Monthly Archives: October 2017

Monoacylglycerol lipase inhibitor JZL184 prevents HIV-1 gp120-induced synapse loss by altering endocannabinoid signaling.

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Neuropharmacology

“Monoacylglycerol lipase (MGL) hydrolyzes 2-arachidonoylglycerol to arachidonic acid and glycerol. Inhibition of MGL may attenuate neuroinflammation by enhancing endocannabinoid signaling and decreasing prostaglandin (PG) production. Almost half of HIV infected individuals are afflicted with HIV-associated neurocognitive disorder (HAND), a neuroinflammatory disease in which cognitive decline correlates with synapse loss. HIV infected cells shed the envelope protein gp120 which is a potent neurotoxin that induces synapse loss. Here, we tested whether inhibition of MGL, using the selective inhibitor JZL184, would prevent synapse loss induced by gp120. The number of synapses between rat hippocampal neurons in culture was quantified by imaging clusters of a GFP-tagged antibody-like protein that selectively binds to the postsynaptic scaffolding protein, PSD95. JZL184 completely blocked gp120-induced synapse loss. Inhibition of MGL decreased gp120-induced interleukin-1β (IL-1β) production and subsequent potentiation of NMDA receptor-mediated calcium influx. JZL184-mediated protection of synapses was reversed by a selective cannabinoid type 2 receptor (CB2R) inverse agonist/antagonist. JZL184 also reduced gp120-induced prostaglandin E2 (PGE2) production; PG signaling was required for gp120-induced IL-1β expression and synapse loss. Inhibition of MGL prevented gp120-induced synapse loss by activating CB2R resulting in decreased production of the inflammatory cytokine IL-1β. Because PG signaling was required for gp120-induced synapse loss, JZL184-induced decreases in PGE2 levels may also protect synapses. MGL presents a promising target for preventing synapse loss in neuroinflammatory conditions such as HAND.”

https://www.ncbi.nlm.nih.gov/pubmed/29061509

http://www.sciencedirect.com/science/article/pii/S0028390817304902?via%3Dihub

Medical Cannabis in Parkinson Disease: Real-Life Patients’ Experience.

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“The use of medical cannabis (MC) is controversial. Support for its benefits is based on small clinical series.

OBJECTIVE:

The aim of this study was to report the results of a standardized interview study that retrospectively assessed the effects of MC on symptoms of Parkinson disease (PD) and its adverse effects in patients treated for at least 3 months.

METHODS:

The survey used telephone interviews using a structured questionnaire based on subjective global impressions of change for various parkinsonian symptoms and yes/no questions on adverse effects.

RESULTS:

Forty-seven nondemented patients with PD (40 men) participated. Their mean age was 64.2 ± 10.8 years, mean disease duration was 10.8 ± 8.3 years, median Hoehn and Yahr (H&Y) was stage III. The duration of MC use was 19.1 ± 17.0 months, and the mean daily dose was 0.9 ± 0.5 g. The delivery of MC was mainly by smoking cigarettes (38 cases, 80.9%). Effect size (r) improvement for falls was 0.89, 0.73 for pain relief, 0.64 for depression, 0.64 for tremor, 0.62 for muscle stiffness, and 0.60 for sleep. The most frequently reported adverse effects from MC were cough (34.9%) in those who used MC by smoking and confusion and hallucinations (reported by 17% each) causing 5 patients (10.6%) to stop treatment.

CONCLUSIONS:

Medical cannabis was found to improve symptoms of PD in the initial stages of treatment and did not cause major adverse effects in this pilot, 2-center, retrospective survey. The extent of use and the reported effects lend support to further development of safer and more effective drugs derived from Cannabis sativa.”

https://www.ncbi.nlm.nih.gov/pubmed/29059132

https://insights.ovid.com/crossref?an=00002826-900000000-99616

Medical Cannabinoids in Children and Adolescents: A Systematic Review

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AAP Gateway

“CONTEXT: Legalization of medical marijuana in many states has led to a widening gap between the accessibility and the evidence for cannabinoids as a medical treatment.

OBJECTIVE: To systematically review published reports to identify the evidence base of cannabinoids as a medical treatment in children and adolescents.

RESULTS: Evidence for benefit was strongest for chemotherapy-induced nausea and vomiting, with increasing evidence of benefit for epilepsy.”  http://pediatrics.aappublications.org/content/early/2017/10/19/peds.2017-1818

“Limited data on medical cannabis use in children. Strongest evidence supports use to reduce seizures, side effects of chemotherapy.”  https://www.sciencedaily.com/releases/2017/10/171023094606.htm

“Marijuana Can Help Children with Seizures, Cancer Nausea”   https://www.healthline.com/health-news/marijuana-can-help-children-with-seizures-cancer-nausea

“Medical Marijuana Reduces CINV, Seizures in Children”  https://www.medscape.com/viewarticle/887616

Sativex in the management of multiple sclerosis-related spasticity: An overview of the last decade of clinical evaluation.

