XWSF Tassell's Journal

Cocoa
The historical background of cacao is quite complex. Although the cacao plant (Theobroma cacao) is indigenous to the forest valleys of the Orinoco and Amazon rivers in Eastern Venezuela, it has been known in Mexico and Central America for several thousands of years. The Aztec and Mayan civilizations of Mexico believed that the cacao plant was of divine origin, and they greatly valued the product. The cacao beans were used to make a beverage known as cacahuatl. Only available to the highest of Aztec society, cacahuatl was made from ground cacao beans and maize, and flavored with vanilla, capsicum and other spices. This drink was a favorite of Montezuma, who consumed more than 50 golden goblets filled with cacahuatl daily. Moreover, cacao beans were used as a form of currency, the value of which was determined by their size. Four beans could buy a turkey, while around 100 beans could purchase a slave. Peter the Martyr described the cacao beans as "blessed money which prevents the owner from greed, since they cannot be stored or hidden in the earth (Nielsen 1995)." Thus, the cacao bean had a unique role as a divine delicacy and monetary unit.

Cacao had been cultivated by the Aztecs for hundreds of years before the conquest of Cortes in 1519. The Aztecs believed that the cacao plant was brought down from the heavens by Quetzalcoatl, god of the air. This belief was the source of cacao's divine presence in Aztec society; however, it was also the cause of the downfall of Aztec society. Because Cortes somewhat resembled their image of Quetzalcoatl, the Aztecs, hoping that their most beloved god had returned, accepted the Spaniards. This enabled the Spanish Army to easily conquer the Aztec empire. In 1528, Cortes returned to Europe with cacao beans and the knowledge of their use. Though the Spaniards kept the Mexican recipe secret for a while, it eventually spread throughout Europe with great popularity. Up to this point in time, cacao beans were prepared in a beverage (cacao liquor), similar to the way the Aztecs made it, but with added sugar. In the 1800's, however, cacao powder was separated from the cacao butter, milk was added, and chocolate as we know it today was first developed.

Today, cacao is cultivated in many other tropical parts of the world, including West Africa, Indonesia, and Malaysia. The chocolate industry flourishes, as people all over the world enjoy the distinct flavor of chocolate. The consumption of chocolate candy per capita in the U.S. alone is 4.6 kg/year, which is small when compared to the 9.9 kg/year per capita chocolate consumption of Switzerland (Rössner 1997). There is obviously a large demand for chocolate throughout the world; however, the implications of chocolate consumption are scarcely understood. Chocolate is the most commonly craved substance in the United States (Weingarten and Elston 1991), but the foundations behind chocolate craving, or chocolate addiction, are only speculative. Whether the craving can be attributed to the pharmacological effect of compounds within chocolate, or whether it is due to sensory perceptions is unclear.

Though sensory properties of the nervous system are likely to be necessary, the relation of chocolate craving to certain drug induced psychoses indicates that the pharmacological effect of active substances in chocolate may also be involved (Di Tomaso et al. 1996). Schifano and Magni display this relation in the experiences of seven subjects who had a history of MDMA ("ecstasy") abuse. The seven subjects consisted of six males and one female, and all of them described the same association. After having quit MDMA, a chocolate craving developed that promoted an intake of up to 2000 calories of chocolate per episode--sometimes they were binges, and sometimes they were not. One episode of chocolate craving per week was the average, and was usually preceded by a weight loss of up to 14 kg (Schifano and Magni 1994). Attributing the changes in appetite to decreased central 5-hydroxytryptamin functioning, the authors also speculate that chocolate may be useful in combatting the effects of MDMA withdrawal because it contains amphetamine-like phenethylamines as well as caffeine and theobromine. These interesting observations shed light on the pharmacological aspect of substituents within chocolate. Thus, an organized approach to coordinate the pharmacological effects of different chemical constituents within chocolate is necessary to fully understand the implications of chocolate consumption.

The conclusions proposed by Schifano and Magni are primarily concerned with the pharmacological effects of the methylxanthines within chocolate, namely, theobromine and caffeine. Theobromine comprises approximately 0.60f the final chocolate product, while caffeine accounts for about 0.1% (Nielsen 1995). Although these percentages seem very small, they reflect a significantly higher caffeine concentration than one cup of tea (0.02%) or one cup of cola (0.018%) (Presti 1999). These methylxanthine compounds act on the central nervous system to produce a stimulant effect. The dose dependent physiological implications of their actions are increased blood pressure, dilated bronchial passages, and diuresis. The mechanism by which these effects are achieved is thought to result from the interaction of methylxanthines with the adenosine receptor. Specifically, theobromine and caffeine act as competetive antagonists at the adenosine receptor, thereby producing a stimulant effect by limiting the inhibitory consequence of adenosine binding.

The physiological stimulus provided by methylxanthines in chocolate could have many implications. Along with the treatment of MDMA withdrawal, this effect could be beneficial in providing a greater general understanding of non-drug cravings. Though non-drug chocolate cravings are most likely involved with the same pleasure and reward pathways that psychoactive drug cravings manipulate, it is unclear exactly how these non-drug cravings manifest and consequently affect behavior. Moreover, it is not clear how the effect of methylxanthines actually influences non-drug cravings--or even if methylxanthines play a role in this respect. In any case, the idea that chocolate cravings may be related to the pharmacological effects of these compounds must be examined further. Also, the role of other pharmacological constituents in chocolate must be considered.

