Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin

Abstract

Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normal waking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen leveldependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/ functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition.receptor P silocybin is the prodrug of psilocin (4-hydroxy-dimethyltryptamine), the primary hallucinogenic component of magic mushrooms, and a classic psychedelic ("mind-manifesting") drug. Psilocybin has been used for centuries in healing ceremonies (1) and more recently in psychotherapy (2); it is capable of stimulating profound existential experiences (3), which can leave a lasting psychological impression (4). However, despite a wealth of literature on its phenomenology, we currently know very little about how its effects are produced in the brain. The present study sought to address this question using complementary functional MRI (fMRI) techniques and a protocol designed to image the transition from normal waking consciousness to the psychedelic state. Two groups of healthy subjects were scanned using arterial spin labeling (ASL) perfusion and blood-oxygen level-dependent (BOLD) fMRI during intravenous infusion of psilocybin. Infused over 60 s (2 mg in 10-mL saline), psilocybin's subjective effects begin within seconds (5), allowing the capture of the corresponding change in brain state.Results ASL Perfusion fMRI. Fifteen healthy, hallucinogen-experienced subjects (five females), mean age 34.1 (SD 8.2) were scanned with ASL. Subjects underwent an anatomical scan followed by two taskfree functional scans, each lasting 18 min. Subjects were instructed to relax and a fixation cross was displayed. Solutions were inf...

Psychedelics

“…A recent fMRI study, however, reported an overall decrease of brain activity in the medial frontal cortex after intravenous administration of psilocybin (Carhart-Harris et al, 2012). Notably, the reported decrease correlates with a suppression of the DMN (Buckner et al, 2008).…”

Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects

“…Altogether, the effects of LSD on PPI in normal humans were consistent with both the PPI deficits after LSD administration in animals and sensorimotor gating deficits in schizophrenia patients. have not yet been studied using LSD in neuroimaging studies, in contrast to several modern investigations that used psilocybin to model psychotic states (24,25).…”

“…Many studies also sought to describe the psychotomimetic effects of LSD but were not designed to measure any positive subjective effects. Modern experimental studies with hallucinogens in humans resumed in the 1990s with N-N-dimethyltryptamine (DMT, ayahuasca) (18)(19)(20)(21), ketamine (21)(22)(23), and psilocybin (24,25) but not with LSD. Both LSD and psilocybin have also been recently evaluated in pilot therapeutic studies as treatments for anxiety in patients with lifethreatening diseases (11,26).…”

Modeling the Flesh of God: Semantic Hyperpriming and the Teonancátl Cults of Mexico

“…The amount of activity decrease in the ACC and medial prefrontal cortex (mPFC) was proportional to the intensity of the subjective "unitive" effect (Carhart-Harris et al, 2012), suggesting the reduction of activity to these inhibitory hub regions enables a state of unrestrained associative and perceptual faculties. These fMRI studies of psilocybin's specific neurological correlates is certainly important and still ripe for interpretation, and certainly give us valuable hints as to the neurophysiology at play during the Mazatec shaman's intentioned transition into specific non-ordinary states of consciousness.…”

“…This sudden surge of priming volume measured in the psilocybin experience (Spitzer et al, 1996) can be conceptualized as a flooding inlet of attention; the pupils dilating in a state of hyperawareness and hypervigilance, the whole nervous system buzzing with vibrant sensation, the eyes allowing more light information to shine inwards from the surroundings, spurring neuronal activation and reducing cerebral bloodflow (Carhart-Harris et al, 2012) to areas of the brain responsible for latent inhibition (LI), or the filtering down of sensory information from conscious awareness. .…”