ABSTRACT
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.
Subject(s)
Amygdala , Brain Mapping/methods , Cues , Hippocampus , Magnetic Resonance Imaging/methods , Marijuana Abuse , Photic Stimulation/methods , Adult , Amygdala/pathology , Amygdala/physiopathology , Behavior, Addictive/diagnosis , Behavior, Addictive/physiopathology , Diagnostic and Statistical Manual of Mental Disorders , Female , Hippocampus/pathology , Hippocampus/physiopathology , Humans , Male , Marijuana Abuse/diagnosis , Marijuana Abuse/physiopathology , Marijuana Abuse/psychology , Middle Aged , Patient Acceptance of Health Care , Predictive Value of Tests , Psychiatric Status Rating Scales , Psychological Techniques , Recurrence , Reward , Substance Abuse Detection/methodsSubject(s)
Psychotherapy/methods , Psychotropic Drugs/therapeutic use , Substance-Related Disorders/therapy , Alcohol-Related Disorders/drug therapy , Alcohol-Related Disorders/psychology , Alcohol-Related Disorders/therapy , Behavior Therapy , Cocaine-Related Disorders/drug therapy , Cocaine-Related Disorders/psychology , Cocaine-Related Disorders/therapy , Combined Modality Therapy , Female , Humans , Marijuana Abuse/drug therapy , Marijuana Abuse/psychology , Marijuana Abuse/therapy , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/psychology , Opioid-Related Disorders/therapy , Pregnancy , Pregnancy Complications/drug therapy , Pregnancy Complications/psychology , Pregnancy Complications/therapy , Substance-Related Disorders/drug therapy , Substance-Related Disorders/psychology , Tobacco Use Disorder/drug therapy , Tobacco Use Disorder/psychology , Tobacco Use Disorder/therapy , Treatment OutcomeABSTRACT
Acute and chronic alcohol abuse impairs various functions of the immune system and thus, has been implicated as a cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) disease progression. We determined whether naltrexone, an opioid receptor antagonist widely used in the treatment of alcoholism, inhibits alcohol-mediated enhancement of HIV infection of T cells. Alcohol enhanced HIV infection of peripheral blood lymphocytes (PBL) and a human lymphoid cell line (CEMX174). Alcohol increased HIV X4 envelope (Env), not murine leukemia virus Env-pseudotyped infection of CEMX174 cells. Naltrexone antagonized the enhancing effect of alcohol on HIV infection of PBL and CEMX174 cells. The specific mu-opioid receptor antagonist, Cys2, Tyr3, Arg5, Pen7 (CTAP) amide, also blocked the enhancing effect of alcohol on HIV infection. Investigation of the underlying mechanism for the alcohol action showed that alcohol significantly increased endogenous beta-endorphin production and induced mu-opioid receptor mRNA expression in PBL and CEMX174 cells. The role of beta-endorphin in alcohol-mediated enhancement of HIV infection was indicated by the observations that naltrexone and CTAP antagonized ether alcohol- or exogenous beta-endorphin-mediated enhancement of HIV infection. These findings suggest a biological mechanism for the potential therapeutic benefit of naltrexone in treating HIV-infected alcoholics.