Proceedings of the National Academy of Sciences
January 23, 2012
Alessandro Colasanti, Robin J. Tyacke, Robert Leech et al.
1,191 citations
Psychedelic drugs like psilocybin, found in magic mushrooms, produce profound changes in consciousness by decreasing activity and connectivity in key brain hub regions. Using functional MRI, researchers observed that psilocybin reduced cerebral blood flow and BOLD signal, especially in the thalamus, anterior cingulate cortex (ACC), and posterior cingulate cortex (PCC). Decreased activity in the ACC and medial prefrontal cortex (mPFC) predicted the intensity of subjective psychedelic effects. Psilocybin also reduced positive coupling between the mPFC and PCC. These findings suggest that psychedelics work by dampening the brain's connector hubs, leading to a state of unconstrained cognition.
Journal of Psychopharmacology
October 5, 2012
Amir Englund, Paul D. Morrison, Judith Nottage et al.
463 citations
Pre-treatment with 600 mg of cannabidiol (CBD) reduced the likelihood of clinically significant psychotic symptoms and paranoia caused by intravenous delta-9-tetrahydrocannabinol (THC, 1.5 mg) in healthy volunteers. Participants who received CBD before THC had lower scores on the State Social Paranoia Scale and smaller declines in episodic memory compared with those who received placebo before THC. The odds of experiencing a clinically significant increase in positive psychotic symptoms were about 78% lower in the CBD group. These results support the view that cannabis products high in THC and low in CBD pose greater mental health risks.
Schizophrenia Bulletin
October 6, 2012
Robin Carhart‐Harris, Robert Leech, David Erritzøe et al.
267 citations
Psilocybin, a classic psychedelic, increases functional connectivity between the default-mode network (DMN) and task-positive network (TPN), reducing the normal orthogonality between these networks. In 15 healthy volunteers, intravenous psilocybin (vs placebo) during resting-state fMRI scans led to greater DMN-TPN connectivity, a pattern also seen in psychosis and meditative states. Thalamocortical connectivity remained unchanged, suggesting it relates to arousal rather than the separateness of internal versus external focus. The findings support psilocybin as a model for early psychosis, where compromised DMN-TPN orthogonality may explain phenomenological overlaps.
Journal of Psychopharmacology
November 6, 2020
Luke A. Jelen, Allan H. Young, James Stone
244 citations
The discovery that the dissociative anaesthetic ketamine produces rapid antidepressant effects is considered the most important breakthrough in depression research in the last 50 years. Ketamine, a racemic mixture of (S)-ketamine and (R)-ketamine, remains an off-label treatment for treatment-resistant depression, limited by dissociative effects and abuse potential. An (S)-ketamine nasal spray is approved in the United States and Europe, though concerns about efficacy and side effects persist. Preclinical evidence suggests (R)-ketamine may have more potent and longer-lasting antidepressant effects than (S)-ketamine with fewer side effects, and a pilot trial showed rapid-acting and sustained antidepressant effects in individuals with treatment-resistant depression. Research continues on the cellular and molecular mechanisms underlying these effects.
Psychological Medicine
May 24, 2013
James Stone, Helen L. Fisher, Barnaby Major et al.
69 citations
Cannabis use is linked to an earlier onset of psychosis and more severe manic symptoms and conceptual disorganization, but not to delusions, hallucinations, negative symptoms, or daily functioning. In a naturalistic cohort of 502 patients with first-episode psychosis assessed at entry to services and after one year, those who reduced or stopped cannabis use showed the greatest improvement in symptoms, while continued users remained more symptomatic than non-users. Effective interventions to reduce cannabis use could yield significant health benefits for this population.
Journal of Psychopharmacology
June 19, 2013
Rl Carhart-Harris, Stefan Brugger, Dj Nutt et al.
43 citations
Five drugs—cannabis, psilocybin, amphetamine, ketamine, and alcohol—were compared for how well they model psychiatric symptoms. Mental health professionals rated how specific certain experiences were to symptom clusters like depression or psychosis. People with personal drug experience then reported how reliably each drug produced those experiences. No experiences were specific to negative or cognitive psychotic symptoms over depression. Psilocybin best modeled positive psychotic symptoms, while acute alcohol and amphetamine best modeled mania. These findings challenge current assumptions about drug models and point to an understudied area needing more research.
Pharmacopsychiatry
July 22, 2010
James Stone, Paul Morrison, Judith Nottage et al.
13 citations
THC impairs subjective time perception and reduces the rate of button pressing in healthy volunteers, but the change in button pressing rate is more closely related to impaired concentration and intoxication than to time perception. The disruption of self-timed actions from THC may arise from a different mechanism than alterations in time perception.
Schizophrenia Research
May 1, 2015
T. Winton-Brown, V. Kumari, F. Windler et al.
Sensorimotor gating—measured by how a quieter sound modifies the eye-blink startle reflex to a loud noise—is altered in people with psychosis, their relatives, and those at high clinical risk. Cannabis use also alters gating, though less strongly, and is a known risk factor for psychosis in susceptible individuals. This study tested prepulse inhibition (PPI) and prepulse facilitation (PPF) in participants with an At Risk Mental State (ARMS) for psychosis and matched controls, some of whom had recently used cannabis (confirmed by urine drug screening). ARMS participants showed reduced PPF and PPI compared to controls; the PPI reduction was driven by an interaction with cannabis use, where recent use reduced PPI only in ARMS participants.