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Increased Mesostriatal Intrinsic Connectivity Associated With Cue Exposure in Adult Cannabis Users: Preliminary Findings.

Natalia M Kleinhans, Garth E Terry, Dahyeon Kang, Sarah F Larsen, Mary E. Larimer

Addiction Biology August 1, 2025 DOI: 10.1111/adb.70067 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Preliminary study, case-control Peer reviewed
Sample size 54
Population Individuals who use cannabis regularly (CU group) and age- and sex-matched controls who had never used cannabis
Topics Cannabis
Keywords Vta Anticorrelation Craving Nucleus accumbens Resting‐State FMRI Ventral tegmental area
Key findings After multimodal cannabis cue exposure, cannabis users showed significantly greater VTA-caudate connectivity compared to controls, and baseline craving was positively correlated with VTA-striatal connectivity in the cannabis user group.

Abstract

Cue-induced craving-the desire to use a drug triggered by exposure to cues associated with prior use-is a central mechanism in the development and maintenance of problematic substance use behaviours. Drug cues have the power to induce craving even in long-term abstinent individuals, which has led clinicians to advise patients to avoid the people, places and objects that are associated with their use. This preliminary study builds on prior behavioural research that demonstrates that exposure to multimodal drug cues can increase craving even after the drug cues are removed from the environment. We used a novel fMRI paradigm that combined multimodal cannabis cue-exposure with resting-state functional connectivity to examine positive and negative functional connectivity (i.e., correlations and anticorrelations) between the ventral tegmental area (VTA) and the striatum, a circuit critically involved in reward processing and addiction. Intrinsic VTA-striatal connectivity was measured in 28 individuals who use cannabis regularly (CU group) and 26 age- and sex-matched controls who had never used cannabis before and after multimodal (visual and olfactory) cannabis cue exposure. Craving was assessed at baseline using the Marijuana Craving Questionnaire-Short Form to test whether VTA-striatal connectivity was correlated with self-reported craving measured prior to the fMRI scan. There were no significant group differences in VTA-striatal connectivity during the baseline resting-state scan. However, following cue exposure, CU participants showed significantly greater VTA-caudate connectivity compared to controls. Further, within the CU group, baseline craving was positively correlated with VTA-striatal connectivity at both time points. Our preliminary findings support prior investigations demonstrating that alterations of mesostriatal connectivity are associated with cannabis use and craving in individuals with problematic cannabis use. In addition, the observation of altered connectivity during the post-cue resting-state scan-after multimodal cannabis cues were removed-suggests a potential neural mechanism by which cue exposure may contribute to relapse vulnerability in individuals with problematic cannabis use.

Comparable studies

Other observational and cohort studies on cannabis, most cited first.

Study Year Design Participants
High-potency cannabis and the risk of psychosis People with first episode of psychosis and healthy controls from the local population 2009 Case-control study n = 454
Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population 2013 Observational study
Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people 2000 Observational
Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Individuals from the general population in Germany aged 14-24 at baseline 2011 Observational cohort n = 1,923
Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases Patients treated for cannabis-induced psychotic symptoms in Denmark between 1994 and... 2005 Observational cohort n = 535

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