Category Archives: Addiction

Overcoming the psychiatric side effects of the cannabinoid CB1 receptor antagonists: Current approaches for therapeutics development.

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“The cannabinoid receptor 1 (CBR1) is involved in a variety of physiological pathways and has long been considered a golden target for therapeutic manipulation. A large body of evidence in both animal and human studies suggests that CB1R antagonism is highly effective for the treatment of obesity, metabolic disorders and drug addiction. However, the first-in-class CB1R antagonist/inverse agonist, rimonabant, though demonstrating effectiveness for obesity treatment and smoking cessation, displays serious psychiatric side effects, including anxiety, depression and even suicidal ideation, resulting in its eventual withdrawal from the European market. Several strategies are currently being pursued to circumvent the mechanisms leading to these side effects by developing neutral antagonists, peripherally restricted ligands, and allosteric modulators. In this review, we describe the progress in the development of therapeutics targeting the cannabinoid receptor 1 in the last two decades.”

https://www.ncbi.nlm.nih.gov/pubmed/31284863

http://www.eurekaselect.com/173316/article

Distinct Functions of Endogenous Cannabinoid System in Alcohol Abuse Disorders.

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British Journal of Pharmacology banner

“Δ9-tetrahydrocannabinol (Δ9 -THC), the principal active component in Cannabis sativa extracts such as marijuana, participates in cell signaling by binding to cell surface receptors. CB1 receptors (CB1 s) are present in both inhibitory and excitatory presynaptic terminals. CB2 receptors (CB2 s) found in neuronal subpopulations in addition to microglial cells and astrocytes and are present in both pre- and postsynaptic terminals.

Subsequent to endocannabinoid (eCB) system discoveries, studies have suggested that alcohol alters the eCB system and that the eCB system plays a major role in the motivation to abuse alcohol.

Preclinical studies have provided evidence that chronic alcohol consumption modulates eCBs and CB1 expression in brain addiction circuits. In addition, studies have further established the distinct function of the eCB system in the development of fetal alcohol spectrum disorders. This review provides a recent and comprehensive assessment of the literature related to the function of the eCB system in alcohol abuse disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31265740

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14780

“Cannabis and Alcohol: From Basic Science to Public Policy.”  https://www.ncbi.nlm.nih.gov/pubmed/31265135

Use of Cannabis to Relieve Pain and Promote Sleep by Customers at an Adult Use Dispensary

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Publication Cover

“Cannabis has been used for pain relief and to promote sleep for thousands of years. Over the past several decades in the United States (U.S.), a therapeutic role for cannabis in mainstream medicine has increasingly emerged. Medical cannabis patients consistently report using cannabis as a substitute for prescription medications. Both pain relief and sleep promotion are common reasons for cannabis use, and the majority of respondents who reported using cannabis for these reasons also reported decreasing or stopping their use of prescription or over-the-counter analgesics and sleep aids. While adult-use laws are frequently called “recreational,” implying that cannabis obtained through the adult use system is only for pleasure or experience-seeking, our findings suggest that many customers use cannabis for symptom relief.”

https://www.ncbi.nlm.nih.gov/pubmed/31264536

https://www.tandfonline.com/doi/full/10.1080/02791072.2019.1626953

“Cannabis Is An Effective Treatment Option For Pain Relief And Insomnia, Study Finds” https://www.inquisitr.com/5509672/cannabis-pain-medications-sleep/

“Marijuana Could Be The Alternative Pain Reliever Replacing Opioids”  https://www.medicaldaily.com/marijuana-alternative-pain-reliever-replacing-opioids-437974

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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“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