Category Archives: Addiction

Targeting Peripheral CB1 Receptors Reduces Ethanol Intake via a Gut-Brain Axis.

Posted on by

Cell Metabolism

“Endocannabinoids acting on the cannabinoid-1 receptor (CB1R) or ghrelin acting on its receptor (GHS-R1A) both promote alcohol-seeking behavior, but an interaction between the two signaling systems has not been explored. Here, we report that the peripheral CB1R inverse agonist JD5037 reduces ethanol drinking in wild-type mice but not in mice lacking CB1R, ghrelin peptide or GHS-R1A. JD5037 treatment of alcohol-drinking mice inhibits the formation of biologically active octanoyl-ghrelin without affecting its inactive precursor desacyl-ghrelin. In ghrelin-producing stomach cells, JD5037 reduced the level of the substrate octanoyl-carnitine generated from palmitoyl-carnitine by increasing fatty acid β-oxidation. Blocking gastric vagal afferents abrogated the ability of either CB1R or GHS-R1A blockade to reduce ethanol drinking. We conclude that blocking CB1R in ghrelin-producing cells reduces alcohol drinking by inhibiting the formation of active ghrelin and its signaling via gastric vagal afferents. Thus, peripheral CB1R blockade may have therapeutic potential in the treatment of alcoholism.”

https://www.ncbi.nlm.nih.gov/pubmed/31105045

https://www.sciencedirect.com/science/article/pii/S1550413119301962?via%3Dihub

Cannabidiol for the Reduction of Cue-Induced Craving and Anxiety in Drug-Abstinent Individuals With Heroin Use Disorder: A Double-Blind Randomized Placebo-Controlled Trial

Posted on by

Image result for american journal of psychiatry“Despite the staggering consequences of the opioid epidemic, limited nonopioid medication options have been developed to treat this medical and public health crisis.

This study investigated the potential of cannabidiol (CBD), a nonintoxicating phytocannabinoid, to reduce cue-induced craving and anxiety, two critical features of addiction that often contribute to relapse and continued drug use, in drug-abstinent individuals with heroin use disorder.

Acute CBD administration, in contrast to placebo, significantly reduced both craving and anxiety induced by the presentation of salient drug cues compared with neutral cues. CBD also showed significant protracted effects on these measures 7 days after the final short-term (3-day) CBD exposure. In addition, CBD reduced the drug cue–induced physiological measures of heart rate and salivary cortisol levels. There were no significant effects on cognition, and there were no serious adverse effects.

 Conclusions:

CBD’s potential to reduce cue-induced craving and anxiety provides a strong basis for further investigation of this phytocannabinoid as a treatment option for opioid use disorder.”

https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2019.18101191

“Study finds CBD effective in treating heroin addiction”  https://www.cnn.com/2019/05/21/health/heroin-opioid-addiction-cbd-study/index.html

“CBD oil may help limit cravings and anxiety in heroin users, study finds”  https://www.nbcnews.com/health/health-news/cbd-oil-may-help-limit-cravings-anxiety-heroin-users-study-n1007856

“Cannabis Compound Eases Anxiety and Cravings of Heroin Addiction”  https://www.scientificamerican.com/article/cannabis-compound-eases-anxiety-and-cravings-of-heroin-addiction/?redirect=1

Gender differences in the effects of cannabidiol on ethanol binge drinking in mice.

Posted on by

Addiction Biology banner“The purpose of this study was to explore the effects of cannabidiol (CBD) on binge drinking and evaluate potential gender-related differences.

Chronic CBD administration (30, 60 and 90 mg/kg) reduced ethanol intake in males, whereas in females a significant reduction was only achieved with the highest dose (90 mg/kg). Repeated administration with CBD (60 mg/kg) significantly reduced TH and OPRM1 in males. In addition, CBD (30 and 60 mg/kg) significantly reduced CB1 r in males. No effect was observed in females.

Taken together, these findings suggest that CBD may be of interest for treating binge-drinking patterns and that gender-related difference may affect the treatment outcome.”

https://www.ncbi.nlm.nih.gov/pubmed/31074060

https://onlinelibrary.wiley.com/doi/abs/10.1111/adb.12765

Endocannabinoid contributions to alcohol habits and motivation: Relevance to treatment.

Posted on by

Addiction Biology banner“Individuals with alcohol use disorder exhibit compulsive habitual behaviors that are thought to be, in part, a consequence of chronic and persistent use of alcohol.

The endocannabinoid system plays a critical role in habit learning and in ethanol self-administration, but the role of this neuromodulatory system in the expression of habitual alcohol seeking is unknown.

