The gastrointestinal tract – a central organ of cannabinoid signaling in health and disease

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“In ancient medicine, extracts of the marijuana plant Cannabis sativa were used against diseases of the gastrointestinal (GI) tract.

Today, our knowledge of the ingredients of the Cannabis plant has remarkably advanced enabling us to use a variety of herbal and synthetic cannabinoid (CB) compounds to study the endocannabinoid system (ECS), a physiologic entity that controls tissue homeostasis with the help of endogenously produced CBs and their receptors.

After many anecdotal reports suggested beneficial effects of Cannabis in GI disorders, it was not surprising to discover that the GI tract accommodates and expresses all the components of the ECS.

The following review summarizes important and recent findings on the role of CB receptors and their ligands in the GI tract with emphasis on GI disorders, such as irritable bowel syndrome, inflammatory bowel disease, and colon cancer.”

https://www.ncbi.nlm.nih.gov/pubmed/27561826

Diuretic effects of cannabinoids.

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“These data indicate that cannabinoids have robust diuretic effects in rats that are mediated via CB1 receptor mechanisms.

Overall, our data indicate that diuresis is a CB1-mediated effect that may serve as a reliable and objective physiologic measure of cannabinoid action in rats; the circumstances under which these results represent a potential therapeutic benefit or potential liability of cannabinoids remain to be determined.

The implications of these findings currently are poorly understood, although a better understanding of mechanisms and sites of action by which cannabinoids increase urine loss may lead to the rational development of novel cannabinergic medications.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533417/

“Diuretics are medicines that help reduce the amount of water in the body. Diuretics are used to treat the buildup of excess fluid in the body that occurs with some medical conditions such ascongestive heart failure, liver disease, and kidney disease. Some diuretics are also prescribed to treat high bloodpressure. These drugs act on the kidneys to increase urine output. This reduces the amount of fluid in the bloodstream,which in turn lowers blood pressure.” http://medical-dictionary.thefreedictionary.com/diuretics

Cannabinol and cannabidiol exert opposing effects on rat feeding patterns.

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“Increased food consumption following ∆(9)-tetrahydrocannabinol-induced cannabinoid type 1 receptor agonism is well documented.

However, possible non-∆(9)-tetrahydrocannabinol phytocannabinoid-induced feeding effects have yet to be fully investigated. Therefore, we have assessed the effects of the individual phytocannabinoids, cannabigerol, cannabidiol and cannabinol, upon feeding behaviors.

Cannabinol induced a CB(1)R-mediated increase in appetitive behaviors via significant reductions in the latency to feed and increases in consummatory behaviors via increases in meal 1 size and duration. Cannabinol also significantly increased the intake during hour 1 and total chow consumed during the test. Conversely, cannabidiol significantly reduced total chow consumption over the test period. Cannabigerol administration induced no changes to feeding behavior.

This is the first time cannabinol has been shown to increase feeding. Therefore, cannabinol could, in the future, provide an alternative to the currently used and psychotropic ∆(9)-tetrahydrocannabinol-based medicines since cannabinol is currently considered to be non-psychotropic.

Furthermore, cannabidiol reduced food intake in line with some existing reports, supporting the need for further mechanistic and behavioral work examining possible anti-obesity effects of cannabidiol.”

https://www.ncbi.nlm.nih.gov/pubmed/22543671

Cannabis sativa and the endogenous cannabinoid system: therapeutic potential for appetite regulation.

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“The herb Cannabis sativa (C. sativa) has been used in China and on the Indian subcontinent for thousands of years as a medicine.

However, since it was brought to the UK and then the rest of the western world in the late 19th century, its use has been a source of controversy. Indeed, its psychotropic side effects are well reported but only relatively recently has scientific endeavour begun to find valuable uses for either the whole plant or its individual components.

Here, we discuss evidence describing the endocannabinoid system, its endogenous and exogenous ligands and their varied effects on feeding cycles and meal patterns.

Furthermore we also critically consider the mounting evidence which suggests non-Δ(9) tetrahydrocannabinol phytocannabinoids play a vital role in C. sativa-induced feeding pattern changes.

Indeed, given the wide range of phytocannabinoids present in C. sativa and their equally wide range of intra-, inter- and extra-cellular mechanisms of action, we demonstrate that non-Δ(9) tetrahydrocannabinol phytocannabinoids retain an important and, as yet, untapped clinical potential.”

https://www.ncbi.nlm.nih.gov/pubmed/21213357

Therapeutic Use of Cannabis in Inflammatory Bowel Disease.

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“The marijuana plant Cannabis sativa and its derivatives, cannabinoids, have grown increasingly popular as a potential therapy for inflammatory bowel disease (IBD). Studies have shown that modulation of the endocannabinoid system, which regulates various functions in the body and has been shown to play a key role in the pathogenesis of IBD, has a therapeutic effect in mouse colitis.

The plant Cannabis sativa has been used in medicinal practice for thousands of years. Anecdotal reports have suggested a therapeutic role for cannabis in the treatment of IBD for hundreds of years. A case report from 1990 describes patients with IBD maintaining remission of disease via cannabis use. Cannabinoids appear to have a clear role in gut pathology and offer a potential target for drug intervention in the treatment of IBD. Cannabis seems to be of symptomatic benefit to patients often refractory to conventional medicines.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5193087/

Cannabis and epilepsy: An ancient treatment returns to the fore.

