It was a hunch, little more, that launched Daniele Piomelli and his coworkers on their search for marijuanalike compounds in chocolate. But their intuition paid off. These neuropharmacologists not only found one such cannabinoid, but perhaps more importantly, they also turned up two related chemicals that they believe could provide therapeutic insights into treating a host of ails, including depression.
Chocolate is one of the world's most widespread passions. The typical Swiss eats more than 21 pounds of this candy each year. Even the average Belgian or Brit downs some 16 pounds annually, and here in the United States, consumption weighs in at roughly 11.5 pounds per year.
Not only is this "the food most commonly craved by women," observes Adam Drewnowski, director of the University of Michigan's Human Nutrition Program, but owing to its hedonistic properties, chocolate can play a major role in a number of disorders, including bulimia, binge eating, and obesity.
In susceptible individuals, for instance, it can fuel an addictionlike desire, especially among people who exercise excessively, such as dancers. Drewnowski found that among ballerinas, "chocolate is a fetish food." They crave it, talk about it endlessly -- even dream about it.
There's some hints that chocolate may possess natural analgesic properties, Drewnowski says. His own studies indicate that eating high-fat, chocolate foods can trigger the brain's production of natural opiates.
Last year, Drewnowski showed that when he used a drug to block the brain's opiate receptors, a binge-eater's desire for sweet, fatty foods -- such as chocolate -- plummeted. One major unanswered question remained: Does the body simply desire anything sweet and fatty, or does it instead feel some special craving for chocolate? In fact, all of the sweet, fatty foods used in Drewnowski's taste trials contained at least some chocolate.
In the Aug. 22 Nature, Piomelli's group identifies a trio of compounds in chocolate that may act independently of fat and sugar -- at least in their ability to enhance a sense of pleasure or well-being.
Two years ago, Piomelli and some European colleagues reported the first evidence that nerve cells in the brain produce anandamide. This chemical activates the same cellular receptors as THC, the agent in marijuana smoke that causes a pleasurable "high". Shortly after the brain makes anandamide, an enzyme breaks it down. The system naturally limits anandamide's lifespan, and, thereby, the duration of this cannabinoid's effects.
Unfortunately, Piomelli confesses, "We really don't know what anandamide does in the brain. But we can draw deductions from the effects of THC because when we give anandamide to animals, it produces the same effects as when you inject them with THC."
In the recent study, Piomelli's group identified two anandamidelike compounds in chocolate -- which go by the unwieldy names of N-oleoylethanolamine and N-linoleoylethanolamine. At least in test-tube experiments, both delay anandamide's breakdown. Moreover, relative to the concentration of anandamide measured in chocolate, those of its chemical cousins proved relatively high.
What made Piomelli look for these compounds? "From a pharmacological standpoint, chocolate is terra incognita" -- largely uncharted territory. "But we knew that chocolate contains a lot of fat, and that there are not many fatty substances that modulate brain activity." Because THC was among the few fat-soluble substances with that ability, Piomelli decided to look for its natural analog.
The big surprise, Piomelli says, was the realization that any pleasure we derive from eating chocolate probably traces less to the candy's anandamide than to its chemical cousins -- and the role they play in prolonging the pleasurable sensations associated with the body's own natural production of anandamide.
Indeed, such an indirect role in pleasure enhancement would go a long way toward explaining why eating chocolate does not create the same giddy euphoria that smoking marijuana does. "If one smokes a joint, its THC goes into the brain and activates all of the [cannabinoid] receptors," Piomelli explains. "So you get a global high." Because anandamide's chemical cousins don't bind to cannabinoid receptors, they may do nothing -- unless anandamide is present. And even then, their effects would be limited to just those regions of the brain where anandamide had been naturally produced.
So all that these cousins may be doing is prolonging the natural and quite localized effects of the body's own anandamide, whatever they turn out to be.
Because opiates and cannabinoids trigger different receptors in the brain, Drewnowski points out that any cannabinoid-system effects should occur independently of the opiate responses he has linked to sweetened fats. After all, he notes, if cannabinoids explained the whole picture, unsweetened cocoa powder should be as enticing as a chocolate bar. Then again, he notes that there can occur a certain amount of "cross talk" between brain-signaling agents. What this means, he says, is that compounds can sometimes indirectly influence opiates and other systems in unexplained ways.
Notwithstanding, Piomelli finds the new cannabinoid data "therapeutically interesting."
Pot smoking often triggers a case of "the munchies" -- a sudden appetite. "If you're anorexic because you don't have an appetite, and a drug suddenly makes your food taste better [as THC does], that can be very good," Piomelli maintains. Or, if someone is depressed, a drug that induces a sense of well being can prove beneficial.
"People already self-prescribe chocolate for depression," Piomelli notes. "But presumably, one can come up with something more potent than these compounds in chocolate," he says. And though it wouldn't taste as good as chocolate, he notes that "there's no reason we can't involve it in chocolate." For instance, he posits, "We could put chocolate around it."
In the mean time, individuals wishing to self-medicate with nonprescription-strength chocolate should reach for cocoa -- or dark chocolate, which can contain two to three times as much of these compounds, per ounce, as milk chocolate.
Chocoholics already know this, however. When people strongly crave chocolate, Drewnowski's data show, inexpensive, low-quality candy won't do. "They want very high fat, dark chocolate." And this would seem to bridge his findings to Piomelli's, he notes, since the dark chocolate delivers plenty of cannabinoid cousins in a package enriched with natural-opiates-inducing cocoa butter.
And who said chocolate was just junk food?
Tomaso, E.d., M. Beltramo, and D. Piomelli. 1996. Brain cannabinoids in chocolate. Nature 382(Aug. 22):677.
Marzo, V.D, . . . and D. Piomelli. 1994. Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 372(Dec. 15):686.
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_____.1996. ...but we eat it for pleasure. Science News 150(October 12):235.
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Human Nutrition Program
School of Public Health
University of Michigan
1420 Washington Heights
Ann Arbor, MI 48109
The Neurosciences Institute
10640 John J. Hopkins Drive
San Diego, CA 92121
Chocolate Manufacturers Association
7900 W. Park Drive, Suite A320
McLean, VA 22102
This week's Food for Thought is prepared by Janet Raloff, senior editor of Science News.
Illustration by Wendy Temple.