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

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

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Medical Cannabis Use in Glioma Patients Treated at a Comprehensive Cancer Center in Florida.

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“Glioma is a devastating primary tumor of the central nervous system with difficult-to-manage symptoms.

Cannabis products have been postulated to potentially benefit glioma patients. Recent state legalization allowed investigators an opportunity to study glioma patients’ adoption of medical marijuana (MM).

Objective: Our goals were to: (1) determine the prevalence of marijuana use, both through physician recommendation and self-medication, and (2) evaluate its perceived risks and benefits in glioma patients.

Results: A total of 73 patients were surveyed. The majority of participants were aware that MM was legal in the state, and most reported learning of this through the media. Over 70% of participants reported having considered using MM, and a third reported using marijuana products after their diagnosis. Most received recommendations from friends/family rather than a medical provider, and only half of the users had obtained a physician’s recommendation. Users generally reported benefits.

Conclusions: With the increasing national conversation that accompanies legalization, glioma patients are pursuing marijuana for the treatment for their symptoms. More research and education is needed to bring health care providers into the conversation.”

“A glioma is a primary brain tumor that originates from the supportive cells of the brain, called glial cells.” http://neurosurgery.ucla.edu/body.cfm?id=159
“Remarkably, cannabinoids kill glioma cells selectively and can protect non-transformed glial cells from death.” https://www.ncbi.nlm.nih.gov/pubmed/15275820
“A meta-analysis of 34 in vitro and in vivo studies of cannabinoids in glioma reported that all but one study confirmed that cannabinoids selectively kill tumor cells.”  https://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq#section/_7
“Since cannabinoids kill tumor cells without toxicity on their non transformed counterparts, they can represent a class of new potential anticancer drugs.”                                        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3835116/ 
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Tetrahydrocannabinol – friend or foe? – Debate.

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“Medical THC is beneficial for various conditions (especially pain relief).”

https://www.ncbi.nlm.nih.gov/pubmed/31062643

https://www.tandfonline.com/doi/abs/10.1080/15563650.2019.1610567?journalCode=ictx20

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Marijuana for Parkinson’s Disease?

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“Marijuana is popular in the United States and is being widely legalized for recreational and medicinal purposes. It remains a Schedule 1 substance without fully proven risks and benefits; yet, it is increasingly available in many US states and territories.

Cannabis might have medicinal efficacy in Parkinson’s disease as a form of medical marijuana. Endocannabinoid receptors exist throughout the nervous system and are documented to influence receptors affecting a wide variety of areas. Neuroprotective aspects might be induced by cannabis exposure that might yield benefit against the nigrostriatal degeneration of patients with Parkinson’s disease.

Animal investigations support suggestions of improvement in bradykinesia and/or tremors, but this is unsubstantiated in human studies. However, some patient surveys and anecdotal or case reports indicate that marijuana attenuates some motor manifestations of parkinsonism and also of non-motor, mood and/or cognitive symptoms. Medical marijuana might benefit motor and nonmotor aspects of Parkinson’s disease patients. Currently, these assertions are not substantiated in human investigations and cannabis can also induce side effects. Until studies clarify the safety and efficacy of pharmacotherapy with cannabis products, medical marijuana remains largely without scientific endorsement. Research has yet to document the full benefits, risks, and clinical applications of marijuana as a treatment for patients with Parkinson’s disease.”

https://www.ncbi.nlm.nih.gov/pubmed/31037227

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Aging circadian rhythms and cannabinoids.

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

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Quality of life in adults enrolled in an open-label study of cannabidiol (CBD) for treatment-resistant epilepsy.

“Treatment-resistant epilepsy (TRE) is associated with low quality of life (QOL). Cannabidiol (CBD) may improve QOL, but it is unclear if such improvements are independent of improvements in seizure control. Our aim was to compare QOL at baseline and after 1 year of treatment with CBD. We hypothesized that QOL would improve independent of changes in seizure frequency (SF) or severity, mood, or adverse events. We assessed QOL using Quality of Life in Epilepsy-89 (QOLIE-89) in an open-label study of purified CBD (Epidiolex®) for the treatment of TRE. All participants received CBD, starting at 5 mg/kg/day and titrated to 50 mg/kg/day in increments of 5 mg/kg/day. We collected QOLIE-89 in adult participants at enrollment and after 1 year of treatment, or at study exit if earlier. We analyzed if the change in QOLIE-89 total score could be explained by the change in SF, seizure severity (Chalfont Seizure Severity Scale, CSSS), mood (Profile of Moods States, POMS), or adverse events (Adverse Event Profile, AEP). Associations among the variables were assessed using bivariate tests and multiple regression. Fifty-three participants completed enrollment and follow-up testing, seven at study termination. Mean QOLIE-89 total score improved from enrollment (49.4 ± 19) to follow-up (57 ± 21.3; p = .004). We also saw improvements in SF, POMS, AEP, and CSSS (all p ≤ .01). Multivariable regression results showed QOLIE-89 at follow-up associated with improvements in POMS at follow-up (p = .020), but not with AEP, CSSS, or SF (p ≥ .135). Improvement in QOL after treatment with CBD is associated with better mood but not with changes in SF, seizure severity, or AEP. Cannabidiol may have beneficial effects on QOL and mood that are independent of treatment response.”

https://www.ncbi.nlm.nih.gov/pubmed/31003195

https://www.epilepsybehavior.com/article/S1525-5050(19)30116-7/fulltext

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Prescription of a THC/CBD-Based Medication to Patients with Dementia: A Pilot Study in Geneva

 

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“Dementia is increasing worldwide. No effective medication is currently available for the treatment of the underlying disease and accompanying behavioral symptoms. Cannabinoids might have a beneficial effect, but clinical studies with (low-dose) synthetic THC have not been conclusive.

