Patterns of brain function associated with cannabis cue-reactivity in regular cannabis users: a systematic review of fMRI studies

Abstract

Rationale Regular cannabis use (i.e. ≥ monthly) is highly prevalent, with past year use being reported by ~ 200 million people globally.High reactivity to cannabis cues is a key feature of regular cannabis use and has been ascribed to greater cannabis exposure and craving, but the underlying neurobiology is yet to be systematically integrated. Objectives We aim to systematically summarise the findings from fMRI studies which examined brain function in cannabis users while exposed to cannabis vs neutral stimuli during a cue-reactivity fMRI task. Methods A systematic search of PsycINFO, PubMed and Scopus databases was pre-registered in PROSPERO (CRD42020171750) and conducted following PRISMA guidelines. Eighteen studies met inclusion/exclusion criteria. Samples comprised 918 participants (340 female) aged 16–38 years. Of these, 603 were regular cannabis users, and 315 were controls. Results The literature consistently reported greater brain activity in cannabis users while exposed to cannabis vs neutral stimuli in three key brain areas: the striatum, the prefrontal (anterior cingulate, middle frontal) and the parietal cortex (posterior cingulate/precuneus) and additional brain regions (hippocampus, amygdala, thalamus, occipital cortex). Preliminary correlations emerged between cannabis craving and the function of partially overlapping regions (amygdala, striatum, orbitofrontal cortex ). Conclusions Exposure to cannabis-cues may elicit greater brain function and thus trigger cravings in regular cannabis users and thus trigger cannabis craving. Standardised and longitudinal assessments of cannabis use and related problems are required to profile with greater precision the neurobiology of cannabis cue-reactivity, and its role in predicting cravings and relapse.

Multimodal MRI data fusion reveals distinct structural, functional and neurochemical correlates of heavy cannabis use

“…57,64 Emerging evidence from fMRI studies (including cuereactivity fMRI tasks) suggests aberrant thalamus activity in cannabis users. 65 Fourth, we also identified GMV alterations of the cingulate gyrus and anterior cingulate cortex (ACC) in HCU. ACC is crucial for integrating cognitive and emotional processes in support of goaldirected behavior.…”

A scoping review of electroencephalographic (EEG) markers for tracking neurophysiological changes and predicting outcomes in substance use disorder treatment

“…As with other psychiatric disorders, SUDs are complex, arising over time from multiple cognitive, brain, genetic, and environmental factors whose interactions are not yet well understood (Gelernter and Polimanti, 2021 ; Heilig et al, 2021 ; Rawls et al, 2021 ; Ray and Grodin, 2021 ). Current models of SUD, mainly based on functional magnetic resonance imaging (fMRI; Devoto et al, 2020 ; Lin et al, 2020 ; Hill-Bowen et al, 2021 ; Klugah-Brown et al, 2021 ; Le et al, 2021 ; Sehl et al, 2021 ; Tolomeo and Yu, 2022 ) suggest chronic alterations in brain systems associated with reward processing (Luijten et al, 2017 ), salience attribution (Zilverstand and Goldstein, 2020 ), inhibitory control (Luijten et al, 2014 ; Le et al, 2021 ) and executive function (Quaglieri et al, 2020 ), which underpin disease-specific behaviors such as craving, compulsive drug-taking, and relapse (Zilverstand and Goldstein, 2020 ; Ceceli et al, 2022 ). However, to date there are no established brain-based biomarkers for precision SUD treatment monitoring and outcome evaluation, partly because these brain systems also show dysregulation in a range of other psychiatric disorders, making SUD-specific biomarker development and validation difficult (García-Gutiérrez et al, 2020 ; Niculescu and Le-Niculescu, 2022 ).…”

Cortico-striatal engagement during cue-reactivity, reappraisal, and savoring of drug and non-drug stimuli predicts craving in heroin addiction

“…The underlying neural mechanisms of drug cue-reactivity 15 are typically mapped while participants passively view drug and non-drug stimuli during functional MRI (fMRI). These mechanisms involve the recruitment of the NAcc and vmPFC/OFC in response to drug vs. neutral cues in individuals with alcohol, 16,17 nicotine, 18,19 cannabis, 20 or cocaine [21][22][23] use disorders. Increased drug cue related activity in these cortico-striatal regions is associated with higher self-reported craving in alcohol, 24 nicotine, 18 and cannabis 20 addiction.…”

“…These mechanisms involve the recruitment of the NAcc and vmPFC/OFC in response to drug vs. neutral cues in individuals with alcohol, 16,17 nicotine, 18,19 cannabis, 20 or cocaine [21][22][23] use disorders. Increased drug cue related activity in these cortico-striatal regions is associated with higher self-reported craving in alcohol, 24 nicotine, 18 and cannabis 20 addiction. Similarly in iHUD and compared to healthy control subjects (HC), passively viewing drug vs. neutral cues elicited enhanced activity in the NAcc and vmPFC/OFC among other nodes of the dopaminergic reward network, [25][26][27][28][29] as associated with heroin craving 25,26 and predictive of subsequent relapse.…”