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 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.
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.
Frontiers in Psychology
May 14, 2020
Marco Colizzi, Mirella Ruggeri, Sagnik Bhattacharyya
50 citations
Evidence suggests a dose-response relationship between cannabis use and psychosis risk, driven by frequent use and high-potency cannabis with high delta-9-tetrahydrocannabinol (Δ9-THC) concentration. Δ9-THC induces transient psychosis-like symptoms in healthy individuals, while low-potency varieties may be less harmful due to lower Δ9-THC and the presence of cannabidiol (CBD), which may mitigate Δ9-THC's detrimental effects. CBD may have protective and therapeutic properties for psychosis. Similar patterns emerge for cognition: Δ9-THC impairs cognition, while CBD prevents such effects and enhances cognition alone. Molecular evidence shows Δ9-THC acts as a partial agonist and CBD as an inverse agonist/antagonist at cannabinoid receptors, with opposite effects on brain function, explaining intoxicating and therapeutic effects.
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.
medRxiv Preprint Server
April 23, 2026
Giada Lombardi, Grace Blest-Hopley, Martina Maria Tarantini et al.
preprint
Regular cannabis users show altered brain responses during reward anticipation and outcome processing, but their actual task performance does not differ from non-users. Using the Monetary Incentive Delay Task, the study found that cannabis users had reduced neural activity in reward-related brain regions during anticipation of potential gains and losses, yet their reaction times and accuracy were comparable to non-users. These findings suggest that regular cannabis use is associated with changes in reward-related brain function without corresponding behavioral deficits.
bioRxiv (Cold Spring Harbor Laboratory)
November 3, 2021
Brandon Gunasekera, Cathy Davies, Grace Blest‐hopley et al.
preprint
A single dose of delta-9-tetrahydrocannabinol (THC) alters brain activation signals in a widespread network of regions, with some areas showing increased and others decreased activity. The magnitude of these changes is directly related to the local expression of the cannabinoid type-1 (CB1) receptor, but not the type-2 (CB2) receptor. THC increased activation in the anterior cingulate, superior frontal cortices, middle temporal and occipital gyri, striatum, amygdala, thalamus, and cerebellum crus II, while decreasing it in the middle temporal gyrus, superior temporal gyrus, angular gyrus, precuneus, cuneus, inferior parietal lobule, and cerebellum lobule IV/V. A dose-response relationship was observed in certain brain regions.