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Rajita Sinha - One of the best experts on this subject based on the ideXlab platform.
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effects of progesterone stimulated allopregnanolone on Craving and stress response in cocaine dependent men and women
Psychoneuroendocrinology, 2016Co-Authors: Verica Milivojevic, Mehmet Sofuoglu, Helen C. Fox, Jonathan Covault, Rajita SinhaAbstract:Abstract Objectives Fluctuations in progesterone levels during the menstrual cycle have been shown to affect physiological and subjective effects of cocaine. Furthermore, our laboratory has demonstrated that following Drug-cue exposure, cocaine dependent women with high levels of circulating progesterone display lower diastolic and systolic blood pressure responses and report lower levels of anxiety and Drug Craving compared to cocaine dependent women with low levels of progesterone. In the current study we examined the role of the progesterone derived neuroactive steroid allopregnanolone (ALLO) on stress arousal, inhibitory control and Drug Craving in cocaine dependent subjects. Methods Plasma levels of ALLO were measured using GC/MS in 46 treatment-seeking cocaine dependent men and women on day 5 of a 7-day treatment regimen of micronized progesterone (15M/8F) (400 mg/day) or placebo (14M/9F) administered in a double blind, randomized manner. As a control, levels of the testosterone derived neurosteroid androstanediol (ADIOL) were also measured. All subjects participated in laboratory sessions on days 5–7 of progesterone/placebo administration in which they were exposed to a series of 5-min personalized guided imagery of either a stressful situation, cocaine use or of a neutral setting and dependent variables including subjective Craving, mood, Stroop task as a measure of inhibitory control performance and plasma cortisol were assessed. Participants were grouped by high or low ALLO level and levels of dependent variables compared between ALLO groups. Results Progesterone relative to placebo significantly increased ALLO levels with no sex differences. There were no effects of micronized progesterone on the testosterone derived ADIOL. Individuals in the high versus the low ALLO group showed decreased levels of cortisol at baseline, and a higher cortisol response to stress; higher positive mood scores at baseline and improved Stroop performance in the Drug-cue and stress conditions, and reduced cocaine Craving across all imagery conditions. Conclusions As expected, cocaine dependent individuals administered progesterone showed significantly higher ALLO plasma levels. High levels of ALLO appeared to normalize basal and stress response levels of cortisol, decrease cocaine Craving and also contribute to improvements in positive emotion and Stroop performance in response to stress and Drug-cue exposures. These findings suggest that the neuroactive steroid ALLO plays a significant role in mediating the positive effects of progesterone on stress arousal, cognitive performance and Drug Craving in cocaine dependence.
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Sex differences in guanfacine effects on Drug Craving and stress arousal in cocaine-dependent individuals.
Neuropsychopharmacology, 2014Co-Authors: Helen C. Fox, Peter T. Morgan, Rajita SinhaAbstract:Currently, no FDA-approved medication exists for the treatment of cocaine use disorder. Furthermore, as women become increasingly more at risk for the consequences of cocaine addiction, the need to establish better-tailored treatment medications is paramount. We examine the effects of the alpha2 adrenergic agonist, guanfacine HCl, on responses to stress and Drug cue in a group of cocaine-dependent men and women who also abuse alcohol and nicotine. Forty early abstinent treatment-seeking cocaine-dependent males and females were randomly assigned to receive either daily placebo (12 M/7 F) or guanfacine (2 or 3 mg) (15 M/6 F) for 3 weeks. In week 4, they participated in a laboratory experiment and were exposed to three 10-min guided imagery conditions (stress/stress, cue/cue, and stress/cue), one per day, consecutively in a random, counterbalanced order. Craving, negative emotion, anxiety, and cardiovascular function were assessed at baseline, immediately following imagery exposure, and at various recovery time points. Guanfacine significantly attenuated cocaine Craving, alcohol Craving, anxiety, and negative emotion following exposure to all three imagery conditions in females, but not males. Guanfacine did, however, reduce sympathetic tone as well as stress and cue-induced nicotine Craving and systolic blood pressure (SBP) in both males and females. These findings highlight sex-specific effects of guanfacine on Drug Craving, anxiety, and negative mood with significant effects in women and not men. The findings suggest further evaluation of guanfacine in the treatment of cocaine use disorder with a specific focus on sex differences in treatment response.
