Category Archives: Uncategorized

Patient-Reported Symptom Relief Following Medical Cannabis Consumption

Posted on by
Reply

Image result for frontiers in pharmacology

“The Releaf AppTM mobile software application (app) data was used to measure self-reported effectiveness and side effects of medical cannabis used under naturalistic conditions.

Results: Releaf AppTM responders used cannabis to treat myriad health symptoms, the most frequent relating to pain, anxiety, and depressive conditions. Significant symptom severity reductions were reported for all the symptom categories, with mean reductions between 2.8 and 4.6 points (ds ranged from 1.29–2.39, ps < 0.001). On average, higher pre-dosing symptom levels were associated with greater reported symptom relief, and users treating anxiety or depression-related symptoms reported significantly more relief (ps < 0.001) than users with pain symptoms. Of the 42 possible side effects, users were more likely to indicate and showed a stronger correlation between symptom relief and experiences of positive (94% of sessions) or a context-specific side effects (76%), whereas negative side effects (60%) were associated with lessened, yet still significant symptom relief and were more common among patients treating a depressive symptom relative to patients treating anxiety and pain-related conditions.

Conclusion: Patient-managed cannabis use is associated with clinically significant improvements in self-reported symptom relief for treating a wide range of health conditions, along with frequent positive and negative side effects.”

https://www.ncbi.nlm.nih.gov/pubmed/30210337

https://www.frontiersin.org/articles/10.3389/fphar.2018.00916/full

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

Posted on by
Reply

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.”

https://www.ncbi.nlm.nih.gov/pubmed/30145543
https://www.sciencedirect.com/science/article/pii/S0093691X18305880?via%3Dihub

A Brief Background on Cannabis: From Plant to Medical Indications.

Posted on by
Reply

 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

http://www.ingentaconnect.com/content/aoac/jaoac/pre-prints/content-jaoac_180208;jsessionid=jbg0paav7wra.x-ic-live-03

Cannabinoid signalling in the immature brain: encephalopathies and neurodevelopmental disorders.

Posted on by
Reply

Biochemical Pharmacology

“The endocannabinoid system exerts a crucial neuromodulatory role in many brain areas that is essential for proper regulation of neuronal activity. The role of cannabinoid signalling controlling neuronal activity in the adult brain is also evident when considering its contribution to adult brain insults or neurodegenerative diseases.

In the context of brain genetic or acquired encephalopathies administration of cannabinoid-based molecules has demonstrated to exert symptomatic relief and hence, they are proposed as new potential therapeutic compounds.

This review article summarizes the main evidences indicating the beneficial action of cannabinoid-derived molecules in preclinical models of neonatal hypoxia/ischemic damage. In a second part, we discuss the available evidences of therapeutic actions of cannabidiol in children with refractory epilepsy syndromes. Finally, we discuss the current view of cannabinoid signalling mechanisms active in the immature brain that affect in neural cell fate and can contribute to long-term neural cell plasticity.”

https://www.ncbi.nlm.nih.gov/pubmed/30118663

https://www.sciencedirect.com/science/article/abs/pii/S0006295218303344

Acute inflammation: endogenous cannabinoids mellow the harsh proinflammatory environment.

Posted on by
Reply

Image result for jci journal of clinical investigation

“Under normal conditions, there is a paucity of neutrophils within the intestinal mucosa; however, these innate immune cells rapidly infiltrate the mucosa in response to infection and are critical for pathogen control. Unfortunately, these cells can cause extensive damage to the intestine if the initial inflammatory influx is not resolved. Factors that promote resolution of inflammation are of great interest, as they have therapeutic potential for limiting uncontrolled inflammatory damage. In this issue of the JCI, Szabady et al. demonstrate that the multidrug resistance transporter P-glycoprotein (P-gp) secretes endocannabinoids into the intestinal lumen that counteract the proinflammatory actions of the eicosanoid hepoxilin A3, which is secreted into the lumen by the efflux pump MRP2 and serves as a potent neutrophil chemoattractant. Moreover, the antiinflammatory actions of P-gp-secreted endocannabinoids were mediated by peripheral cannabinoid receptor CB2 on neutrophils. Together, the results of this study identify an important mechanism by which endogenous endocannabinoids facilitate the resolution of inflammation; this mechanism has potential to be therapeutically exploited.”

 https://www.ncbi.nlm.nih.gov/pubmed/30102253
https://www.jci.org/articles/view/122885
“Cannabinoids as novel anti-inflammatory drugs” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828614/

Intestinal P-glycoprotein exports endocannabinoids to prevent inflammation and maintain homeostasis.

