Category Archives: Addiction

Alcohol-induced conditioned place preference is modulated by CB2 cannabinoid receptors and modifies levels of endocannabinoids in the mesocorticolimbic system.

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Pharmacology Biochemistry and Behavior

“The endocannabinoid (eCB) system is a particularly important neuronal mechanism implicated in alcohol use disorders. Animal models are key to broadening our knowledge of the neurobiological mechanisms underlying alcohol dependence.

This study has two main aims: i) to assess how eCB levels in different brain areas are modified by alcohol-induced conditioning place preference (CPP), and ii) to study how cannabinoid type 2 receptor (CB2R) is involved in alcohol-rewarding properties, using pharmacological manipulation in C57BL/6 mice.

Our results suggest that the eCB system is dysregulated throughout the mesocorticolimbic system by repeated alcohol exposure during the CPP paradigm, and that levels of anandamide (AEA) and several other N-acylethanolamines are markedly decreased in the medial prefrontal cortex and ventral midbrain of alcohol-CPP mice.

We also observed that the administering an antagonist/inverse agonist of the CB2R (AM630) during the acquisition phase of CPP reduced the rewarding effects of alcohol. However, activating CB2R signalling using the agonist JWH133 seems to reduce both alcohol- and food-rewarding behaviours. Therefore, our findings indicate that the rewarding effects of alcohol are related to its disruptive effect on AEA and other N-acylethanolamine signalling pathways.

Thus, pharmacological manipulation of CB2R is an interesting candidate treatment for alcohol use disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31220547

https://www.sciencedirect.com/science/article/pii/S0091305719300656?via%3Dihub

Opioid-Sparing Effects of Cannabinoids on Morphine Analgesia: Participation of CB1 and CB2 Receptors.

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British Journal of Pharmacology banner“Much of the opioid epidemic arose from abuse of prescription opioid drugs.

This study sought to determine if the combination of a cannabinoid with an opioid could produce additive or synergistic effects on pain, allowing reduction in the opioid dose needed for maximal analgesia.

CONCLUSIONS AND IMPLICATIONS:

The ability of a cannabinoid to produce an additive or synergistic effect on analgesia when combined with morphine varies with the pain assay and may be mediated by CB1 or CB2 receptors. These results hold the promise of using cannabinoids to reduce the dose of opioids for analgesia in certain pain conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/31218677

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14769

Cannabidiol inhibits sucrose self-administration by CB1 and CB2 receptor mechanisms in rodents.

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Addiction Biology banner

“A growing number of studies suggest therapeutic applications of cannabidiol (CBD), a recently U.S. Food and Drug Administration (FDA)-approved medication for epilepsy, in treatment of many other neuropsychological disorders. However, pharmacological action and the mechanisms by which CBD exerts its effects are not fully understood.

Here, we examined the effects of CBD on oral sucrose self-administration in rodents and explored the receptor mechanisms underlying CBD-induced behavioral effects using pharmacological and transgenic approaches.

Systemic administration of CBD produced a dose-dependent reduction in sucrose self-administration in rats and in wild-type (WT) and CB1-/- mice but not in CB2-/- mice. CBD appeared to be more efficacious in CB1-/- mice than in WT mice.

Similarly, pretreatment with AM251, a CB1R antagonist, potentiated, while AM630, a selective CB2R antagonist, blocked CBD-induced reduction in sucrose self-administration, suggesting the involvement of CB1 and CB2 receptors.

Taken together, the present findings suggest that CBD may have therapeutic potential in reducing binge eating and the development of obesity.”

https://www.ncbi.nlm.nih.gov/pubmed/31215752

https://onlinelibrary.wiley.com/doi/abs/10.1111/adb.12783

Marijuana as a Substitute for Prescription Medications: A Qualitative Study.

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Publication Cover

“Over the past few decades in the United States, marijuana for medical purposes has become increasingly prevalent. Initial qualitative and epidemiological research suggests that marijuana may be a promising substitute for traditional pharmacotherapies.

Objectives: This qualitative study examined perceptions relating to (1) using medical marijuana in comparison to other prescription medications and (2) user perception of policy issues that limit adoption of medical marijuana use.

Results: Three themes emerged related to medical marijuana use, including (1) comparison of medical marijuana to other medications (i.e., better and/or fewer side effects than prescription medications, improves quality of life), (2) substitution of marijuana for other medications (i.e., in addition to or instead of), and (3) how perception of medical marijuana policy impacts use (i.e., stigma, travel, cost, and lack of instruction regarding use).

