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.
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.
Addiction Biology
March 3, 2016
Laura Blanco‐Hinojo, Jesus Pujol, Ben J. Harrison et al.
52 citations
Chronic cannabis use is associated with reduced motivation, and this study examined how it affects functional connectivity between the basal ganglia and brain regions involved in internal (frontal cortex) and external (sensory cortices) motivation signals. Resting-state fMRI in 28 chronic cannabis users and 29 controls showed that cannabis exposure attenuated the positive correlation between the striatum and limbic frontal-basal ganglia circuits, and attenuated the negative correlation between the striatum and the fusiform gyrus, which is important for recognizing significant visual features. These connectivity alterations were linked to lower arousal in response to affective pictures. Changes tended to normalize after one month of abstinence, indicating that cannabis impairs fine-tuning of the motivation system, but this effect is reversible.