A rather novel approach at attempting to associate chocolate craving with compounds in chocolate was conducted by Di Tomaso, Beltramo, and Piomelli (1996). They considered that since chocolate is rich in fat, it might contain lipids that are chemically and pharmacologically related to anandamide. Actually, they found three compounds that eluted from the gas chromatography at the same retention times as anandamide, N-oleoylethanolamine, and N-linoleoylethanolamine. These compounds also displayed electron-impact mass spectra representative of these N-acylethanolamines. In the samples tested, the total concentration of N-acylethanolamines ranged from 0.5 to 90 mg/ g, and each particular compound was present in a certain order of concentration--N-oleoylethanolamine > N-linoleoylethanolamine > anandamide (Di Tomaso et al. 1996). Anandamide alone was present at concentrations varying from 0.05 to 57mg/ g of chocolate. The authors also found that there were no unsaturated N-acylethanolamines in brewed espresso coffee or white chocolate, which is used as a control in behavioral studies.

Anandamide (N-arachidonoylethanolamine) was determined by Devane et al. (1992) to be the endogenous ligand for the cannabinoid receptor. It's name is derived from the Sanskrit term "ananda," meaning bliss, since the this compound produces Cannabis-like activity. Anandamide binds to the cannabinoid receptor with high affinity, mimicking the psychoactive effects of plant-derived cannabinoid drugs, but is less potent and has a shorter duration of action than D9-tetrahydrocannabinol. Also, there is evidence that it may be considered an endogenous cannabinoid neurotransmitter, since it is released from neurons and is rapidy metabolized by selective enzyme activity. In any case, anandamide in chocolate may reveal the meaning behind chocolate craving, and possibly provide a link between non-drug craving and the endogenous cannabinoid system.

In order to understand the relationship at hand, the underlying mechanisms of anandamide functioning must be considered. Anandamide was found to "specifically bind to membranes from cells transiently (African green monkey kidney- COS) or stably (Chinese hamster ovary) transfected with an expression plasmid carrying the cannabinoid receptor DNA, but not to membranes from control non-transfected cells (Mechoulam et al. 1996)." Further effects support anandamide's similarity to the D9-tetrahydrocannabinol. For example, anandamide inhibits forskolin-stimulated adenylyl cyclase in cells that were transfected with or that normally expressed cannabinoid receptors, but did not have the same effect in control cells. Also, it activates the hypothalamo-pituitary adrenal axis, increasing the serum levels of ACTH and corticosterone in a dose-dependent manner. Anandamide binds to both CB1 and CB2 receptors, however, produces different functions through each. When bound to CB2 receptors, anandamide is inactive, and actually has an antagonistic effect at the receptor, blocking the action of palmitoyl ethanolamide. On the contrary, anandamide has been shown to cause apoptosis and inhibit the proliferation of b lymphocytes in cells containing the CB1 receptor (Mechoulam et al. 1996).

The exact physiological role of anandamide and the cannabinoid receptors is not yet known, but certain conclusions can be made. The conclusions are based on the anatomical distribution of the cannabinoid receptors, the specific activity of D9-tetrahydrocannabinol, and the activity of the endogenous cannabinoid ligands. Via the cannabinoid receptors in the cerebellum and in the basal ganglia, anandamide and other Cannabis agonists are thought to act on the coordination of movement and time perception. Moreover, high density binding to receptors in the hippocampus suggest an effect on memory, and receptor binding in the cerebral cortex affects perception and reasoning. All of these results are well documented effects of marijuana intoxication; however, the complicated nature of the underlying biological processes ensures that there is still more that we do not know. Nevertheless, anandamide could contribute to the understanding of these mechanisms in the future, and could consequently reveal a link to non-drug cravings, such as chocolate craving.

However, the link between non-drug craving and the endogenous cannabinoid system of the brain is not only dependent on the anandamide in chocolate. The other two N-acylethanolamines that were discovered in chocolate also play a role in the pharmacological impact of chocolate. Although their exact biological actions are yet to be defined, N-oleoylethanolamine and N-linoleoylethanolamine seem to participate in regulating the level of endogenous anandamide. These compounds do not directly activate brain cannibinoid receptors; rather, they were found to inhibit anandamide amidohydrolase activity. The degradation of anandamide by neurons is catalyzed by anandamide amidohydrolase, which hydrolyzes the amide bond to form arachidonic acid and ethanolamine. The inhibitory effect of N-oleoylethanolamine and N-linoleoylethanolamine on this enzyme results in increased levels of anandamide. This effect was demonstrated in rat microsomes and intact cells. For instance, rat cortical astrocytes, which normally hydrolyze exogenous anandamide in culture, were significantly affected by N-linoleoylethanolamine. In the presence of this substance, the degradation of anandamide was strongly reduced, and there was a corresponding increase in the amount of residual anandamide (Di Tomaso et al. 1996).

