Category Archives: Uncategorized

Cannabidivarin completely rescues cognitive deficits and delays neurological and motor defects in male Mecp2 mutant mice.

Posted on by

SAGE Journals“Recent evidence suggests that 2-week treatment with the non-psychotomimetic cannabinoid cannabidivarin (CBDV) could be beneficial towards neurological and social deficits in early symptomatic Mecp2 mutant mice, a model of Rett syndrome (RTT). The aim of this study was to provide further insights into the efficacy of CBDV in Mecp2-null mice using a lifelong treatment schedule to evaluate its effect on recognition memory and neurological defects in both early and advanced stages of the phenotype progression. CBDV rescues recognition memory deficits in Mecp2 mutant mice and delays the appearance of neurological defects. CBDV administration exerts an enduring rescue of memory deficits in Mecp2 mutant mice. CBDV delays neurological defects but this effect is only transient.” https://www.ncbi.nlm.nih.gov/pubmed/31084246

“Chronic treatment with the phytocannabinoid Cannabidivarin (CBDV) rescues behavioural alterations and brain atrophy in a mouse model of Rett syndrome.”  https://www.ncbi.nlm.nih.gov/pubmed/30056123

Terpenes in Cannabis sativa – From plant genome to humans.

Posted on by

Plant Science“Cannabis sativa (cannabis) produces a resin that is valued for its psychoactive and medicinal properties. Despite being the foundation of a multi-billion dollar global industry, scientific knowledge and research on cannabis is lagging behind compared to other high-value crops. This is largely due to legal restrictions that have prevented many researchers from studying cannabis, its products, and their effects in humans. Cannabis resin contains hundreds of different terpene and cannabinoid metabolites. Our understanding of the genomic and biosynthetic systems of these metabolites in cannabis, and the factors that affect their variability, is rudimentary. As a consequence, there is concern about lack of consistency with regard to the terpene and cannabinoid composition of different cannabis ‘strains’. Likewise, claims of some of the medicinal properties attributed to cannabis metabolites would benefit from thorough scientific validation.”
https://www.ncbi.nlm.nih.gov/pubmed/31084880 

https://www.sciencedirect.com/science/article/pii/S0168945219301190?via%3Dihub

“Medicinal properties of terpenes found in Cannabis sativa”   https://www.ncbi.nlm.nih.gov/pubmed/30096653

“Terpene synthases from Cannabis sativa”   https://www.ncbi.nlm.nih.gov/pubmed/28355238

Cannabinoid interactions with ion channels and receptors.

Posted on by

Publication Cover

“Cannabidiol (CBD), the non-psychoactive component of Cannabis sativa, acts on a diverse selection of membrane proteins with promising therapeutic potential in epilepsy and chronic pain. In this review, we will outline the studies that report reproducible results of CBD and other cannabinoids changing membrane channel function, with particular interest on Nav. Nav are implicated in fatal forms of epilepsy and are also associated with chronic pain. This makes Nav potential targets for CBD interaction since it has been reported to reduce pain and seizures. This discovery will not only prompt further research towards CBD’s characterization, but also promotes the application of cannabinoids as potentially therapeutic compounds for diseases like epilepsy and pain.” https://www.ncbi.nlm.nih.gov/pubmed/31088312
https://www.tandfonline.com/doi/full/10.1080/19336950.2019.1615824

Tetrahydrocannabinol Reduces Hapten-Driven Mast Cell Accumulation and Persistent Tactile Sensitivity in Mouse Model of Allergen-Provoked Localized Vulvodynia.

Posted on by

ijms-logo

“Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology.

Therapeutic intra-vaginal administration of Δ9-tetrahydrocannabinol (THC) reduced mast cell accumulation and tactile sensitivity.

Mast cell-targeted therapeutic strategies may therefore provide new ways to manage and treat vulvar pain potentially instigated by repeated allergenic exposures.”

https://www.ncbi.nlm.nih.gov/pubmed/31052404

https://www.mdpi.com/1422-0067/20/9/2163

“Marijuana Relieves Chronic Pain, Research Shows”  https://www.webmd.com/pain-management/news/20100830/marijuana-relieves-chronic-pain-research-show#1

Towards A Molecular Understanding of The Cannabinoid Related Orphan Receptor GPR18: A Focus on Its Constitutive Activity.

