Cocoa and the Search for Dietary Cannabinoids
(10/31/2010) Since the discovery of cannabinoid compounds outside of the Cannabis plant, researchers have continued bio-prospecting other fruits and vegetables for cannabinoid activity. Current research suggests new sources of plant cannabinoids may continue to be found.
Some of the results have been promising, for instance polyphenols found in tea may activate cannabinoid receptors and there is even a dietary cannabinoid that is found in nearly all edible plants. Additionally, the smelly molecules found in plants called terpenes are common across different species. Terpenes or terpenoids found on the Cannabis and other plants may also have some interesting effects in humans.
A.I. generated depiction of a scientist investigating cocoa plants.
The first strong evidence of cannabinoids as part of the human diet began in 1996. Nature published an article by Emmanuel di Tomaso, Massimilliano Beltramo, and Daniele Piomelli describing the discovery of endocannabinoids in chocolate. The authors were excited as they thought the presence of these endocannabinoids could explain the "chocolate craving, common of western society' and "the association of chocolate craving with drug-induced psychoses."
Endocannabinoids are lipids that are made by our body. The active constituents in Cannabis mimic these compounds by activating the same receptors as endocannabinoids. Endocannabinoids and their receptors appear to have important roles in bone health and depression.
Endocannabinoids that are made by the body include 2-AG, oleamide, and anandamide. Recent evidence suggests that the endocannabinoid system is important for healthy development. Interestingly, 2-AG is found in significantly high levels in human breast milk.
These lipids act upon the cannabinoid receptors. There are two types of cannabinoid receptors. The type 1 receptor is the one of the most abundant receptors in the human brain and is found on nerve cells throughout the body. The type 2 receptor is abundantly expressed on immune cells.
Piomelli and colleagues thought the fat in chocolate might contain lipids that were similar to anandamide or other endocannabinoids. The researchers found three structurally related compounds known as N-acylethanolamines (NEAs). The authors demonstrated that the NEAs could directly and indirectly activate cannabinoid receptors. The NEAs can activate cannabinoid receptors by preventing the degradation of anandamide, like Aspirin, thus raising the levels of endocannabinoids leading to increased receptor activity.
However, the results needed to be confirmed in an animal model or in humans, to determine if these cocoa compounds are available in high enough amounts to cause an effect.
Artistic depiction of a chocolate-induced high
So, in 1998 Nature again published findings on cannabinoids in chocolate. This time researchers tested the effects of orally administered cannabinoids in a model of mouse behavior. Some of the compounds were found to cause an effect at high doses but the authors determined that only about 1-5% of these cannabinoids are extracted from dietary sources. Thus the possibility of achieving a cannabis-like effect is small unless these compounds can act synergistically.
In response to this 1998 article, Massimiliano Beltramo and Daniele Piomelli reviewed the research and concluded"...although the results of DiMarzo et al.’s study will reassure manufacturing companies that the risks of chocolate consumption do not include cannabis-like intoxication, they provide little new information on the intriguing psychopharmacology of cocoa. This substance remains, in R. J. Huxtable’s apt words, “more than a food but less than a drug.”
