4. Neural response to reward anticipation after acute exposure to cannabis with and without cannabidiol in adults and adolescents

Introduction/ issues: Cannabis, and its main psychoactive compound Δ⁹-tetrahydrocannabinol (THC), may affect reward processing in the brain. Cannabidiol (CBD) has been shown to attenuate some of the acute effects of THC. Adolescents may be more vulnerable to the adverse effects of cannabis than adults. Few acute neuroimaging studies have examined the effect of cannabis on reward processing, and none have compared adults and adolescents directly.Design and methods: In this pre-registered randomised double-blind crossover trial, we investigated reward anticipation in 23 adults (26-29 years) and 24 adolescents (16-17 years) after acute exposure to inhaled placebo, THC (0.107 mg/kg), and THC+CBD (0.107 mg/kg THC, 0.320 mg/kg CBD), using the Monetary Incentive Delay task during functional magnetic resonance imaging. We performed region of interest analyses in the right and left ventral striatum (VS), right and left anterior cingulate cortex (ACC), and right insula. Key findings: There was a significant main effect of Drug in the right VS, left VS, and insula. Participants had decreased activation during THC compared to placebo in the right VS (t46=2.94, p<.01, d=0.43), left VS (t46=3.12, p<.01, d=0.46), and insula (t46=2.70, p=.01, d=0.39). Participants also had decreased activation during THC+CBD compared to placebo in the right VS (t46=2.53, p=.01, d=0.37) and insula (t46=3.37, p<.01, d=0.49). There were no differences between THC and THC+CBD, and no Drug*Age-group interactions in any region. Discussions and conclusions: Acute cannabis may result in blunted neural responses to reward anticipation in key reward regions. There was no evidence suggesting adolescent vulnerability, or that CBD attenuated the acute effects of THC on reward processing.