Δ9-Tetrahydrocannabinol (THC) and AM 404 protect against cerebral ischaemia in gerbils through a mechanism involving cannabinoid and opioid receptors

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“It has been suggested that the endocannabinoid system elicits neuroprotection against excitotoxic brain damage.

In the present study the therapeutic potential of AM 404 on ischaemia-induced neuronal injury was investigated in vivo and compared with that of the classical cannabinoid receptor type 1 (CB1) agonist, Δ9-tetraydrocannabinol (THC), using a model of transient global cerebral ischaemia in the gerbil.

Our findings demonstrate that AM 404 and THC reduce neuronal damage caused by bilateral carotid occlusion in gerbils and that this protection is mediated through an interaction with CB1 and opioid receptors.

Endocannabinoids might form the basis for the development of new neuroprotective drugs useful for the treatment of stroke and other neurodegenerative pathologies.

There is some evidence from experiments with mice that increasing anandamide or 2-arachidonoyl glycerol content may lead to neuroprotection.

Collectively, our data demonstrate that AM 404 and THC protect against neuronal ischaemia-induced injury through a mechanism involving cannabinoid and opioid receptors but not vanilloid receptors.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2189998/

Short-Term Efficacy of CBD-Enriched Hemp Oil in Girls with Dysautonomic Syndrome after Human Papillomavirus Vaccination.

“Cannabidiol (CBD)-based treatments for several diseases, including Tourette’s syndrome, multiple sclerosis, epilepsy, movement disorders and glaucoma, are proving to be beneficial and the scientific clinical background of the drug is continuously evolving.

OBJECTIVES:

To investigate the short-term effect of CBD-enriched hemp oil for relieving symptoms and improving the life quality (QOL) in young girls with adverse drug effects (ADRs) following human papillomavirus (HPV) vaccine.

METHODS:

In this anecdotal, retrospective, “compassionate-use”, observational, open-label study, 12 females (age 12-24 years) with severe somatoform and dysautonomic syndrome following HPV vaccination were given sublingual CBD-rich hemp oil drops, 25 mg/kg per day supplemented by 2-5 mg/ml CBD once a week until a maximum dose of 150 mg/ml CBD per day was reached over a 3 month period. Patients’ quality of life was evaluated using the medical outcome short-form health survey questionnaire (SF-36).

RESULTS:

Two patients dropped out due to iatrogenic adverse events and another two patients stopped the treatment early due to lack of any improvement. SF-36 showed significant benefits in the physical component score (P < 0.02), vitality (P < 0.03) and social role functioning (P < 0.02) after the treatment. The administration of hemp oil also significantly reduced body pain according to the SF-36 assessment. No significant differences from the start of treatment to several months post-treatment were detected in role limitations due to emotional reactions (P = 0.02).

CONCLUSIONS:

This study demonstrated the safety and tolerability of CBD-rich hemp oil and the primary efficacy endpoint. Randomized controlled trials are warranted to characterize the safety profile and efficacy of this compound.”

https://www.ncbi.nlm.nih.gov/pubmed/28457055

“This study demonstrated the safety and tolerability of CBD-rich hemp oil and the primary efficacy endpoint” https://www.ima.org.il/imaj/viewarticle.aspx?year=2017&month=02&page=79

The Role of Cannabinoids in the Treatment of Cancer in Pediatric Patients.

“Cannabis has been used in folk medicine to alleviate pain, depression, amenorrhea, inflammation and numerous other medical conditions. In cancer patients specifically, cannabinoids are well known to exert palliative effects; their best-established use is the inhibition of chemotherapy-induced nausea and vomiting, but they are applied also to alleviate pain, stimulate appetite, and attenuate wasting. More recently, cannabinoids have gained special attention for their role in cancer cell proliferation and death.