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a variant on the kappa opioid receptor gene oprk1 is associated with stress response and related Drug Craving limbic brain activation and cocaine relapse risk
Translational Psychiatry, 2013Co-Authors: D Seo, D Goldman, Colin A Hodgkinson, Rajita SinhaAbstract:Stress increases Drug Craving and relapse risk. The kappa opioid receptor gene (OPRK1) mediates stress responses. Here, we examined whether the OPRK1 rs6989250 C>G affects stress-induced cocaine Craving and cortisol responses, subsequent cocaine relapse risk and the neural response to stress using functional magnetic resonance imaging (fMRI) in cocaine dependence. Sixty-seven treatment-engaged, abstinent cocaine-dependent African-Americans were genotyped (CG: N=10; CC: N=57) and participated in a 3-day experiment in which they were exposed to personalized script-driven imagery of stress, Drug cues and neutral scenarios, one condition per day, randomly assigned and counterbalanced across subjects. Repeated measures of Craving and cortisol were obtained. The subjects were followed prospectively for 90 days to assess relapse risk. A follow-up preliminary fMRI experiment assessed neural responses to stress, Drug cue and neutral conditions in matched CG (N=5) and CC (N=8) subgroups. We found greater stress-induced Craving (P=0.019), higher cortisol during stress and cue relative to the neutral condition (P's<0.003), and increased cocaine relapse risk (P=0.0075) in the CG compared with the CC group. The CG relative to the CC group also showed greater activation of limbic and midbrain regions during stress and cues relative to the neutral condition with additional stress-induced activation in the right amygdala/hippocampus (P<0.05, whole-brain corrected). These results suggest that OPRK1 is associated with stress-induced Craving and cortisol, hyperactive hypothalamus/thalamus-midbrain-cerebellum responses, and also associated with greater subsequent cocaine relapse risk. Future studies to replicate these findings in a larger sample size are warranted.
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The clinical neurobiology of Drug Craving
Current Opinion in Neurobiology, 2013Co-Authors: Rajita SinhaAbstract:Drug Craving has re-emerged as a relevant and important construct in the pathophysiology of addiction with its inclusion in DSM-V as a key clinical symptom of addictive disorders. This renewed focus has been due in part to the recent neurobiological evidence on Craving-related neural activation and clinical evidence supporting its association with Drug use, relapse, and recovery processes. This review covers the neurobiology of Drug Craving and relapse risk with a primary focus on cocaine addiction and a secondary emphasis on alcohol addiction. A conceptualization of Drug Craving on the continuum of healthy desire and compulsive seeking, and the associated neurobiological adaptations associated with the development of an increased Craving/wanting state is presented. Altered dopamine neurochemistry as well as disrupted prefrontal control and hyperactive striatal-limbic responses in experiencing Drug cues, stress, Drug intake and in basal relaxed states are identified as neurobiological signatures that predict Drug Craving and Drug use. Thus, the clinical and neurobiological features of the Craving/wanting state are presented with specific attention to alterations in these cortico-limbic-striatal and prefrontal self-control circuits that predict Drug Craving and relapse risk. The methodological challenges that need to be addressed to further develop the evolving conceptual approach to the neuroscience of Drug Craving is presented, with a focus on identification and validation of biomarkers associated with the Craving state and treatment approaches that may be of benefit in reversing the neurobiological adaptations associated with Drug Craving to improve treatment outcomes in addiction.
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The effects of exogenous progesterone on Drug Craving and stress arousal in cocaine dependence: impact of gender and cue type.
Psychoneuroendocrinology, 2013Co-Authors: Helen C. Fox, Mehmet Sofuoglu, Peter T. Morgan, Keri Tuit, Rajita SinhaAbstract:Summary Aims Exogenous progesterone has been shown to attenuate the rewarding effects of cocaine. However, its effects on provoked Drug Craving, stress arousal and cognitive performance has not been systematically investigated in cocaine dependent men and women. Thus, we conducted a double-blind placebo-controlled study assessing the efficacy of progesterone in reducing provoked Drug Craving, stress system arousal and improving cognitive performance in cocaine dependent men and women. Methods Forty-two early abstinent treatment-seeking cocaine dependent individuals were randomly assigned to either daily doses of placebo (12M/9F) or micronized progesterone (12M/9F) (400 mg/day), for 7 days. Under experimental conditions, all subjects were exposed to three 5-min personalized guided imagery conditions (stress, cocaine cue, relaxing), one per day, consecutively in a random, counterbalanced order. Subjective Craving, mood, hypothalamic-pituitary-adrenal (HPA) and cardiovascular output, and a cognitive measure of inhibitory control (Stroop Color Word Task) were assessed pre- and post imagery. Results Progesterone relative to placebo significantly decreased cue-induced Craving and cortisol responses and increased cue-induced ACTH. In addition, women but not men receiving progesterone reported lower ratings of negative emotion and higher ratings of relaxed mood following stress exposure. Improved Stroop performance was observed in all participants receiving progesterone, across all conditions. Conclusions Progesterone was selectively effective in reducing cocaine cue-induced but not stress-related cocaine Craving as well as specific measures of the provoked arousal state. Findings suggest that progesterone's effects on Drug Craving and arousal are moderated by both the type of environmental cue exposure and gender.