Conclusions: Several factors prevent pervasive medical marijuana use, including stigma, cost, and the inability for healthcare providers to relay instructions regarding dosing, strain, and method of use. Findings suggest that medical patients consider marijuana to be a viable alternative for opioids and other prescription medications, though certain policy barriers inhibit widespread implementation of marijuana as a treatment option.”

https://www.ncbi.nlm.nih.gov/pubmed/31179810

https://www.tandfonline.com/doi/abs/10.1080/10826084.2019.1618336?journalCode=isum20

The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake.

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Addiction Biology banner“The administration of cannabidiol has shown promising evidence in the treatment of some neuropsychiatric disorders, including cocaine addiction. However, little information is available as to the mechanisms by which cannabidiol reduces drug use and compulsive seeking.

We investigated the role of adult hippocampal neurogenesis in reducing cocaine voluntary intake produced by repeated cannabidiol treatment in mice.

Cannabidiol (20 mg/kg) reduced cocaine self-administration behaviour acquisition and total cocaine intake and enhanced adult hippocampal neurogenesis.

The present study confirms that adult hippocampal neurogenesis is one of the mechanisms by which cannabidiol lowers cocaine reinforcement and demonstrates the functional implication of adult hippocampal neurogenesis in cocaine voluntary consumption in mice.

Such findings highlight the possible use of cannabidiol for developing new pharmacotherapies to manage cocaine use disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31162770

https://onlinelibrary.wiley.com/doi/abs/10.1111/adb.12778

Medical Cannabis: Effects on Opioid and Benzodiazepine Requirements for Pain Control.

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SAGE Journals

“The objective of this study was to determine if the use of medical cannabis affects the amount of opioids and benzodiazepines used by patients on a daily basis.

METHODS:

This single-center, retrospective cohort study evaluated opioid and benzodiazepine doses over a 6-month time period for patients certified to use medical cannabis for intractable pain. All available daily milligram morphine equivalents (MMEs) and daily diazepam equivalents (DEs) were calculated at baseline and at 3 and 6 months.

RESULTS:

A total of 77 patients were included in the final analysis. There was a statistically significant decrease in median MME from baseline to 3 months (-32.5 mg; P = 0.013) and 6 months (-39.1 mg; P = 0.001). Additionally, there was a non-statistically significant decrease in median DE at 3 months (-3.75 mg; P = 0.285) and no change in median DE from baseline to 6 months (-0 mg; P = 0.833). Conclusion and Relevance: Over the course of this 6-month retrospective study, patients using medical cannabis for intractable pain experienced a significant reduction in the number of MMEs available to use for pain control. No significant difference was noted in DE from baseline. Further prospective studies are warranted to confirm or deny the opioid-sparing effects of medical cannabis when used to treat intractable pain.”

https://www.ncbi.nlm.nih.gov/pubmed/31129977

https://journals.sagepub.com/doi/abs/10.1177/1060028019854221?journalCode=aopd

Effects of cannabidiol on alcohol-related outcomes: A review of preclinical and human research.

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Cover image for Experimental and Clinical Psychopharmacology

“This article reviews preclinical and human studies examining the effects of CBD administration on alcohol responses. Preliminary preclinical results suggest that CBD can attenuate alcohol consumption and potentially protect against certain harmful effects of alcohol, such as liver and brain damage.”

https://www.ncbi.nlm.nih.gov/pubmed/31120285

https://psycnet.apa.org/doiLanding?doi=10.1037%2Fpha0000272

Therapeutic prospects of cannabidiol for alcohol use disorder and alcohol-related damages on the liver and the brain

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 Image result for frontiers in pharmacology“Cannabidiol (CBD) is a natural compound of cannabis, which exerts complex and widespread immunomodulatory, antioxidant, anxiolytic, and antiepileptic properties. Many experimental data suggest that CBD could have several types of application in alcohol use disorder (AUD) and alcohol-related damage on the brain and the liver.

Experimental studies converge to find that CBD reduces the overall level of alcohol drinking in animal models of AUD by reducing ethanol intake, motivation for ethanol, relapse, and by decreasing anxiety and impulsivity. Moreover, CBD has been shown to reduce alcohol-related steatosis and fibrosis in the liver by reducing lipid accumulation, stimulating autophagy, modulating inflammation, reducing oxidative stress, and inducing death of activated hepatic stellate cells. Last, CBD has been found to reduce alcohol-related brain damage, preventing neuronal loss by its antioxidant and immunomodulatory properties.

CBD could directly reduce alcohol drinking in subjects with AUD. But other original applications warrant human trials in this population. By reducing alcohol-related processes of steatosis in the liver, and brain alcohol-related damage, CBD could improve both the hepatic and neurocognitive outcomes of subjects with AUD, regardless of the individual drinking trajectories. This might pave the way for testing new harm reduction approaches in AUD, i.e., for protecting the organs of subjects with an ongoing AUD.”

https://www.frontiersin.org/articles/10.3389/fphar.2019.00627/abstract

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

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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

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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