Effects of feeding a source of omega-3 fatty acid during the early postpartum period on the endocannabinoid system in the bovine endometrium.

Theriogenology

“A total of sixteen Holstein dairy cows (35 ± 1.1 kg/d of milk yield) were randomly assigned to consider the effects of feeding omega-3 sources on endometrial endocannabinoids system (ECS) genes expression to understand the effect mechanism of omega-3 on reproductive performances during the early postpartum period to evaluate to what extent can be intervened in reproduction, e.g. via nutrition to improve fertility. Experimental diets were 1) either protected palm oil (control) or 2) extruded linseed (linseed). Cows (n = 16) were fed from calving date to 70 days in milk (DIM). There was no difference between groups (mean ± S.E.M.) in parity (3.0 ± 1.00) or body condition score (BCS) at calving day (3.1 ± 0.25). At 30 DIM, the ovulatory cycles of cows were synchronized using two injections of prostaglandin F2α (PGF2α) with a 14-day interval. On day 15 of synchronized estrous cycle (d0 = ovulation) uterine endometrial biopsies were collected to evaluate the expression of genes related to ECS (endocannabinoid receptor (CNR2), N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), monoglyceride lipase (MGLL)) and PGF2α. Results showed that dry matter intake and milk yield were not affected by diets. Uterine endometrial NAAA (7.69 fold), and MGLL (1.96 fold) genes expression were greater (P < 0.05) in cows fed linseed compared with control ones. The messenger RNA (mRNA) levels of CNR-2 (4.26 fold), and NAPEPLD (20.0 fold) were decreased (P < 0.05) in animals fed linseed compared to control cows. The expression of mRNA for the FAAH was not influenced by the diets. First service conception rate was greater in cows fed linseed compared to control cows (75 vs. 25%). Pregnancy loss within 32-60 day after artificial insemination (AI) was lower in cows fed linseed compared to control cows (0 vs. 100%). In conclusion these data demonstrated that positive effect of omega-3 on reproduction may act through a mechanism involving the ECS. However, more studies to be undertaken to confirm these results.”

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The ameliorative effect of hemp seed hexane extracts on the Propionibacterium acnes-induced inflammation and lipogenesis in sebocytes.

“In this study, we investigated the anti-microbial, anti-inflammatory, and anti-lipogenic effects of hemp (Cannabis sativa L.) seed hexane extracts, focusing on the Propionibacterium acnes-triggered inflammation and lipogenesis.

Hemp seed hexane extracts (HSHE) showed anti-microbial activity against P. acnes.

The expression of iNOS, COX-2, and the subsequent production of nitric oxide and prostaglandin increased after infection of P. acnes in HaCaT cells, however, upon treating with HSHE, their expressions were reduced. P. acnes-induced expressions of IL-1β and IL-8 were also reduced.

HSHE exerted anti-inflammatory effects by regulating NF-κB and MAPKs signaling and blunting the translocation of p-NF-κB to the nucleus in P. acnes-stimulated HaCaT cells. Moreover, P. acnes-induced phosphorylation of ERK and JNK, and their downstream targets c-Fos and c-Jun, was also inhibited by HSHE. In addition, the transactivation of AP-1 induced by P. acnes infection was also downregulated by HSHE.

Notably, HSHE regulated inflammation and lipid biosynthesis via regulating AMPK and AKT/FoxO1 signaling in IGF-1-induced inflammation and lipogenesis of sebocytes. In addition, HSHE inhibited 5-lipoxygenase level and P. acnes-induced MMP-9 activity, and promoted collagen biosynthesis in vitro.

Thus, HSHE could be utilized to treat acne vulgaris, through its anti-microbial, anti-inflammatory, anti-lipogenic, and collagen-promoting properties.”

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Targeting the Endocannabinoid System for Prevention or Treatment of Chemotherapy-Induced Neuropathic Pain: Studies in Animal Models.