Edythe D. London - One of the best experts on this subject based on the ideXlab platform.
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Gray-Matter Volume, Midbrain Dopamine D2/D3 Receptors and Drug Craving in Methamphetamine Users
2016Co-Authors: Angelica A. Morales, Milky Kohno, Chelsea L. Robertson, Andy C, Mark A. M, Edythe D. LondonAbstract:Dysfunction of the mesocorticolimbic system plays a critical role in clinical features of addiction. Despite evidence suggesting that midbrain dopamine receptors influence amphetamine-induced dopamine release and that dopamine is involved in methamphetamine-induced neurotoxicity, associations between dopamine receptors and gray-matter volume have been unexplored in methamphetamine users. Here we used magnetic resonance imaging and [18F]fallypride positron emission tomography, respectively, to measure gray-matter volume (in 58 methamphetamine users) and dopamine D2/D3 receptor availability (binding potential relative to nondisplaceable uptake of the radiotracer, BPND) (in 31 methamphetamine users and 37 control participants). Relationships between these measures and self-reported Drug Craving were examined. Although no difference in midbrain D2/D3 BPND was detected between methamphetamine and control groups, midbrain D2/D3 BPND was positively correlated with gray-matter volume in the striatum, prefrontal cortex, insula, hippocampus and temporal cortex in methamphetamine users, but not in control participants (group-by-midbrain D2/D3 BPND interaction, p<0.05 corrected for multiple comparisons). Craving for methamphetamine was negatively associated with gray-matter volum
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midbrain dopamine d2 d3 receptor availability and Drug Craving are associated with mesocorticolimbic gray matter volume in methamphetamine users
Molecular Psychiatry, 2015Co-Authors: Angelica M. Morales, Milky Kohno, Chelsea L. Robertson, Andy C. Dean, M. Mandelkern, Edythe D. LondonAbstract:Midbrain dopamine D2/D3 receptor availability and Drug Craving are associated with mesocorticolimbic gray matter volume in methamphetamine users
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gray matter volume midbrain dopamine d2 d3 receptors and Drug Craving in methamphetamine users
Molecular Psychiatry, 2015Co-Authors: Angelica M. Morales, Milky Kohno, Chelsea L. Robertson, Andy C. Dean, M. Mandelkern, Edythe D. LondonAbstract:Dysfunction of the mesocorticolimbic system has a critical role in clinical features of addiction. Despite evidence suggesting that midbrain dopamine receptors influence amphetamine-induced dopamine release and that dopamine is involved in methamphetamine-induced neurotoxicity, associations between dopamine receptors and gray-matter volume have been unexplored in methamphetamine users. Here we used magnetic resonance imaging and [(18)F]fallypride positron emission tomography, respectively, to measure gray-matter volume (in 58 methamphetamine users) and dopamine D2/D3 receptor availability (binding potential relative to nondisplaceable uptake of the radiotracer, BPnd) (in 31 methamphetamine users and 37 control participants). Relationships between these measures and self-reported Drug Craving were examined. Although no difference in midbrain D2/D3 BPnd was detected between methamphetamine and control groups, midbrain D2/D3 BPnd was positively correlated with gray-matter volume in the striatum, prefrontal cortex, insula, hippocampus and temporal cortex in methamphetamine users, but not in control participants (group-by-midbrain D2/D3 BPnd interaction, P<0.05 corrected for multiple comparisons). Craving for methamphetamine was negatively associated with gray-matter volume in the insula, prefrontal cortex, amygdala, temporal cortex, occipital cortex, cerebellum and thalamus (P<0.05 corrected for multiple comparisons). A relationship between midbrain D2/D3 BPnd and methamphetamine Craving was not detected. Lower midbrain D2/D3 BPnd may increase vulnerability to deficits in gray-matter volume in mesocorticolimbic circuitry in methamphetamine users, possibly reflecting greater dopamine-induced toxicity. Identifying factors that influence prefrontal and limbic volume, such as midbrain BPnd, may be important for understanding the basis of Drug Craving, a key factor in the maintenance of substance-use disorders.