Therefore, the anandamide, N-oleoylethanolamine, and N-linoleoylethanolamine in chocolate could possibly have a synergistic effect on increasing the levels of anandamide in the brain after chocolate consumption, producing a slight cannabimimetic effect within the central nervous system. This provides support for the association between chocolate craving and the pharmacological effects of substances in chocolate. The link between non-drug, or chocolate craving, with the endogenous cannabinoid system of the brain seems to exist, but the question remains as to how activation of this system actually influences the subjective feelings associated with chocolate consumption. Because cannabinoids are known to raise sensitivity and produce a euphoric state, it is possible that elevated brain anandamide levels could induce a similar effect, intensifying the sensory properties of chocolate that are assumed to be essential to craving. However, elevated brain anandamide levels could also cooperate with the effects of other pharmacologically active components of chocolate, such as theobromine or caffeine, to produce a certain temporary psychological state, or feeling of pleasure, that is able to fulfill the craving for chocolate (Di Tomaso et al. 1996). Similar to the connection between the pharmacological effects of theobromine and caffeine to chocolate cravings, a further examination of the pharmacological effects of N-acylethanolamines in chocolate must be carried out.

Although some research does indicate a link between the endogenous cannabinoid system and chocolate craving, there is yet another perspective. Di Marzo et al. (1998) state that they "believe that the content of endocannabinoids in foods, and in cocoa in particular, is not sufficient to produce cannabis-like effects in mammals." They believe that besides chocolate, endocannabinoids can be found in other foods. They found N-acylethanolamines in human milk at varying concentrations (0.003 to 0.024 mg/ml) along with 2-arachidonoylglycerol at relatively high concentrations (0.33±0.11 mg/ml) (Di Marzo et al. 1998). They also noted that the content of N-acylethanolamides in chocolate is similar to that found in other plant-derived foods, such as soybean, hazelnuts, and oatmeal. These foods contained 2.3 mg/g oleamide, 1.1 mg/g N-oleoylethanolamide, and 2.8 mg/g N-linoleoylethanolamide. According to the authors, these concentrations, and the concentrations present in chocolate are not enough to induce cannabimimetic effects.

In order to determine the extent to which these substituents reached the blood stream--and, hence, were able to produce pharmacological effects after being consumed orally--anandamide and 2-arachidonoylglycerol were assayed after oral administration in a series of in vivo tests. Four of the five behavioral tests showed that both compounds were active, but only at higher concentrations than are readily available in foods. On the contrary, small doses of D9-tetrahydrocannabinol provided a significant effect in all five tests. Comparing the activity of these substances after oral administration to the activity when administered intraperitoneally suggests that only 1.6-50f the orally consumed substances enter the bloodstream and are able to produce a pharmacological effect (Di Marzo et al. 1998). The rest of the compounds are presumably degraded in the gastrointestinal tract by fatty acid amide hydrolases, or anandamide amidohydrolases. Because such small amounts traverse the intestinal epithelia, Di Marzo et al. (1998) conclude that it is unlikely that the amounts of anandamide and 2-arachidonoylglycerol found in chocolate and other foods are sufficient to cause observable psychotropic effects.

However, a distinction must be made between observable effects and pharmacological effects that are clearly cannabimimetic by nature. Although certain effects may not be behaviorally conspicuos at all, there could be underlying consequences involving the reward pathways of the brain. Any effect, whether minute in nature or significant enough to observe on the behavioral level of expression, could affect the hedonic capacity of food intake, and chocolate consumption, in particular. The relation of chocolate craving, then, to the endogenous cannabinoid system in the brain seems quite inevitable. This link indeed reinforces the idea that the pharmacological impact of certain compounds within chocolate is associated with chocolate craving as well as sensory-specific factors.

Human food consumption is characterized by a multitude of factors including "physiological state, acquired and innate likes and dislikes, palatability, the availability of foods, economics and sociocultural influences (Hetherington and MacDiarmid 1995)." Because food intake is governed by so many different elements, the analysis of chocolate craving and consequent chocolate consumption is very difficult. Each dependent factor influences the hedonic judgements made by a person, and those judgements consequently affect the person's decision-making ability. This interrelation can also be described between the neurochemistry of the brain and the actions, thoughts, and feeling that comprise human behavior. Therefore, the connection between the pharmacological effect of components in chocolate and chocolate craving should be considered part of the equation. The cannabimimetic effects of N-acylethanolamines in chocolate, as well as the stimulant effects of the methylxanthines in chocolate, should then be studied more closely in order to elucidate their role in chocolate craving.

Indeed, the link between the pharmacological effects of the compounds within chocolate and chocolate craving must be further investigated, and the role of methylxanthines and N-acylethanolamines in this respect cannot be ruled out. Hence, the study of chocolate craving can further the understanding of general non-drug cravings as well. Since sensory perceptions and pharmacological properties seem to be interrelated and since both seem to play a role in chocolate craving, it is no wonder that the demand for chocolate and the pleasure received from eating it has been shared across centuries. Chocolate, the divine food of the gods, is definitely a unique entity, which remains, in the words of R. J. Huxtable, "more than a food but less than a drug (Huxtable 1994)."

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