Tag Archives: Cannabinoids

Synergistic attenuation of chronic pain using mu opioid and cannabinoid receptor 2 agonists.

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“The misuse of prescription opiates is on the rise with combination therapies (e.g. acetaminophen or NSAIDs) resulting in severe liver and kidney damage. In recent years, cannabinoid receptors have been identified as potential modulators of pain and rewarding behaviors associated with cocaine, nicotine and ethanol in preclinical models. Yet, few studies have identified whether mu opioid agonists and CB2 agonists act synergistically to inhibit chronic pain while reducing unwanted side effects including reward liability.

We determined if analgesic synergy exists between the mu-opioid agonist morphine and the selective CB2 agonist, JWH015, in rodent models of acute and chronic inflammatory, post-operative, and neuropathic pain using isobolographic analysis. We also investigated if the MOR-CB2 agonist combination decreased morphine-induced conditioned place preference (CPP) and slowing of gastrointestinal transit. Co-administration of morphine with JWH015 synergistically inhibited preclinical inflammatory, post-operative and neuropathic-pain in a dose- and time-dependent manner; no synergy was observed for nociceptive pain. Opioid-induced side effects of impaired gastrointestinal transit and CPP were significantly reduced in the presence of JWH015.

Here we show that MOR + CB2 agonism results in a significant synergistic inhibition of preclinical pain while significantly reducing opioid-induced unwanted side effects.

The opioid sparing effect of CB2 receptor agonism strongly supports the advancement of a MOR-CB2 agonist combinatorial pain therapy for clinical trials.”

https://www.ncbi.nlm.nih.gov/pubmed/28007501

Marijuana use and inpatient outcomes among hospitalized patients: analysis of the nationwide inpatient sample database

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Cancer Medicine

“The purpose of this paper is to examine the relationship between marijuana use and health outcomes among hospitalized patients, including those hospitalized with a diagnosis of cancer.

A total of 387,608 current marijuana users were identified based on ICD-9 codes for marijuana use among hospitalized patients in the Nationwide Inpatient Sample database between 2007 and 2011. Logistic regression analysis was performed to determine the association between marijuana use and heart failure, cardiac disease, stroke, and in-hospital mortality. All models were adjusted for age, gender, race, residential income, insurance, residential region, pain, and number of comorbidities.

Among hospitalized patients, marijuana use was associated with a 60% increased odds of stroke (OR: 1.60, 95% CI: 1.44–1.77) compared with non-users, but significantly reduced odds of heart failure (OR: 0.78, 95% CI: 0.75–0.82), cardiac disease (OR: 0.86, 95% CI: 0.82–0.91), or in-hospital mortality (OR: 0.41, 95% CI: 0.38–0.44).

Among cancer patients, odds of in-hospital mortality was significantly reduced among marijuana users compared with non-users (OR: 0.44, 95% CI: 0.35–0.55).

Hospitalized marijuana users were more likely to experience a stroke compared with non-users, but less likely to experience in-hospital mortality.”

http://onlinelibrary.wiley.com/doi/10.1002/cam4.968/full

CB2 receptors regulate natural killer cells that limit allergic airway inflammation in a murine model of asthma.

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“Allergic asthma is a chronic airway inflammatory disease involving the complementary actions of innate and adaptive immune responses.

Endogenously generated cannabinoids, acting via CB2 receptors play important roles in both homeostatic and inflammatory processes. However, the contribution of CB2-acting eicosanoids to the innate events preceding sensitization to the common house dust mite (HDM) allergen, remain to be elucidated. We investigated the role of CB2 activation during allergen-induced pulmonary inflammation and NK cell effector function.

CONCLUSIONS:

Collectively, these results reveal that CB2 activation is crucial in regulating pulmonary NK cell function, and suggest that NK cells serve to limit ILC2 activation and subsequent allergic airway inflammation. CB2 inhibition may present an important target to modulate NK cell response during pulmonary inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/27992060

In vitro Antimicrobial and Antioxidant Activity of Extracts from Six Chemotypes of Medicinal Cannabis

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“Nowadays, medicinal cannabis (Cannabis sativa L) is in the focus of the researches not only for its high content of tetrahydrocannabinol (THC), but for other cannabinoids as well.

It has been reported that some of the identified substances (e.g. cannabidiol, cannabinochromene) possess anti-inflammatory and antimicrobial properties, which corresponds to its traditional use as wound healing agent at Pakistan.

The aim of this study was to evaluate antimicrobial and antioxidant ability of extracts from high potent Cannabis sativa chemotypes.

The six ethanolic extracts prepared from dried inflorescence of five medicinal cannabis chemotypes (Nurse Jackie, Jilly Bean, Nordle, Jack Cleaner, Conspiracy Kush) were tested by standard microdilution method against Staphylococcus aureus (three strains), Streptococcus pyogenes and the yeast Candida albicans.

Those microbial strains are present on skin and can cause complication during wound healing process.

The antioxidative activity, which plays an important role in wound healing process, was tested by oxygen radical absorbance capacity test (ORAC).

All tested extracts demonstrated high antimicrobial activity against two strains of S. aureus and S. pyogenes (MIC ranged from 4 – 16 µg·mL-1), moreover high antioxidant capacity was observed (ORAC ranged from 800 – 1300 µg TE/mg of extract).

The results indicate that cannabis has high potential to be used in ointments and other material for wound healing.

