Kristen Morris, San Diego, Calif. Douglas Taren University of Arizona, Tucson, Ariz.
Reposted from http://www.karger.com/gazette/68/morristaren/art_3.htm

In the spring of 2004, a woman walked into Woolworths with a yearning for chocolate and walked out with 10,000 Mars bars. In April of the same year, a man in the throes of a late-night craving shot a sales clerk who would not exchange his expired bag of chocolates. One month later, a small town’s police department started handing out chocolate bars to late-night bar-goers as a new “weapon for deterring drunks” from violent outbreaks. Throughout the USA, Chocolate Lovers’ Weekend packages – replete with chocolate spa treatments and tastings – entice consumers. The Hotel Hershey has even opened a special spa where men and women can have their dreams fulfilled – to be covered from head to toe in melted chocolate with treatments such as whipped cocoa baths, chocolate hydrotherapy, chocolate bean polishes, and chocolate fondue wraps.

Surprising? Yes, and no. According to the US Department of Commerce, the average American eats 4.9 kg of chocolate per year. (While per capita sales figures for Switzerland, the highest in the world, are 11.6 kg a year. However, since some of this represents purchases by tourists, the average Swiss citizen isn’t quite consuming two 100-g bars of chocolate a week.) American surveys have shown that chocolate cravings represent close to 50% of all food cravings. That makes it the most commonly craved food in North America, especially among women. The taste and aroma of chocolate can tempt even the most disciplined among us. But, why do we feel such a passion for chocolate? What makes chocolate so seductive? The simple answer is that it tastes great and makes us feel good. But, what is it in chocolate that makes us feel so good, that drives us to crave and in some cases become addicted?

Chocolate has always been considered unique among foods. From its historical use as a sacred substance up to its prominence today as the food of romance, celebration, and indulgence, it has always held a special place in society. We do not classify chocolate as part of any of the four basic plant groups of food (whole grains, vegetables, fruit, and legumes). Nor do we call it a drug. But curiously, chocolate has properties of both. A food is defined as “any substance taken into and assimilated by a plant or animal to keep it alive and enable it to grow and repair tissue; nourishment; nutriment,” while a drug is “a substance used as a medicine or as a narcotic,” or “a chemical substance, such as a narcotic or hallucinogen, that affects the central nervous system, causing changes in behavior and often addiction.” Chocolate is defined as “a paste, powder, syrup, or bar made from cacao seeds that have been roasted and ground.” It contains nutrients, provides nourishment, and fits the definition of a food. Ask chocolate lovers to define chocolate, however, and they will describe it as “the love drug,” “the eighth wonder,” “the food of the gods,” “a wicked pleasure,” “better than sex,” and “the secret drug of happiness.”

It is becoming increasingly clear that chocolate contains several biologically active compounds, some of which have potential mind-altering properties that may explain the feelings that people have toward chocolate [1]. These compounds include: cannabinoid-like fatty acids that are structurally similar to the active molecule in marijuana (tetrahydrocannabinol); methylxanthines, including one of the most widely consumed drugs with documented addictive properties (caffeine); alkaloids including the same compounds that are found in alcohol and that are thought to be partially responsible for alcoholism (tetrahydro-beta-carbolines); and biogenic amines, including phenylethylamine, otherwise known as the “love drug” because it induces physiological and psychological effects similar to those caused by being in love. While each of these pharmacological agents is present only in small amounts, the combined effects of these compounds, together with the unique sensory properties of chocolate, might be sufficient to induce a chocolate high that triggers and reinforces chocolate cravings.

The combined psychological and pharmacological effects of chocolate have been a topic of increasing interest among nutritional scientists who are now localizing in the body and brain the sites where chocolate acts, and identifying the precise compounds involved.

The endorphin effect: the sensory properties of chocolate

The most widely accepted explanation for chocolate cravings focuses on its sensory properties, its unique combination of sweetness, taste, and texture. Chocolate contains large amounts of sugar and fat (cocoa butter). Cocoa butter melts at body temperature, and it is this feature that is largely responsible for the overall pleasurable, mouth-watering experience of chocolate consumption. Chocolate also contains more than 400 distinct flavor compounds (more than twice as many as any other food). One would have difficulty arguing against the statement that at least part of chocolate’s allure is driven by its unique, highly enjoyable sensory appeal.

