Theoretical Explanation for Reduced Body Mass Index and Obesity Rates in Cannabis Users

Abstract

Introduction: Obesity is treatment-resistant, and is linked with a number of serious, chronic diseases. Adult obesity rates in the United States have tripled since the early 1960s. Recent reviews show that an increased ratio of omega-6 to omega-3 fatty acids contributes to obesity rates by increasing levels of the endocannabinoid signals AEA and 2-AG, overstimulating CB₁R and leading to increased caloric intake, reduced metabolic rates, and weight gain. Cannabis, or THC, also stimulates CB₁R and increases caloric intake during acute exposures. Goals: To establish the relationship between Cannabis use and body mass index, and to provide a theoretical explanation for this relationship. Results: The present meta-analysis reveals significantly reduced body mass index and rates of obesity in Cannabis users, in conjunction with increased caloric intake. Theoretical explanation: We provide for the first time a causative explanation for this paradox, in which rapid and long-lasting downregulation of CB₁R following acute Cannabis consumption reduces energy storage and increases metabolic rates, thus reversing the impact on body mass index of elevated dietary omega-6/omega-3 ratios.

Keywords: Cannabis; body mass index; obesity; omega-6 fatty acid; theory.

FIG. 1.

The impact of the modern western diet on the endocannabinoid system. (A) In the presence of a natural omega-6/omega-3 ratio, production of the endocannabinoid signals AEA and 2-AG and resulting stimulation of CB1R are compatible with a healthy BMI. (B) The modern western diet, with its elevated omega-6/omega-3 ratio, leads to excess production of AEA and 2-AG. This overstimulates CB₁R, leading to weight gain and metabolic dysregulation. Modified from Freitas et al. (22). AEA, anandamide; N-arachidonoylethanolamide; 2-AG, 2-arachidonoylglycerol; BMI, body mass index.

FIG. 2.

A comparison of BMI (kg/m²) of Cannabis users and nonusers. Data from current user, highest dosage presented in Table 1. Available data show that nonusers are overweight on average, whereas the mean BMI of users is not different from the upper limit of the healthy weight range. Data are expressed as mean±SEM (N=12 data points from 11 studies, p<0.001; Hedges g statistic=−1.16).

FIG. 3.

The impact of Cannabis use on the endocannabinoid system of people consuming a diet characterized by an elevated omega-6/omega-3 ratio. Acute effects of Cannabis and/or THC consumption include hypothermia and hyperphagia, leading to increased energy intake and storage. However, Cannabis use also causes long-term downregulation of CB₁R, leading to decreased CB₁R activity, as shown in the insert on the lower right, in which each spike follows acute Cannabis ingestion, while the overall activity level remains depressed. Decreased CB₁R activity results in a decrease in energy assimilation and an increase in metabolic rates, resulting in a decline in body mass despite stimulation of CB₁R during acute exposure. THC, Δ⁹-tetrahydrocannabinol.

FIG. 4.

Proposed weight loss therapy based on theory. Daily omega-3 fatty acid supplements (especially with decreased dietary omega-6 fatty acids) will reduce levels of AEA and 2-AG, reducing stimulation of CB₁R, while weekly Cannabis use will cause downregulation of CB₁R. Thus, this approach will act to both reduce levels of the endocannabinoid signals and reduce the sensitivity of target cells to those signals. The net effect is predicted to be a more potent weight loss strategy than diet alone.