RationaleAnecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence.ObjectivesThe objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning.MethodsIn study 1, 17 participants each received three acute vaporized treatments, namely Cann-CBD (8 mg THC), Cann + CBD (8 mg THC + 10 mg CBD) and matched placebo, followed by a 50 % dose top-up 1.5 h later, and completed the Effort Expenditure for Rewards Task (EEfRT). In study 2, 20 cannabis-dependent participants were compared with 20 non-dependent, drug-using control participants on the EEfRT and the Probabilistic Reward Task (PRT) in a non-intoxicated state.ResultsCann-CBD reduced the likelihood of high-effort choices relative to placebo (p = 0.042) and increased sensitivity to expected value compared to both placebo (p = 0.014) and Cann + CBD (p = 0.006). The cannabis-dependent and control groups did not differ on the EEfRT. However, the cannabis-dependent group exhibited a weaker response bias than the control group on the PRT (p = 0.007).ConclusionsCannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. In contrast, cannabis dependence was associated with preserved motivation alongside impaired reward learning, although confounding factors, including depression, cannot be disregarded. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-016-4383-x) contains supplementary material, which is available to authorized users.

Background: Two major constituents of cannabis are D 9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the main psychoactive component; CBD may buffer the user against the harmful effects of THC. Aims: We examined the effects of two strains of cannabis and placebo on the human brain's resting-state networks using fMRI. Methods: 17 healthy volunteers (experienced with cannabis, but not regular users) underwent three drug treatments and scanning sessions. Treatments were cannabis containing THC (Cann-CBD; 8mg THC), cannabis containing THC with CBD (Cann+CBD; 8mg THC + 10mg CBD), and matched placebo cannabis. Seed-based resting-state functionalconnectivity analyses were performed on three brain networks: the default mode (DMN; defined by positive connectivity with the posterior cingulate cortex: PCC+), executive control (ECN; defined by negative connectivity with the posterior cingulate cortex: PCC-) and salience (SAL; defined by positive connectivity with the anterior insula: AI+) network. Results: Reductions in functional connectivity (relative to placebo) were seen in the DMN (PCC+) and SAL (AI+) networks for both strains of cannabis, with spatially dissociable effects. Across the entire salience network (AI+) Cann-CBD reduced connectivity relative to Cann+CBD. The PCC in the DMN was specifically disrupted by Cann-CBD and this effect correlated with subjective drug effects including feeling 'stoned', and 'high'. Conclusions: THC disrupts the default mode network and the PCC is a key brain region involved in the subjective experience of THC intoxication. CBD restores disruption of the salience network by THC, which may explain its potential to treat disorders of salience such as psychosis and addiction. Declaration of interest and funding This study was funded by Drug Science, Channel 4 Television, and the Beckley Foundation. Author AF is involved with a cannabis-related business: Beckley Canopy Therapeutic. All other authors declare no relevant conflicts of interest.

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BackgroundDespite the current shift towards permissive cannabis policies, few studies have investigated the pleasurable effects users seek. Here, we investigate the effects of cannabis on listening to music, a rewarding activity that frequently occurs in the context of recreational cannabis use. We additionally tested how these effects are influenced by cannabidiol, which may offset cannabis-related harms.MethodsAcross 3 sessions, 16 cannabis users inhaled cannabis with cannabidiol, cannabis without cannabidiol, and placebo. We compared their response to music relative to control excerpts of scrambled sound during functional Magnetic Resonance Imaging within regions identified in a meta-analysis of music-evoked reward and emotion. All results were False Discovery Rate corrected (P<.05).ResultsCompared with placebo, cannabis without cannabidiol dampened response to music in bilateral auditory cortex (right: P=.005, left: P=.008), right hippocampus/parahippocampal gyrus (P=.025), right amygdala (P=.025), and right ventral striatum (P=.033). Across all sessions, the effects of music in this ventral striatal region correlated with pleasure ratings (P=.002) and increased functional connectivity with auditory cortex (right: P< .001, left: P< .001), supporting its involvement in music reward. Functional connectivity between right ventral striatum and auditory cortex was increased by cannabidiol (right: P=.003, left: P=.030), and cannabis with cannabidiol did not differ from placebo on any functional Magnetic Resonance Imaging measures. Both types of cannabis increased ratings of wanting to listen to music (P<.002) and enhanced sound perception (P<.001).ConclusionsCannabis dampens the effects of music in brain regions sensitive to reward and emotion. These effects were offset by a key cannabis constituent, cannabidol.