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“Cannabis has been associated with the treatment of epilepsy throughout history, and if ancient Assyrian sources referring to “hand of ghost” are considered credible, this relationship may span four millennia.

A tradition of usage continued in Arabic medicine and Ayurvedic practice in India, which led, in turn, to early experiments in Europe and North America with “Indian hemp.”

Lack of standardization, bioavailability issues, and ultimately prohibition were all factors in cannabis-based medicines failing to maintain mainstream usage in seizure treatment, but investigation was resumed in the 1970s with interesting signals noted in both laboratory and clinical settings.

Early case studies showed promise, but lacked sufficient rigor. Resumption of research coupled with mass experimentation by families of epilepsy patients has led to intense interest in cannabis-based medicines for its treatment once more, with greatest focus on cannabidiol, but additional investigation of tetrahydrocannabinol, tetrahydrocannabinolic acid, and other phytocannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/27989385

Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells.

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“In the last years, mesenchymal stromal cells (MSCs) from oral tissues have received considerable interest in regenerative medicine since they can be obtained with minimal invasive procedure and exhibit immunomodulatory properties.

This study was aimed to investigate whether in vitro pre-treatment of MSCs obtained from human gingiva (hGMSCs) with Cannabidiol (CBD), a cannabinoid component produced by the plant Cannabis sativa, may promote human gingiva derived MSCs to differentiate towards neuronal precursor cells.

From our results we hypothesize that human gingiva-derived MSCs conditioned with CBD could represent a valid method for improving the hGMSCs phenotype and thus might be a potential therapeutic tool in the treatment of neurodegenerative diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/27918106

Targeting the Endocannabinoid System in Psychiatric Illness.

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“Prevalence of psychiatric disorders continues to rise globally, yet remission rates and patient outcome remain less than ideal. As a result, novel treatment approaches for these disorders are necessary to decrease societal economic burden, as well as increase individual functioning.

The recent discovery of the endocannabinoid system has provided an outlet for further research into its role in psychiatric disorders, because efficacy of targeted treatments have been demonstrated in medical illnesses, including cancers, neuropathic pain, and multiple sclerosis.

The present review will investigate the role of the endocannabinoid system in psychiatric disorders, specifically schizophrenia, depressive, anxiety, and posttraumatic stress disorders, as well as attention-deficit hyperactivity disorder.

Controversy remains in prescribing medicinal cannabinoid treatments due to the fear of adverse effects. However, one must consider all potential limitations when determining the safety and tolerability of cannabinoid products, specifically cannabinoid content (ie, Δ-tetrahydrocannabinol vs cannabidiol) as well as study design.

The potential efficacy of cannabinoid treatments in the psychiatric population is an emerging topic of interest that provides potential value going forward in medicine.”

Δ9-THC Intoxication by Cannabidiol-Enriched Cannabis Extract in Two Children with Refractory Epilepsy: Full Remission after Switching to Purified Cannabidiol.

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“Animal studies and preliminary clinical trials have shown that cannabidiol (CBD)-enriched extracts may have beneficial effects for children with treatment-resistant epilepsy.

We describe the cases of two children with treatment-resistant epilepsy (Case A with left frontal dysplasia and Case B with Dravet Syndrome) with initial symptom improvement after the introduction of CBD extracts followed by seizure worsening after a short time.

The children presented typical signs of intoxication by Δ9-THC (inappropriate laughter, ataxia, reduced attention, and eye redness) after using a CBD-enriched extract.

The extract was replaced by the same dose of purified CBD with no Δ9-THC in both cases, which led to improvement in intoxication signs and seizure remission.

These cases support pre-clinical and preliminary clinical evidence suggesting that CBD may be effective for some patients with epilepsy.

Moreover, the cases highlight the need for randomized clinical trials using high-quality and reliable substances to ascertain the safety and efficacy of cannabinoids as medicines.”

https://www.ncbi.nlm.nih.gov/pubmed/27746737

Cannabis: A Treasure Trove or Pandora’s Box?

 

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“Cannabis is one of the earliest cultivated plants.

Cannabis of industrial utility and culinary value is generally termed as hemp.

Conversely, cannabis that is bred for medical, spiritual and recreational purposes is called marijuana.

The female marijuana plant produces a significant quantity of bio- and psychoactive phytocannabinoids, which regained the spotlight with the discovery of the endocannabinoid system of the animals in the early 90’s.

Nevertheless, marijuana is surrounded by controversies, debates and misconceptions related to its taxonomic classification, forensic identification, medical potential, legalization and its long-term health consequences.

In the first part, we provide an in-depth review of the botany and taxonomy of Cannabis. We then overview the biosynthesis of phytocannabinoids within the glandular trichomes with emphasis on the role of peculiar plastids in the production of the secreted material. We also compile the analytical methods used to determine the phytocannabinoid composition of glandular trichomes.

In the second part, we revisit the psychobiology and molecular medicine of marijuana. We summarize our current knowledge on the recreational use of cannabis with respect to the modes of consumption, short-term effects, chronic health consequences and cannabis use disorder.

Next, we overview the molecular targets of a dozen major and minor bioactive cannabinoids in the body. This helps us introduce the endocannabinoid system in an unprecedented detail: its up-to-date molecular biology, pharmacology, physiology and medical significance, and beyond.

In conclusion, we offer an unbiased survey about cannabis to help better weigh its medical value versus the associated risks.”

https://www.ncbi.nlm.nih.gov/pubmed/27719666