Patients’ and clinicians’ perspectives of co-use of cannabis and opioids for chronic non-cancer pain management in primary care.

International Journal of Drug Policy

“The prevalence of opioid-associated morbidity and mortality underscores the need for research on non-opioid treatments for chronic non-cancer pain (CNCP). Pain is the most common medical condition for which patients request medical cannabis. Limited research indicates that patients are interested in cannabis as a potential addition to or replacement for opioid medication. This analysis reports on CNCP patient and clinician perceptions about the co-use of cannabis and opioids for CNCP management.

METHODS:

We interviewed 23 clinicians and 46 CNCP patients, using semi-structured interview guides, from six safety-net clinics across the San Francisco Bay Area, and 5 key stakeholders involved in CNCP management. We used a modified grounded theory approach to code and analyze transcripts.

RESULTS:

CNCP patients described potential benefits of co-use of cannabis and opioids for pain management and concerns about dosing and addictive potential. Patients reported seeking cannabis when unable to obtain prescription opioids. Clinicians stated that their patients reported cannabis being helpful in managing pain symptoms. Clinicians expressed concerns about the potential exacerbation of mental health issues resulting from cannabis use.

CONCLUSION:

Clinicians are hampered by a lack of clinically relevant information about cannabis use, efficacy and side-effects. Currently no guidelines exist for clinicians to address opioid and cannabis co-use, or to discuss the risk and benefits of cannabis for CNCP management, including side effects. Cannabis and opioid co-use was commonly reported by patients in our sample, yet rarely addressed during clinical CNCP care. Further research is needed on the risks and benefits of cannabis and opioid co-use.”

https://www.ncbi.nlm.nih.gov/pubmed/30472467

https://www.sciencedirect.com/science/article/pii/S0955395918302287

Impact of recreational and medicinal marijuana on surgical patients: A review.

American Journal of Surgery Home

“As medicinal and recreational marijuana use broadens across the United States, knowledge of its effects on the body will become increasingly important to all health care providers, including surgeons.

DATA SOURCES:

We performed a literature review of Pubmed for articles discussing the basic science related to cannabinoids, as well as articles regarding cannabinoid medications, and cannabis use in surgical patients.

CONCLUSIONS:

The primary components in the cannabis plant, tetrahydrocannabinol (THC) and cannabidiol (CBD), have been made available in numerous forms and formulations to treat multiple medical conditions, and recreational access to marijuana is increasing. Of particular importance to the surgeon may be their effects on prolonging intestinal motility, decreasing inflammation, increasing hunger, mitigating pain, and reducing nausea and vomiting. Perioperative use of medicinal or recreational marijuana will become increasingly prevalent, and the surgeon should be aware of the positive and negative effects of these cannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/30471810

https://www.americanjournalofsurgery.com/article/S0002-9610(18)31123-1/fulltext

Cannabinoids for Treating Cardiovascular Disorders: Putting Together a Complex Puzzle.

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“Cannabinoids have been increasingly gaining attention for their therapeutic potential in treating various cardiovascular disorders. These disorders include myocardial infarction, hypertension, atherosclerosis, arrhythmias, and metabolic disorders.

The aim of this review is to cover the main actions of cannabinoids on the cardiovascular system by examining the most recent advances in this field and major literature reviews.

It is well recognized that the actions of cannabinoids are mediated by either cannabinoid 1 or cannabinoid 2 receptors (CB2Rs). Endocannabinoids produce a triphasic response on blood pressure, while synthetic cannabinoids show a tissue-specific and species-specific response.

Blocking cannabinoid 1 receptors have been shown to be effective against cardiometabolic disorders, although this should be done peripherally. Blocking CB2Rs may be a useful way to treat atherosclerosis by affecting immune cells. The activation of CB2Rs was reported to be useful in animal studies of myocardial infarction and cardiac arrhythmia.