Angelica M. Morales - One of the best experts on this subject based on the ideXlab platform.
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midbrain dopamine d2 d3 receptor availability and Drug Craving are associated with mesocorticolimbic gray matter volume in methamphetamine users
Molecular Psychiatry, 2015Co-Authors: Angelica M. Morales, Milky Kohno, Chelsea L. Robertson, Andy C. Dean, M. Mandelkern, Edythe D. LondonAbstract:Midbrain dopamine D2/D3 receptor availability and Drug Craving are associated with mesocorticolimbic gray matter volume in methamphetamine users
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gray matter volume midbrain dopamine d2 d3 receptors and Drug Craving in methamphetamine users
Molecular Psychiatry, 2015Co-Authors: Angelica M. Morales, Milky Kohno, Chelsea L. Robertson, Andy C. Dean, M. Mandelkern, Edythe D. LondonAbstract:Dysfunction of the mesocorticolimbic system has a critical role in clinical features of addiction. Despite evidence suggesting that midbrain dopamine receptors influence amphetamine-induced dopamine release and that dopamine is involved in methamphetamine-induced neurotoxicity, associations between dopamine receptors and gray-matter volume have been unexplored in methamphetamine users. Here we used magnetic resonance imaging and [(18)F]fallypride positron emission tomography, respectively, to measure gray-matter volume (in 58 methamphetamine users) and dopamine D2/D3 receptor availability (binding potential relative to nondisplaceable uptake of the radiotracer, BPnd) (in 31 methamphetamine users and 37 control participants). Relationships between these measures and self-reported Drug Craving were examined. Although no difference in midbrain D2/D3 BPnd was detected between methamphetamine and control groups, midbrain D2/D3 BPnd was positively correlated with gray-matter volume in the striatum, prefrontal cortex, insula, hippocampus and temporal cortex in methamphetamine users, but not in control participants (group-by-midbrain D2/D3 BPnd interaction, P<0.05 corrected for multiple comparisons). Craving for methamphetamine was negatively associated with gray-matter volume in the insula, prefrontal cortex, amygdala, temporal cortex, occipital cortex, cerebellum and thalamus (P<0.05 corrected for multiple comparisons). A relationship between midbrain D2/D3 BPnd and methamphetamine Craving was not detected. Lower midbrain D2/D3 BPnd may increase vulnerability to deficits in gray-matter volume in mesocorticolimbic circuitry in methamphetamine users, possibly reflecting greater dopamine-induced toxicity. Identifying factors that influence prefrontal and limbic volume, such as midbrain BPnd, may be important for understanding the basis of Drug Craving, a key factor in the maintenance of substance-use disorders.
Jie Shi - One of the best experts on this subject based on the ideXlab platform.
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A Memory Retrieval-Extinction Procedure to Prevent Drug Craving and Relapse
Science, 2012Co-Authors: Yan-xue Xue, Chen Chen, Zengbo Ding, Yi-xiao Luo, Hai-shui Shi, Li-fen Xue, Wei-li Zhu, Yanping Bao, Jie ShiAbstract:Drug use and relapse involve learned associations between Drug-associated environmental cues and Drug effects. Extinction procedures in the clinic can suppress conditioned responses to Drug cues, but the extinguished responses typically reemerge after exposure to the Drug itself (reinstatement), the Drug-associated environment (renewal), or the passage of time (spontaneous recovery). We describe a memory retrieval-extinction procedure that decreases conditioned Drug effects and Drug seeking in rat models of relapse, and Drug Craving in abstinent heroin addicts. In rats, daily retrieval of Drug-associated memories 10 minutes or 1 hour but not 6 hours before extinction sessions attenuated Drug-induced reinstatement, spontaneous recovery, and renewal of conditioned Drug effects and Drug seeking. In heroin addicts, retrieval of Drug-associated memories 10 minutes before extinction sessions attenuated cue-induced heroin Craving 1, 30, and 180 days later. The memory retrieval-extinction procedure is a promising nonpharmacological method for decreasing Drug Craving and relapse during abstinence.
