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1.  Modulation of the Endocannabinoid System: Vulnerability Factor and New Treatment Target for Stimulant Addiction 
Cannabis is one of the most widely used illicit substance among users of stimulants such as cocaine and amphetamines. Interestingly, increasing recent evidence points toward the involvement of the endocannabinoid system (ECBS) in the neurobiological processes related to stimulant addiction. This article presents an up-to-date review with deep insights into the pivotal role of the ECBS in the neurobiology of stimulant addiction and the effects of its modulation on addictive behaviors. This article aims to: (1) review the role of cannabis use and ECBS modulation in the neurobiological substrates of psychostimulant addiction and (2) evaluate the potential of cannabinoid-based pharmacological strategies to treat stimulant addiction. A growing number of studies support a critical role of the ECBS and its modulation by synthetic or natural cannabinoids in various neurobiological and behavioral aspects of stimulants addiction. Thus, cannabinoids modulate brain reward systems closely involved in stimulants addiction, and provide further evidence that the cannabinoid system could be explored as a potential drug discovery target for treating addiction across different classes of stimulants.
doi:10.3389/fpsyt.2013.00109
PMCID: PMC3780360  PMID: 24069004
addiction; stimulants; psychostimulants; cocaine; cannabis; cannabinoids or endocannabinoids
2.  A case of hypomania during nicotine cessation treatment with bupropion 
Antidepressants can increase the spontaneous risk of hypomania or mania when used for treatment in affective disorders. When prescribed as an antidepressant, bupropion is generally considered to have a lower relative risk of inducing mood shifts. We describe the case of a 67-year-old man known for dysthymic disorder in remission on quetiapine and venlafaxine who experienced a first lifetime episode of hypomania with the introduction of bupropion SR for smoking cessation. To the best of our knowledge, this is the first case report of bupropion-induced mood shift when used specifically for nicotine cessation in a nonbipolar patient. This case highlights the need for clinicians who prescribe bupropion for smoking cessation to perform regular and systematic mood follow-ups during treatment. These follow-ups could even be more important when bupropion is selected to quit smoking in a patient already taking an antidepressant.
doi:10.1186/1940-0640-8-22
PMCID: PMC3878104  PMID: 24359680
Nicotine; Smoking cessation; Bupropion; Antidepressant; Hypomania; Venlafaxine
3.  Cannabis-Dependence Risk Relates to Synergism between Neuroticism and Proenkephalin SNPs Associated with Amygdala Gene Expression: Case-Control Study 
PLoS ONE  2012;7(6):e39243.
Background
Many young people experiment with cannabis, yet only a subgroup progress to dependence suggesting individual differences that could relate to factors such as genetics and behavioral traits. Dopamine receptor D2 (DRD2) and proenkephalin (PENK) genes have been implicated in animal studies with cannabis exposure. Whether polymorphisms of these genes are associated with cannabis dependence and related behavioral traits is unknown.
Methodology/Principal Findings
Healthy young adults (18–27 years) with cannabis dependence and without a dependence diagnosis were studied (N = 50/group) in relation to a priori-determined single nucleotide polymorphisms (SNPs) of the DRD2 and PENK genes. Negative affect, Impulsive Risk Taking and Neuroticism-Anxiety temperamental traits, positive and negative reward-learning performance and stop-signal reaction times were examined. The findings replicated the known association between the rs6277 DRD2 SNP and decisions associated with negative reinforcement outcomes. Moreover, PENK variants (rs2576573 and rs2609997) significantly related to Neuroticism and cannabis dependence. Cigarette smoking is common in cannabis users, but it was not associated to PENK SNPs as also validated in another cohort (N = 247 smokers, N = 312 non-smokers). Neuroticism mediated (15.3%–19.5%) the genetic risk to cannabis dependence and interacted with risk SNPs, resulting in a 9-fold increase risk for cannabis dependence. Molecular characterization of the postmortem human brain in a different population revealed an association between PENK SNPs and PENK mRNA expression in the central amygdala nucleus emphasizing the functional relevance of the SNPs in a brain region strongly linked to negative affect.
Conclusions/Significance
Overall, the findings suggest an important role for Neuroticism as an endophenotype linking PENK polymorphisms to cannabis-dependence vulnerability synergistically amplifying the apparent genetic risk.
doi:10.1371/journal.pone.0039243
PMCID: PMC3382183  PMID: 22745721

Results 1-3 (3)