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Multiple Sclerosis and Related Disorders Home

“Spasticity is a common symptom of multiple sclerosis (MS) affecting about 80% of MS patients. Numerous lines of evidence suggest that spasticity due to its complexity is not adequately managed with conventional anti-spastic therapies. Therefore, in order to improve the outcomes for the majority of MS patients, alternative approaches are needed to be discovered. Over the last years, the use of cannabinoid compounds as a potential treatment for MS-related symptoms has aroused great interest, owing to encouraging preclinical and clinical studies. To date, Sativex, an oromucosal spray containing tetrahydrocannabinol and cannabidiol in approximately 1:1 ratio, is the only commercially available formulation containing cannabinoids used as add-on therapy for treatment of spasticity in adult MS patients who are not responding to conventional antispastic therapies.

METHODS:

Here, by performing a literature search, we provided an overview of the last decade of clinical evaluations as well as post-marketing studies about effectiveness and safety of Sativex in the management of MS-related spasticity.

RESULTS:

Sativex was proven effective in treating spasticity and also in improving the patient’s quality of life. In addition, a low incidence of adverse reactions Sativex-related supports the good safety profile and its tolerability.

CONCLUSION:

This review by recognizing the clinical effectiveness of Sativex in spasticity management, opened a new opportunity for many patients with spasticity resistant to common antispastic drugs.”

https://www.ncbi.nlm.nih.gov/pubmed/29055461

http://www.msard-journal.com/article/S2211-0348(17)30148-7/fulltext

THC/CBD oromucosal spray in patients with multiple sclerosis overactive bladder: a pilot prospective study.

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“Lower urinary tract dysfunctions (LUTDs) are commonly reported in multiple sclerosis (MS) patients and are mainly related to neurogenic overactive bladder (OAB).

The aim of this observational study was to assess the effect of a tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray on resistant OAB by means of clinical and instrumental tools.

The THC/CBD treatment successfully reduced the OAB symptoms.

THC/CBD oromucosal spray has shown to be effective in improving overactive bladder symptoms in MS patients demonstrating a favorable impact on detrusor overactivity.”

https://www.ncbi.nlm.nih.gov/pubmed/29052091

Novel Peripherally Restricted Cannabinoid 1 Receptor Selective Antagonist TXX-522 with Prominent Weight-Loss Efficacy in Diet Induced Obese Mice.

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“The clinical development of the first generation of globally active cannabinoid 1 receptor (CB1R) antagonists was suspended because of their adverse neuropsychiatric effects. Selective blockade of peripheral CB1Rs has the potential to provide a viable strategy for the treatment of severe obesity while avoiding these central nervous system side effects.

In the current study, a novel compound (TXX-522) was rationally designed based on the parent nucleus of a classical CB1R-selective antagonist/inverse agonist, rimonabant (SR141716A). Docking assays indicate that TXX-522 was bound with the CB1R in a mode similar to that of SR141716A. TXX-522 showed good binding, CB1R-selectivity (over the CB2R), and functional antagonist activities in a range of in vitro molecular and cellular assays.

In vivo analysis of the steady state distribution of TXX-522 in the rat brain and blood tissues and the assay of its functional effects on CB1R activity collectively showed that TXX-522 showed minimal brain penetration. Moreover, the in vivopharmacodynamic study further revealed that TXX-522 had good oral bioavailability and a potent anti-obesity effect, and ameliorated insulin resistance in high-fat diet-induced obese mice. No impact on food intake was observed in this model, confirming the limited brain penetration of this compound.

Thus, the current study indicates that TXX-522 is a novel and potent peripherally acting selective CB1R antagonist with the potential to control obesity and related metabolic disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/29051736

https://www.frontiersin.org/articles/10.3389/fphar.2017.00707/full

Inverse association of marijuana use with nonalcoholic fatty liver disease among adults in the United States.

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“The impact of marijuana on nonalcoholic fatty liver disease (NAFLD) is largely unknown. We studied the association between marijuana and NAFLD utilizing cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) from 2005-2014 and NHANES III (1988-1994).