Here, we investigated the role of the endocannabinoid system in established alcohol habits using contingency degradation in male C57BL/6 mice.

These results demonstrate an important role for endocannabinoid signaling in the motivation to seek ethanol, in ethanol-motivated habits, and suggest that pharmacological manipulations of endocannabinoid signaling could be effective therapeutics for treating alcohol use disorder.”

https://www.ncbi.nlm.nih.gov/pubmed/31056846

https://onlinelibrary.wiley.com/doi/abs/10.1111/adb.12768

Δ9-tetrahydrocannabinol attenuates oxycodone self-administration under extended access conditions.

Posted on by

Neuropharmacology

“Growing nonmedical use of prescription opioids is a global problem, motivating research on ways to reduce use and combat addiction.

Medical cannabis (“medical marijuana”) legalization has been associated epidemiologically with reduced opioid harms and cannabinoids have been shown to modulate effects of opioids in animal models.

This study was conducted to determine if Δ9-tetrahydrocannabinol (THC) enhances the behavioral effects of oxycodone.

Together these data demonstrate additive effects of THC and oxycodone and suggest the potential use of THC to enhance therapeutic efficacy, and to reduce the abuse, of opioids.”

https://www.ncbi.nlm.nih.gov/pubmed/30980837

“Δ9-tetrahydrocannabinol (THC) enhances the antinociceptive effects of oxycodone. Vaporized and injected THC reduces oxycodone self-administration. Cannabinoids may reduce opioid use for analgesia. Cannabinoids may reduce nonmedical opioid use.”  

https://www.sciencedirect.com/science/article/pii/S0028390819301212?via%3Dihub

Investigating the Relationships Between Alcohol Consumption, Cannabis Use, and Circulating Cytokines: A Preliminary Analysis.

Posted on by

Alcoholism: Clinical and Experimental Research banner

“In recent years, human and animal studies have converged to support altered inflammatory signaling as a molecular mechanism underlying the pathophysiology of alcohol use disorders (AUDs). Alcohol binds to receptors on immune cells, triggering signaling pathways that produce pro-inflammatory cytokines. Chronic inflammation is associated with tissue damage, which may contribute to negative effects of AUD. Conversely, cannabis is associated with decreased inflammatory signaling, and animal studies suggest that cannabinoids may impact alcohol-induced inflammation. Thus, the impact of cannabis on inflammation in AUDs in humans warrants examination.

METHODS:

We explored the relationship between self-reported alcohol and cannabis use and circulating levels of the pro-inflammatory cytokines interleukin 6 (IL-6), IL-8, and IL-1β in the blood. Among 66 regular drinkers (mean age = 30.08), we examined circulating cytokines and administered questionnaires assessing alcohol consumption and days of cannabis use over the past 90 days. We examined whether alcohol consumption, cannabis use, and gender were associated with changes in circulating cytokines, and whether there was a significant interaction between alcohol and cannabis use predicting blood levels of circulating cytokines.

RESULTS:

A positive association between alcohol and IL-6 emerged. We also observed a negative association between cannabis and IL-1β. Follow-up moderation analyses indicated a cannabis by alcohol interaction predicting circulating IL-6, such that cannabis nonusers showed a stronger relationship between alcohol and IL-6 compared to cannabis users.

CONCLUSIONS:

These preliminary findings suggest that cannabinoid compounds may serve to mitigate inflammation associated with alcohol use. In addition, the present results provide data to inform future investigations, with the goal of ultimately leveraging knowledge of the role of inflammation in AUDs to develop more effective treatments focused on novel immune targets.”

https://www.ncbi.nlm.nih.gov/pubmed/29286537

https://onlinelibrary.wiley.com/doi/abs/10.1111/acer.13592

Illicit drug use and prescription drug misuse among young adult medical cannabis patients and non-patient users in Los Angeles

Posted on by

Drug and Alcohol Dependence

“Young adults have the highest rates of cannabis and other drug use, as compared to other age groups, and contribute a significant proportion to the total population of medical cannabis patients (MCP). However, little is known about the relationships between various cannabis practices and illicit drug use/prescription drug misuse among young adult cannabis users with and without legal access to medical cannabis.

RESULTS:

Illicit drug use was associated with being non-Hispanic white (AOR = 3.0, 95% CI 1.8-5.1), use of cannabis concentrates (AOR = 2.8, 95% CI 1.6-4.9), while self-reported medical cannabis use was associated with lower probability of illicit drug use (AOR = 0.5, 95% CI 0.3-0.9). The odds of prescription drug misuse were increased for participants who reported use of cannabis edibles (AOR = 2.0, 95% CI 1.1-3.5), and decreased with age (AOR = 0.9, 95% CI 0.8-1.0) and for those who used cannabis alone (AOR = 0.5, 95% CI 0.3-0.9).