Chocolate contains approximately 50% fat and close to 50% carbohydrate; this combination of nutrients results in a powerful effect whereby all brain chemicals (specifically serotonin, dopamine, and opiate peptides) are positioned at optimal levels for positive mood and euphoric feelings. Palatable foods such as chocolate, cakes, and ice cream stimulate the release of brain opiates known as endorphins, which make you feel good and may even increase appetite. As endorphins are chemically similar to morphine, the brain responds to them in the same way as it responds to morphine. These brain opiates are largely responsible for the body’s response to pleasure, stress, and pain, and are known to be involved in drug addictions. It is now believed that cravings for sweet and high-fat foods such as chocolate may be partly mediated by these brain opiates.

If sensory experience, mediated by opiates, rather than chocolate’s drug-like constituents, is the ultimate object of chocolate craving, then only chocolate should satisfy the craving. Investigations involving “white chocolate” have been useful in delineating the extent to which the sensory qualities of chocolate contribute to cravings. “White chocolate” has the texture and sweetness of chocolate as it also contains cocoa butter and sugar. However, because it contains no chocolate liquor, “white chocolate” does not emit chocolate’s distinctive aroma, nor does it contain chocolate’s many pharmacological constituents. In an experiment whose aim was to isolate the sensory effects of chocolate from the potential pharmacological effects, the researchers found that “white chocolate” produced only an intermediate effect in reducing craving, significantly less than milk chocolate, which largely alleviated craving [2]. These findings lend credence to either a notable sensory effect of chocolate’s aroma and/or a pharmacological effect of its biologically active compounds.

Drug-like chemicals in chocolate

Evidence is accumulating to suggest that chocolate contains several pharmacologically active compounds that may have drug-like effects on the body and mind.

Anandamides (cannabinoid-like fatty acids)

One of the most interesting new findings on chocolate’s pharmacological properties is that it may contain a molecule that mimics the actions of cannabinoids. Cannabinoids, including marijuana, have been used medicinally for over 4000 years to treat migraine, muscle spasms, seizures, glaucoma, pain, and nausea. They have also been used recreationally for their mind-altering, relaxing, and mood-elevating effects.

Recently, a study undertaken at the Neurosciences Institute in San Diego, California, identified a group of biologically active constituents in chocolate, most notably anandamide, that appear to target the endogenous cannabinoid system of the brain [3]. Anandamide, which literally means “internal bliss,” is a lipid that binds to and activates cannabinoid receptors within the brain, mimicking the psychoactive effects of cannabinoid drugs, such as heightened sensitivity and euphoria.

In addition to anandamide itself, chocolate and cocoa both appear to contain two other unsaturated fatty acids, which are chemically and pharmacologically related to anandamide. These fatty acids are known as N-acyl-ethanolamines (NAEs; N-oleoylethanolamine, N-linoleoylethanolamine) and could mimic endocannabinoid ligands such as anandamide either directly (by activating cannabinoid receptors) or indirectly (by slowing the breakdown of anandamide, thereby increasing anandamide levels and prolonging the action in the brain). Elevated brain anandamide levels have been suggested to magnify the sensory properties of chocolate, which are fundamental to craving, and could also interact with other biologically active constituents of chocolate (i.e., caffeine, theobromine) to induce a noticeable sense of well-being. No unsaturated NAEs have been detected in “white chocolate” or in brewed espresso coffee. The two chocolate NAEs also appear to interfere with the ability of the brain to break anandamide down and remove it from the brain and hence may extend the consequent sense of well-being following chocolate consumption.

Critics contend, however, that you would need to eat an enormous amount of chocolate to experience the characteristic high induced by cannabinoids such as marijuana. Some have estimated that it would take around 11 kg of chocolate eaten in one sitting to produce a response similar to that experienced following marijuana use.