Anti-cancer efficacy of cannabinoids:

The ability of cannabinoids to reduce tumor growth was reported for the first time by Munson et al. in 1975. They showed by in vitro and in vivo experiments that several phytocannabinoids, including THC, decreased Lewis lung adenocarcinoma proliferation in a dose-dependent manner. Nevertheless, it was not until the 2000s that the interest in these compounds as anti-cancer agents was renewed, predominantly due to the work of Guzman in gliomas, and the demonstration of cannabinoids’ anti-cancer effects on various types of tumors. The anti-tumorigenic effect of the endo- and phytocannabinoids was demonstrated in several in vitro and in vivo models of a wide variety of adult tumors including glioma, prostate, breast, leukemia, lymphoma, pancreas, melanoma, thyroid, colorectal and hepatocellular carcinoma tumors.

Given our positive results, we suggest that non-THC cannabinoids such as CBD might provide a basis for the development of novel therapeutic strategies without the typical psychotropic effects of THC that limit its use in pediatric patients.

Overall, the cannabinoids, and specifically the non-psychoactive CBD, may show future promise in the treatment of cancer”

https://www.ima.org.il/FilesUpload/IMAJ/0/228/114216.pdf

https://www.ima.org.il/imaj/ViewArticle.aspx?aId=4044

https://www.ncbi.nlm.nih.gov/pubmed/28457057

Cannabis in Inflammatory Bowel Diseases: from Anecdotal Use to Medicalization?

“Inflammatory bowel diseases (IBD) are disorders of chronic intestinal inflammation of unknown etiology. The basic pathophysiological process is that of immune mediated inflammation affecting the intestinal tract. This process is dependent on and governed by both genetic and environmental factors. There are two distinct forms of IBD – ulcerative colitis and Crohn’s disease.

There is no curative medical treatment. Furthermore, over 30% of patients, and over 70% with Crohn’s disease, will need surgical intervention for their disease. Thus, it comes as no surprise that many patients will turn to complementary or alternative medicine at some stage of their disease. Recent information reveals that between 16% and 50% of patients admit to having tried marijuana for their symptoms.

There is a long list of gastrointestinal symptoms that have been reported to be relieved by cannabis. These include anorexia, nausea, abdominal pain, diarrhea, gastroparesis – all of which can be part of IBD. These effects are related to the fact that the gastrointestinal tract is rich in cannabinoid (CB) receptors and their endogenous ligands, comprising together the endocannabinoid system (ECS).

In conclusion, use of cannabis is common in IBD, and it seems to be mostly safe. Accumulating preliminary data from human studies support a beneficial role of cannabinoids in IBD.”

https://www.ima.org.il/FilesUpload/IMAJ/0/228/114217.pdf

https://www.ima.org.il/imaj/ViewArticle.aspx?aId=4045

https://www.ncbi.nlm.nih.gov/pubmed/28457058

Efficacy of Medical Cannabis for Treatment of Refractory Epilepsy in Children and Adolescents with Emphasis on the Israeli Experience.

“The effectiveness of marijuana in the treatment of epilepsy was originally reported as early as 1800 BC.

There is now concrete evidence to suggest the efficacy of cannabis in the treatment of epilepsy, particularly in the refractory group.

To summarize, in view of the good outcome in a significant number of patients, which is not significantly worse than other accepted options for patients with refractory epilepsy, it seems that medical cannabis should be considered a viable treatment option.”

https://www.ima.org.il/FilesUpload/IMAJ/0/228/114213.pdf

https://www.ima.org.il/imaj/ViewArticle.aspx?aId=4041

https://www.ncbi.nlm.nih.gov/pubmed/28457054

Cannabis Use in Palliative Oncology: A Review of the Evidence for Popular Indications.

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“A flowering plant of variegated ingredients and psychoactive qualities, cannabis has long been used for medicinal and recreational purposes. Currently, cannabis is approved in several countries for indications of symptomatic alleviation. However, limited knowledge on the benefits and risks precludes inclusion of cannabis in standard treatment guidelines. This review provides a summary of the available literature on the use of cannabis and cannabinoid-based medicines in palliative oncology. Favorable outcomes are demonstrated for chemotherapy-induced nausea and vomiting and cancer-related pain, with evidence of advantageous neurological interactions. Benefit in the treatment of anorexia, insomnia and anxiety is also suggested. Short- and long-term side effects appear to be manageable and to subside after discontinuation of the drug. Finally, cannabinoids have shown anti-neoplastic effects in preclinical studies in a wide range of cancer cells and some animal models. Further research is needed before cannabis can become a part of evidence-based oncology practice.”

https://www.ncbi.nlm.nih.gov/pubmed/28457056

Cannabidiol Treatment for Refractory Seizures in Sturge-Weber Syndrome.

