GPR55 – a putative “type 3” cannabinoid receptor in inflammation.

“G protein-coupled receptor 55 (GPR55) shares numerous cannabinoid ligands with CB1 and CB2 receptors despite low homology with those classical cannabinoid receptors. The pharmacology of GPR55 is not yet fully elucidated; however, GPR55 utilizes a different signaling system and downstream cascade associated with the receptor. Therefore, GPR55 has emerged as a putative “type 3″ cannabinoid receptor, establishing a novel class of cannabinoid receptor. Furthermore, the recent evidence of GPR55-CB1 and GPR55-CB2 heteromerization along with its broad distribution from central nervous system to peripheries suggests the importance of GPR55 in various cellular processes and pathologies and as a potential therapeutic target in inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/26669245

https://www.degruyter.com/view/j/jbcpp.2016.27.issue-3/jbcpp-2015-0080/jbcpp-2015-0080.xml

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The Effect of Medical Marijuana Laws on the Health and Labor Supply of Older Adults: Evidence from the Health and Retirement Study

 Journal of Policy Analysis and Management banner

“Older adults are at elevated risk of reducing labor supply due to poor health, partly because of high rates of symptoms that may be alleviated by medical marijuana. Yet, surprisingly little is known about how this group responds to medical marijuana laws (MMLs). We quantify the effects of state medical marijuana laws on the health and labor supply of adults age 51 and older, focusing on the 55 percent with one or more medical conditions with symptoms that may respond to medical marijuana. We use longitudinal data from the Health and Retirement Study to estimate event study and differences‐in‐differences regression models. Three principle findings emerge from our analysis. First, active state medical marijuana laws lead to lower pain and better self‐assessed health among older adults. Second, state medical marijuana laws lead to increases in older adult labor supply, with effects concentrated on the intensive margin. Third, the effects of MMLs are largest among older adults with a health condition that would qualify for legal medical marijuana use under current state laws. Findings highlight the role of health policy in supporting work among older adults and the importance of including older adults in assessments of state medical marijuana laws.”

https://onlinelibrary.wiley.com/doi/10.1002/pam.22122

https://www.jhsph.edu/news/news-releases/2019/medical-marijuana-laws-linked-to-health-and-labor-supply-benefits-in-older-adults.html?fbclid=IwAR2X_qV1jKU4Hj41KBHAr25o20CBZrWEIqfkcxCxzepC_2NLvsSRxeCNA9g

“Medical marijuana may increase productivity in older adults, Johns Hopkins study suggests” https://www.news5cleveland.com/news/national/medical-marijuana-may-increase-productivity-in-older-adults-johns-hopkins-study-suggests

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Daily Practice Managing Resistant Multiple Sclerosis Spasticity With Delta-9-Tetrahydrocannabinol: Cannabidiol Oromucosal Spray: A Systematic Review of Observational Studies.

 Image result for journal of central nervous system disease“Spasticity is one of the most common symptoms in people with multiple sclerosis (MS). Conventional anti-spasticity agents have limitations in their efficacy and tolerability.

Delta-9-tetrahydrocannabinol: cannabidiol (THC:CBD) spray, a cannabinoid-based medicine, is approved as an add-on therapy for MS spasticity not adequately controlled by other anti-spasticity medications. The results from randomized controlled trials (RCTs) have demonstrated a reduction in the severity of spasticity and associated symptoms. However, RCTs do not always reflect real-life outcomes. We systematically reviewed the complementary evidence from non-interventional real-world studies.

METHODS:

A systematic literature review was conducted to identify all non-RCT publications on THC:CBD spray between 2011 and 2017. Data on study design, patient characteristics, effectiveness, and safety outcomes were extracted from those publications meeting our inclusion criteria.

