Cannabinoid receptor activation on hematopoietic cells and enterocytes protects against colitis

Posted on December 30, 2020 by David Worrell

“Cannabinoid receptor (CB) activation can attenuate inflammatory bowel disease (IBD) in experimental models and human cohorts. However, the role of the microbiome, metabolome, or the respective contributions of hematopoietic and non-hematopoietic cells in the anti-colitic effects of cannabinoids has yet to be determined.

Methods: Female C57BL/6 mice were treated with either cannabidiol (CBD), Δ 9-tetrahydrocannabinol (THC), a combination of CBD and THC or vehicle, in several models of chemically induced colitis. Clinical parameters of colitis were assessed by colonoscopy, histology, flow cytometry and detection of serum biomarkers; single-cell RNA sequencing and qRT-PCR were used to evaluate the effects of cannabinoids on enterocytes. Immune cell transfer from CB2 knockout mice was used to evaluate the contribution of hematopoietic and non-hematopoietic cells to colitis protection.

Results: We found that THC prevented colitis, and that CBD, at the dose tested, provided little benefit to the amelioration of colitis, or when added synergistically with THC. THC increased colonic barrier integrity by stimulating mucus, tight junction and antimicrobial peptide production, and these effects were specific to the large intestine. THC increased colonic gram-negative bacteria, but the anti-colitic effects of THC were independent of the microbiome. THC acted on both immune cells via CB2 and on enterocytes to attenuate colitis.

Conclusions: Our findings demonstrate how cannabinoid receptor activation on both immune cells and colonocytes is critical to prevent colonic inflammation. These studies also suggest how cannabinoid receptor activation can be used as a preventive and therapeutic modality against colitis.”

https://pubmed.ncbi.nlm.nih.gov/33331878/

https://academic.oup.com/ecco-jcc/advance-article-abstract/doi/10.1093/ecco-jcc/jjaa253/6040793?redirectedFrom=fulltext

Cannabis Therapeutics and the Future of Neurology.

Posted on November 9, 2018 by David Worrell

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“Neurological therapeutics have been hampered by its inability to advance beyond symptomatic treatment of neurodegenerative disorders into the realm of actual palliation, arrest or reversal of the attendant pathological processes. While cannabis-based medicines have demonstrated safety, efficacy and consistency sufficient for regulatory approval in spasticity in multiple sclerosis (MS), and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges remain. This review will examine the intriguing promise that recent discoveries regarding cannabis-based medicines offer to neurological therapeutics by incorporating the neutral phytocannabinoids tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), and cannabis terpenoids in the putative treatment of five syndromes, currently labeled recalcitrant to therapeutic success, and wherein improved pharmacological intervention is required: intractable epilepsy, brain tumors, Parkinson disease (PD), Alzheimer disease (AD) and traumatic brain injury (TBI)/chronic traumatic encephalopathy (CTE). Current basic science and clinical investigations support the safety and efficacy of such interventions in treatment of these currently intractable conditions, that in some cases share pathological processes, and the plausibility of interventions that harness endocannabinoid mechanisms, whether mediated via direct activity on CB₁ and CB₂ (tetrahydrocannabinol, THC, caryophyllene), peroxisome proliferator-activated receptor-gamma (PPARγ; THCA), 5-HT_1A (CBD, CBDA) or even nutritional approaches utilizing prebiotics and probiotics. The inherent polypharmaceutical properties of cannabis botanicals offer distinct advantages over the current single-target pharmaceutical model and portend to revolutionize neurological treatment into a new reality of effective interventional and even preventative treatment.” https://www.ncbi.nlm.nih.gov/pubmed/30405366 https://www.frontiersin.org/articles/10.3389/fnint.2018.00051/full

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A New Study Suggests Cannabis Could Treat Cervical Cancer

Posted on October 11, 2016 by David Worrell

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“A new study suggests that cannabis might be useful in treating cervical cancer.

Through in vitro, or test tube/petri dish, analysis, researchers from the biochemistry department at North-West University in Potchefstroom, South Africa found that the non-psychotropic cannabinoid, or chemical compound, CBD (cannabidiol), taken from a Cannabis sativa extract, could hold anticarcinogenic properties. They pointed out that cannabis acted on the cancerous cells through apoptosis, or a process of cell death, causing only the cancerous cells to kill themselves, and inhibiting their growth.

