Archives of General Psychiatry
January 1, 2009
Paolo Fusar‐poli, José A. Crippa, Sagnik Bhattacharyya et al.
461 citations
In healthy men with minimal prior cannabis use, the two main psychoactive compounds in cannabis had opposite effects on anxiety and brain activity. Delta9-tetrahydrocannabinol (THC) increased anxiety, intoxication, sedation, and psychotic symptoms, while cannabidiol (CBD) showed a trend toward reducing anxiety. When participants viewed intensely fearful faces, THC increased skin conductance fluctuations (a measure of autonomic arousal), whereas CBD decreased them. CBD also dampened brain activation in the amygdala and anterior and posterior cingulate cortex, and this suppression correlated with reduced arousal. THC mainly altered activation in frontal and parietal areas. These distinct neural effects may explain why cannabis can both relieve and provoke anxiety.
Current Pharmaceutical Design
September 12, 2012
Rocío Martín‐Santos, José Alexandre S. Crippa, Albert Batalla et al.
288 citations
Delta-9-tetrahydrocannabinol (THC), but not cannabidiol (CBD), produces marked acute behavioral and physiological effects. In a randomized, double-blind, placebo-controlled trial with 16 healthy male volunteers, oral THC (10 mg) caused anxiety, dysphoria, positive psychotic symptoms, physical and mental sedation, subjective intoxication, and increased heart rate relative to placebo and CBD. CBD (600 mg) showed no differences from placebo on any symptomatic or physiological measure, indicating it is safe and well tolerated. The two main cannabis constituents thus have quite different acute effects.
Archives of General Psychiatry
April 1, 2009
Sagnik Bhattacharyya, Paolo Fusar‐poli, Stefan Borgwardt et al.
250 citations
Delta9-tetrahydrocannabinol (THC), a psychoactive constituent of cannabis, increased psychotic symptoms, anxiety, intoxication, and sedation in healthy men with minimal prior cannabis use, while cannabidiol had no significant effect on these measures. Verbal learning performance was not significantly affected by either drug. THC altered brain activation in the parahippocampal gyrus during encoding and in the ventrostriatum during retrieval, with the ventrostriatal change directly correlating with induced psychotic symptoms. These findings suggest THC modulates mediotemporal and ventrostriatal function, potentially underlying cannabis's effects on verbal learning and psychosis.
Psychological Medicine
July 23, 2009
R. Martín-Santos, Ana B. Fagundo, José Alexandre S. Crippa et al.
207 citations
A systematic review of neuroimaging studies published up to January 2009 assessed evidence for cannabis effects on brain structure and function. Among 41 included studies, functional imaging indicated that resting global and prefrontal blood flow are lower in cannabis users than in controls. Activation studies during cognitive tasks produced inconsistent results. Acute administration of THC or marijuana increased resting activity and activation of the frontal and anterior cingulate cortex during cognitive tasks. Only three of eight structural imaging studies found differences between users and controls, providing minimal evidence of major effects of cannabis on brain structure.
The British Journal of Psychiatry
September 1, 1994
Philip Mcguire, Helen Cope, Thomas Fahy
187 citations
MDMA (Ecstasy) use may be linked to a wider range of mental health problems than previously recognized. In a series of 13 patients who developed psychiatric symptoms after using MDMA, eight had psychotic syndromes, two experienced visual disturbances, one had panic attacks, one suffered depression, and one reported chronic depersonalization. The psychotic symptoms in these patients closely resembled those seen in psychotic patients with no history of drug use, suggesting MDMA can trigger psychosis similar to primary psychotic disorders.
The International Journal of Neuropsychopharmacology
September 24, 2009
Paolo Fusar‐poli, Paul Allen, Sagnik Bhattacharyya et al.
165 citations
Cannabidiol (CBD), but not delta-9-tetrahydrocannabinol (THC), disrupts forward connectivity between the amygdala and the anterior cingulate cortex during the neural response to fearful faces. This disruption may represent a neurophysiological correlate of CBD's anxiolytic properties. The study used dynamic causal modelling and Bayesian model selection to analyze effective connectivity in 15 healthy subjects under a double-blind, randomized, placebo-controlled fMRI paradigm while they viewed faces eliciting different levels of anxiety.
BMJ
March 23, 1991
Philip Mcguire, Thomas Fahy
128 citations
MDMA (ecstasy), a hallucinogenic amphetamine combining effects of amphetamines and LSD, has grown in popularity in the UK. Two cases of chronic paranoid psychosis developed after heavy misuse of the drug.
Schizophr Bull
January 26, 2012
Oliver D. Howes, Paul Shotbolt, Michael Bloomfield et al.
94 citations
Auditory hallucinations in healthy individuals are associated with altered dopamine function in the brain. Using [18F]-DOPA PET imaging, the study found that healthy people who experience auditory hallucinations show differences in dopaminergic activity compared to those who do not, suggesting that dopamine dysfunction may be a trait marker along the psychosis spectrum. The findings indicate that even in the absence of a clinical diagnosis, hallucination proneness is linked to measurable neurochemical variations.
Psychological Medicine
October 1, 2012
Zerrin Atakan, Sagnik Bhattacharyya, Paul Allen et al.
54 citations
A double-blind, placebo-controlled study of 21 healthy men with minimal cannabis experience found that oral administration of 10 mg THC induced transient psychotic symptoms in 11 participants but not in the other 10. Those who became transiently psychotic made more inhibition errors and showed opposite patterns of brain activation in the left parahippocampal gyrus, left and right middle temporal gyri, and right cerebellum compared to the non-psychotic group. The findings suggest that variability in sensitivity to THC's psychotogenic effects is linked to differential activation in ventral and medial temporal cortex and cerebellum.
Cannabis and Cannabinoid Research
December 9, 2022
Lucy Chester, Amir Englund, Edward Chesney et al.
20 citations
Inhaling vaporized cannabis containing 10 mg of THC acutely increased blood levels of the endocannabinoid anandamide by 18% and several related noncannabinoid lipids, but adding 10, 20, or 30 mg of CBD did not alter these effects. Over four sessions spaced about two weeks apart, pre-inhalation levels of anandamide and one related compound progressively declined, possibly due to repeated THC exposure or reduced anxiety. The findings suggest that CBD, at the doses tested, does not modulate THC's acute influence on endocannabinoid concentrations, though higher or chronic CBD doses might have an effect.
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.
British Journal of Psychiatry
December 3, 2024
E. Chesney, Thomas J. Reilly, Fraser Scott et al.
Abruptly stopping heavy, daily cannabis use can trigger psychosis, both in people experiencing their first episode and in those with a pre-existing psychotic disorder. A systematic review of 21 studies identified 44 individuals whose psychosis began after cannabis withdrawal, and a health-record search found another 68 cases. Almost all were daily users who stopped abruptly. Those who resumed cannabis after the acute psychotic episode were far more likely to relapse than those who abstained (odds ratio 13.9). The findings indicate that acute psychotic symptoms can emerge after cannabis cessation, not only during its use.
Psychiatry and Clinical Neurosciences
April 18, 2023
Lucy Chester, L. Valmaggia, M. Kempton et al.
Cannabis use is associated with an increased risk of developing psychotic disorders among people already at clinical high risk for psychosis. In a prospective study of this population, cannabis use was linked to a higher incidence of psychotic disorders and to more persistent psychotic symptoms, as well as poorer functional outcomes. The findings strengthen evidence that cannabis acts as a risk factor for psychosis, though the direction of causality remains debated.
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.