Cannabis has been known for millennia as a means to stimulate appetite and encourage consumption of food, and has long been used as a treatment for anorexia and related eating disorders. Now, modern research is finding that the link between the endocannabinoid system and diseases like anorexia is far deeper than ever suspected.
Although cannabis has been investigated as a potential treatment for anorexia and related eating disorders for decades, results have not always been positive.
An early double-blind crossover study published in 1983 compared the effect of THC and diazepam (an active placebo) on the appetites of anorexia nervosa sufferers. The study found that administration of THC didn’t lead to an increase in caloric intake or overall weight gain, and in fact caused “significant psychic disturbance” in several patients.
However, a more recent double-blind crossover study found that the synthetic THC analogue dronabinol led to “small but significant” weight gain in female sufferers of anorexia nervosa compared to placebo, and with no significant adverse psychotropic effects.
And a small pilot study on cannabis use in adult female suffering from anorexia showed that cannabis may be especially helpful for the psychological symptoms that go hand in hand with anorexia nervosa.
Several studies investigating animal models of anorexia have also found that administration of THC or other cannabinoid receptor agonists led to weight gain and improved appetite in their test subjects. One study found that in mice with induced activity-based anorexia, daily administration of 0.5mg THC “decreased survival” in the test group, but increased feeding rates in the survivors. Daily administration of a synthetic anandamide analogue, OMDM-2 (3 mg/kg), increased feeding rates without affecting overall survival rates, but not enough to reverse weight loss.
However, researchers are still investigating how cannabis may affect weight overall and have theorized how it’s possible some cannabis users have a lower BMI (body mass index) despite higher calorie intake.
Cannabis as an appetite stimulant
Few studies exist that specifically investigate the effect of cannabis on the appetites of anorexia nervosa sufferers. However, there are multiple studies into the effect of cannabis and cannabinoids on the form of anorexia that can affect individuals suffering from certain debilitating illnesses such as cancer, AIDS or hepatitis.
A 1994 phase-II study of the effect of THC on the appetites of cancer patients found that of eighteen subjects, thirteen reported an improvement in appetite following use of THC, and with no significant ill-effects. On that basis, cannabis was deemed an effective and safe appetite stimulant for cancer patients.
However, a more recent double-blind, placebo-controlled clinical trial conducted in 2006 found no significant differences in quality of life for either cannabis extract or THC compared to placebo.
While the various studies out there may differ greatly in results, it’s clear that the endocannabinoid system has an important role to play in the management of appetite and feeding. These studies have enabled scientists to gain a deeper understanding of the underlying mechanisms of the endocannabinoid system, and the extensive role that it has to play in the regulation of essential biological processes such as appetite, food intake and satiety.
The endocannabinoid system & regulation of food intake
As our understanding of the endocannabinoid system advances, the role it plays in the development and management of diseases such as anorexia is beginning to emerge.
A study published in 2005 found that in individuals suffering from anorexia nervosa and binge-eating disorder, blood levels of the endogenous cannabinoid anandamide were significantly heightened, although they remained normal in patients diagnosed with bulimia nervosa. The researchers also found that anandamide levels were inversely associated with levels of ghrelin, another molecule that’s deeply involved in the regulation of appetite and food intake.
The relationship between ghrelin signalling and the endocannabinoid system has been studied extensively, and it’s been observed that THC can effectively act as a stimulant for ghrelin production in cancer sufferers receiving chemotherapy.
The role of ghrelin is to stimulate the peripheral nervous system and ultimately the brain, in order to produce sensations of hunger when the stomach is empty. If ghrelin is absent for some reason (in chemotherapy patients, certain drugs inhibit the release of ghrelin), no sensations of hunger manifest even if the stomach is empty, and the patient can become anorexic.
Given that anandamide fulfils many of the same biological functions as THC, it’s understandable that in patients with a binge-eating disorder, a flood of anandamide would encourage excessive eating. It’s unclear how the flood of anandamide in patients with anorexia nervosa affects their ability to resist the desire to eat..
Could a dysfunctional endocannabinoid system cause anorexia?
Not only is the endocannabinoid system fundamental to the regulation of appetite and food intake, it’s now thought that anorexia nervosa and related disorders could in fact be caused by underlying imbalances that could potentially be corrected by targeted cannabinoid therapies.
In a study from 2011, researchers studied the brains of anorexic, bulimic and healthy women using positron emission topography (PET). The researchers found that sufferers of anorexia nervosa exhibited a significant overall increase in CB1-receptor density in the cortical and subcortical regions of the brain, while both bulimic and anorexic subjects exhibited significantly higher CB1-receptor density in a particular region of the brain known as the insular cortex. Levels of naturally-occurring endocannabinoids were also found to be significantly lower in both bulimics and anorexics, particularly in the insular cortex.
The researchers suggested that in anorexia sufferers, the overall increase in CB1-receptor density could be a compensatory mechanism for an underactive endocannabinoid system. They also noted that the increase in CB1-receptor density in the insular cortex seen in both bulimics and anorexics is likely to be associated with the underlying dysfunction of the pleasure-reward system, as the insular cortex is known to be fundamentally involved in these processes.
There have also been several studies investigating the possibility that mutations in genes related to the endocannabinoid system may lead to a higher chance of developing eating disorders such as anorexia. A study published in 2009 concluded that a couple of polymorphisms may contribute to a biological sensitivity to anorexia and bulimia nervosa. These include the CNR1 gene that encodes for the expression of the cannabinoid receptor type I and another that controls production of the anandamide-degradation molecule FAAH.
Cannabis use by anorexia sufferers
There are several studies that have assessed the rate of substance use and misuse in people suffering from eating disorders and have found it to be higher-than-average for cannabis. It’s not surprising that cannabis is the most commonly reported illicit drug used by sufferers of eating disorders, since that’s consistent with population norms. It isn’t just cannabis, though: sufferers also reportedly turn to alcohol, tobacco and many other substances, too.
There have been no studies into the possibility that cannabis use could cause anorexia or facilitate sufferers in their self-starvation, but there are indications that cannabis can cause appetite suppression in certain circumstances. In fact, cannabis’ role in medicine as an appetite stimulant has been widely studied.
However, research indicates that this effect depends on the presence of high levels of CBD or THCV, two cannabinoids that have been found to have appetite-dulling properties. Research conducted by British cannabinoid science company GW Pharmaceuticals demonstrated that the two cannabinoids exerted an appetite-suppressing effect when administered to mice. The effect is derived from the fact that the compounds are an antagonist and an inverse agonist of the cannabinoid receptors, and block the appetite-stimulating effects of agonists such as anandamide or THC.
CBD and THCV might therefore be interesting cannabinoids for conditions that require appetite-suppressant medicines. However, it’s unlikely that they’re responsible for the increase of cannabis use among anorexics, as CBD and THCV levels are very low in recreational cannabis. Instead, CBD and THCV levels are higher in hemp-like cannabis varieties.
And if a dysfunctional endocannabinoid system truly proves to be the underlying cause of anorexia, use of THC-rich cannabis may bring heightened subjective reward to those lacking in or unable to effectively utilize anandamide (THC’s endogenous analogue).
Plenty of research remains to be done before our understanding of the endocannabinoid system is complete enough to allow us a full understanding of its relationship to the development and management of diseases like anorexia nervosa. However, it’s clear that its role is fundamental, and that deeper understanding will enable us to develop targeted therapies for anorexia, bulimia and various related disorders.
- Disclaimer:This article is not a substitute for professional medical advice, diagnosis, or treatment. Always consult with your doctor or other licensed medical professional. Do not delay seeking medical advice or disregard medical advice due to something you have read on this website.