Category Archives: Addiction

Cannabinoid CB2 receptors protect against alcoholic liver disease by regulating Kupffer cell polarization in mice.

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“Activation of Kupffer cells plays a central role in the pathogenesis of alcoholic liver disease.

Because cannabinoid CB2 receptors (CB2) display potent anti-inflammatory properties, we investigated their role in the pathogenesis of alcoholic liver disease, focusing on the impact of CB2 on Kupffer cell polarization and the consequences on liver steatosis.

Altogether, these findings demonstrate that CB2 receptors display beneficial effects on alcohol-induced inflammation by regulating M1/M2 balance in Kupffer cells, thereby reducing hepatocyte steatosis via paracrine interactions between Kupffer cells and hepatocytes.

These data identify CB2 agonists as potential therapeutic agents for the management of alcoholic liver disease.”

http://www.ncbi.nlm.nih.gov/pubmed/21735467

http://www.thctotalhealthcare.com/category/liver-disease/

Effects of the novel cannabinoid CB1 receptor antagonist PF 514273 on the acquisition and expression of ethanol conditioned place preference.

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“The centrally expressed cannabinoid receptor (CB1) has been considered a potential therapeutic target in treating alcoholism.

Though CB1 receptors have been shown to modulate primary and conditioned ethanol reward, much of this research employed animal models that require ethanol ingestion or oral routes of administration. This is problematic considering CB1 antagonist drugs have high anorectic liability and have been used clinically in the treatment of obesity. Therefore, the present study examined CB1 antagonism in DBA/2J mice using an unbiased ethanol-induced conditioned place preference (CPP) procedure, a paradigm that does not require ethanol ingestion…

Results from the present study appear inconsistent with other studies that have demonstrated a role for CB1 antagonism in ethanol reward using oral administration paradigms.

Our findings suggest that CB1 antagonism may have greater involvement in consummatory behavior than ethanol reward.”

http://www.ncbi.nlm.nih.gov/pubmed/24954022

http://www.thctotalhealthcare.com/category/addiction/

Δ9-tetrahydrocannabinol prevents methamphetamine-induced neurotoxicity.

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“Methamphetamine (METH) is a potent psychostimulant with neurotoxic properties…

Preclinical studies have shown that natural (Δ9-tetrahydrocannabinol, Δ9-THC) and synthetic cannabinoid CB1 and CB2 receptor agonists exert neuroprotective effects on different models of cerebral damage. Here, we investigated the neuroprotective effect of Δ9-THC on METH-induced neurotoxicity…

Our results indicate that Δ9-THC reduces METH-induced brain damage via inhibition of nNOS expression and astrocyte activation through CB1-dependent and independent mechanisms, respectively.”

http://www.ncbi.nlm.nih.gov/pubmed/24844285

Full-text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028295/

Relationship between working-memory network function and substance use: a 3-year longitudinal fMRI study in heavy cannabis users and controls.

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“The aim of this 3-year longitudinal neuro-imaging study was to investigate the relationship between substance use (e.g. alcohol, cannabis, nicotine, illegal psychotropic drugs) and working-memory network function over time in heavy cannabis users and controls.

Within the group of cannabis users, cannabis-related problems remained stable, whereas alcohol-related problems, nicotine dependence and illegal psychotropic substance use increased over time. At both measurements, behavioral performance and network functionality during the n-back task did not differ between heavy cannabis users and controls. Although n-back accuracy improved, working-memory network function remained stable over time.

Within the group of cannabis users, working-memory network functionality was not associated with substance use.

These results suggest that sustained moderate to heavy levels of cannabis, nicotine, alcohol and illegal psychotropic substance use do not change working-memory network functionality.

Moreover, baseline network functionality did not predict cannabis use and related problems three years later, warranting longitudinal studies in more chronic or dependent cannabis users.”

http://www.ncbi.nlm.nih.gov/pubmed/24589297

Changes in Cerebral CB1 Receptor Availability after Acute and Chronic Alcohol Abuse and Monitored Abstinence.

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“Involvement of the type 1 cannabinoid receptor (CB1R) in the effects of alcohol on the brain is supported by animal experiments…

In conclusion, whereas the acute alcohol effect is an increase in CB1R availability, chronic heavy drinking leads to reduced CB1R availability that is not reversible after 1 month of abstinence. Longer follow-up is required to differentiate whether this is a compensatory effect of repeated endocannabinoid overstimulation or an enduring trait-like feature.

An enhanced CB1R signaling may offer a new therapeutic direction for treatment of the negative affective state produced by alcohol withdrawal and abstinence, which is critical for the maintenance of alcohol addiction.”

http://www.ncbi.nlm.nih.gov/pubmed/24553924

Basolateral amygdala CB1 cannabinoid receptors mediate nicotine-induced place preference.

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“In the present study, the effects of bilateral microinjections of cannabinoid CB1 receptor agonist and antagonist into the basolateral amygdala (intra-BLA) on nicotine-induced place preference were examined in rats.

Taken together, these findings support the possible role of endogenous cannabinoid system of the BLA in the acquisition and the expression of nicotine-induced place preference. Furthermore, it seems that there is a functional interaction between the BLA cannabinoid receptors and nicotine in producing the rewarding effects.”

http://www.ncbi.nlm.nih.gov/pubmed/24468643

Use of Dronabinol for Cannabis Dependence: Two Case Reports and Review

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“Based on recent laboratory studies, dronabinol (delta-9-tetrahydrocannabinol) has been shown to reduce cannabis withdrawal symptoms and the subjective effects of marijuana.

Given that agonist agents have been found to be effective for opiate and nicotine dependence, the clinical utility of dronabinol for cannabis dependence is a reasonable approach…

It is clear from the two cases that both patients found the induction onto dronabinol helpful.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2733248/

Dronabinol for the Treatment of Cannabis Dependence: A Randomized, Double-Blind, Placebo-Controlled Trial

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“… there are no effective medications for cannabis dependence. The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, in treating cannabis dependence.

This is the first trial using an agonist substitution strategy for treatment of cannabis dependence. Dronabinol showed promise, it was well-tolerated, and improved treatment retention and withdrawal symptoms…

In conclusion, agonist substitution pharmacotherapy with dronabinol, a synthetic form of THC, showed promise for treatment of cannabis dependence, reducing withdrawal symptoms and improving retention in treatment…

The trial showed that among adult cannabis-dependent patients, dronabinol was well accepted, with good adherence and few adverse events.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154755/

 

Cannabinoid type-1 receptor ligands, alone or in combination with cocaine, affect vigilance-related behaviors of marmoset monkeys.

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“Endocannabinoids (eCB) have been functionally linked to cocaine’s rewarding effects.

…changes in CB1r function – alone and in combination with cocaine – affected stereotyped vigilance-related behaviors… further implicating the eCB system in the neurobiological mechanisms of cocaine addiction.”

http://www.ncbi.nlm.nih.gov/pubmed/24445195

Nabiximols as an Agonist Replacement Therapy During Cannabis Withdrawal: A Randomized Clinical Trial.

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“The cannabis extract nabiximols (Sativex), developed as a multiple sclerosis treatment, offers a potential agonist medication for cannabis withdrawal…

Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal…

The data support further evaluation of nabiximols for management of cannabis dependence and withdrawal in treatment-seeking populations.”

http://www.ncbi.nlm.nih.gov/pubmed/24430917