Therapeutic impact of orally administered cannabinoid oil extracts in an experimental autoimmune encephalomyelitis animal model of multiple sclerosis.

Posted on by

Biochemical and Biophysical Research Communications“There is a growing surge of investigative research involving the beneficial use of cannabinoids as novel interventional alternatives for multiple sclerosis (MS) and associated neuropathic pain (NPP).

Using an experimental autoimmune encephalomyelitis (EAE) animal model of MS, we demonstrate the therapeutic effectiveness of two cannabinoid oil extract formulations (10:10 & 1:20 – tetrahydrocannabinol/cannabidiol) treatment.

Our research findings confirm that cannabinoid treatment produces significant improvements in neurological disability scoring and behavioral assessments of NPP that directly result from their ability to reduce tumor necrosis factor alpha (TNF-α) production and enhance brain derived neurotrophic factor (BDNF) production.

Henceforth, this research represents a critical step in advancing the literature by scientifically validating the merit for medical cannabinoid use and sets the foundation for future clinical trials.”

https://www.ncbi.nlm.nih.gov/pubmed/31213295

“Cannabinoid treatment produces improvements in neurological disability scoring. Cannabinoid treatment also improves behavioral assessments of neuropathic pain.”

https://www.sciencedirect.com/science/article/pii/S0006291X19311568?via%3Dihub

Cannabidiol inhibits sucrose self-administration by CB1 and CB2 receptor mechanisms in rodents.

Posted on by

Addiction Biology banner

“A growing number of studies suggest therapeutic applications of cannabidiol (CBD), a recently U.S. Food and Drug Administration (FDA)-approved medication for epilepsy, in treatment of many other neuropsychological disorders. However, pharmacological action and the mechanisms by which CBD exerts its effects are not fully understood.

Here, we examined the effects of CBD on oral sucrose self-administration in rodents and explored the receptor mechanisms underlying CBD-induced behavioral effects using pharmacological and transgenic approaches.

Systemic administration of CBD produced a dose-dependent reduction in sucrose self-administration in rats and in wild-type (WT) and CB1-/- mice but not in CB2-/- mice. CBD appeared to be more efficacious in CB1-/- mice than in WT mice.

Similarly, pretreatment with AM251, a CB1R antagonist, potentiated, while AM630, a selective CB2R antagonist, blocked CBD-induced reduction in sucrose self-administration, suggesting the involvement of CB1 and CB2 receptors.

Taken together, the present findings suggest that CBD may have therapeutic potential in reducing binge eating and the development of obesity.”

https://www.ncbi.nlm.nih.gov/pubmed/31215752

https://onlinelibrary.wiley.com/doi/abs/10.1111/adb.12783

The Impact of Cannabis Consumption on Mortality, Morbidity, and Cost in Acute Pancreatitis Patients in the United States: A 10-Year Analysis of the National Inpatient Sample.

Posted on by

Image result for Pancreas journal

“The aim of this study was to identify the prevalence of cannabis use among all patients admitted with acute pancreatitis (AP) in the United States and to investigate the impact of cannabis use on AP mortality, morbidity, and cost of care.

RESULTS:

More than 2.8 million patients with AP patients were analyzed. Cannabis-exposed (CE) patients’ prevalence was 0.3%. Patients exposed to cannabis were younger and mostly males compared with non-cannabis-exposed patients. After adjusting for these factors, the CE group had significantly lower inpatient mortality compared with the noncannabis group (odds ratio, 0.17; 95% confidence interval, 0.06-0.53). Cannabis-exposed patients also had decreased length of stay, inflation-adjusted charges, acute kidney injury, ileus, shock, acute respiratory distress syndrome, and parenteral nutrition requirement.

CONCLUSIONS:

Cannabis-exposed hospitalized patients with AP had lower age-adjusted, mortality, morbidity, and hospitalization-cost than non-cannabis-exposed patients.”

 https://www.ncbi.nlm.nih.gov/pubmed/31210668
https://insights.ovid.com/crossref?an=00006676-201907000-00017

The origins of cannabis smoking: Chemical residue evidence from the first millennium BCE in the Pamirs.