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“Sturge-Weber syndrome results in leptomeningeal vascular malformations, medically refractory epilepsy, stroke(s), and cognitive impairments. Cannabidiol, a cannabinoid without psychoactive properties, has been demonstrated in preclinical models to possibly have anticonvulsant, antioxidant, and neuroprotective actions.

CONCLUSION:

This study suggests that cannabidiol may be well tolerated as adjunctive medication for seizure management and provides initial data supporting further study of cannabidiol in individuals with Sturge-Weber syndrome.”

https://www.ncbi.nlm.nih.gov/pubmed/28454984

Marijuana compounds show promise in treatment of cardiac disease

Marijuana compounds show promise in treatment of cardiac disease

“A Nevada company is hoping to develop new medicines for heart failure using compounds in marijuana and a novel therapy identified by a University of Hawaiʻi at Mānoa researcher. Dr. Alexander Stokes, assistant research professor in the Department of Cell and Molecular Biology at the UH John A. Burns School of Medicine, obtained a U.S. patent for his novel therapy in 2015. The patent claims the cannabinoid receptor TRPV1 can be regulated therapeutically by plant-based cannabinoids.”  https://medicalxpress.com/news/2017-01-marijuana-compounds-treatment-cardiac-disease.html

“Marijuana compounds show promise in treatment of cardiac disease”  http://manoa.hawaii.edu/news/article.php?aId=8355

“Marijuana compounds show promise in treatment of cardiac disease”  http://www.hawaii.edu/news/2017/01/12/marijuana-compounds-show-promise-in-treatment-of-cardiac-disease/

 

Significant Tic Reduction in An Otherwise Treatment-Resistant Patient with Gilles de la Tourette Syndrome Following Treatment with Nabiximols.

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“Early anecdotal reports and preliminary studies suggested that cannabinoid-based medicines such as delta-9-tetrahydrocannabinol (THC) are effective in the treatment of Gilles de la Tourette syndrome (TS).

We report a single case study of a patient with otherwise treatment-resistant TS successfully treated with nabiximols.

Our results provide further evidence that treatment with nabiximols may be effective in the treatment of patients with TS.

Given the positive response exhibited by the patient highlighted in this report, further investigation of the effects of nabiximols is proposed on a larger group of patients in a clinical trial setting.”

Cannabinoids as Modulators of Cell Death: Clinical Applications and Future Directions.

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“Endocannabinoids are bioactive lipids that modulate various physiological processes through G-protein-coupled receptors (CB1 and CB2) and other putative targets. By sharing the activation of the same receptors, some phytocannabinoids and a multitude of synthetic cannabinoids mimic the effects of endocannabinoids.

In recent years, a growing interest has been dedicated to the study of cannabinoids properties for their analgesic, antioxidant, anti-inflammatory and neuroprotective effects. In addition to these well-recognized effects, various studies suggest that cannabinoids may affect cell survival, cell proliferation or cell death. These observations indicate that cannabinoids may play an important role in the regulation of cellular homeostasis and, thus, may contribute to tissue remodelling and cancer treatment.

For a long time, the study of cannabinoid receptor signalling has been focused on the classical adenylyl cyclase/cyclic AMP/protein kinase A (PKA) pathway. However, this pathway does not totally explain the wide array of biological responses to cannabinoids. In addition, the diversity of receptors and signalling pathways that endocannabinoids modulate offers an interesting opportunity for the development of specific molecules to disturb selectively the endogenous system.

Moreover, emerging evidences suggest that cannabinoids ability to limit cell proliferation and to induce tumour-selective cell death may offer a novel strategy in cancer treatment.

This review describes the main properties of cannabinoids in cell death and attempts to clarify the different pathways triggered by these compounds that may help to understand the complexity of respective molecular mechanisms and explore the potential clinical benefit of cannabinoids use in cancer therapies.”

https://www.ncbi.nlm.nih.gov/pubmed/28425013