Lysergic acid diethylamide (LSD) is a potent psychedelic with increasing therapeutic interest, yet qualification of target engagement using in vivo neuroimaging has not yet been performed. Using simultaneous positron emission tomography-magnetic resonance imaging technology, we describe multiple brain actions of LSD in seven healthy volunteers blinded to LSD dose received. Here we show that LSD...
Abstract Classic psychedelics, including lysergic acid diethylamide (LSD), are currently under investigation for the treatment of major depressive disorder (MDD). Cognitive dysfunction is common in MDD, but effects of psychedelic treatment on cognitive brain function, measured by magnetic resonance imaging, are sparsely reported. The present study investigated effects of LSD treatment on...
A prominent theory of psychedelics is that they increase brain entropy. Thirteen studies have evaluated psychedelic effects on fMRI brain entropy, each applying a distinct measure. Here we evaluated these metrics in an independent 28-participant healthy cohort with 121 pre- and post-psilocybin fMRI scans. We assessed relations between brain entropy and objective and subjective psychedelic drug...
Abstract Psilocybin and other serotonergic drugs acutely alter human brain function and large-scale connectivity as measured with BOLD fMRI, but whether these effects are frequency-specific remains unknown. We applied multitaper spectral and cross-spectral analyses to resting-state fMRI data from 28 healthy volunteers scanned multiple times acutely following oral psilocybin administration (0.2...
Classical psychedelics have regained interest for their potential to treat psychiatric and neurological disorders, and explore neural mechanisms supporting perception, cognition, and mood. Acute psychedelic effects have been linked to increases in brain complexity and entropy, but it is unclear if these changes are specific to psychedelics or reflect more general psychoactive effects. Here, we...
In this study, we provide the first study to integrate molecular and functional neuroimaging during psychedelic drug effects in humans. Using simultaneous PET-MRI technology, we describe multiple brain actions of lysergic acid diethylamide (LSD) in healthy volunteers. We quantify the occupancy of LSD at cerebral serotonin 2A receptors and show that LSD increases global cerebral blood flow and...
Psilocin, the active metabolite of psilocybin, is a psychedelic and agonist at the serotonin 2A receptor (5-HT2AR) that has shown positive therapeutic effects for brain disorders such as depression. To elucidate the brain effects of psilocybin, we directly compared the acute effects of 5-HT2AR agonist (psilocybin) and antagonist (ketanserin) on cerebral blood flow (CBF) using pseudo-continuous...
Understanding neuromodulatory effects of serotonin 2A receptor (5-HT 2A R) agonists with diverse pharmacological profiles is relevant to advancing psychedelic-related drug applications. We performed simultaneous positron emission tomography (PET) and pharmacological magnetic resonance imaging (phMRI) in anesthetized nonhuman primates (NHP; N = 3) to examine partial agonists with varying 5-HT 2A...
Motivation: Acute effects of psychedelic drugs are under-reported in neuroimaging studies, warranting further investigation of their immediate pharmacology to explore the potential to monitor treatment response with imaging. Goal(s): Our goal was to assess acute impacts of serotonergic (psychedelic and non-psychedelic) agonists on hemodynamics in non-human primates (NHP). Approach:...
The serotonergic psychedelic psilocybin acutely induces changes in emotional states. However, it remains unresolved whether psilocybin acutely modulates amygdala reactivity to emotions, a brain region critically involved in emotion processing. Using functional magnetic resonance imaging (fMRI), we examined in 26 healthy individuals whether amygdala responses to angry, fearful and neutral faces...