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effect of rapamycin on cue induced Drug Craving in abstinent heroin addicts
European Journal of Pharmacology, 2009Co-Authors: Jie Shi, Liyan Zhao, Yan-xue Xue, Wang Jun, Xiang Yang Zhang, Thomas R KostenAbstract:The mammalian target of rapamycin is an evolutionarily conserved serine-threonine kinase (mTOR), which controls protein synthesis and catabolism in response to environmental cues. This randomized double-blind clinical trial enrolled 60 abstinent heroin addicts and randomly assigned them to three groups: placebo, 2.5 mg and 5 mg rapamycin. The participants were given the cue-reactivity paradigm with 5 min exposures to neutral and Drug-related imagery while Craving, anxiety, blood pressure and heart rate pre- and post-exposure were assessed. We found that Drug-related cues increased both Craving and anxiety of abstinent heroin addicts, and had no effect on blood pressure and heart rate. A single high-dose of rapamycin significantly reduced the Craving, but not anxiety induced by Drug-related cues. Our findings suggested that rapamycin merits outpatient clinical trials as a potential pharmacotherapy for relapse prevention from Drug-related cue induced Craving.
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tetrodotoxin reduces cue induced Drug Craving and anxiety in abstinent heroin addicts
Pharmacology Biochemistry and Behavior, 2009Co-Authors: Jie Shi, Liyan Zhao, David H Epstein, Xi Wang, Tingting Liu, Xiao-li ZhangAbstract:Background Tetrodotoxin (TTX) is a neurotoxin found in puffer fish and other marine animals. New clinical studies suggest that low-dose TTX can safely relieve severe, treatment-resistant cancer pain. The therapeutic potential of TTX in addiction is supported by studies in laboratory animals. The purpose of this double-blind, placebo-controlled study was to assess the effect of a single intramuscular dose of TTX on cue-induced Craving and anxiety in abstinent heroin addicts.
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Abnormal pain response in pain-sensitive opiate addicts after prolonged abstinence predicts increased Drug Craving
Psychopharmacology, 2009Co-Authors: Zhen-yu Ren, Jie Shi, David H Epstein, Jun WangAbstract:Rationale Craving is a primary feature of opiate addiction and is clinically significant because of its potential to trigger opiate use and relapse. Opiate use can also produce abnormal pain perception. We predicted that for opiate addicts (OAs), there may be an association between these two major features of addiction (Drug Craving and abnormal pain responses).
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PET imaging of dopamine transporter and Drug Craving during methadone maintenance treatment and after prolonged abstinence in heroin users.
European Journal of Pharmacology, 2007Co-Authors: Jie Shi, Marc L. Copersino, Yu-xia Fang, Yingmao Chen, Yinliang Shuai, Yanping Deng, Jiahe Tian, Liyan Zhao, Jun JinAbstract:It has been documented that methadone maintenance treatment is effective in reducing Drug Craving and relevant risk behaviors in heroin users. However, it is not understood whether methadone maintenance treatment impairs the dopamine transporter in the striatum. To establish whether chronic opiate use might impair brain dopamine neurons in humans, we assessed dopamine transporter (DAT) uptake function in the striatum (caudate and putamen), and analyzed the correlation between DAT in the striatum and heroin Craving and subjective anxiety in former heroin users with prolonged abstinence and in patients receiving methadone maintenance treatment. Binding of [(11)C]-2beta-carbomethoxy-3beta-aryltropane ([(11)C] CFT) as a brain dopamine transporter ligand was measured with positron emission tomography (PET) in eleven former heroin users with prolonged abstinence, ten patients receiving methadone maintenance treatment and ten healthy control subjects. Heroin Craving and subjective anxiety in prolonged abstinence and methadone maintenance treatment groups were assessed and the correlations between DAT of striatum and heroin Craving or subjective anxiety were determined. In comparison with healthy control subjects, methadone maintenance treatment subjects had lower DAT uptake function in the bilateral caudate and putamen and prolonged abstinence subjects showed significantly lower DAT uptake function in the bilateral caudate. Moreover, in comparison to the prolonged abstinence subjects, the methadone maintenance treatment subjects showed significant decreases of DAT uptake in the bilateral putamen. DAT uptake function in bilateral striatum was not associated with heroin Craving in prolonged abstinence or in methadone maintenance treatment subjects; however, DAT uptake function in the bilateral caudate was significantly correlated with subjective anxiety in methadone maintenance treatment subjects. Our findings suggest that chronic opioid use induces long-lasting striatum dopamine neuron impairment, and prolonged withdrawal from opioids can benefit the recovery of impaired dopamine neurons in the brain.