Cervical cancer is no longer a leading cause of death as much as it used to be in the United States, thanks in large part to the widespread use of pap smears, but it’s still a widespread threat. And in Sub-Saharan Africa, it kills 250,000 women every year. “This makes it the most lethal cancer amongst black women and calls for urgent therapeutic strategies,” the study’s authors wrote in the BMC Complementary and Alternative Medicine journal. “In this study we compare the anti-proliferative effects of crude extract of Cannabis sativa and its main compound cannabidiol on different cervical cancer cell lines.”

It will take much more research before cannabis can be integrated into official cervical cancer treatments in sub-Saharan Africa. But earlier studies also shows that cannabis has been useful in treating not only the symptoms of cancer and chemotherapy, but also the cancer itself.

One study from the journal of Current Clinical Pharmacology found that cannabis served as a preventative agent, reducing inflammation, which researchers also said was useful in reducing the likelihood of cancer. Another study from Oncology Hematology also noted cannabis’ anti-cancer effects, explaining how the plant’s cannabinoids inhibited tumor growth in vitro, such as in a petri dish or test tube, and in vivo, or a living organism.

A handful of other studies have also looked into cannabis as a treatment specifically for cervical cancer. Another from the University Hospital in Geneva, Switzerland, found that the cannabinoids, including the body’s own endocannabinoids, offered “attractive opportunities for the development of novel potent anticancer drugs.”

With that said, often medical marijuana is ingested via capsules, tinctures, vaporizable oils, and other non-smokeable, more pharmaceutical-style forms. Should cannabis eventually become approved for cervical cancer treatment in Africa, it may be up for debate whether whole plant therapy (in which all the cannabinoids work synergistically through the “entourage effect”) or specific cannabinoid therapy is best.”

http://motherboard.vice.com/read/a-new-study-suggests-cannabis-could-treat-cervical-cancer

The therapeutic potential of the phytocannabinoid cannabidiol for Alzheimer’s disease.

Posted on July 30, 2016 by David Worrell

“Alzheimer’s disease (AD) is the most common neurodegenerative disorder, characterized by progressive loss of cognition. Over 35 million individuals currently have AD worldwide. Unfortunately, current therapies are limited to very modest symptomatic relief.

The brains of AD patients are characterized by the deposition of amyloid-β and hyperphosphorylated forms of tau protein. AD brains also show neurodegeneration and high levels of oxidative stress and inflammation.

The phytocannabinoid cannabidiol (CBD) possesses neuroprotective, antioxidant and anti-inflammatory properties and reduces amyloid-β production and tau hyperphosphorylation in vitro.

CBD has also been shown to be effective in vivo making the phytocannabinoid an interesting candidate for novel therapeutic interventions in AD, especially as it lacks psychoactive or cognition-impairing properties.

CBD treatment would be in line with preventative, multimodal drug strategies targeting a combination of pathological symptoms, which might be ideal for AD therapy.

Thus, this review will present a brief introduction to AD biology and current treatment options before outlining comprehensively CBD biology and pharmacology, followed by in-vitro and in-vivo evidence for the therapeutic potential of CBD. We will also discuss the role of the endocannabinioid system in AD before commenting on the potential future of CBD for AD therapy (including safety aspects).”

http://www.ncbi.nlm.nih.gov/pubmed/27471947

Review of Various Herbal Supplements as Complementary Treatments for Oral Cancer.

Posted on February 13, 2016 by David Worrell

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“In the United States, nearly 44,000 people are diagnosed with oral or pharyngeal cancer annually. The life expectancy for those who are diagnosed have a survival rate of 57% after five years. Among them, oral cancer can be classified as benign or malignant tumors and is diagnosed at several stages in the development: premalignant conditions, premalignant lesions, and malignant cancer. The early signs of oral cancer often go unnoticed by the individual and are often discovered during routine dental examinations. Early detection and treatment may help to increase patient survival rates. The most widely used treatments for oral cancer include surgery, radiation, and chemotherapy-alone or in combination.

Preclinical and clinical evidence for the use of green tea, raspberry, asparagus, and cannabis extracts is discussed in this review. Diet changes, supplementation with antioxidants, high-dose vitamin C therapy, and cannabinoid use have been suggested to decrease cancer cell replication and increase chance of remission.

Early detection and lifestyle changes, including the use of dietary supplements in at-risk populations, are critical steps in preventing and successfully treating oral cancer. The main evidence for supplement use is currently in cancer prevention rather than treatment.

