Obesity is caused by a chronic imbalance between energy intake and energy expenditure. The increasing incidence of obesity, especially in children and adolescents, is a major public health problem.
Cannabis has been used medicinally for centuries to treat a variety of disorders, including those related to the gastrointestinal tract.
The general opinion contemplate that the relation of cannabis with respect to obesity has nothing to do with weight loss; on the contrary, it is believed that it generates the increase in body mass due to the known increase in appetite, but the reality is completely different.
Interestingly, cannabis users seem to have an increase in caloric intake contrasted with weight loss. Studies conducted on cannabis suggest that the two phytocannabinoids that are found in the greatest percentage in the plant can be used as alternatives to lose weight, these are THC and CBD which despite having opposite reactions in neurotransmitters can directly or indirectly generate weight loss.
In the same way, several investigations reveal that phytocannabinoids play an important and sometimes surprising role. The endocannabinoid system participates in the control of a variety of gastrointestinal functions, including motility, ingestion of gut-brain fat and hunger signaling, intestinal inflammation and permeability, dynamics, and even with interactions with the gut microbiota.
The evidence also suggests that deregulation of the endocannabinoid system may play a role in intestinal disorders, including inflammatory bowel disease, irritable bowel syndrome, and obesity.
Polymorphisms of a single nucleotide in the genes of the constituents of the endocannabinoid system, including fatty acid amide hydrolase (FAAH), the endocannabinoid degrading enzyme, anandamide and the cannabinoid receptor type 1 (CB1R), are associated with an increased colonic transport and irritable bowel syndrome.
The Endocannabinoid System
The endocannabinoid system (ECS) is a lipid signaling system comprising the endogenous cannabis-like ligands (endocannabinoids) anandamide (AEA) and 2-arachidonoylglycerol (2-AG) (the first endogenous ligands, the AEA and the 2-AG, were discovered in 1992 and 1995, respectively), which are derived from arachidonic acid. These bind to a family of receptors coupled to the G protein, called CB1 and CB2; these cannabinoid receptors were first identified in 1988.
The cannabinoid receptor 1 (CB1R) is distributed in areas of the brain associated with motor control, emotional responses, motivated behavior and energy homeostasis. In the periphery, the same receptor is expressed in the adipose tissue, the pancreas, the liver, the gastrointestinal tract, the skeletal muscles, the heart and the reproductive system.
CB2R is expressed mainly in the immune system that regulates its functions. Endocannabinoids are synthesized and release emotional impulses and energy homeostasis according to the demand of receptor signals. This acts as a messenger of retrograde signaling in glutamatergic synapses and GABA, and as a modulator of postsynaptic transmission, interacting with other neurotransmitters.
The endocannabinoids are transported to the cells by a specific uptake system and are degraded by the fatty acid hydrolase (FAAH) and monoacylglycerol lipase (MAGL) enzymes. The ECS is involved in diverse physiopathological conditions in the central and peripheral tissues. It is involved in the hormonal regulation of food intake, cardiovascular, gastrointestinal, immunological, and behavioral functions.
The CB1 coupled to the G protein is the most studied and relevant cannabinoid target; also known as the most abundant GPCR in the brain that gives specific cellular responses in response to a wide variety of stimuli from photons and small molecules to peptides and proteins, such as hormones, neurotransmitters and paracrine agents. One of the functions of CB1 is the control of energy homeostasis. Induction of CB1 signaling stimulates feeding by increasing appetite, whereas blockade of CB1 signaling induces hypophagia by an appetite suppressing effect.
The ECS regulates the appetite and food intake through the hypothalamus, while the mesolimbic system modulates the reward function of the food.
Δ 9 tetra-hydrocannabivarin (THCV) is a naturally analogue of the psychoactive principle of cannabis, Δ 9 tetra-hydrocannabinol (THC). However, unlike THC, which is a cannabinoid agonist CB1 and CB2, THCV, and its isomer Δ 8 tetra-hydrocannabivarin, behaves as a neutral CB1 antagonist and depending on in vitro and in vivo assays as an agonist or CB2 antagonist.
Reverse agonists of the cannabinoid receptor type 1 (CB1) improve type 2 diabetes and dyslipidemia, but their use was discontinued due to adverse psychiatric effects. Δ 9 -Tetrahydrocannabivarin (THCV) is a neutral antagonist of CB1 that produces hypophagia and reduction of body weight in thin mice. THCV did not significantly affect food intake or body weight gain in any of the studies, but produced an early and transient increase in energy expenditure. Depending on the dose, reduces glucose intolerance in ob / ob mice and improves glucose tolerance, it also increases insulin sensitivity in DIO mice, without constantly affecting plasma lipids.
THCV also restores insulin signaling in hepatocytes and insulin resistant myotubes. THCV is a new potential treatment against glucose intolerance associated with obesity with pharmacology different from that of CB1 reverse agonists / antagonists.
It is known that THC is the main psychoactive component of cannabis mediated by the activation of CB1 receptors in the central nervous system, this element is also responsible for the increase in appetite.
Studies in THC found that this produces changes in the gut microbiome and is thought to be an important factor in maintaining a healthy weight. These microbes work to break down food and promote weight loss or gain, which is why it was used in products such as Rimonabant. A Canadian THC experiment in 2015 examined mice and discovered that obese mice exposed to THC lost weight, but thin mice were not affected, this means that in addition to controlling the parasites that are in the body can prevent the increase of weight despite eating foods with high fat content. However, this same psychoactive mechanism limits its commercial use due to adverse effects caused by its interaction with neurotransmitters such as serotonin and dopamine. It is now accepted that other phytocannabinoids with weak or no psychoactivity represent a hope as therapeutic agents in humans.
It is a non-psychoactive phytocannabinoid that acts as an appetite suppressant, it is in a lower percentage compared to THC. The CBD has been taken into account for analysis due to its characteristics that make it a star product in the loss of body mass.
This phytocannabinoid does not prevent eating completely, but it does produce a feeling of fullness. Several studies on this subject show positive results, in which it is concluded that food intake decreases considerably
Another mechanism of action that is taken into account is the process known as "Browning" where the white adipose tissue is converted into brown adipose tissue thus increasing the speed of fat burning. The expansion and / or activation of brown fat results in increased energy expenditure, a negative energy balance and restricts weight gain. Brown fat is also able to use glucose and lipids in the blood and improves the metabolism of glucose and lipids in the blood regardless of weight loss.