However, further research on the identification of the active components is needed.”

https://www.thieme-connect.com/DOI/DOI?10.1055/s-0036-1596302

The use of cannabinoids (CBs) for the treatment of chemotherapy-induced peripheral neuropathy (CIPN): A retrospective review.

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“CIPN is a common toxicity associated with the use of chemotherapy (CT) agents such as platinums, taxanes and vinca alkaloids. Patients (pts) may suffer from pain that adversely affects their quality of life, regardless of their disease trajectory.

Preclinical research has shown CBs to be effective in preventing CIPN.

CBs can be beneficial for cancer pain, although their specific benefit in pts with CIPN remains unknown.

Treatment with CBs appears to benefit some pts with CIPN.

Further research is needed to explore the optimal use of CBs in pts with CIPN.”

https://www.ncbi.nlm.nih.gov/pubmed/27962037

Cannabinoid 2 Receptor Agonist Improves Systemic Sensitivity to Insulin in High-Fat Diet/Streptozotocin-Induced Diabetic Mice.

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“The endocannabinoid signalling (ECS) system has been known to regulate glucose homeostasis.

Previous studies have suggested that the cannabinoid 2 (CB2) receptor may play a regulatory role on insulin secretion, immune modulation and insulin resistance.

Given that diabetes and insulin resistance are attributable to elevated inflammatory tone, we investigated the role of CB2 receptor on glucose tolerance and insulin sensitivity in high-fat diet (HFD)/streptozotocin (STZ)-induced mice.

Our data suggest a lipolytic role of SER601 in HFD/STZ-induced diabetic mice, which results in significant improvement of systemic insulin sensitivity.

Thus, the CB2 receptor may be considered a promising target for therapeutic development against insulin resistance and obesity-related diabetes.”

https://www.ncbi.nlm.nih.gov/pubmed/27960161

Fetal Syndrome of Endocannabinoid Deficiency (FSECD) In Maternal Obesity.

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“The theory of a fetal origin of adult diseases links many pathological conditions to very early life events and is known as a “developmental programming” phenomenon. The mechanisms of this phenomenon are not quite understood and have been explained by inflammation, stress, etc. In particular the epidemic of obesity, with more than 64% of women being overweight or obese, has been associated with conditions in later life such as mental disorders, diabetes, asthma, and irritable bowel syndrome.

Interestingly, these diseases were classified a decade ago as Clinical Syndrome of Endocannabinoid Deficiency (CECD), which was first described by Russo in 2004.

Cannabinoids have been used for the treatment of chronic pain for millenniums and act through the mechanism of “kick-starting” the components of the endogenous cannabinoid system (ECS).

ECS is a pharmacological target for the treatment of obesity, inflammation, cardiovascular and neuronal damage, and pain.

We hypothesize that the deteriorating effect of maternal obesity on offspring health is explained by the mechanism of Fetal Syndrome of Endocannabinoid Deficiency (FSECD), which accompanies maternal obesity. Here we provide support for this hypothesis.”

https://www.ncbi.nlm.nih.gov/pubmed/27959272

Compensatory activation of cannabinoid CB2 receptor inhibition of GABA release in the rostral ventromedial medulla (RVM) in inflammatory pain.

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“The rostral ventromedial medulla (RVM) is a relay in the descending pain modulatory system and an important site of endocannabinoid modulation of pain.

These studies demonstrate that endocannabinoid signaling to CB1- and CB2-receptors in adult RVM is altered in persistent inflammation.

The emergence of CB2 receptor function in the RVM provides additional rationale for the development of CB2 receptor-selective agonists as useful therapeutics for chronic inflammatory pain.”

https://www.ncbi.nlm.nih.gov/pubmed/27940994

Tamoxifen Isomers and Metabolites Exhibit Distinct Affinity and Activity at Cannabinoid Receptors: Potential Scaffold for Drug Development.

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“Tamoxifen (Tam) is a selective estrogen receptor (ER) modulator (SERM) that is an essential drug to treat ER-positive breast cancer. Aside from known actions at ERs, recent studies have suggested that some SERMs like Tam also exhibit novel activity at cannabinoidsubtype 1 and 2 receptors (CB1R and CB2Rs).

Collectively, these results suggest that the SERMs Tam, 4OHT and End elicit ER-independent actions via CBRs in an isomer-specific manner.

As such, this novel structural scaffold might be used to develop therapeutically useful drugs for treatment of a variety of diseases mediated via CBRs.”

 https://www.ncbi.nlm.nih.gov/pubmed/27936172

Paradoxical increase in synthetic cannabinoid emergency-related presentations after a citywide ban: Lessons from Houston, Texas.

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“Synthetic cannabinoids (SCs) have become a major drug of abuse associated with severe hospital presentations. There have been a variety of legislative efforts to regulate these drugs: The authors focus on trends in SC-related hospitalizations at Ben Taub General Hospital before and after a ban enacted by the city of Houston.

Data from all consults seen by Ben Taub’s Licensed Chemical Dependency Counselor were examined for changes in SC-related presentations before and after the ban. The findings were compared alongside other reports of current SC use.

A significant increase was found in the prevalence of SC-related presentations at Ben Taub Hospital following Houston’s citywide ban. These findings are consistent with other state and national data.

Houston’s ordinance was expected to decrease harmful effects of SC in the community; however, the data suggest an increase in presentations since the legislation was passed.

While further study is needed, it initially appears that the threat of SCs is still considerable despite policy efforts. These results suggest the need for further monitoring of SC use and continued collaboration toward effective public health measures.”

https://www.ncbi.nlm.nih.gov/pubmed/27936903