Although cannabinoids show promising effects in animal models, this does not always translate into human studies, and therefore, extensive clinical studies are needed to truly establish their utility in treating cardiovascular disease.”

https://www.ncbi.nlm.nih.gov/pubmed/30464888

Activating Cannabinoid Receptor 2 Protects Against Diabetic Cardiomyopathy Through Autophagy Induction.

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“Cannabinoid receptor 2 (CB2) has been reported to produce a cardio-protective effect in cardiovascular diseases such as myocardial infarction. Here in this study, we investigated the role of CB2 in diabetic cardiomyopathy (DCM) and its underlying mechanisms.

In conclusion, we initially demonstrated that activating CB2 produced a cardio-protective effect in DCM as well as cardiomyocytes under HG challenge through inducing the AMPK-mTOR-p70S6K signaling-mediated autophagy.”

https://www.ncbi.nlm.nih.gov/pubmed/30459625

“Taken together, in this study, we initially showed that activating CB2 produced a cardio-protective effect in DCM as well as cardiomyocytes under HG challenge through the induction of the AMPK-mTOR-p70S6K signaling-mediated autophagy process. We believe that the findings of this study might enhance our knowledge on the understanding of the pathogenesis and progression of DCM and provide a novel insight in the development of therapeutic strategies against DCM.”

https://www.frontiersin.org/articles/10.3389/fphar.2018.01292/full

Naturally occurring compounds as pancreatic cancer therapeutics.

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“Naturally occurring small molecule compounds have long been in the spotlight of pancreatic cancer research as potential therapeutics to prevent cancer progression and sensitize chemoresistant tumors. The hope is that terminal pancreatic cancer patients receiving aggressive chemotherapy can benefit from an increase in treatment efficacy without adding further toxicity by way of utilizing natural compounds. While preclinical studies on a number of natural compounds, such as resveratrol, curcumin, rapalogs and cannabinoids, show promising preclinical results, little has translated into clinical practice, though a number of other compounds hold clinical potential. Nevertheless, recent advances in compound formulation may increase the clinical utility of these compounds.”

https://www.ncbi.nlm.nih.gov/pubmed/30459936

“The combination of natural products and standard of care chemotherapy has the potential to increase quality of life and lifespan in pancreatic cancer patients, even though a number of hurdles need to be overcome for routine clinical use.”  http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=26234&path[]=81769

“Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress–Related Genes. In conclusion, results presented here show that cannabinoids exert a remarkable antitumoral effect on pancreatic cancer cells in vitro and in vivo due to their ability to selectively induce apoptosis of these cells via activation of the p8-ATF-4-TRB3 proapoptotic pathway.”  http://cancerres.aacrjournals.org/content/66/13/6748

IMPACT OF NEUROIMMUNE ACTIVATION INDUCED BY ALCOHOL OR DRUG ABUSE ON ADOLESCENT BRAIN DEVELOPMENT.

International Journal of Developmental Neuroscience

“Evidence obtained in recent decades has demonstrated that the brain still matures in adolescence. Changes in neural connectivity occur in different regions, including cortical and subcortical structures, which undergo modifications in white and gray matter densities. These alterations concomitantly occur in some neurotransmitter systems and hormone secretion, which markedly influence the refinement of certain brain areas and neural circuits.

The immaturity of the adolescent brain makes it more vulnerable to the effects of alcohol and drug abuse, whose use can trigger long-term behavioral dysfunction.

This article reviews the action of alcohol and drug abuse (cannabis, cocaine, opioids, amphetamines, anabolic androgenic steroids) in the adolescent brain, and their impact on both cognition and behavioral dysfunction, including predisposition to drug abuse in later life. It also discusses recent evidence that indicates the role of the neuroimmune system response and neuroinflammation as mechanisms that participate in many actions of ethanol and drug abuse in adolescence, including the neurotoxicity and alterations in neurocircuitry that contribute to the dysfunctional behaviors associated with addiction.