RESULTS:

In total, we reviewed 14 real-world publications including observational studies and treatment registries. The proportion of patients reaching the threshold of minimal clinical important difference (MCID), with at least a 20% reduction of the spasticity Numeric Rating Scale (NRS) score after 4 weeks ranged from 41.9% to 82.9%. The reduction in the mean NRS spasticity score after 4 weeks was maintained over 6-12 months. The average daily dose was five to six sprays. Delta-9-tetrahydrocannabinol: cannabidiol was well tolerated in the evaluated studies in the same way as in the RCTs. No new or unexpected adverse events or safety signals were reported in everyday clinical practice.

CONCLUSIONS:

The data evaluated in this systematic review provide evidence for the efficacy and safety of THC:CBD in clinical practice and confirm results obtained in RCTs.”

https://www.ncbi.nlm.nih.gov/pubmed/30886530

https://journals.sagepub.com/doi/10.1177/1179573519831997

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The endocannabinoid system in migraine: from bench to pharmacy and back.

 Image result for curr opin neurol“Migraine is a common, highly disabling disorder. Its treatment involves acute and preventive therapy. Many of available preventive medications are not well tolerated, which results in poor compliance and limited effectiveness. Cannabinoids have been proposed for the treatment of migraine but their efficacy and tolerability are controversial.

RECENT FINDINGS:

Cannabinoids modulate functions and activity of signaling pathways that have a key role in pain control. Growing preclinical evidence and initial clinical findings suggest that modulation of the endocannabinoid system, via endogenous or exogenous cannabinoids may be relevant for migraine via multiple mechanisms.

SUMMARY:

The endocannabinoid system qualifies as an interesting area of research worth exploration in the quest for therapeutic targets for the treatment of migraine.”

https://www.ncbi.nlm.nih.gov/pubmed/30883435

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Role of the endocannabinoid system in neurological disorders.

International Journal of Developmental Neuroscience

“Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that begins in infancy. Although the etiology and pathogenesis are poorly understood, many studies have shown that ASD is closely related to structural and functional defects in the nervous system, especially synaptic transmission. The endocannabinoid (eCB) system is an important regulatory system of the central nervous system that regulates neurotransmission and synaptic plasticity and plays an important role in emotional and social responses and cognitive function. The relationship between eCB system and ASD has attracted increasing attention from scholars. In this review, we discuss the complex lipid signaling network of the eCB system, intracellular transport pathways, abnormal expression and association with various neurological diseases, and direct and indirect evidence for the link between eCB and ASD. Collectively, the findings to date indicate that the eCB system plays a key role in the pathophysiology of ASD and can provide new insights into potential interventions and rehabilitation strategies for ASD.”

https://www.ncbi.nlm.nih.gov/pubmed/30858029

https://www.sciencedirect.com/science/article/abs/pii/S0736574818302995?via%3Dihub

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Are cannabis users less likely to gain weight? Results from a national 3-year prospective study.

International Journal of Epidemiology

“Pre-clinical studies indicate increased food intake and weight gain as cannabinoid effects. Cross-sectional epidemiological studies, however, indicate lower prevalence of obesity among cannabis users. Here, we aim to study the weight-gain research question in the prospectively conducted National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).

RESULTS:

At W2, 77% of the participants never used cannabis, 18% had discontinued use (‘quit’), 3% were initiates and 2% were persistent users. Estimated W1-to-W2 BMI change shows an increase for all subgroups. Compared with never-users (reference), inverse slope estimates and attenuated change (%) in BMI between W1 and W2 are seen for cannabis-use subgroups: quitters [β = -0.81; 95% confidence interval (CI) = -1.01, -0.60], initiates (β = -0.97; 95% CI = -1.36, -0.57) and persistent users (β = -1.26; 95% CI = -1.81, -0.72).

CONCLUSION:

This new prospective study builds from anecdotes, pre-clinical studies and cross-sectional evidence on inverse associations linking cannabis use and obesity and shows an inverse cannabis-BMI increase association. Confirmatory studies with rigorous cannabis and BMI assays will be needed.”

https://www.ncbi.nlm.nih.gov/pubmed/30879064

https://academic.oup.com/ije/advance-article-abstract/doi/10.1093/ije/dyz044/5382155?redirectedFrom=fulltext

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Cannabimimetic plants: are they new cannabinoidergic modulators?