Further research, determination, and mechanism of action for bioactive compounds such as epigallocatechin, epicatechin-3-gallate, and Bowman-Birk inhibitor concentrate, through in vitro, in vivo, and clinical trials need to be completed to support the use of natural products and their effectiveness in preventative care and supporting therapeutic approaches.” http://www.ncbi.nlm.nih.gov/pubmed/26863913

http://www.tandfonline.com/doi/abs/10.3109/19390211.2015.1122693?journalCode=ijds20

http://www.thctotalhealthcare.com/category/oral-cancer/

Activation of cannabinoid receptors prevents antigen-induced asthma-like reaction in guinea pigs.

Posted on June 24, 2015 by David Worrell

“In this study we evaluated the effects of the CB1/CB2 cannabinoid receptor agonist on antigen-induced asthma-like reaction in sensitized guinea pigs…

These findings suggest that targeting cannabinoid receptors could be a novel preventative therapeutic strategy in asthmatic patients.”

http://www.ncbi.nlm.nih.gov/pubmed/18266975

Long-Term Cannabidiol Treatment Prevents the Development of Social Recognition Memory Deficits in Alzheimer’s Disease Transgenic Mice.

Posted on July 16, 2014 by David Worrell

“Impairments in cognitive ability and widespread pathophysiological changes caused by neurotoxicity, neuroinflammation, oxidative damage, and altered cholesterol homeostasis are associated with Alzheimer’s disease (AD).

Cannabidiol (CBD) has been shown to reverse cognitive deficits of AD transgenic mice and to exert neuroprotective, anti-oxidative, and anti-inflammatory properties in vitro and in vivo…

This study is the first to demonstrate CBD’s ability to prevent the development of a social recognition deficit in AD transgenic mice.

Our findings provide the first evidence that CBD may have potential as a preventative treatment for AD with a particular relevance for symptoms of social withdrawal and facial recognition.”

http://www.ncbi.nlm.nih.gov/pubmed/25024347

Spinal gene expression profiling and pathways analysis of a CB2 agonist (MDA7)-targeted prevention of paclitaxel-induced neuropathy.

Posted on December 24, 2013 by David Worrell

“Patients receiving paclitaxel often develop peripheral neuropathies. We found that a novel selective cannabinoid CB2 receptor agonist (MDA7) prevents paclitaxel-induced mechanical allodynia in rats and mice…

The preventive effect of MDA7 on paclitaxel-induced peripheral allodynia in rats may be associated with genes involved in signal pathways in central sensitization, microglial activation, and neuroinflammation in the spinal cord.”

http://www.ncbi.nlm.nih.gov/pubmed/24361916

Preventive and treatment effects of a hemp seed (Cannabis sativa L.) meal protein hydrolysate against high blood pressure in spontaneously hypertensive rats.

Posted on December 8, 2013 by David Worrell

“This work determined the ability of hemp seed meal protein hydrolysate (HMH)-containing diets to attenuate elevated blood pressure (hypertension) development in spontaneously hypertensive rats (SHRs)…

CONCLUSIONS: The results suggest that HMH with strong hypotensive effects in SHRs could be used as a therapeutic agent for both the prevention and treatment of hypertension.”

http://www.ncbi.nlm.nih.gov/pubmed/24292743

Activation of Cortical Type 2 Cannabinoid Receptors Ameliorates Ischemic Brain Injury, Study Suggests

Posted on June 10, 2013 by David Worrell

“A new study published in the March issue of The American Journal of Pathology suggests that cortical type 2 cannabinoid (CB2) receptors might serve as potential therapeutic targets for cerebral ischemia.

Researchers found that the cannabinoid trans-caryophyllene (TC) protected brain cells from the effects of ischemia in both in vivo and in vitro animal models. In rats, post-ischemic treatment with TC decreased cerebral infarct size and edema. In cell cultures composed of rat cortical neurons and glia exposed to oxygen-glucose deprivation and reoxygenation (OGD/R), TC decreased neuronal injury and mitochondrial depolarization, specifically through type 2 cannabinoid receptor (CB2R) pathways.

“To our knowledge, novel data presented in this study provide evidence for the first time supporting a previously unappreciated role of cortical CB2R, especially neuronal CB2Rs, in ischemia,” says lead investigator Won-Ki Kim, PhD, of the Department of Neuroscience, College of Medicine, Korea University in Seoul. “This study suggests that further investigation is warranted to establish the clinical usefulness of TC as a preventative and therapeutic agent for treatment of stroke.””

More: http://www.sciencedaily.com/releases/2013/02/130221141140.htm

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