The new data suggest the therapeutic potential of anti-inflammatory targets to prevent the long-term consequences of drug abuse in adolescence.”

https://www.ncbi.nlm.nih.gov/pubmed/30468786

https://www.sciencedirect.com/science/article/pii/S073657481830251X?via%3Dihub

“Cannabinoids as novel anti-inflammatory drugs.”  https://www.ncbi.nlm.nih.gov/pubmed/20191092

Activation of GPR55 induces neuroprotection of hippocampal neurogenesis and immune responses of neural stem cells following chronic, systemic inflammation.

Brain, Behavior, and Immunity

“New neurons are continuously produced by neural stem cells (NSCs) within the adult hippocampus. Numerous diseases, including major depressive disorder and HIV-1 associated neurocognitive disorder, are associated with decreased rates of adult neurogenesis. A hallmark of these conditions is a chronic release of neuroinflammatory mediators by activated resident glia.

Recent studies have shown a neuroprotective role on NSCs of cannabinoid receptor activation. Yet, little is known about the effects of GPR55, a candidate cannabinoid receptor, activation on reductions of neurogenesis in response to inflammatory insult.

In the present study, we examined NSCs exposed to IL-1β in vitro to assess inflammation-caused effects on NSC differentiation and the ability of GPR55 agonists to attenuate NSC injury.

Taken together, these results suggest a neuroprotective role of GPR55 activation on NSCs in vitro and in vivo and that GPR55 provides a novel therapeutic target against negative regulation of hippocampal neurogenesis by inflammatory insult.”

The level of evidence of medical marijuana use for treating disabilities: a scoping review.

Publication Cover

“There is sufficient evidence that medical marijuana is effective in treating epileptic seizures and chronic pain.

Medical marijuana may improve the level of functioning and quality of life for individuals with certain disabilities.”

https://www.ncbi.nlm.nih.gov/pubmed/30456993

https://www.tandfonline.com/doi/abs/10.1080/09638288.2018.1523952?journalCode=idre20

Cannabis for the treatment of paediatric epilepsy? An update for Canadian paediatricians.

Issue Cover

“The plant Cannabis sativa produces over 140 known cannabinoids. These chemicals generate considerable interest in the medical research community for their possible application to several intractable disease conditions. Recent reports have prompted parents to strongly consider Cannabis products to treat their children with drug resistant epilepsy. Physicians, though, are reluctant to prescribe Cannabis products due to confusion about their regulatory status and limited clinical data supporting their use. We provide the general paediatrician with a brief review of cannabinoid biology, the literature regarding their use in children with drug resistant epilepsy, the current Health Canada and Canadian Paediatric Society recommendations and also the regulations from the physician regulatory bodies for each province and territory. Given the complexities of conducting research on Cannabis products for children with epilepsy, we also discuss outstanding research objectives that must be addressed to support Cannabis products as an accepted treatment option for children with refractory epilepsy.”

https://www.ncbi.nlm.nih.gov/pubmed/30455572

https://academic.oup.com/pch/article-abstract/23/6/368/4961446?redirectedFrom=fulltext

The endocannabinoid signaling system in cancer

Image result for trends in pharmacological sciences“Changes in lipid metabolism are intimately related to cancer. Several classes of bioactive lipids play roles in the regulation of signaling pathways involved in neoplastic transformation and tumor growth and progression.

The endocannabinoid system, comprising lipid-derived endocannabinoids, their G-protein-coupled receptors (GPCRs), and the enzymes for their metabolism, is emerging as a promising therapeutic target in cancer.

This report highlights the main signaling pathways for the antitumor effects of the endocannabinoid system in cancer and its basic role in cancer pathogenesis, and discusses the alternative view of cannabinoid receptors as tumor promoters.

We focus on new players in the antitumor action of the endocannabinoid system and on emerging crosstalk among cannabinoid receptors and other membrane or nuclear receptors involved in cancer. We also discuss the enzyme MAGL, a key player in endocannabinoid metabolism that was recently recognized as a marker of tumor lipogenic phenotype.”

https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(13)00044-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0165614713000448%3Fshowall%3Dtrue