Methylxanthines

Chocolate also contains significant amounts of methylxanthines, most notably caffeine and theobromine (a caffeine-like substance found almost exclusively in chocolate). Both are stimulants, and caffeine can cause noticeable behavioral effects. Although the methylxanthines are bases, they have a very low pKa (0.5) and, hence, are highly fat soluble and are absorbed from the stomach and through the walls of the intestines, easily crossing both the blood-brain and placental barriers. In animals, theobromine appears to have effects congruent to those of caffeine, although theobromine causes less stimulation and takes longer to induce a peak pharmacological effect. Moreover, recent clinical studies have suggested that theobromine suppresses vagus nerve activity, which is responsible for coughing. In fact, theobromine has been shown to be nearly 30% more effective in stopping persistent coughs than the leading medicine codeine. Consequently, chocolate is now being marketed as the new, effective cough suppressant.

While the quantities of methylxanthines in chocolate are variable even within a brand, a typical 1.65-oz Hershey milk chocolate bar contains only 10 mg of caffeine (22 mg/200 g) and 92 mg of theobromine (197 mg/100 g). For comparison, a cup of coffee usually contains 80–100 mg caffeine, and no theobromine. While the relative concentrations of methylxanthines in chocolate are low, the caffeine and theobromine are nevertheless likely to play a large role in the pharmacological effects of chocolate. Although the dosage typically found in chocolate appears to exert only modest, caffeine-like symptoms, the combined effects of theobromine and caffeine in cocoa products may differ from those of either compound alone. Moreover, a recent study demonstrated that when comparing cocoa powder with just the isolated methylxanthines, the two groups exhibited similar pharmacological effects. The researchers concluded that since the cocoa powder (which contains all of the active compounds in chocolate) had similar activity to the isolated methylxanthines, the pharmacological effects of chocolate are most likely largely due to the methylxanthines.

Biogenic amines

Another group of compounds found in chocolate are the biogenic amines, most notably tyramine and phenyl-ethylamine (PEA). Biogenic amines are naturally occurring, biologically active compounds that act primarily as neurotransmitters and are capable of affecting mental functioning and regulating several bodily processes such as blood pressure and body temperature. Tyramine is an amino acid that acts to contract blood vessels and is often implicated as a major contributor to migraine headaches in susceptible individuals. PEA occurs naturally as a neurotransmitter in the brain and is thought to stimulate the nervous system and produce feelings such as those experienced when a person is “in love.” For that reason, PEA has been touted as the “love drug” and has been credited for chocolate’s aphrodisiac properties.

On a normal basis, PEA is evenly distributed throughout the central nervous system and at physiological doses may act to stimulate the release and transmission of dopamine, a neurotransmitter that inhibits appetite and improves mood, alertness, ability to cope with stress, and mental functioning. PEA is structurally and pharmacologically similar to catecholamines and amphetamine, substances that when released into the blood increase heart rate, blood pressure, breathing rate, muscle strength, and mental alertness. They also reduce the amount of blood going to the skin and increase blood flow to the major organs (such as the brain, heart, and kidneys). In fact, PEA has even earned the nickname “chocolate amphetamine” due to its amphetamine-like structure and its ability to promote feelings of attraction, excitement, giddiness, and apprehension. PEA is known to reach peak levels during orgasm.

While PEA is produced naturally by brain tissue, studies have also demonstrated that it is pharmacologically active and stimulatory when administered. PEA initiates the activity of dopamine production and transmission in the brain, thereby stimulating the brain’s pleasure centers.

In fact, several studies have suggested that PEA is an important modulator of mood and that a deficit may contribute to depression. PEA is reduced in the biological tissues and fluids of depressed subjects, and replacement with PEA and/or its amino acid precursor, L-phenylalanine, appears to improve some types of depression. PEA is found in substantial concentrations in chocolate (0.4–6.6 µg/g) and some experts have contended that craving for chocolate may be an attempt to self-regulate brain PEA and mood.

Alkaloids

A recent study conducted in Spain found that the same alkaloid compounds found in alcohol are also present in chocolate (the darker the chocolate, the more alkaloids). Specifically, the researchers demonstrated that ordinary cocoa and chocolate bars contain two groups of alkaloids known as tetrahydro-beta-carbolines (THBCs) and tetrahydroisoquinolines (TIQs) [4]. The concentration of two THBCs in chocolate and cocoa has been found to be comparable to that of alcoholic beverages such as wine, beer, and liquor, which contain a relatively high amount of those compounds.