Posted on by

 Science Advances: 5 (6)“Cannabis is one of the oldest cultivated plants in East Asia, grown for grain and fiber as well as for recreational, medical, and ritual purposes. It is one of the most widely used psychoactive drugs in the world today, but little is known about its early psychoactive use or when plants under cultivation evolved the phenotypical trait of increased specialized compound production. The archaeological evidence for ritualized consumption of cannabis is limited and contentious. Here, we present some of the earliest directly dated and scientifically verified evidence for ritual cannabis smoking. This phytochemical analysis indicates that cannabis plants were burned in wooden braziers during mortuary ceremonies at the Jirzankal Cemetery (ca. 500 BCE) in the eastern Pamirs region. This suggests cannabis was smoked as part of ritual and/or religious activities in western China by at least 2500 years ago and that the cannabis plants produced high levels of psychoactive compounds.”

https://www.ncbi.nlm.nih.gov/pubmed/31206023

https://advances.sciencemag.org/content/5/6/eaaw1391

“Earliest evidence for cannabis smoking discovered in ancient tombs”  https://www.nationalgeographic.com/culture/2019/06/earliest-evidence-cannabis-marijuana-smoking-china-tombs/

“The First Evidence of Smoking Pot Was Found in a 2,500-Year-Old Pot”  https://www.smithsonianmag.com/smart-news/2500-year-old-chinese-cemetery-offers-earliest-physical-evidence-cannabis-smoking-180972410/

“Earliest Evidence of People “Smoking” Weed Found in 2,500-Year-Old Chinese Pots”  https://www.sciencealert.com/ancient-pots-from-china-reveal-humans-smoking-cannabis-2-500-years-ago

“Oldest evidence of marijuana use discovered in 2500-year-old cemetery in peaks of western China” https://www.sciencemag.org/news/2019/06/oldest-evidence-marijuana-use-discovered-2500-year-old-cemetery-peaks-western-china

“Cannabis use for medicinal purposes dates back at least 3,000 years.”  https://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq#section/_7

“Cannabis has been used for medicinal purposes for thousands of years.” https://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq

“The use of Cannabis for medicinal purposes dates back to ancient times.” http://www.cancer.gov/about-cancer/treatment/cam/patient/cannabis-pdq#section/all

Safety and effectiveness of cannabinoids for the treatment of neuropsychiatric symptoms in dementia: a systematic review.

Posted on by

SAGE Journals“Neuropsychiatric symptoms (NPS) in dementia impact profoundly on the quality of life of people living with dementia and their care givers. Evidence for the effectiveness and safety of current therapeutic options is varied.

Cannabinoids have been proposed as an alternative therapy, mainly due to their activity on CB1 receptors in the central nervous system. However, little is known regarding the safety and effectiveness of cannabinoid therapy in people with dementia.

A literature review was undertaken to identify, describe and critically appraise studies investigating cannabinoid use in treating NPS in dementia.

RESULTS:

Twelve studies met the inclusion criteria. There was considerable variability across the studies with respect to study design (50% randomized controlled trials), intervention [dronabinol (33%), nabilone (25%) or delta-9 tetrahydrocannabinol (THC; 42%)] and outcome measures.

Dronabinol (three studies) and THC (one study) were associated with significant improvements in a range of neuropsychiatric scores.

The most common adverse drug event (ADE) reported was sedation. A high risk of bias was found in eight studies. The highest-quality trial found no significant improvement in symptoms or difference in ADE rate between treatment arms. Included studies used low doses of oral cannabinoids and this may have contributed to the lack of demonstrated efficacy.

CONCLUSION:

While the efficacy of cannabinoids was not proven in a robust randomized control trial, observational studies showed promising results, especially for patients whose symptoms were refractory. In addition, the safety profile is favourable as most of the ADEs reported were mild. Future trials may want to consider dose escalation and formulations with improved bioavailability.”

https://www.ncbi.nlm.nih.gov/pubmed/31205674

https://journals.sagepub.com/doi/10.1177/2042098619846993

Effect of cannabidiol on endocannabinoid, glutamatergic and GABAergic signalling markers in male offspring of a maternal immune activation (poly I:C) model relevant to schizophrenia.

Posted on by

Progress in Neuro-Psychopharmacology and Biological Psychiatry

“The mainstay treatment for schizophrenia is antipsychotic drugs (APDs), which are mostly effective against the positive symptoms (e.g. hallucinations), but provide minimal benefits for the negative symptoms (e.g. social withdrawal) and cognitive deficits.

We have recently shown that treatment with the non-intoxicating phytocannabinoid, cannabidiol (CBD), can improve cognition and social interaction deficits in a maternal immune activation (MIA) model relevant to the aetiology of schizophrenia, however, the mechanisms underlying this effect are unknown.

