Journal of Psychopharmacology
September 2, 2011
Paul Stokes, Alice Egerton, Ben Watson et al.
62 citations
Cannabis use during adolescence is considered a risk factor for psychosis, and animal studies indicate that THC, the psychoactive component, alters striatal dopamine transmission. This study compared striatal dopamine D2/D3 receptor availability in ten volunteers with a history of cannabis use and ten controls using PET scans. No significant differences in receptor availability were found between groups, nor any correlation with lifetime cannabis use frequency. However, limbic striatal receptor availability was ten percent lower in current nicotine smokers. These results suggest that, unlike other drugs of abuse, a history of cannabis use is not associated with changes in striatal dopamine D2/D3 receptor availability.
Journal of Psychopharmacology
August 5, 2020
Will Lawn, J. P. Hill, Chandni Hindocha et al.
23 citations
A single 600 mg oral dose of cannabidiol did not alter brain activity related to anticipating or receiving rewards in healthy adults. Using functional magnetic resonance imaging during a monetary incentive delay task, the expected reward-related brain regions—including the insula, caudate, nucleus accumbens, anterior cingulate, and orbitofrontal cortex—were activated, but no difference was observed between cannabidiol and placebo. Bayesian analyses confirmed that activity in these regions was similar under both conditions, and behavioral measures of motivation for reward also showed no significant difference. The findings suggest that acute cannabidiol does not affect the neural correlates of reward anticipation or feedback in healthy individuals.
Journal of Psychopharmacology
May 20, 2022
Matthew B. Wall, Tom P. Freeman, Chandni Hindocha et al.
21 citations
THC strongly disrupts connectivity between the striatum and cortex, but co-administering CBD mitigates this effect in the limbic striatum network. In one study, inhaled cannabis with 8 mg THC or 8 mg THC plus 10 mg CBD disrupted associative and sensorimotor networks, while THC alone also disrupted the limbic striatum network. In a second study, oral 600 mg CBD increased connectivity in the associative network and caused minor disruptions in limbic and sensorimotor networks. The insula emerges as a key region affected by cannabinoid-induced changes in functional connectivity, with implications for understanding cannabis-related disorders and developing cannabinoid therapeutics.
World Psychiatry
January 14, 2023
Oliver Howes, Luke Baxter
16 citations
Between 2011 and 2021, the FDA approved only 12 new drugs in psychiatry, compared to 50 in neurology and 135 in oncology, highlighting a deadlock in psychiatric drug development. Challenges include high placebo response rates in clinical trials, which necessitate large, expensive, multi-site studies that may worsen the problem, and the withdrawal of major pharmaceutical companies from the field. Most drugs in development target existing mechanisms rather than novel ones. Potential solutions include using fewer, higher-quality trial sites, digital technologies for standardization, and smart trial designs. Attracting new companies requires sustained investment in translational research, government and charitable funding, pre-competitive partnerships, and incentives like tax breaks. Advancing understanding of neurobiology and developing biomarkers are essential for creating mechanistically distinct treatments.
bioRxiv (Cold Spring Harbor Laboratory)
November 21, 2020
Matthew B. Wall, Tom P. Freeman, Chandni Hindocha et al.
4 citations
preprint
Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are two major cannabis constituents with contrasting actions: THC is psychoactive and addiction-promoting, while CBD may have opposite effects. In two placebo-controlled, double-blind studies, inhaled THC (8 mg) strongly disrupted functional connectivity in associative and sensorimotor striatal networks, and this disruption was selectively alleviated in the limbic striatum when co-administered with CBD (10 mg). Oral CBD (600 mg) alone increased connectivity in the associative network but caused minor decreases in limbic and sensorimotor networks. The insula emerged as a key region affected by cannabinoid-induced connectivity changes, with implications for cannabis-related disorders and cannabinoid therapeutics.
bioRxiv (Cold Spring Harbor Laboratory)
June 5, 2025
Ekaterina Shatalina, Natalie Ertl, Kat Petrilli et al.
1 citation
preprint
Inhaling cannabis with THC alone or THC plus CBD reduces resting-state functional connectivity in brain networks that are rich in CB1 and CB2 cannabinoid receptors. Co-administering CBD with THC produced more widespread reductions than THC alone, affecting regions involved in cognition and emotion such as the prefrontal cortex, cingulate cortex, insula, hippocampus, amygdala, and putamen. Higher THC levels in the blood were linked to greater connectivity decreases when CBD was also present. Subjective drug effects correlated with connectivity changes in a region-specific way. The findings suggest that CBD may enhance rather than dampen THC's effects on brain connectivity, contrary to some earlier expectations.