“Phytochemicals and secondary metabolites able to interact with the endocannabinoid system (Cannabimimetics) have been recently described in a broad range of plants and fruits. These findings can open new alternative avenues to explore for the development of novel therapeutic compounds. The cannabinoids regulate many physiological and pathological functions in both animals and plants. Cannabis sativa is the main plant that produces phytocannabinoids inside resins capable to defend the plant from the aggression of parasites and herbivores. Animals produce anandamide and 2-arachidonoyl glycerol, which thanks to binding with main receptors such as type-1 cannabinoid receptor (CB1R) and the type-2 cannabinoid receptor (CB2R) are involved in inflammation processes and several brain functions. Endogenous cannabinoids, enzymes for synthesis and degradation of cannabinoids, and CB1R and CB2R constitute the endocannabinoid system (ECS). Other plants can produce cannabinoid-like molecules such as perrottetinene extracted from Radula perrottetii, or anandamide and 2-arachidonoyl glycerol extracted from some bryophytes. Moreover, several other secondary metabolites can also interact with the ECS of animals and take the name of cannabimimetics. These phytoextracts not derived from Cannabis sativa can act as receptor agonists or antagonist, or enzyme inhibitors of ECS and can be involved in the inflammation, oxidative stress, cancer, and neuroprotection. Finally, given the evolutionary heterogeneity of the cannabimimetic plants, some authors speculated on the fascinating thesis of the evolutionary convergence between plants and animals regarding biological functions of ECS. The review aims to provide a critical and complete assessment of the botanical, chemical and therapeutic aspects of cannabimimetic plants to evaluate their spread in the world and medicinal potentiality.”

https://www.ncbi.nlm.nih.gov/pubmed/30877436

https://link.springer.com/article/10.1007%2Fs00425-019-03138-x

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Analyzing the role of cannabinoids as modulators of Wnt/β-catenin signaling pathway for their use in the management of neuropathic pain.

Bioorganic & Medicinal Chemistry Letters

“Neuropathic pain is a debilitating form of treatment-resistant chronic pain caused by damage to the nervous system. Cannabinoids have been known for suppressing neuropathic pain by modulating the endo cannabinoid system. Since the canonical Wnt/β-catenin signaling has recently been implicated in pain sensation, we investigated the impact of major cannabinoids (1-6) from the leaves of Cannabis sativa and an epoxy derivative of compound 2, here upon referred to as 2a, on modulating Wnt/β-catenin signaling pathway. The results presented in this study show that compound 1, 2 and 2a exhibited potent inhibitory activity against Wnt/β-catenin pathway in a dose-dependent manner. Compound 2a was seen to inhibit this pathway at slightly lower concentrations than its parent molecule 2, under similar conditions. Taken together, compound 1, 2 and 2a, by virtue of their inhibition of Wnt/β-catenin signaling pathway, could be developed as effective neuroprotective agents for the management of neuropathic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/30871771

https://www.sciencedirect.com/science/article/pii/S0960894X19301428?via%3Dihub

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CBD as the New Medicine in the Pain Provider’s Armamentarium.

“As providers who currently treat some chronic pain patients with CBD oil as part of a multimodal analgesic treatment regimen, we have found great benefit of this new weapon recently being utilized in our armamentarium. As mentioned in the article, the current political climate surrounding CBD is both vague and ever-changing, which can and does impact treatment and subsequent patient outcomes as pain medicine providers. If we want to make cannabis and CBD into a legitimate medicinal treatment, there must be more regulations on CBD oil production and accurate labeling. Patients will continue to seek CBD oil as an additional option to treat their chronic pain as it gains popularity, so it is our duty as providers to protect them and ensure they have safe options of this new medication to choose from.”
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Illicit drug use and prescription drug misuse among young adult medical cannabis patients and non-patient users in Los Angeles

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

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