Category Archives: Addiction

Cannabinoid Receptor 1 (CNR1) Gene Variant Moderates Neural Index of Cognitive Disruption during Nicotine Withdrawal.

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“Nicotine withdrawal-related disruption of cognitive control may contribute to the reinforcement of tobacco use.

Identification of gene variants that predict this withdrawal phenotype may lead to tailored pharmacotherapy for smoking cessation.

Variation on the cannabinoid receptor 1 gene (CNR1) has been related to nicotine dependence, and CNR1 antagonists may increase attention and memory functioning.

The current findings suggest potential efficacy of cannabinoid RECEPTOR antagonism as a pharmacotherapy approach for smoking cessation among individuals who exhibit greater nicotine withdrawal-related cognitive disruption.”

http://www.ncbi.nlm.nih.gov/pubmed/27453054

The Cannabinoid Receptor 2 Protects Against Alcoholic Liver Disease Via a Macrophage Autophagy-Dependent Pathway.

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“Kupffer cells, the resident macrophages of the liver, play a major role in the pathogenesis of alcoholic liver disease. We have previously demonstrated that CB2 receptor protects against alcoholic liver disease by inhibiting alcohol-induced inflammation and steatosis via the regulation of Kupffer cell activation.

Here, we explored the mechanism underlying these effects and hypothesized that the anti-inflammatory properties of CB2 receptor in Kupffer cells rely on activation of autophagy.

Altogether these results demonstrate that CB2 receptor activation in macrophages protects from alcohol-induced steatosis by inhibiting hepatic inflammation through an autophagy-dependent pathway.”

http://www.ncbi.nlm.nih.gov/pubmed/27346657

Fatty Acid Amide Hydrolase Binding in Brain of Cannabis Users: Imaging With the Novel Radiotracer [11C]CURB.

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“One of the major mechanisms for terminating the actions of the endocannabinoid anandamide is hydrolysis by fatty acid amide hydrolase (FAAH), and inhibitors of the enzyme were suggested as potential treatment for human cannabis dependence.

In cannabis users, FAAH binding was significantly lower by 14%-20% across the brain regions examined than in matched control subjects.

Lower FAAH binding levels in the brain may be a consequence of chronic and recent cannabis exposure and could contribute to cannabis withdrawal. This effect should be considered in the development of novel treatment strategies for cannabis use disorder that target FAAH and endocannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/27345297

Dissecting the signaling pathways involved in the crosstalk between mGlu5 and CB1 receptors.

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“The metabotropic glutamate (mGlu) receptor 5 and the cannabinoid type 1 (CB1) receptor are G-protein-coupled receptors (GPCR) that are widely expressed in the central nervous system (CNS). mGlu5 receptors, present at the postsynaptic site, are coupled to Gαq/11 proteins and display an excitatory response upon activation, while the CB1 receptor, mainly present at presynaptic terminals, is coupled to the Gi/o protein and triggers an inhibitory response. Recent studies suggest that the glutamatergic and endocannabinoid systems exhibit a functional interaction to modulate several neural processes. In this review we discuss possible mechanisms involved in this crosstalk and its relationship with physiological and pathological conditions, including nociception, addiction and fragil X syndrome.”

http://www.ncbi.nlm.nih.gov/pubmed/27338080

Basolateral amygdala CB1 cannabinoid receptors are involved in cross state-dependent memory retrieval between morphine and ethanol.

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“Ethanol and morphine are largely co-abused and affect memory formation.

The present study intended to investigate the involvement of cannabinoid CB1 receptors of the basolateral amygdala (BLA) in cross state-dependent memory retrieval between morphine and ethanol.

Taken together, it can be concluded that morphine and ethanol can induce state-dependent memory retrieval.

In addition, the BLA endocannabinoid system mediates via CB1 receptors the functional interaction of morphine and ethanol state-dependent memory retrieval which may depend on the rewarding effects of the drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/27327764

Exercise as an adjunctive treatment for cannabis use disorder.

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“Despite cannabis being the most widely used illicit substance in the United States, individuals diagnosed with cannabis use disorder (CUD) have few well-researched, affordable treatment options available to them.

Although found to be effective for improving treatment outcomes in other drug populations, exercise is an affordable and highly accessible treatment approach that has not been routinely investigated in cannabis users. The aim of this paper is to inform the topic regarding exercise’s potential as an adjunctive treatment for individuals with CUD.

