For all of the states that initially passed medical cannabis legislation, cancer was not only an approved condition but also a major data point supporting such legislation. Specifically, cancer patients, forced to undergo exhausting chemotherapy treatments, lose appetite. This drastic, prolonged loss of appetite, similar to anorexia, decreases body weight and in turn, decreases overall health. Cannabis has long been observed to increase appetite in humans (we’ve written several Cornerstone blog posts on the “munchies”), with the most active ingredient identified as THC, the psychoactive component of cannabis. Unfortunately, not all patients enjoy or can tolerate this psychoactivity. Originally, this posed a serious downside to treatment with cannabis. However, with the discovery of the endocannabinoid system, researchers realized that the effects of THC might be achieved, without psychoactivity, via other cannabinoids. Additionally, research has confirmed that cannabis containing no THC can still restore appetite. In line with this thinking, one paper, published last month in the medical research journal, Psychopharmacology, tested a molecule known as cannabigerol (CBG) on rodents to observe changes in feeding patterns.
Readers may be surprised to learn that cannabigerol, unlike many other cannabinoids, found mostly in the resin of medicinal plants, exists in higher concentrations in plain hemp. Most medicinal strains, in fact, have concentrations lower than 1%. CBG also binds to the CB1 receptor at a much lower rate than THC and may even serve to temporarily disable the receptor. However, CBG has also been shown to be a 5-HT1A receptor agonist and an alpha2-adrenergic receptor agonist. In other words, CBG has several mechanisms of action that have not fully been explored. However, none of these have been shown to be psychoactive. Of course, in the interest of finding a practical appetite stimulant, psychoactivity is not the only barrier to use. Medicines that disturb motor function or encourage sleep may also prevent normal use or cause adverse effects for patients. As a result, researchers cleverly also tested motor function in rodents given CBG.
To proceed with testing, CBG was first “dissolved directly into sesame seed oil…to produce a max working concentration of 120 mg/ml,” and then diluted to 60 and 30 mg/ml concentrations. On testing days, animals were administered CBG in randomly assigned amounts of 0, 30, 60, and 120 mg/kg of body weight, exactly an hour before the start of testing. Researchers then submitted the rodents to a battery of motor function tests. The first, the open-field test, places rodents in a maze with an open center and closed corridors. Nervous rodents spend less time in the relatively vulnerable center of the open field, and as a result, measuring the time they spend in that area helps to evaluate confidence. The second test, the static beam test, allows rodents to walk along a one meter, raised beam to an end/goal box. Rodents are scored on how quickly they complete the task, how many tries, and how many slips they accrue in an effort to reach the goal box (if they do at all), which gives researchers a clear picture of how the rodents normal locomotor activities are affected. Finally, researchers applied the forelimb grip strength test, which as it sounds, measures the strength of rodents grip by placing their forelimbs on a trapeze bar and uniformly pulling the rodents down from the bar by the base of the tail. The amount of force this takes, as recorded by a digital force gauge attached to the trapeze, indicates how powerful the rodents’ forearms are. Taken together, all three tests give researchers a good picture of how rodents’ physical movement/ability might be affected.
Perhaps unsurprisingly, CBG had no effect on the performance of rodents on these tests, at any concentration/dose. Having established, therefore, that CBG would not serve as a disruptive medicine to rodents, researchers began to observe the effect of administration on diet. In this process, researchers allowed rodents to acclimate to feeding at will over several days until constant feed rates were reached. On testing days, rodents were allowed to eat normally, then administered CBG, returned to their cages for one hour, and finally allowed to feed again for a period of two hours. During this two-hour time period, researchers measured number of feedings, length of feedings, and mass of feedings, using leftover food as an indication of food consumed (subtracted from the initial amount available).
Immediately, researchers observed a dose-dependent increase in feeding following CBG administration. The rodents “consumed 1.66 grams and 1.89 grams [on average] following 120 and 240 mg/kg doses of CBG”, respectively, as “compared to 0.85 grams [on average] for vehicle-treated animals” (animals receiving no CBG). This represents a feeding rate over twice as high as normal. The number of feeding sessions during the two-hour period also spiked, while the food consumed per session remained relatively constant. This would indicate that the change in consumption is a result of greater number of feeding sessions.
While this research has yet to be duplicated (having only been published in mid-October), it deserves immediate attention as the first study to investigate and report appetite stimulation via CBG. Furthermore, due to the study’s efforts to test motor function, we have reason to believe that CBG might actually be a viable human drug with no major drawbacks. While CBG is long way from the pharmaceutical market and clinical tests, high-CBG strains are currently available on the medicinal cannabis market. With no known toxicity and what appears to be no major risks, CBG-enriched cannabis may prove a helpful tool for appetite stimulation in current cancer patients.
Daniel Brierley, James Samuesl, Marnie Duncan, et al. “Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats.” Psychopharmacology (2016) 233:3603-3613. DOI: 10.1007/s00213-016-4397-4.