Posted on by

ijms-logo

“The orphan G-protein coupled receptor (GPCR), GPR18, has been recently proposed as a potential member of the cannabinoid family as it recognizes several endogenous, phytogenic, and synthetic cannabinoids. Potential therapeutic applications for GPR18 include intraocular pressure, metabolic disorders, and cancer. GPR18 has been reported to have high constitutive activity, i.e., activation/signaling occurs in the absence of an agonist. This activity can be reduced significantly by the A3.39N mutation. At the intracellular (IC) ends of (transmembrane helices) TMH3 and TMH6 in GPCRs, typically, a pair of oppositely charged amino acids form a salt bridge called the “ionic lock”. Breaking of this salt bridge creates an IC opening for coupling with G protein. The GPR18 “ionic lock” residues (R3.50/S6.33) can form only a hydrogen bond. In this paper, we test the hypothesis that the high constitutive activity of GPR18 is due to the weakness of its “ionic lock” and that the A3.39N mutation strengthens this lock. To this end, we report molecular dynamics simulations of wild-type (WT) GPR18 and the A3.39N mutant in fully hydrated (POPC) phophatidylcholine lipid bilayers. Results suggest that in the A3.39N mutant, TMH6 rotates and brings R3.50 and S6.33 closer together, thus strengthening the GPR18 “ionic lock”.”

https://www.ncbi.nlm.nih.gov/pubmed/31075933

https://www.mdpi.com/1422-0067/20/9/2300

Cannabis Use Does Not Affect Outcomes After Total Knee Arthroplasty.

Posted on by

Journal of Arthroplasty Home

“The self-reported use of cannabis has increased since its recent legalization in several states. The primary purpose of this study is to report total knee arthroplasty (TKA) outcomes in patients using cannabis.

RESULTS:

No difference in length of stay was noted between the users (46.9 hours ± 15.7) and nonusers (49.3 hours ± 20.4) (P = .464). In-hospital total morphine equivalents did not differ between the 2 groups (user = 137 ± 104 mg, nonuser = 146 ± 117 mg, P = .634). Postoperative range of motion did not differ between users (128.4° ± 10.4°) and nonusers (126.9° ± 7.5°) (P = .346). No mean differences in follow-up KSS (user = 180.1 ± 24.9, nonuser = 172.0 ± 33.9, P = .106) or total change (user = 61.7 ± 32.8, nonuser = 62.7 ± 30.7, P = .852) in KSS were noted. Likewise, no significant mean differences in Veterans RAND-12 (mental component scores: user = 54.8 ± 9.3, nonuser = 55.9 ± 8.79, P = .472; physical component scores: user = 48.3 ± 9.9, nonuser = 45.8 ± 10.1, P = .145) scores were demonstrated. There were no differences in readmissions (user = 5, nonuser = 4, P = .730) or reoperations (user = 5, nonuser = 2, P = .238).

CONCLUSION:

Cannabis use does not appear to influence (adverse or beneficial) short-term outcomes in patients undergoing a primary TKA. Further studies are warranted to determine the efficacy and safety of cannabis as a constituent of multimodal pain management following TKA before endorsements can be made by orthopedic surgeons.”

https://www.ncbi.nlm.nih.gov/pubmed/31072746

https://www.arthroplastyjournal.org/article/S0883-5403(19)30347-X/fulltext

Cannabidiol attenuates aggressive behavior induced by social isolation in mice: Involvement of 5-HT1A and CB1 receptors.

Posted on by

Progress in Neuro-Psychopharmacology and Biological Psychiatry

“Long-term single housing increases aggressive behavior in mice, a condition named isolation-induced aggression or territorial aggression, which can be attenuated by anxiolytic, antidepressant, and antipsychotic drugs.

Preclinical and clinical findings indicate that cannabidiol (CBD), a non-psychotomimetic compound from Cannabis sativa, has anxiolytic, antidepressant, and antipsychotic properties. Few studies, however, have investigated the effects of CBD on aggressive behaviors.

Here, we investigated whether CBD (5, 15, 30, and 60 mg/kg; i.p.) could attenuate social isolation-induced aggressive behavior in the resident-intruder test.

