It’s well-known that use of marijuana, either recreationally or medicinally, often results in fridge-raiding and constant snacking — ergo: “the munchies.” This is indeed one of the beneficial effects experienced by medical marijuana-using chemotherapy or anorexia patients whose illnesses or their therapies result in loss of appetite. But what are the physiological and biochemical mechanisms underlying the marijuana munchies phenomenon?
To find out, a European Research Council funded study by a research team led by Dr. Giovanni Marsicano, a Research Director at the research agency INSERM at Bordeaux, France (NeuroCentre Magendie, Bordeaux), has succeeded in elucidating how the endocannabinoid system controls food intake through its effects on the perception of smells. These results are published in the journal Nature Neuroscience on 9 February 2014.
The paper, entitled “Mechanism elucidated: how smell perception influences food intake,” is co-authored by an international team of colleagues from 11 research institutions in France, Germany, Spain, and Italy. The researchers note that hunger arouses sensory perception, eventually leading to an increase in food intake, but observe that the underlying mechanisms remain poorly understood.
In animals and humans, hunger mechanisms are known to stimulate food intake. Hunger triggers a set of mechanisms that encourage eating, for example by increasing sensory perceptions such as the sense of smell. The researchers have now succeeded in revealing what links hunger and increased smell perception in the brain, and the resulting urge to eat.
The researchers discovered how this mechanism is initiated in the endocannabinoid system in mice. This system interconnects receptors located in the brain and involved in different sensations such as euphoria, anxiety, or even pain, that are also sensitive to cannabinoid substances, such as cannabis (marijuana). They found that cannabinoid type-1 (CB1) receptors promote food intake in fasted mice by increasing odor detection, and that “CB1 receptors were abundantly expressed on axon terminals of centrifugal cortical glutamatergic neurons that project to inhibitory granule cells of the main olfactory bulb (MOB).” The researchers discovered that the CB1 cannabinoid receptors control a circuit that connects the olfactory bulb (the region in the nervous system that initially handles olfactory information, located above the nose) to the olfactory cortex (higher structures of the brain). When the sensation of hunger is felt, it triggers the activity of the cannabinoid receptors, which in turn activate the olfactory circuit, which then becomes more responsive.
Cannabinoids are the bioactive components of the Cannabis plant that display a diverse range of therapeutic qualities. Two forms of cannabidiol (CBD), two forms of cannabigerol (CBG) and two forms of cannabigevarin (CBGV) represent the most common cannabinoids found in the cannabis plant apart from the main psychoactive cannabinlid tetrahydrocannabinol (THC).
Cannabinoids (CBs), either produced within the body or taken from an external source (ie: Pharmaceutical or Medicinal Marijuana), are believed to exert effects that medical marijuana advocates maintain may also be of benefit to patients with Irritable Bowel Syndrome (IBS) and certain types of Inflammatory Bowel Disease (IBD), including Crohn’s Disease and Ulcerative Colitis. It is believed that medicinal marijuana affects Cannabinoid Receptors (CB) in the Gastrointestinal Tract and can exert effects that help relieve symptoms. These effects include a reduction of: Pain, Inflammation, Diarrhea, Gastrointestinal Hypermotility and Secretion. Cannabis can reduce painful Gastrointestinal cramping as it is a smooth muscle relaxant, and can relax the Intestinal spasms. Cannabinoids can also increase healing of injured Epithelial Tissues. Many of these effects are attributed to Cannabinoid stimulation of Cannabinoid Receptors (CB) located in many parts of the body.
A study, entitled: “Cannabis Finds Its Way into Treatment of Crohn’s Disease” (International Journal of Experimental and Clinical Pharmacology, Vol. 93, No. 1-2, 2013 Dec 17;93(1-2):1-3. © 2013 S. Karger AG, Basel. PMID: 24356243) is co-authored by Rudolf Schicho, PhD and M. Storr, both of the Institute of Experimental and Clinical Pharmacology, Medical University of Graz in Graz, Austria. In the study abstract, Schicho and Storr note that In ancient medicine, cannabis was widely used to treat and cure bowel disturbances and inflammation, and a recent clinical study now shows that the medicinal herb Cannabis sativa lived up to expectations and proved to be highly efficient in cases of inflammatory bowel diseases.
The human body produces and utilizes its own cannabinoids, but can also utilize cannabinoids from external sources such as cannabis. In their paper, Schicho and Storr observe that over the past decade there has been a steady increase in the number of publications addressing the anti-inflammatory effects of Cannabinoids and potential underlying mechanisms, and in particular that preclinical data on the ameliorating effect of synthetic and natural CBs in animal models mimicking features of IBD have been rapidly evolving. Experimental studies have suggested that Cannabinoids may provide anti-inflammatory effects and symptomatic benefit in patients with IBD.
In the Nature Neuroscience paper, Dr. Marsicano and his colleagues note that local pharmacological and genetic manipulations revealed that both endocannabinoids and exogenous cannabinoids increased odor detection and food intake in fasted mice by decreasing excitatory drive from olfactory cortex areas to the MOB. Consistently, cannabinoid agonists dampened in vivo optogenetically stimulated excitatory transmission in the same circuit.
They conclude that their data indicate that cortical feedback projections to the MOB crucially regulate food intake via CB1 receptor signaling, linking the feeling of hunger to stronger odor processing. Thus, CB1 receptor–dependent control of cortical feedback projections in olfactory circuits couples internal states to perception and behavior. It is therefore determined that this biological mechanism brings about the increased sensitivity to smell during hunger, explaining one of the reasons for food intake and attraction to food among marijuana users.
Dr. Marsicano and his research team conclude that the circuit involved in the olfactory system is altered in obese or anorexic patients, and that sensitivity to smell may be more or less strong compared to normal. Understanding of the biological mechanism it work will allow better management of these types of pathologies.