These same chemicals in alcohol have been found to exhibit neuroactive properties and have been linked to alcoholism. Many recovering alcoholics use chocolate to curb their craving for alcohol, especially early in sobriety. In fact, the book Alcoholics Anonymous actually recommends using chocolate to satisfy alcohol cravings [5]. Interestingly, no connection between compulsive drinking and chocolate craving has been established.

These neuroactive alkaloids in chocolate are currently being investigated for possible influences on mood and behavior. Preliminary evidence suggests that they may influence the production of endogenous opioids (endorphins), the feel-good chemicals produced by the brain. Other studies suggest that THBCs might play a role as neuromodulators via effects on monoamine oxidase (MAO), the enzyme that is largely involved in the production and breakdown of neurotransmitters (i.e., serotonin and dopamine) that are critical to functions such as appetite, motivation, cravings, mood, and sleep. Specifically, THBCs appear to inhibit MAO, thereby potentiating the effects of biogenic amines in chocolate (i.e., PEA, tryptamine, and others), reducing the breakdown of neurotransmitters and extending their duration of action.

The TIQs found in chocolate include salsolinol (SAL) and salsoline. SAL is a dopaminergic active compound, which binds largely to dopamine receptors. These receptors are specifically responsible for reinforcement and reward, and have been associated with neuropsychiatric disorders such as drug addiction. Preliminary evidence suggests that SAL may influence the production of endogenous opioids (endorphins) and the amount of SAL ingested in 100 g of chocolate is sufficient to interact with the dopamine receptors [6]. Although the concentration of SAL in chocolate products is small, the brain effects may be significant, especially in combination with the other biologically active components of chocolate, and SAL has been deemed one of the main psychoactive compounds present in cocoa and chocolate.

Chocolate and the brain

So, what is really going on in the brain of a “chocoholic”? How are chocolate’s unique sensory properties and pharmacologically active compounds interpreted by the brain during and after chocolate consumption? Many chocolate lovers exhibit a heightened sense of well-being during consumption and others report that just thinking about chocolate can evoke a pleasurable response.

It has been suggested that all drugs of abuse act on the brain’s reward system and cause the brain to interpret drug signals as biologically rewarding or potentially important stimuli comparable to food or sex. This may also be true for chocolate. The mere sight and smell of pleasurable foods can cause brain dopamine levels to rise in brain regions associated with food motivation (such as the dorsal striatum). This means that the dopamine reward system can be triggered by food even when there is no pleasure associated with it. The spike in dopamine observed following exposure to palatable foods, like chocolate, is similar to that seen in drug addicts when they are craving drugs.

So what types of chocolate-related cues or signals might the brain interpret as biologically rewarding or significant? Cues such as images, scents, and emotions associated with chocolate activate similar brain regions and circuitries as those activated following exposure to drug-associated cues. A study involving brain scans of normal, hungry chocolate lovers showed that their brains lit up when they saw and smelled chocolate in the same way that the brain of a cocaine addict responds when the addict thinks about his or her next high. Likewise, in a study designed to investigate why cravings for both drugs and chocolate can be triggered by environmental cues that have come to be associated with the craved substance, the researchers found that exposure to chocolate-associated stimuli induces a pattern of gene expression in the prefrontal cortex that shows many similarities to the pattern elicited by drug cues (the prefrontal cortex is a brain region responsible for several aspects of drug addiction) [7]. The researchers concluded that both chocolate and drugs of abuse induce long-term physiological changes in brain regions that are responsible for certain aspects of addiction. So, the brain areas responsible for drug addiction respond to chocolate-related cues in the same way as they respond to drugs of abuse.

