Objective: Determining the brain substrates underlying the motivation to abuse addictive drugs is critical for understanding and treating addictive disorders. Laboratory neuroimaging studies have demonstrated differential activation of limbic and motivational circuitry (eg, amygdala, hippocampus, ventral striatum, insula, and orbitofrontal cortex) triggered by cocaine, heroin, nicotine, and alcohol cues. The literature on neural responses to marijuana cues is sparse. Thus, the goals of this study were to characterize the brain's response to marijuana cues, a major motivator underlying drug use and relapse, and determine whether these responses are linked to self-reported craving in a clinically relevant population of treatment-seeking marijuana-dependent subjects.
Methods: Marijuana craving was assessed in 12 marijuana-dependent subjects using the Marijuana Craving Questionnaire–Short Form. Subsequently, blood oxygen level dependent functional magnetic resonance imaging data were acquired during exposure to alternating 20-second blocks of marijuana-related versus matched nondrug visual cues.
Results: Brain activation during marijuana cue exposure was significantly greater in the bilateral amygdala and the hippocampus. Significant positive correlations between craving scores and brain activation were found in the ventral striatum and the medial and lateral orbitofrontal cortex (P < 0.0001).
Conclusions: This study presents direct evidence for a link between reward-relevant brain responses to marijuana cues and craving and extends the current literature on marijuana cue reactivity. Furthermore, the correlative relationship between craving and brain activity in reward-related regions was observed in a clinically relevant sample (treatment-seeking marijuana-dependent subjects). Results are consistent with prior findings in cocaine, heroin, nicotine, and alcohol cue studies, indicating that the brain substrates of cue-triggered drug motivation are shared across abused substances.
From the Department of Psychiatry (MG, RPS-R, KJ, ZW, YL, JJS, KK, CPO, ARC, TRF), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; Philadelphia Veterans Affairs Medical Center and VISN 4 Mental Illness Research, Education, and Clinical Center (RNE, JJS, CPO, ARC), Philadelphia; and Department of Neurology (ZW), Center for Functional Neuroimaging, University of Pennsylvania, Philadelphia.
Send correspondence and reprint requests to Marina Goldman, MD, Department of Psychiatry, University of Pennsylvania, 3900 Chestnut St, Philadelphia, PA 19104. E-mail: firstname.lastname@example.org.
A portion of the data contained in this article was presented at the 71st Annual Scientific Meeting of the College on Problems of Drug Dependence, June 20–25, 2009, Reno-Sparks, NV.
Supported by grants from the National Institute of Drug Abuse (Dr. O'Brien, principle investigator: 5-P60-DA-05186 and T32-DA-07241), the Philadelphia Veterans Affairs Medical Center and VISN 4 Mental Illness Research, Education & Clinical Center, the Pennsylvania Department of Health (Dr. Childress, principle investigator: CURE Center of Excellence: Brain Mechanisms of Relapse and Recovery), and imaging and infrastructure support for this work was kindly provided by the National Institute of Health/National Institute of NeurologicaI Disorders and Stroke (P30 NS045839). The funding agencies had no further role in the conduct of the research, preparation of the manuscript, study design, collection, analysis and interpretation of data, writing of the report, and the decision to submit the paper for publication.
The authors declare no conflict of interest.
Received February 7, 2012
Accepted September 9, 2012