to 24 h. The pharmacokinetic-subjective response relationship was evaluated. LSD showed dose-proportional pharmacokinetics and first-order elimination and dose-dependently induced subjective responses starting at the 25 µg dose. A ceiling effect was observed for good drug effects at 100 µg. The 200 µg dose of LSD induced greater ego dissolution than the 100 µg dose and induced significant anxiety. The average duration of subjective effects increased from 6.7 to 11 h with increasing doses of 25-200 µg. LSD moderately increased blood pressure and heart rate. Ketanserin effectively prevented the response to 200 µg LSD. The LSD dose-response curve showed a ceiling effect for subjective good effects, and ego dissolution and anxiety increased further at a dose above 100 µg. These results may assist with dose finding for future LSD research. The full psychedelic effects of LSD are primarily mediated by serotonin 5-HT2A receptor activation.

Holze, F., Vizeli, P., Ley, L., Müller, F., Dolder, P., Stocker, M., Duthaler, U., Varghese, N., Eckert, A., Borgwardt, S., & Liechti, M. E. (2021). Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 46(3), 537–544. https://doi.org/10.1038/s41386-020-00883-6

Link to full text

Psilocybin exerts distinct effects on resting state networks associated with serotonin and dopamine in mice

February 21, 2022 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychopharmacology / Leave a Comment / By / , , , , , , ,

Abstract

Hallucinogenic agents have been proposed as potent antidepressants; this includes the serotonin (5-HT) receptor 2A agonist psilocybin. In human subjects, psilocybin alters functional connectivity (FC) within the default-mode network (DMN), a constellation of inter-connected regions that displays altered FC in depressive disorders. In this study, we investigated the effects of psilocybin on FC across the entire brain with a view to investigate underlying mechanisms. Psilocybin effects were investigated in lightly-anaesthetized mice using resting-state fMRI. Dual-regression analysis identified reduced FC within the ventral striatum in psilocybin- relative to vehicle-treated mice. Refinement of the analysis using spatial references derived from both gene expression maps and viral tracer projection fields revealed two distinct effects of psilocybin: it increased FC between 5-HT-associated networks and cortical areas, including elements of the murine DMN, thalamus, and midbrain; it decreased FC within dopamine (DA)-associated striatal networks. These results suggest that interactions between 5-HT- and DA-regulated neural networks contribute to the neural and therefore psychological effects of psilocybin. Furthermore, they highlight how information on molecular expression patterns and structural connectivity can assist in the interpretation of pharmaco-fMRI findings.

Grandjean, J., Buehlmann, D., Buerge, M., Sigrist, H., Seifritz, E., Vollenweider, F. X., Pryce, C. R., & Rudin, M. (2021). Psilocybin exerts distinct effects on resting state networks associated with serotonin and dopamine in mice. NeuroImage, 225, 117456. https://doi.org/10.1016/j.neuroimage.2020.117456

Link to full text

30 April - Q&A with Rick Strassman

REGISTER NOW!
X