Posted on by
Reply

Image result for jci journal of clinical investigation

“Neutrophil influx into the intestinal lumen is a critical response to infectious agents, but is also associated with severe intestinal damage observed in idiopathic inflammatory bowel disease. The chemoattractant hepoxilin A3, an eicosanoid secreted from intestinal epithelial cells by the apically restricted efflux pump multidrug resistance protein 2 (MRP2), mediates this neutrophil influx. Information about a possible counterbalance pathway that could signal the lack of or resolution of an apical inflammatory signal, however, has yet to be described. We now report a system with such hallmarks. Specifically, we identify endocannabinoids as the first known endogenous substrates of the apically restricted multidrug resistance transporter P-glycoprotein (P-gp) and reveal a mechanism, which we believe is novel, for endocannabinoid secretion into the intestinal lumen. Knockdown or inhibition of P-gp reduced luminal secretion levels of N-acyl ethanolamine-type endocannabinoids, which correlated with increased neutrophil transmigration in vitro and in vivo. Additionally, loss of CB2, the peripheral cannabinoid receptor, led to increased pathology and neutrophil influx in models of acute intestinal inflammation. These results define a key role for epithelial cells in balancing the constitutive secretion of antiinflammatory lipids with the stimulated secretion of proinflammatory lipids via surface efflux pumps in order to control neutrophil infiltration into the intestinal lumen and maintain homeostasis in the healthy intestine.”

https://www.ncbi.nlm.nih.gov/pubmed/30102254

https://www.jci.org/articles/view/96817

Treatment of Periodontal Ligament Stem Cells with MOR and CBD Promotes Cell Survival and Neuronal Differentiation via the PI3K/Akt/mTOR Pathway.

Posted on by
Reply

ijms-logo

“Periodontal ligament mesenchymal stem cells (hPDLSCs), as well as all mesenchymal stem cells, show self-renewal, clonogenicity, and multi-tissue differentiation proprieties and can represent a valid support for regenerative medicine. We treated hPDLSCs with a combination of Moringin (MOR) and Cannabidiol (CBD), in order to understand if treatment could improve their survival and their in vitro differentiation capacity. Stem cells survival is fundamental to achieve a successful therapy outcome in the re-implanted tissue of patients. Through NGS transcriptome analysis, we found that combined treatment increased hPDLSCs survival, by inhibition of apoptosis as demonstrated by enhanced expression of anti-apoptotic genes and reduction of pro-apoptotic ones. Moreover, we investigated the possible involvement of PI3K/Akt/mTOR pathway, emphasizing a differential gene expression between treated and untreated cells. Furthermore, hPDLSCs were cultured for 48 h in the presence or absence of CBD and MOR and, after confirming the cellular viability through MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazoliumbromide) assay, we examined the presence of neuronal markers, through immunofluorescence analysis. We found an increased expression of Nestin and GAP43 (growth associated protein 43) in treated cells. In conclusion, hPDLSCs treated with Moringin and Cannabidiol showed an improved survival capacity and neuronal differentiation potential.”

https://www.ncbi.nlm.nih.gov/pubmed/30096889

http://www.mdpi.com/1422-0067/19/8/2341

Medical marijuana laws and workplace fatalities in the United States

Posted on by
Reply

International Journal of Drug Policy

“The aim of this research was to determine the association between legalizing medical marijuana and workplace fatalities.

To date, 29 states and the District of Columbia have legalized the use of marijuana for medicinal purposes. Although there is increasing concern that legalizing medical marijuana will make workplaces more dangerous, little is known about the relationship between medical marijuana laws (MMLs) and workplace fatalities.

 

Findings

Legalizing medical marijuana was associated with a 19.5% reduction in the expected number of workplace fatalities among workers aged 25–44 (incident rate ratio [IRR], 0.805; 95% CI, .662–.979). The association between legalizing medical marijuana and workplace fatalities among workers aged 16–24, although negative, was not statistically significant at conventional levels. The association between legalizing medical marijuana and workplace fatalities among workers aged 25–44 grew stronger over time. Five years after coming into effect, MMLs were associated with a 33.7% reduction in the expected number of workplace fatalities (IRR, 0.663; 95% CI, .482–.912). MMLs that listed pain as a qualifying condition or allowed collective cultivation were associated with larger reductions in fatalities among workers aged 25–44 than those that did not.

