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

Tetrahydrocannabinol and endocannabinoids in feeding and appetite.

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“The physiological control of appetite and satiety, in which numerous neurotransmitters and neuropeptides play a role, is extremely complex. Here we describe the involvement of endocannabinoids in these processes.

These endogenous neuromodulators enhance appetite in animals.

The same effect is observed in animals and in humans with the psychotropic plant cannabinoid Delta(9)-tetrahydrocannabinol, which is an approved appetite-enhancing drug.

The CB(1) cannabinoid receptor antagonist SR141716A blocks the effects on feeding produced by the endocannabinoids. If administered to mice pups, this antagonist blocks suckling.

In obese humans, it causes weight reduction.

Very little is known about the physiological and biochemical mechanisms involved in the effects of Delta(9)-tetrahydrocannabinol and the cannabinoids in feeding and appetite.”

https://www.ncbi.nlm.nih.gov/pubmed/12182965

Non-Δ⁹tetrahydrocannabinol phytocannabinoids stimulate feeding in rats.

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“Cannabinoid type 1 receptor-mediated appetite stimulation by Δ⁹tetrahydrocannabinol (Δ⁹THC) is well understood.

Recently, it has become apparent that non-Δ⁹THC phytocannabinoids could also alter feeding patterns.

Here, we show definitively that non-Δ⁹THC phytocannabinoids stimulate feeding.

Twelve male, Lister-Hooded rats were prefed to satiety prior to administration of a standardized cannabis extract or to either of two mixtures of pure phytocannabinoids (extract analogues) comprising the phytocannabinoids present in the same proportions as the standardized extract (one with and one without Δ⁹THC). Hourly intake and meal pattern data were recorded and analysed using two-way analysis of variance followed by one-way analysis of variance and Bonferroni post-hoc tests.

Administration of both extract analogues significantly increased feeding behaviours over the period of the test. All three agents increased hour-one intake and meal-one size and decreased the latency to feed, although the zero-Δ⁹THC extract analogue did so to a lesser degree than the high-Δ⁹THC analogue.

Furthermore, only the analogue containing Δ⁹THC significantly increased meal duration.

The data confirm that at least one non-Δ⁹THC phytocannabinoid induces feeding pattern changes in rats, although further trials using individual phytocannabinoids are required to fully understand the observed effects.”

https://www.ncbi.nlm.nih.gov/pubmed/22157176

A low-Δ9 tetrahydrocannabinol cannabis extract induces hyperphagia in rats.

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“Appetite stimulation via partial agonism of cannabinoid type 1 receptors by Δtetrahydrocannabinol (ΔTHC) is well documented and can be modulated by non-ΔTHC phytocannabinoids.

ΔTHC concentrations sufficient to elicit hyperphagia induce changes to both appetitive (reduced latency to feed) and consummatory (increased meal one size and duration) behaviours.

Here, we show that a cannabis extract containing too little ΔTHC to stimulate appetite can induce hyperphagia solely by increasing appetitive behaviours.

These results show only the increase in appetitive behaviours, which could be attributed to non-ΔTHC phytocannabinoids in the extract rather than ΔTHC.

Although further study is required to determine the constituents responsible for these effects, these results support the presence of non-ΔTHC cannabis constituent(s) that exert a stimulatory effect on appetite and likely lack the detrimental psychoactive effects of ΔTHC.”

https://www.ncbi.nlm.nih.gov/pubmed/20975531

Peripheral endocannabinoid signaling controls hyperphagia in western diet-induced obesity.

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“The endocannabinoid system in the brain and periphery plays a major role in controlling food intake and energy balance.

We reported that tasting dietary fats was met with increased levels of the endocannabinoids, 2-arachidonoyl-sn-glycerol (2-AG) and anandamide, in the rat upper small intestine, and pharmacological inhibition of this local signaling event dose-dependently blocked sham feeding of fats.

We now investigated the contribution of peripheral endocannabinoid signaling in hyperphagia associated with chronic consumption of a western-style diet in mice ([WD] i.e., high fat and sucrose).

These results suggest that endogenous activity at peripheral CB1Rs in WD mice is critical for driving hyperphagia.

In support of this hypothesis, levels of 2-AG and anandamide in both, jejunum mucosa and plasma, of ad-libitum fed WD mice increased when compared to SC mice. Furthermore, expression of genes for primary components of the endocannabinoid system (i.e., cannabinoid receptors, and endocannabinoid biosynthetic and degradative enzymes) was dysregulated in WD mice when compared to SC mice.

Our results suggest that hyperphagia associated with WD-induced obesity is driven by enhanced endocannabinoid signaling at peripheral CB1Rs.”

https://www.ncbi.nlm.nih.gov/pubmed/28065722

Medical Cannabis in the Palliation of Malignant Wounds—A Case Report

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“Anecdotal accounts of the use of topical extracts from the cannabis plant being used on open wounds date back to antiquity. In modern times, cannabinoid therapies have demonstrated efficacy as analgesic agents in both pharmaceutical and botanical formats. Medical cannabis (MC), also known as medical marijuana,…

The endogenous cannabinoid system, consisting of cannabinoid receptors and their endogenous ligands, is ubiquitous throughout the human bodyAvailable research shows that cancer cells express higher levels of the cannabinoid receptors, CB1 and CB2, relative to their noncancer counterparts, while also demonstrating an overall state of upregulationHuman in vitro studies, using nonmelanoma skin lines, have demonstrated direct induction of tumor cell apoptosis and inhibition of tumor-related angiogenesis, both by way of activation of cannabinoid receptors.

