Mapping brain function associated with cue-reactivity and changes pre-to-post a mindfulness-based intervention in cannabis use disorder

Globally, cannabis is used by ~210 million people and 10-to-30% endorse symptoms consistent with a cannabis use disorder (CUD), which constitutes a substantial social burden including health and treatment services. CUD is characterised by a loss of control over cannabis consumption despite significant adverse outcomes including strong cravings when exposed to cannabis cues. Such outcomes have been (partly) ascribed to altered brain function in addiction related pathways.

Preliminary functional magnetic resonance imaging (fMRI) evidence in cannabis users, show different brain activity when exposed to cannabis (vs neutral) cues, in prefrontal, striatal and parietal regions. However, no study has examined cannabis users with a DSM-5 diagnosis of CUD, or tested if psychological interventions targeting cravings (e.g., mindfulness-based interventions [MBI]) reduce neural cue-reactivity in CUD. This thesis comprises three studies aimed to examine brain activity during cannabis cue-reactivity in cannabis users and CUD, and whether such activity can be reduced with a MBI.

Study 1 was a systematic review of the fMRI literature on brain function during cue-reactivity in cannabis users. It synthesised findings on brain function during fMRI cue-reactivity tasks (cannabis vs neutral stimuli) in regular cannabis users, and their association with behavioural variables (e.g., craving). Eighteen studies showed that cannabis users had greater activity in prefrontal, striatal, and parietal regions, some of which (orbitofrontal cortex [OFC]) correlated with and greater subjective craving. The literature was limited by the lack of assessment of CUD using the DSM-5 and the inclusion of a non-using control group.

Study 2 aimed to examine differences in brain activity during a cue-reactivity task (cannabis vs neutral images), i) between 49 adults with moderate-to-severe CUD and 30 controls; and ii) their association with craving, cannabis exposure and mental health. CUD vs controls had greater activity in the lingual gyrus (FWE-corrected p < .05, k > 10), and in the MFG, medial OFC, and cerebellum (uncorrected, p < .001, k > 10). Greater MFG activity correlated with more past month cannabis grams.

Overall, the findings from this thesis provide novel information on the current understanding of the neural correlates of cannabis cue-reactivity in CUD. The results of the first two studies suggest that CUD has a (partly) overlapping neurobiology with that of other SUDs as per prominent neuroscientific theories of addiction. Different brain function during cannabis cue-reactivity may reflect alterations in reward processing, including salience evaluation and attention pathways resulting from regular exposure to cannabis/related cues; or predating CUD. As such, interventions that target these regions may be effective at reducing cue-reactivity/craving in CUD.

Study 3 was a double-blind fMRI experiment. It aimed to investigate for the first time if a brief MBI compared to both an active relaxation and passive no intervention placebo controls, reduces neural cue-reactivity in the regions of interest (ROIs) functionally different in Study 2 (i.e., MFG, OFC, lingual gyrus and cerebellum), in the same sample with CUD (N = 40). It also explored if changes in brain activity pre-to-post MBI were associated with changes in behaviour. It was hypothesised that the greater activity in the ROIs would significantly decrease pre-to-post the MBI only. A significant decrease in the activity of the OFC was observed pre-to-post all three interventions, as well as in subjective craving and arousal rating of cannabis images. No correlations emerged.

Overall, the findings from the research in this thesis demonstrates that cannabis cue-reactivity in CUD is associated with different activity in selected brain pathway implicated in salience and reward processing; and the activity of some of these regions (e.g. OFC) can be reduced during a brief engagement with monitoring of daily cannabis use, cravings and mood. More research in larger samples is required to identify with precision the neurobiology of cannabis cue-reactivity in CUD and to reduce these with novel interventions. Such new knowledge is necessary to alleviate the harmful impacts of the increasing prevalence of CUD to both the individual and to society, particularly when cannabis products and related cues are increasingly accessible and visible to vulnerable members of the community.