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“There is a scarcity of drugs to either prevent or properly manage chemotherapy-induced neuropathic pain (CINP). Cannabis or cannabinoids have been reported to improve pain measures in patients with neuropathic pain.

For this review, a search was done in PubMed for papers that examined the expression of and/or evaluated the use of cannabinoids or drugs that prevent or treat established CINP in a CB receptor-dependent manner in animal models.

Studies suggest there is a specific deficiency of endocannabinoids in the periphery during CINP.

Inhibitors of FAAH and MGL, enzymes that degrade the endocannabinoids, CB receptor agonists, desipramine, and coadministered indomethacin plus minocycline were found to either prevent the development and/or attenuate established CINP in a CB receptor-dependent manner.

The studies analysed suggest that targeting the endocannabinoid system for prevention and treatment of CINP is a plausible therapeutic option. Almost 90% of the studies on animal models of CINP analysed utilised male rodents. Taking into consideration clinical and experimental findings that show gender differences in the mechanisms involved in pain including CINP and in response to analgesics, it is imperative that future studies on CINP utilise more female models.”

“Cannabis or cannabinoids have been reported to improve pain measures in patients with neuropathic or cancer pain. The studies analysed suggest that targeting the endocannabinoid system for prevention and treatment of CINP is a plausible therapeutic option.” https://www.hindawi.com/journals/prm/2018/5234943/
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Variability of Multiple Sclerosis Spasticity Symptoms in Response to THC:CBD Oromucosal Spray: Tracking Cases through Clinical Scales and Video Recordings.

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“Multiple sclerosis (MS) is an inflammatory and neurodegenerative autoimmune demyelinating disease of the central nervous system. Patients exhibit heterogeneous patterns of disabling symptoms, including spasticity. In the majority of patients with MS spasticity, it and its associated symptoms contribute to disability, interfere with performance of everyday activities, and impair quality of life. Even under treatment with oral antispasticity drugs, about a third of patients continue to experience spasticity of moderate to severe intensity, underscoring the need for additional treatment options.

The efficacy of tetrahydrocannabinol: cannabidiol (THC:CBD) oromucosal spray as add-on therapy in patients with refractory MS spasticity has been demonstrated in clinical trials and observational studies.

To gain insight into patients’ response to treatment at the individual level, in-depth changes from baseline in various clinical scales and video-assessed parameters were evaluated in patients with resistant MS spasticity before and after 1 month of treatment with THC:CBD oromucosal spray. All 6 patients showed ≥20% improvement in the spasticity Numerical Rating Scale (i.e., were initial responders to treatment), but displayed individual variability in other spasticity-related parameters.

Improved Modified Ashworth Scale scores were observed in 5 cases, with a reduction of -2/-3 points in lower limb scores for 1 patient who also showed benefit in terms of a more stable gait but modest improvement in the timed 10-meter walk test (10MWT). Improvement in the 10MWT (or 25-foot walk test) was noted in 4 of the 6 cases. THC:CBD oromucosal spray also improved upper limb function as indicated by faster 9-Hole Peg Test results.”

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The Consumption of Cannabis by Fibromyalgia Patients in Israel.

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“OBJECTIVE:

To report on the habits of cannabis consumption among fibromyalgia patients in Israel.

RESULTS:

Of 2,705 people, 383 (14%) responded to the questionnaire, with a mean age of 42.2±14.2 years. Of the responders, 84% reported consuming cannabis, and 44% were licensed for MC. The mean amount per month of cannabis consumed was 31.4±16.3g, and 80% of cannabis consumers (CC) smoked pure cannabis or cannabis mixed with tobacco. Pain relief was reported by 94% of CC, while 93% reported improved sleep quality, 87% reported improvement in depression, and 62% reported improvement in anxiety. Of MC-licensed CC, 55% bought cannabis beyond the medical allowance on the black market. Adverse effects were reported by 12% of CC. Only 8% reported dependence on cannabis. Most CC (64%) worked either full- or part-time jobs, and 74% reported driving “as usual” under cannabis use.

