March 1999; Volume 1: 28-29
By Adriane Fugh-Berman, MD
It’s not news to female readers that chocolate contains psychoactive substances. But what those psychoactive ingredients are, however, is still a matter of debate. Chocolate contains a plethora of possibilities: theobromine is a methylxanthine with caffeine-like effects; phenylethylamine has amphetamine-like qualities; and phenylalanine and tyrosine are both precursors to norepinephrine and dopamine.1 Additionally, eating carbohydrates, especially chocolate, increases uptake of tryptophan by the brain and subsequently increases 5-hydroxytryptophan in the central nervous system.
One case series reported a high rate of chocolate craving among MDMA (Ecstasy) abusers. MDMA causes long-term 5HT depletion and the authors of this case series postulate that eating chocolate may have been an unconscious effort to raise 5HT levels.1
However, an experimental study aimed at separating physiological from sensory factors found no evidence for a physiological basis for chocolate craving.2 This study compared the effect of chocolate bars, cocoa capsules, white chocolate, white chocolate plus cocoa capsules, placebo, or nothing on satiation of chocolate craving in 72 students who served as their own controls. White chocolate is made from a cocoa butter base and does not contain the pharmacological components of chocolate or cocoa.
Only 34 students turned in at least one observation for each treatment (this study is notable for having more dropouts than completers). Milk chocolate was the standard for craving relief. White chocolate produced intermediate scores. Cocoa capsules, however, did not reduce craving any more than placebo.
Cannabinoid Mimics in Chocolate
In 1996, a letter in Nature3 terrified parents and husbands by announcing the isolation of psychoactive compounds in chocolate that act in a similar manner as the psychoactive compounds in marijuana—tetrahydrocannabinol (THC) and related compounds. Actually, it’s no use hiding the chocolate; the human brain makes its own version of THC, which explains the presence of receptors that are specific for cannabinoids. Anandamide is a brain lipid that binds to cannabinoid receptors and mimics the psychoactive effects of marijuana.
The chocolate researchers isolated three unsaturated N-acylethanolamines from chocolate that may act as cannabinoid mimics. It is unclear whether these compounds directly activate cannabinoid receptors or act indirectly by increasing anandamide levels.
Nestlé Responds: Chocolate No More Addictive Than Oatmeal
A recent research letter to Nature4 sought to reassure those worried that chocolate might lead to the hard stuff. A multinational group from Naples, Jerusalem, and the Nestlé Research Centre in Lausanne found that NAEs in chocolate were no higher than soybeans, hazelnuts, oatmeal, and millet. Additionally, they tested anandamide and the endocannabinoid 2-arachidonoylglycerol (found in milk and cocoa) in an in vivo test used to assess cannabimimetics and concluded that although the compounds were active in four of five behavioral tests, they were only active at much higher concentrations than delta9-THC. Another experiment found that most of these compounds are hydrolyzed in the gastrointestinal tract and that less than 5% of orally administered compounds entered the bloodstream.
Beltramo and Piomelli5 criticized the above study in a reply which implied that Di Marzo et al definitively answered a question that no one had asked. The finding that NAEs do not cause overt cannabis-like effects was hardly a surprise since no one ever claimed that marijuana and chocolate have comparable psychoactive effects. The two most prevalent NAEs in chocolate (N-oleyl-ethanolamine and N-linoleylethanolamine) weren’t tested at all—a particular lapse given that these NAEs are produced in the brain by a similar mechanism to that which produces anandamide. Additionally, substances in chocolate may prevent anandamide degradation rather than act as anandamide agonists. Lastly, Beltramo and Piomelli point out that NAEs may act synergistically, so that individual NAEs should be tested against cocoa.
More research clearly needs to be done. If milk contains relatively high levels of endocannabinoids, would hot cocoa be expected to have potentiated psychoactive effects, and could this be the real reason ski trips put people in a good mood? Updates on the chocolate wars will be provided when available.
1. Schifano F, Magni G. MDMA ("ecstasy") abuse: Psychopathological features and craving for chocolate: A case series. Biol Psychiatry 1994;36:763-767.
2. Michener W, Rozin P. Pharmacological versus sensory factors in the satiation of chocolate craving. Physiol Behav 1994;56:419-422.
3. di Tomaso E, et al. Brain cannabinoids in chocolate. Nature 1996;382:677-678.
4. Di Marzo V, et al. Trick or treat from food endocannabinoids? Nature 1998;396:636.
5. Beltramo M, Piomelli D. [letter] Nature 1998;396: 636-637.