Milky Kohno - One of the best experts on this subject based on the ideXlab platform.
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Gray-Matter Volume, Midbrain Dopamine D2/D3 Receptors and Drug Craving in Methamphetamine Users
2016Co-Authors: Angelica A. Morales, Milky Kohno, Chelsea L. Robertson, Andy C, Mark A. M, Edythe D. LondonAbstract:Dysfunction of the mesocorticolimbic system plays a critical role in clinical features of addiction. Despite evidence suggesting that midbrain dopamine receptors influence amphetamine-induced dopamine release and that dopamine is involved in methamphetamine-induced neurotoxicity, associations between dopamine receptors and gray-matter volume have been unexplored in methamphetamine users. Here we used magnetic resonance imaging and [18F]fallypride positron emission tomography, respectively, to measure gray-matter volume (in 58 methamphetamine users) and dopamine D2/D3 receptor availability (binding potential relative to nondisplaceable uptake of the radiotracer, BPND) (in 31 methamphetamine users and 37 control participants). Relationships between these measures and self-reported Drug Craving were examined. Although no difference in midbrain D2/D3 BPND was detected between methamphetamine and control groups, midbrain D2/D3 BPND was positively correlated with gray-matter volume in the striatum, prefrontal cortex, insula, hippocampus and temporal cortex in methamphetamine users, but not in control participants (group-by-midbrain D2/D3 BPND interaction, p<0.05 corrected for multiple comparisons). Craving for methamphetamine was negatively associated with gray-matter volum
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midbrain dopamine d2 d3 receptor availability and Drug Craving are associated with mesocorticolimbic gray matter volume in methamphetamine users
Molecular Psychiatry, 2015Co-Authors: Angelica M. Morales, Milky Kohno, Chelsea L. Robertson, Andy C. Dean, M. Mandelkern, Edythe D. LondonAbstract:Midbrain dopamine D2/D3 receptor availability and Drug Craving are associated with mesocorticolimbic gray matter volume in methamphetamine users
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gray matter volume midbrain dopamine d2 d3 receptors and Drug Craving in methamphetamine users
Molecular Psychiatry, 2015Co-Authors: Angelica M. Morales, Milky Kohno, Chelsea L. Robertson, Andy C. Dean, M. Mandelkern, Edythe D. LondonAbstract:Dysfunction of the mesocorticolimbic system has a critical role in clinical features of addiction. Despite evidence suggesting that midbrain dopamine receptors influence amphetamine-induced dopamine release and that dopamine is involved in methamphetamine-induced neurotoxicity, associations between dopamine receptors and gray-matter volume have been unexplored in methamphetamine users. Here we used magnetic resonance imaging and [(18)F]fallypride positron emission tomography, respectively, to measure gray-matter volume (in 58 methamphetamine users) and dopamine D2/D3 receptor availability (binding potential relative to nondisplaceable uptake of the radiotracer, BPnd) (in 31 methamphetamine users and 37 control participants). Relationships between these measures and self-reported Drug Craving were examined. Although no difference in midbrain D2/D3 BPnd was detected between methamphetamine and control groups, midbrain D2/D3 BPnd was positively correlated with gray-matter volume in the striatum, prefrontal cortex, insula, hippocampus and temporal cortex in methamphetamine users, but not in control participants (group-by-midbrain D2/D3 BPnd interaction, P<0.05 corrected for multiple comparisons). Craving for methamphetamine was negatively associated with gray-matter volume in the insula, prefrontal cortex, amygdala, temporal cortex, occipital cortex, cerebellum and thalamus (P<0.05 corrected for multiple comparisons). A relationship between midbrain D2/D3 BPnd and methamphetamine Craving was not detected. Lower midbrain D2/D3 BPnd may increase vulnerability to deficits in gray-matter volume in mesocorticolimbic circuitry in methamphetamine users, possibly reflecting greater dopamine-induced toxicity. Identifying factors that influence prefrontal and limbic volume, such as midbrain BPnd, may be important for understanding the basis of Drug Craving, a key factor in the maintenance of substance-use disorders.