CONCLUSIONS:

Cannabis consumption among fibromyalgia patients in our country is very common and is mostly not licensed. Nearly all CC reported favorable effects on pain and sleep, and few reported adverse effects or feeling of dependence on cannabis.”

“The results of our study should encourage both the Rheumatology Association in our country and the MCA to reconsider their stand on cannabis and include fibromyalgia among the indications for MC under certain restrictions.”
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A Brief Background on Cannabis: From Plant to Medical Indications.

 Ingenta Connect

“Cannabis has been used as a medicinal plant for thousands of years.

As a result of centuries of breeding and selection, there are now over 700 varieties of cannabis that contain hundreds of compounds, including cannabinoids and terpenes.

Cannabinoids are fatty compounds that are the main biological active constituents of cannabis. Terpenes are volatile compounds that occur in many plants and have distinct odors.

Cannabinoids exert their effect on the body by binding to receptors, specifically cannabinoid receptors types 1 and 2. These receptors, together with endogenous cannabinoids and the systems for synthesis, transport, and degradation, are called the Endocannabinoid System.

The two most prevalent and commonly known cannabinoids in the cannabis plant are delta-9-tetrahydrocannabinol (THC) and cannabidiol.

The speed, strength, and type of effects of cannabis vary based on the route of administration. THC is rapidly distributed through the body to fatty tissues like the brain and is metabolized by the cytochrome P450 system to 11-hydroxy-THC, which is also psychoactive.

Cannabis and cannabinoids have been indicated for several medical conditions.

There is evidence of efficacy in the symptomatic treatment of nausea and vomiting, pain, insomnia, post-traumatic stress disorder, anxiety, loss of appetite, Tourette’s syndrome, and epilepsy. Cannabis has also been associated with treatment for glaucoma, Huntington’s Disease, Parkinson’s Disease, and dystonia, but there is not good evidence to support its efficacy. Side effects of cannabis include psychosis and anxiety, which can be severe.

Here, we provided a summary of the history of cannabis, its pharmacology, and its medical uses.”

https://www.ncbi.nlm.nih.gov/pubmed/30139415

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Cannabinoids in dermatology: a scoping review.

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“The therapeutic applications of cannabis and cannabinoids are an increasingly conspicuous topic as de-criminalization and legalization of these products continues to expand.

A limited number of cannabinoid compounds have been approved for a specific set of conditions. However, the current role of cannabinoids for the treatment of dermatologic conditions remains to be defined.

We conducted a review of the current literature to determine the applications of cannabinoids for the therapy of various skin diseases.

After conducting our analysis, we found that cannabinoid products have the potential to treat a variety of skin conditions, including acne vulgaris, allergic contact dermatitis, asteatotic dermatitis, atopic dermatitis, hidradenitis suppurativa, Kaposi sarcoma, pruritus, psoriasis, skin cancer, and the cutaneous manifestations of systemic sclerosis. However, the majority of available data on these compounds are pre-clinical and there is a corresponding lack of high-quality randomized, controlled trials that evaluate their effects.

Cannabinoids have shown some initial promise as therapy for a variety of skin diseases. However, there is a requirement for thorough pre-clinical research and large-scale, randomized, controlled trials before cannabinoids can be considered safe and effective treatments for these conditions.”

“The endocannabinoid system of the skin. A potential approach for the treatment of skin disorders”  https://www.sciencedirect.com/science/article/abs/pii/S0006295218303484

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The endocannabinoid system of the skin. A potential approach for the treatment of skin disorders.

Biochemical Pharmacology

“The skin is the largest organ of the body and has a complex and very active structure that contributes to homeostasis and provides the first line defense against injury and infection.

In the past few years it has become evident that the endocannabinoid system (ECS) plays a relevant role in healthy and diseased skin.

Specifically, we review how the dysregulation of ECS has been associated to dermatological disorders such as atopic dermatitis, psoriasis, scleroderma and skin cancer. Therefore, the druggability of the ECS could open new research avenues for the treatment of the pathologies mentioned.