CONCLUSION:

Use of alternative cannabis forms, but not cannabis use frequency, were associated with greater odds of other drug use. Self-reported medical cannabis use, but not MCP status, decreased probability of illicit drug use.”

https://www.ncbi.nlm.nih.gov/pubmed/30861391

https://www.sciencedirect.com/science/article/pii/S0376871619300596?via%3Dihub

Does morning affect contribute to daily Cannabis use?

Posted on by

Addictive Behaviors

“Several theories posit that cannabis and other substances are used to reduce negative affect. This daily report study considered whether variations in positive and negative affect, reported each morning, contributed to the likelihood of cannabis use later that day. We also explored whether levels of positive and negative affect reported immediately after cannabis use improved, relative to that day’s morning levels. The sample included 183 men and 183 women representing heterosexual, cannabis-using couples from the community. Participants made independent, daily reports of affect and cannabis use episodes for 30 consecutive days. Using multilevel modeling, we modeled men’s and women’s use of cannabis on a given day as a function of morning levels of positive, hostile, and anxious affect, accounting for partner cannabis use that day, and mean levels of positive and negative affect. Men and women were more likely to use cannabis on a given day when morning positive affect was lower than typical for the person and when partner used cannabis that day. Neither hostile nor anxious affect contributed to later use of cannabis. Immediately after cannabis use, positive affect increased, and hostile and anxious affect decreased relative to that day’s morning levels. The improved affect immediately after use suggests a mechanism of positive reinforcement.”

https://www.ncbi.nlm.nih.gov/pubmed/30856545

https://www.sciencedirect.com/science/article/abs/pii/S030646031831339X?via%3Dihub

The Endocannabinoid System and Cannabidiol’s Promise for the Treatment of Substance Use Disorder.

Posted on by

 Related image“Substance use disorder is characterized by repeated use of a substance, leading to clinically significant distress, making it a serious public health concern. The endocannabinoid system plays an important role in common neurobiological processes underlying substance use disorder, in particular by mediating the rewarding and motivational effects of substances and substance-related cues. In turn, a number of cannabinoid drugs (e.g., rimonabant, nabiximols) have been suggested for potential pharmacological treatment for substance dependence. Recently, cannabidiol (CBD), a non-psychoactive phytocannabinoid found in the cannabis plant, has also been proposed as a potentially effective treatment for the management of substance use disorder. Animal and human studies suggest that these cannabinoids have the potential to reduce craving and relapse in abstinent substance users, by impairing reconsolidation of drug-reward memory, salience of drug cues, and inhibiting the reward-facilitating effect of drugs. Such functions likely arise through the targeting of the endocannabinoid and serotonergic systems, although the exact mechanism is yet to be elucidated. This article seeks to review the role of the endocannabinoid system in substance use disorder and the proposed pharmacological action supporting cannabinoid drugs’ therapeutic potential in addictions, with a focus on CBD. Subsequently, this article will evaluate the underlying evidence for CBD as a potential treatment for substance use disorder, across a range of substances including nicotine, alcohol, psychostimulants, opioids, and cannabis. While early research supports CBD’s promise, further investigation and validation of CBD’s efficacy, across preclinical and clinical trials will be necessary.”

https://www.ncbi.nlm.nih.gov/pubmed/30837904

https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00063/full

New Insights in Cannabinoid Receptor Structure and Signaling.

Posted on by

“Cannabinoid has long been used for medicinal purposes. Cannabinoid signaling has been considered the therapeutic targets for treating pain, addiction, obesity, inflammation, and other diseases. Recent studies have suggested that in addition to CB1 and CB2, there are non-CB1 and non-CB2 cannabinoid-related orphan GPCRs including GPR18, GPR55, and GPR119. In addition, CB1 and CB2 display allosteric binding and biased signaling, revealing correlations between biased signaling and functional outcomes. Interestingly, new investigations have indicated that CB1 is functionally present within mitochondria of striated and heart muscles directly regulating intramitochondrial signaling and respiration.

CONCLUSION:

In this review, we summarize the recent progress in cannabinoid-related orphan GPCRs, CB1/CB2 structure, Gi/Gs coupling, allosteric ligands and biased signaling, and mitochondria-localized CB1, and discuss the future promise of this research.”

https://www.ncbi.nlm.nih.gov/pubmed/30767756

http://www.eurekaselect.com/170011/article