An imbalance in the main excitatory (glutamate) and inhibitory (GABA) neurotransmitter systems in the brain plays a role in the pathophysiology of schizophrenia. Therefore, the endocannabinoid system could represent a therapeutic target for schizophrenia as a regulator of glutamate and GABA release via the CB1 receptor (CB1R).

Overall, these findings show that CBD can restore cannabinoid/GABAergic signalling deficits in regions of the brain implicated in schizophrenia pathophysiology following maternal poly I:C exposure. These findings provide novel evidence for the potential mechanisms underlying the therapeutic effects of CBD treatment in the poly I:C model.”

https://www.ncbi.nlm.nih.gov/pubmed/31202911

https://www.sciencedirect.com/science/article/pii/S027858461930106X?via%3Dihub

Cannabis and multiple sclerosis.

Posted on by

BMJ Journals

“Patients with multiple sclerosis have long turned to complementary therapies to manage symptoms that licensed products can only partially control. Around half of patients with multiple sclerosis admit to previous or current cannabis use for medicinal purposes and would endorse legalisation. Despite many governments worldwide relaxing regulations around medicinal cannabis, there remain many unanswered questions as to how clinicians should prescribe or recommend products, and access to pharmaceutical-grade products remains highly restricted. Here we address what adult neurologists need to know about cannabis and its use in multiple sclerosis.”

https://www.ncbi.nlm.nih.gov/pubmed/31201234

https://pn.bmj.com/content/early/2019/06/14/practneurol-2018-002137

“There are many anectodal reports of multiple sclerosis (MS) sufferers using the drug and reporting beneficial effects on spasticity, pain, tremor and mood.”  https://pn.bmj.com/content/2/3/154?int_source=trendmd&int_campaign=usage-042019&int_medium=cpc

Endogenous and synthetic cannabinoids induce the downregulation of cannabinoid CB1 receptor in retina.

Posted on by

Experimental Eye Research

“Endogenous and synthetic cannabinoids have been shown to provide neuroprotection to retinal neurons in acute animal models of retinopathy.

Chronic exposure to cannabinoid receptor (CB1R) agonists has been reported to induce downregulation of the CB1R in brain and behavioral tolerance.

The aim of this study was to investigate the effect of subchronic/chronic cannabinoid administration on CB1R downregulation in normal rat retina, its downstream prosurvival signaling and subsequent effect on retinal neuroprotection against AMPA excitotoxicity.

This study provides novel information regarding agonist-induced CB1R downregulation in rat retina after subchronic/chronic cannabinoid treatment, and its effect on downstream prosurvival signaling and neuroprotection.”

https://www.ncbi.nlm.nih.gov/pubmed/31199905

https://www.sciencedirect.com/science/article/pii/S0014483519301216?via%3Dihub

The Important Role of the Endocannabinoid System and the Endocannabinoidome in Gut Health.

Posted on by

Image result for Altern Ther Health Med journal “The endocannabinoid system is an endogenous pathway comprised of the cannabinoid receptors 1 and 2 (CB1 and CB2), their endogenous ligands known as endocannabinoids, and the enzymes responsible for their synthesis and degradation. The endocannabinoidome extends this system to include other receptors such as TRPV1, PPARα, GPR55 and 5-HT1A. An extensive amount of research is now linking the endocannabinoidome to intestinal health through fascinating mechanisms that include endocannabinoid receptor expression in the gut and interplay with the intestinal microbiota. A dysregulated endocannabinoid system may lead to inflammatory bowel disease and colon cancer.”

https://www.ncbi.nlm.nih.gov/pubmed/31202201

The Endocannabinoid System and its Modulation by Cannabidiol (CBD).

Posted on by

Image result for Altern Ther Health Med. “The endocannabinoid system (ECS) is an extensive endogenous signaling system with multiple elements, the number of which may be increasing as scientists continue to elucidate its role in human health and disease. The ECS is seemingly ubiquitous in animal species and is modulated by diet, sleep, exercise, stress, and a multitude of other factors, including exposure to phytocannabinoids, like Cannabidiol (CBD). Modulating the activity of this system may offer tremendous therapeutic promise for a diverse scope of diseases, ranging from mental health disorders, neurological and movement disorders, pain, autoimmune disease, spinal cord injury, cancer, cardiometabolic disease, stroke, TBI, osteoporosis, and others.”

https://www.ncbi.nlm.nih.gov/pubmed/31202198