Taken together, our findings suggest that CBD may be therapeutically useful to treat aggressive behaviors that are usually associated with psychiatric disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31054943

https://www.sciencedirect.com/science/article/pii/S0278584618308340?via%3Dihub

“cannabidiol reduces aggressiveness, study concludes”  https://globalhealthnewswire.com/2019/07/31/cannabidiol-reduces-aggressiveness-study-concludes/

Comparison of different methods for the extraction of cannabinoids from cannabis.

Posted on by

 Publication Cover

“Cannabis oils, namely concentrated cannabis extracts, are getting plenty of attention because of their therapeutic potential for treatment of patients with cancer, HIV, multiple sclerosis and several other pathologies. Here we propose the use of ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) as alternative methods to the current protocols followed by pharmacists, the only authorized to manipulate standardized Cannabis. A third method, consisting of the use of Tween 20 as surfactant, was considered. Our best extraction methodology for commercial hemp extraction was applied to medicinal cannabis. Here we report the results obtained for ‘Eletta campana’, ‘Carmagnola selezionata’, Bediol®, FM2® and Bedrocan®.”

https://www.ncbi.nlm.nih.gov/pubmed/31035854

https://www.tandfonline.com/doi/abs/10.1080/14786419.2019.1601194?journalCode=gnpl20

Aging circadian rhythms and cannabinoids.

Posted on by

Neurobiology of Aging

“Numerous aspects of mammalian physiology exhibit cyclic daily patterns known as circadian rhythms. However, studies in aged humans and animals indicate that these physiological rhythms are not consistent throughout the life span. The simultaneous development of disrupted circadian rhythms and age-related impairments suggests a shared mechanism, which may be amenable to therapeutic intervention.

Recently, the endocannabinoid system has emerged as a complex signaling network, which regulates numerous aspects of circadian physiology relevant to the neurobiology of aging.

Agonists of cannabinoid receptor-1 (CB1) have consistently been shown to decrease neuronal activity, core body temperature, locomotion, and cognitive function. Paradoxically, several lines of evidence now suggest that very low doses of cannabinoids are beneficial in advanced age.

One potential explanation for this phenomenon is that these drugs exhibit hormesis-a biphasic dose-response wherein low doses produce the opposite effects of higher doses. Therefore, it is important to determine the dose-, age-, and time-dependent effects of these substances on the regulation of circadian rhythms and other processes dysregulated in aging.

This review highlights 3 fields-biological aging, circadian rhythms, and endocannabinoid signaling-to critically assess the therapeutic potential of endocannabinoid modulation in aged individuals. If the hormetic properties of exogenous cannabinoids are confirmed, we conclude that precise administration of these compounds may bidirectionally entrain central and peripheral circadian clocks and benefit multiple aspects of aging physiology.”

https://www.ncbi.nlm.nih.gov/pubmed/31035036

https://www.sciencedirect.com/science/article/pii/S0197458019300867?via%3Dihub

The Endocannabinoid System Is Present in Rod Outer Segments from Retina and Is Modulated by Light.

Posted on by

“The aim of the present research was to evaluate if the endocannabinoid system (enzymes and receptors) could be modulated by light in rod outer segment (ROS) from bovine retina. First, we analyzed endocannabinoid 2-arachidonoylglycerol (2-AG) metabolism in purified ROS obtained from dark-adapted (DROS) or light-adapted (LROS) retinas. To this end, diacylglycerol lipase (DAGL), monoacylglycerol lipase (MAGL), and lysophosphatidate phosphohydrolase (LPAP) enzymatic activities were analyzed using radioactive substrates. The protein content of these enzymes and of the receptors to which cannabinoids bind was determined by immunoblotting under light stimulus. Our results indicate that whereas DAGL and MAGL activities were stimulated in retinas exposed to light, no changes were observed in LPAP activity. Interestingly, the protein content of the main enzymes involved in 2-AG metabolism, phospholipase C β1 (PLCβ1), and DAGLα (synthesis), and MAGL (hydrolysis), was also modified by light. PLCβ1 content was increased, while that of lipases was decreased. On the other hand, light produced an increase in the cannabinoid receptors CB1 and CB2 and a decrease in GPR55 protein levels. Taken together, our results indicate that the endocannabinoid system (enzymes and receptors) depends on the illumination state of the retina, suggesting that proteins related to phototransduction phenomena could be involved in the effects observed.”

https://www.ncbi.nlm.nih.gov/pubmed/31016476

https://link.springer.com/article/10.1007%2Fs12035-019-1603-5