Numerous studies have reported that phytocannabinoids and their biological analogues modulate a complex network pharmacology involved in the modulation of ECS, focusing on classical cannabinoid receptors, transient receptor potential channels (TRPs), and peroxisome proliferator-activated receptors (PPARs).

The combined targeting of several end-points seems critical to provide better chances of therapeutically success, in sharp contrast to the one-disease-one-target dogma that permeates current drug discovery campaigns.”

https://www.ncbi.nlm.nih.gov/pubmed/30138623

https://www.sciencedirect.com/science/article/abs/pii/S0006295218303484

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Efficacy and Safety of Adjunctive Cannabidiol in Patients with Lennox-Gastaut Syndrome: A Systematic Review and Meta-Analysis.

“Lennox-Gastaut syndrome (LGS) is a severe developmental epileptic encephalopathy, and available interventions fail to control seizures in most patients. Cannabidiol (CBD) is a major chemical of marijuana, which has anti-seizure properties and different mechanisms of action compared with other approved antiepileptic drugs (AEDs).

OBJECTIVE:

The aim was to evaluate the efficacy and safety of CBD as adjunctive treatment for seizures in patients with LGS using meta-analytical techniques.

METHODS:

Randomized, placebo-controlled, single- or double-blinded trials were identified. Main outcomes included the ≥ 50% reduction in baseline drop and non-drop seizure frequency, and the incidence of treatment withdrawal and adverse events (AEs). Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated through the inverse variance method.

RESULTS:

Two trials were included involving 396 participants. Patients presenting ≥ 50% reduction in drop seizure frequency during the treatment were 40.0% with CBD and 19.3% with placebo [RR 2.12 (95% CI 1.48-3.03); p < 0.001]. The rate of non-drop seizure frequency was reduced by 50% or more in 49.4% of patients in the CBD and 30.4% in the placebo arms [RR 1.62 (95% CI 1.09-2.43); p = 0.018]. The RR for CBD withdrawal was 4.93 (95% CI 1.50-16.22; p = 0.009). The RR to develop any AE during CBD treatment was 1.24 (95% CI 1.11-1.38; p < 0.001). AEs significantly associated with CBD were somnolence, decreased appetite, diarrhea and increased serum aminotransferases.

CONCLUSIONS:

Adjunctive CBD resulted in a greater reduction in seizure frequency and a higher rate of AEs than placebo in patients with LGS presenting seizures uncontrolled by concomitant AEDs.”

“Cannabidiol in the Lennox-Gastaut Syndrome.”  https://www.nejm.org/doi/10.1056/NEJMc1807878

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Cannabinoids and reduced risk of hepatic steatosis in HIV-HCV co-infection: paving the way for future clinical research

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“Whether or not cannabis itself or cannabinoids contained in it may help to reduce hepatic steatosis in HIV-HCV coinfected patients remains an open question. The existing body of knowledge on the interactions between cannabis and the liver suggest a protective effect of cannabinoids on insulin resistance, diabetes, and NAFLD in the general population. Clinical research with randomized study designs is needed to evaluate the efficacy and safety of cannabis-based pharmacotherapies in HIV-HCV coinfected patients. Targeting the endocannabinoid system seems essential to differently manage several pathological conditions such as intestinal inflammation, obesity, diabetes and fatty liver disease. However, to date, few drugs have been tested in clinical trials. CB1-antagonists and CB2 agonists appear to be viable therapeutic options that need to be explored for the management of liver diseases. As HCV cure rates are coming close to 100% in the era of direct-acting antivirals, it is especially important to be able to identify modifiable risk factors of complications and death in HIV-HCV coinfected patients, as well as possible levers for intervention. Given the persistence of metabolic risk factors after HCV eradication, cannabis-based therapies need to be evaluated both as preventive and therapeutic tools in patients living with or at risk of liver steatosis, possibly in combination with existing conventional approaches.”

https://www.tandfonline.com/doi/full/10.1080/14787210.2018.1473764

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