RESULTS:

Of the 14,080 (NHANES 2005-2014) and 8,286 (NHANES III) participants, prevalence of suspected NAFLD and ultrasonographically-diagnosed NAFLD were inversely associated with marijuana use (p < 0.001). Compared to marijuana-naïve participants, marijuana users were less likely to have suspected NAFLD (odds ratio [OR]: 0.90, 95% confidence interval [CI]: 0.82-0.99 for past user; OR: 0.68, 95% CI: 0.58-0.80 for current user) and ultrasonographically-diagnosed NAFLD (OR: 0.75, 95% CI: 0.57-0.98 for current user) in the age, gender, ethnicity-adjusted model. On multivariate analysis, the ORs for suspected NAFLD comparing current light or heavy users to non-users were 0.76 (95% CI 0.58-0.98) and 0.70 (95% CI 0.56-0.89), respectively (P for trend = 0.001) with similar trends in ultrasonographically-diagnosed NAFLD (OR: 0.77, 95% CI: 0.59-1.00 for current user; OR: 0.71, 95% CI: 0.51-0.97 for current light user). In insulin resistance-adjusted model, marijuana use remained an independent predictor of lower risk of suspected NAFLD.

CONCLUSIONS:

In this nationally representative sample, active marijuana use provided a protective effect against NAFLD independent of known metabolic risk factors. The pathophysiology is unclear and warrants further investigation.”

https://www.ncbi.nlm.nih.gov/pubmed/29049354

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186702

Reprint of: survey of medicinal cannabis use among childbearing women: patterns of its use in pregnancy and retroactive self-assessment of its efficacy against ‘morning sickness’.

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Complementary Therapies in Clinical Practice

“A majority of women experience some nausea and/or vomiting during pregnancy. This condition can range from mild nausea to extreme nausea and vomiting, with 1-2% of women suffering from the life-threatening condition hyperemesis gravidarum.

Cannabis (Cannabis sativa) may be used therapeutically to mitigate pregnancy-induced nausea and vomiting.

This paper presents the results of a survey of 84 female users of medicinal cannabis, recruited through two compassion societies in British Columbia, Canada. Of the seventy-nine respondents who had experienced pregnancy, 51 (65%) reported using cannabis during their pregnancies. While 59 (77%) of the respondents who had been pregnant had experienced nausea and/or vomiting of pregnancy, 40 (68%) had used cannabis to treat the condition, and of these respondents, 37 (over 92%) rated cannabis as ‘extremely effective’ or ‘effective.’

Our findings support the need for further investigations into cannabis therapy for severe nausea and vomiting during pregnancy.”

https://www.ncbi.nlm.nih.gov/pubmed/19880090

“Marijuana use is common in pregnancy but may not be an independent risk factor for poor neonatal outcomes in term pregnancies.”  http://www.sciencedirect.com/science/article/pii/S000293781500527X

http://www.sciencedirect.com/science/article/pii/S1744388109000796?via%3Dihub

Marijuana use and HIV treatment outcomes among PWH receiving care at an urban HIV clinic.

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Journal of Substance Abuse Treatment

“While marijuana use is prevalent among persons with HIV (PWH), few studies have examined the relationship between marijuana use and HIV treatment outcomes independent of alcohol and other drug use.

METHODS:

We conducted a prospective cohort study to examine the relationships between frequency of marijuana use and antiretroviral therapy (ART) adherence and viral suppression in patients enrolled in the Johns Hopkins HIV Clinical Cohort between September 2013 through November 2015 (N=1377). We categorized marijuana use as no use, none in the last 3months, monthly use or less, weekly/daily. Our outcomes of interest were use of ART, ≥90 ART adherence, and viral suppression (HIV1-RNA<200 copies). We conducted multivariable analyses to examine associations between the frequency of marijuana use and our treatment outcomes, using generalized estimating equations to account for repeated measures. Other independent variables of interest included alcohol use, other drug use, and depressive symptoms. Analyses were adjusted for age, race, sex and HIV acquisition risk factor.

RESULTS:

In multivariable analyses we found no statistically significant association between frequency of marijuana use and our treatment outcomes. Alcohol use, other drug use and depressive symptoms were associated with lower odds of ART adherence and viral suppression.

CONCLUSIONS:

In this sample of PWH in care, frequency of marijuana use independent of other substance use does not appear to be associated with negative HIV treatment outcomes. Our results indicate that unlike alcohol, other substances and depression, marijuana use may not be a barrier to the effective treatment of HIV.”

https://www.ncbi.nlm.nih.gov/pubmed/29021107

http://www.journalofsubstanceabusetreatment.com/article/S0740-5472(17)30225-8/fulltext

Efficacy, tolerability and safety of cannabis-based medicines for chronic pain management – An overview of systematic reviews.

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European Journal of Pain

“Medicinal cannabis has already entered mainstream medicine in some countries.

Cannabis-based medicines undoubtedly enrich the possibilities of drug treatment of chronic pain conditions.

It remains the responsibility of the health care community to continue to pursue rigorous study of cannabis-based medicines to provide evidence that meets the standard of 21st century clinical care.”

https://www.ncbi.nlm.nih.gov/pubmed/29034533

http://onlinelibrary.wiley.com/doi/10.1002/ejp.1118/abstract