Conclusions

The results provide evidence that legalizing medical marijuana improved workplace safety for workers aged 25–44. Further investigation is required to determine whether this result is attributable to reductions in the consumption of alcohol and other substances that impair cognitive function, memory, and motor skills.”

https://www.sciencedirect.com/science/article/pii/S0955395918301968

“Workplace Deaths Drop After States Legalize Medical Marijuana”  https://www.marijuanamoment.net/workplace-deaths-drop-after-states-legalize-medical-marijuana/

“Medical Marijuana States Have Lower Rates Of Workplace Death, According To New Study” https://www.civilized.life/articles/medical-marijuana-states-have-lower-rates-of-workplace-death-according-to-new-study/

“States with legal medical marijuana have seen a drop in workplace deaths” https://www.businessinsider.com/fatal-work-injuries-decline-in-states-with-medical-marijuana-laws-2019-4

“Legalizing Medical Marijuana Could Make Workplaces Safer.”  https://thefreshtoast.com/cannabis/legalizing-medical-marijuana-could-make-workplaces-safer/

Neuronal preservation and reactive gliosis attenuation following neonatal sciatic nerve axotomy by a fluorinated cannabidiol derivative.

Posted on by
Reply

Neuropharmacology

“Immature peripheral nervous system damage, such as the transection of a peripheral nerve, results in the extensive degeneration of motoneurons and dorsal root ganglia (DRG) sensory neurons, mostly due to apoptotic events.

We have previously shown that cannabidiol (CBD), the most abundant non-psychotropic molecule present in the Cannabis sativa plant, exhibits neuroprotective action when administered daily at a dose of 15 mg/kg.

This study shows that use of the fluorinated synthetic version of CBD (4′-fluoro-cannabidiol, HUF-101) significantly improves neuronal survival by 2-fold compared to that achieved with traditional CBD at one-third the dose. Furthermore, we show that HUF-101 administration significantly upregulates anti-apoptotic genes and blocks the expression of pro-apoptotic nuclear factors.

Two-day-old Wistar rats were subjected to unilateral sectioning of the sciatic nerve and treated daily with HUF-101 (1, 2.5, 5 mg/kg/day, i.p.) or a vehicle solution for five days.

The results were evaluated by Nissl staining, immunohistochemistry, and qRT-PCR. Neuronal counting revealed a 47% rescue of spinal motoneurons and a 79% rescue of DRG neurons (HUF-101, 5 mg/kg). Survival was associated with complete depletion of p53 and a 60-fold elevation in BCL2-like 1 gene expression.

Additionally, peroxisome proliferator-activated receptor gamma (PPAR-gamma) gene expression was downregulated by 80%. Neuronal preservation was coupled with a high preservation of synaptic coverage and a reduction in astroglial and microglial reactions that were evaluated in nearby spinal motoneurons present in the ventral horn of the lumbar intumescence.

Overall, these data strongly indicate that HUF-101 exerts potent neuroprotective effects that are related to anti-apoptotic protection and the reduction of glial reactivity.”

 https://www.ncbi.nlm.nih.gov/pubmed/30096328
https://www.sciencedirect.com/science/article/pii/S0028390818304830?via%3Dihub

Medicinal properties of terpenes found in Cannabis sativa and Humulus lupulus.

Posted on by
Reply

European Journal of Medicinal Chemistry

“Cannabaceae plants Cannabis sativa L. and Humulus lupulus L. are rich in terpenes – both are typically comprised of terpenes as up to 3-5% of the dry-mass of the female inflorescence.

Terpenes of cannabis and hops are typically simple mono- and sesquiterpenes derived from two and three isoprene units, respectively. Some terpenes are relatively well known for their potential in biomedicine and have been used in traditional medicine for centuries, while others are yet to be studied in detail.

The current, comprehensive review presents terpenes found in cannabis and hops. Terpenes’ medicinal properties are supported by numerous in vitro, animal and clinical trials and show anti-inflammatory, antioxidant, analgesic, anticonvulsive, antidepressant, anxiolytic, anticancer, antitumor, neuroprotective, anti-mutagenic, anti-allergic, antibiotic and anti-diabetic attributes, among others.

Because of the very low toxicity, these terpenes are already widely used as food additives and in cosmetic products. Thus, they have been proven safe and well-tolerated.”

 https://www.ncbi.nlm.nih.gov/pubmed/30096653
https://www.sciencedirect.com/science/article/pii/S0223523418306408?via%3Dihub