Neuroimage
July 1, 2008
Jacob M Hooker, Youwen Xu, Wynne Schiffer et al.
106 citations
Salvinorin A, the psychoactive component of the mint plant Salvia divinorum, is a uniquely potent agonist at kappa-opioid receptors. Positron emission tomography (PET) studies in 6 adult female baboons showed extremely rapid brain uptake, reaching a peak of 3.3% of the total administered dose within 40 seconds and clearing with a half-life of 8 minutes. The compound distributed throughout the brain, with highest concentration in the cerebellum and notable concentration in the visual cortex, which may account for visual hallucinations when smoked. Naloxone did not reduce overall concentration or alter regional distribution. The rapid brain kinetics match the brief time-course of visual hallucinations, and effects may occur at less than 10 micrograms in the human brain, emphasizing its remarkable potency.
ACS Chemical Neuroscience
June 25, 2024
Jingyuan Chen, Frederick A. Bagdasarian, Hanne D. Hansen et al.
11 citations
Using fMRI in nonhuman primates, this work compared how two different hallucinogens—psilocybin, a serotonergic psychedelic, and salvinorin-A, a kappa-opioid receptor agonist—alter resting-state functional connectivity. Both drugs acutely desynchronized the default mode network and affected a network involving the claustrum, prefrontal cortex, anterior cingulate cortices, and angular gyrus, supporting a cortico-claustro-cortical model for probing hallucinogen effects regardless of serotonergic activity. Thalamo-cortical changes appeared dependent on 5-HT2AR activation. The findings offer a framework for understanding mechanisms common across hallucinogenic drug classes.
ACS Chemical Neuroscience
May 17, 2023
Khalyd J Clay, Ava E Axelrod, Christina M MacLaughlin et al.
2 citations
Several naturally occurring molecules, including entheogens—plant-derived compounds used by Indigenous groups for religious or spiritual purposes—show unique potential for treating psychiatric illnesses and are being pursued in therapeutic development. This viewpoint argues that labeling such compounds as "DARK" in ACS Chemical Neuroscience issues perpetuates harmful stigmas. The authors propose reframing these substances in the light and beauty of their cultural and historical contexts, urging a shift in language surrounding entheogens and psychedelics more broadly.
Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition
August 14, 2024
Frederick A. Bagdasarian, Hanne D. Hansen, Chi‐hyeon Yoo et al.
Psilocybin, a serotonergic agonist, and Salvinorin-A, a kappa-opioid receptor agonist, both alter functional connectivity in the brains of non-human primates, but their effects overlap and differ in specific regions. Using fMRI, the study examined how these psychedelics influence connections within the default mode network and the claustrum. The findings suggest that each substance targets distinct receptor systems, leading to both shared and unique patterns of brain network activity, which may help explain their different mechanisms of action.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
December 1, 2015
Michael S. Placzek, Genevieve C Van de Bittner, Hsiao‐ying Wey et al.
Kappa opioid receptor (KOR) binding availability in the brain was measured in living rats using positron emission tomography (PET) after administration of the KOR agonist salvinorin A. At lower doses, salvinorin A briefly competed for receptor binding but had no lasting effect. At a dose of 0.60 mg/kg, however, it induced a sustained decrease in KOR binding of 40–49% that persisted for up to 2.5 hours after the drug had left the brain, suggesting an adaptive response by the receptor not previously observed in vivo with PET.