Objective: To test the acceptability, practical aspects, and clinical outcomes of the introduction of a THC/CBD-based oral medication in severely demented patients in a specialized nursing home in Geneva.

Methods: This was a prospective observational study.

Results: Ten female demented patients with severe behavior problems received oral medication with on average 7.6 mg THC/13.2 mg CBD daily after 2 weeks, 8.8 mg THC/17.6 mg CBD after 1 month, and 9.0 mg THC/18.0 mg CBD after 2 months. The THC/CBD-based oil was preferred. Neuropsychiatric Inventory, Cohen-Mansfield Agitation Inventory score, and a behavior problem visual analog scale decreased by 40% after 2 months, rigidity score by 50%. Half of the patients decreased or stopped other psychotropic medications. The staff appreciated the decrease in rigidity, making daily care and transfers easier, the improved direct contact with the patients, the improvement in behavior, and the decrease in constipation with less opioids. There was no withholding of the medication for reasons of side effects, and the effects persisted after 2 months.

Conclusions: An oral cannabis extract with THC/CBD, in higher dosages than in other studies, was well tolerated and greatly improved behavior problems, rigidity, and daily care in severely demented patients.”

https://www.karger.com/Article/Abstract/498924

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Cannabinoid CB2R receptors are upregulated with corneal injury and regulate the course of corneal wound healing.

Experimental Eye Research

“CB2R receptors have demonstrated beneficial effects in wound healing in several models. We therefore investigated a potential role of CB2R receptors in corneal wound healing. We examined the functional contribution of CB2R receptors to the course of wound closure in an in vivo murine model. We additionally examined corneal expression of CB2R receptors in mouse and the consequences of their activation on cellular signaling, migration and proliferation in cultured bovine corneal epithelial cells (CECs). Using a novel mouse model, we provide evidence that corneal injury increases CB2R receptor expression in cornea. The CB2R agonist JWH133 induces chemorepulsion in cultured bovine CECs but does not alter CEC proliferation. The signaling profile of CB2R activation is activating MAPK and increasing cAMP accumulation, the latter perhaps due to Gs-coupling. Lipidomic analysis in bovine cornea shows a rise in acylethanolamines including the endocannabinoid anandamide 1 h after injury. In vivo, CB2R deletion and pharmacological block result in a delayed course of wound closure. In summary, we find evidence that CB2R receptor promoter activity is increased by corneal injury and that these receptors are required for the normal course of wound closure, possibly via chemorepulsion.”

https://www.ncbi.nlm.nih.gov/pubmed/30905716

https://www.sciencedirect.com/science/article/pii/S0014483518307206?via%3Dihub

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Beneficial and deleterious effects of cannabinoids in the brain: the case of ultra-low dose THC.

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“This article reviews the neurocognitive advantages and drawbacks of cannabinoid substances, and discusses the possible physiological mechanisms that underlie their dual activity. The article further reviews the neurocognitive effects of ultra-low doses of ∆9-tetrahydrocannabinol (THC; 3-4 orders of magnitude lower than the conventional doses) in mice, and proposes such low doses of THC as a possible remedy for various brain injuries and for the treatment of age-related cognitive decline.”

https://www.ncbi.nlm.nih.gov/pubmed/30864864

https://www.tandfonline.com/doi/abs/10.1080/00952990.2019.1578366?journalCode=iada20

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Cannabinoid derivatives acting as dual PPARγ/CB2 agonists as therapeutic agents for Systemic Sclerosis.

Biochemical Pharmacology

“The endocannabinoid system(ECS) may play a role in the pathophysiology of systemic sclerosis (SSc). Cannabinoids actingas dual PPARγ/CB2agonists, such as VCE-004.8 and Ajulemic acid (AjA), havebeen shown to alleviate skin fibrosis and inflammation in SSc models. Since bothcompounds are being tested in humans, we compared their activities in the bleomycin(BLM) SSc model.Specifically, the pharmacotranscriptomicsignature of the compounds was determined by RNA-Seq changes in the skin of BLM mice treated orallywith AjA or EHP-101, a lipidicformulation of VCE-004.8. While both compounds down-regulatedthe expression of genes involved in the inflammatoryand fibrotic components of the disease and the pharmacotranscriptomicsignatures were similar for both compounds in some pathways, we found keydifferences between the compounds in vasculogenesis. Additionally, we found 28 specific genes withtranslation potential by comparing with a list of humanscleroderma genes. Immunohistochemical analysis revealed that both compounds prevented fibrosis, collagen accumulation andTenascin C (TNC) expression. Theendothelial CD31+/CD34+ cells and telocyteswere reduced in BLM mice and restored only byEHP-101 treatment. Finally, differences were found inplasmatic biomarker analysis; EHP-101, but not AjA, enhanced the expressionof some factors related to angiogenesisand vasculogenesis. Altogether the results indicate that dual PPARγ/CB2agonists qualify as a novel therapeutic approach for the treatment of SSc and other fibrotic diseases. EHP-101 demonstratedunique mechanisms of action related to the pathophysiology of SSc that could be beneficial in the treatment of this complex disease without current therapeutic options.”

https://www.ncbi.nlm.nih.gov/pubmed/30825431

https://www.sciencedirect.com/science/article/abs/pii/S0006295219300772?via%3Dihub

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