Given that exercise is a potent activator of the eCB system, it is mechanistically plausible that exercise could be an optimal method to supplement cessation efforts by reducing psychophysical withdrawal, managing stress, and attenuating drug cravings.”

http://www.ncbi.nlm.nih.gov/pubmed/27314543

“Exercise activates the endocannabinoid system.”  http://www.ncbi.nlm.nih.gov/pubmed/14625449

Estradiol impacts the endocannabinoid system in female rats to influence behavioral and structural responses to cocaine.

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“Compared with men, women show enhanced responses to drugs of abuse, and consequently are thought to be more vulnerable to addiction.

The ovarian hormone estradiol has emerged as a key facilitator in the heightened development of addiction in females. These actions of estradiol appear mediated by estrogen receptor (ER) activation of metabotropic glutamate receptor type 5 (mGluR5). However, the downstream effectors of this ER/mGluR5 signaling pathway are unknown.

Here we investigate whether cannabinoid 1 receptor (CB1R) activation is a part of the mechanism whereby estradiol influences behavioral and synaptic correlates of addiction.

Following repeated cocaine administration, estradiol-treated ovariectomized rats exhibited both sensitized locomotor responses and decreases in the dendritic spine density of nucleus accumbens core medium-spiny neurons in comparison to oil-treated controls. Both effects of estradiol were blocked by AM251, a CB1R inverse agonist.

These results indicate that part of the signaling mechanism through which estradiol impacts behavioral and synaptic correlates of addiction in female rats requires activation of CB1Rs.”

http://www.ncbi.nlm.nih.gov/pubmed/27266915

Sativex Associated With Behavioral-Relapse Prevention Strategy as Treatment for Cannabis Dependence: A Case Series.

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“The current lack of pharmacological treatments for cannabis dependence warrants the use of novel approaches and further investigation of promising pharmacotherapy.

In this case series, we assessed the use of self-titrated dosages of Sativex (1:1, Δ-tetrahydrocannabinol [THC]/cannabidiol [CBD] combination) and motivational enhancement therapy and cognitive behavioral therapy (MET/CBT) for the treatment of cannabis dependence among 5 treatment-seeking community-recruited cannabis-dependent subjects.

THC/CBD metabolite concentration indicated reduced cannabis use and compliance with medication.

CONCLUSIONS:

In summary, this pilot study found that with Sativex in combination with MET/CBT reduced cannabis use while preventing increases in craving and withdrawal in the 4 participants completing the study. Further systematic exploration of Sativex as a pharmacological treatment option for cannabis dependence should be performed.”

http://www.ncbi.nlm.nih.gov/pubmed/27261670

Endocannabinoid Modulation of Orbitostriatal Circuits Gates Habit Formation.

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“Everyday function demands efficient and flexible decision-making that allows for habitual and goal-directed action control. An inability to shift has been implicated in disorders with impaired decision-making, including obsessive-compulsive disorder and addiction. Despite this, our understanding of the specific molecular mechanisms and circuitry involved in shifting action control remains limited. Here we identify an endogenous molecular mechanism in a specific cortical-striatal pathway that mediates the transition between goal-directed and habitual action strategies. Deletion of cannabinoid type 1 (CB1) receptors from cortical projections originating in the orbital frontal cortex (OFC) prevents mice from shifting from goal-directed to habitual instrumental lever pressing. Activity of OFC neurons projecting to dorsal striatum (OFC-DS) and, specifically, activity of OFC-DS terminals is necessary for goal-directed action control. Lastly, CB1 deletion from OFC-DS neurons prevents the shift from goal-directed to habitual action control. These data suggest that the emergence of habits depends on endocannabinoid-mediated attenuation of a competing circuit controlling goal-directed behaviors.”

http://www.ncbi.nlm.nih.gov/pubmed/27238866

Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans.

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:”The cannabinoid (CB) system is a rational novel target for treating opioid dependence, a significant public health problem around the world. This proof-of-concept study examined the potential efficacy of a CB1 receptor partial agonist, dronabinol, in relieving signs and symptoms of opioid withdrawal.

CONCLUSION:

CB1 receptor activation is a reasonable strategy to pursue for the treatment of opioid withdrawal; however, dronabinol is not a likely candidate given its modest withdrawal suppression effects of limited duration and previously reported tachycardia during opioid withdrawal.”

http://www.ncbi.nlm.nih.gov/pubmed/27234658