The analgesic outcomes observed in this case are supported by the results of a recent systematic review and meta-analysis of cannabinoids for medical useUnlike intact skin, which is polar and hydrophilic, wounds lack epithelial coverage and are nonpolar and lipophilic. Therefore, lipophilic compounds such as the THC and CBD cannabinoids may be readily absorbed through cutaneous wounds.

Before the use of topical MC oil, the patient’s wound was growing rapidly. Yet, after a few weeks, a modest regression of his malignant wound was observed while the patient used topical MC. This secondary outcome suggests that topical MC may promote antineoplastic activity as per the findings of Casanova et al.

In summary, this is the first case report to demonstrate the potential for MC to provide effective pain and symptom management in the setting of malignant wounds. The rapid onset of analgesia after topical placement suggests that the effects were mediated through absorption of the THC and CBD cannabinoids that subsequently interacted with peripheral nociceptors, immune cells, and cancer cells. The postapplication analgesia may be because of the gastrointestinal absorption of ingested residual MC oil. This case suggests that MC delivered in vaporized and topical oil formats warrants further investigation in human malignancy, including randomized controlled trials capable of establishing long-term efficacy, optimal dosage, schedules of administration, mixture composition, and safety.”

http://www.jpsmjournal.com/article/S0885-3924(16)30328-1/fulltext

“Can Cannabis Oil Help Heal Wounds?”                              http://www.livescience.com/57500-can-medical-cannabis-help-heal-wounds.html

“Oral cancer patient, 44, claims cannabis oil helped to shrink a hole in his cheek that was caused by the disease” http://www.dailymail.co.uk/health/article-4124752/Oral-cancer-patient-44-claims-cannabis-oil-helped-shrink-hole-cheek-caused-disease.html

“Miracle plant: Can medical marijuana heal wounds?” http://www.nydailynews.com/life-style/medical-marijuana-heal-wounds-article-1.3384572

“Cannabis Oil Shows Potential To Heal Cancer Wounds Fast”  http://www.healthaim.com/cannabis-oil-shows-potential-heal-cancer-wounds-fast/71395

Extravirgin olive oil up-regulates CB₁ tumor suppressor gene in human colon cancer cells and in rat colon via epigenetic mechanisms.

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“Extravirgin olive oil (EVOO) represents the typical lipid source of the Mediterranean diet, an eating habit pattern that has been associated with a significant reduction of cancer risk. Diet is the more studied environmental factor in epigenetics, and many evidences suggest dysregulation of epigenetic pathways in cancer.

The aim of our study was to investigate the effects of EVOO and its phenolic compounds on endocannabinoid system (ECS) gene expression via epigenetic regulation in both human colon cancer cells (Caco-2) and rats exposed to short- and long-term dietary EVOO.

Taken together, our findings demonstrating CB₁ gene expression modulation by EVOO or its phenolic compounds via epigenetic mechanism, both in vitro and in vivo, may provide a new therapeutic avenue for treatment and/or prevention of colon cancer.”

https://www.ncbi.nlm.nih.gov/pubmed/25533906

Circulating levels of endocannabinoids respond acutely to voluntary exercise, are altered in mice selectively bred for high voluntary wheel running, and differ between the sexes.

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“The endocannabinoid system serves many physiological roles, including in the regulation of energy balance, food reward, and voluntary locomotion.

Signaling at the cannabinoid type 1 receptor has been specifically implicated in motivation for rodent voluntary exercise on wheels.

We studied four replicate lines of high runner (HR) mice that have been selectively bred for 81 generations based on average number of wheel revolutions on days five and six of a six-day period of wheel access.

Our results suggest that voluntary exercise alters circulating levels of endocannabinoids, and further demonstrate that selective breeding for voluntary exercise is associated with evolutionary changes in the endocannabinoid system.”

https://www.ncbi.nlm.nih.gov/pubmed/28017680

“Exercise activates the endocannabinoid system.”  https://www.ncbi.nlm.nih.gov/pubmed/14625449

Expression of Cannabinoid Type 1 Receptors in Human Odontoblast Cells.

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“The aim of this study was to investigate the functional expression of cannabinoid type 1 (CB1) receptors in human odontoblasts (HODs) and the possible internal mechanism.

In the present study, we examined the molecular and functional expression of the CB1 receptors in cultured HOD-like cells and native HODs obtained from healthy wisdom teeth.

We conclude that HODs can express functional CB1 receptors that may play an important role in mediating the physiological function in tooth pulp.”

https://www.ncbi.nlm.nih.gov/pubmed/27989582

“Involvement of the endocannabinoid system in periodontal healing.”  https://www.ncbi.nlm.nih.gov/pubmed/20233580

Two Janus cannabinoids that are both CB2 agonists and CB1 antagonists.

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“The cannabinoid signaling system includes two G protein coupled receptors, CB1 and CB2. These receptors are widely distributed throughout the body and have each been implicated in many physiologically important processes.

Though the cannabinoid signaling system has therapeutic potential, a persistent hurdle has remained the development of receptor-selective ligands. Because CB1 and CB2 are involved in diverse processes, it would be advantageous develop ligands that differentially engaging CB1 and CB2.

In summary we have determined that GW405833 and AM1710 are not only CB2 agonists but also CB1 antagonists, with distinctive and complex signaling properties. Thus experiments using these compounds must take into account their potential activity at CB1 receptors.”

https://www.ncbi.nlm.nih.gov/pubmed/27927913