The brain of a“chocoholic” also responds to eating chocolate in the same way the brain of a drug addict responds to appeasing a drug craving. In one study, participants melted chocolate slowly in their mouths while their brain activity was measured as they became satisfied and then beyond, to a point where they ate despite feeling satiated. The researchers found that different brain regions were activated selectively depending on whether the subjects were eating chocolate when they were hungry or whether they were continuing to eat chocolate despite being full [8]. For the hungry “chocoholics,” presentation of chocolate significantly increased the metabolism in regions of the brain that are largely associated with addiction (the superior temporal, anterior insula, and orbitofrontal cortex). In contrast, the pattern of brain activity was different for participants when they were full, and eating chocolate was considered aversive. Interestingly, the brain regions that were activated in the hungry “chocoholics” are the same regions that are activated in cocaine users when they have thoughts about the drug. Together, these findings support the idea that the brain may interpret chocolate as a drug and that the activation of this dopamine reward system likely plays an integral role in the explanation of chocolate’s appeal.

Women’s special relationship with chocolate

Why do more women than men experience chocolate cravings? Why is chocolate often an uncontrollable addiction for women, one that can sabotage a healthy diet, weight control and/or disease prevention?

Many scientists believe that the cycle of fat and sugar cravings in women coincides with reproductive needs. Women consistently report heightened fat and sugar cravings during puberty and following ovulation (premenstrually), which allows for building up energy stores in preparation for pregnancy. Men, on the other hand, report preferences for high-protein foods, consistent with their species-survival need for greater muscle mass.

Other scientists explain gender differences and the cyclic nature of food cravings strictly by differences in hormonal production, as women’s cravings for sweet high-fat foods increase dramatically prior to menstruation. Studies have shown that of the 40% of women who experience regular chocolate cravings, almost half experience heightened chocolate cravings before and during menses.

Finally, some researchers suggest that chocolate cravings in women may also have a cultural explanation. Considering the immense amount of chocolate advertising that targets women, and its association with romance, perhaps it is not surprising that women, more than men, have come to associate chocolate with sex, love, and comfort.

How chocolate could influence brain and behavior

Summary

Chocolate’s unique characteristics, including its sensory properties, pharmacologically active compounds, and drug-like effects on the brain and behavior have been studied extensively. However, the exact reason for the unique magnetism of chocolate, particularly among women, has not yet been established. The sensory reward of chocolate, shaped by its pharmacological properties and cognitive effects, is an exceptionally potent force and appears to be the predominant factor contributing to chocolate’s noble status. It is becoming clear, however, that chocolate is not just a delicious food that represents romance, love, and celebration. Rather, chocolate is a cocktail of pharmacological agents hidden within a sweet, velvety, and, to many if not all, irresistible dessert that has the potential to induce drug-like effects on the body and the mind.


References

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3. di Tomaso E, Beltramo M, Piomelli D: Brain cannabinoids in chocolate.
Nature 1996;382:677–678

4  Herraiz T: Tetrahydro-beta-carbolines, potential neuroactive alkaloids, in chocolate and cocoa.
J Agric Food Chem 2000;48:4900–4904

5 . AA Services. Alcoholics Anonymous – Big Book 4th Edition.
Hazelden, 2002.

6. Melzig MF, Putscher I, Henklein P, Haber H: In vitro pharmacologicalactivity of the tetrahydroisoquinol-ine salsolinol present in products from Theobroma cacao L. like cocoa and chocolate.
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7 . Schroeder BE, Binzak JM, Kelley AE: A common profile of prefrontal cortical activation following exposure to nicotine- or chocolate-associated contextual cues. Neuroscience 2001;105:535–545.

6. Small DM, Zatorre RJ, Dagher A, Evans AC, Jones-Gotman M: Changes in brain activity related to eating chocolate: from pleasure to aversion. Brain 2001;124:1720–1733.

Kristen Morris (maiden name: Bruinsma) is a nutritional scientist with several years of clinical nutrition research experience. Holding a BA in biology from the University of Virginia, and an MS in nutritional science from the University of Arizona, she has been employed as a medical writer for Healthshop.com, has authored several articles published in scientific journals, and has contributed to the research for other scientific articles. Currently employed at a biopharmaceutical company in San Diego, California, she has been a speaker on behalf of the company at pharmaceutical development investigator conferences in the United States and Europe.

Kristen Morris, MS
Elan Biopharmaceuticals, Inc.
Global Safety Surveillance
7475 Lusk Boulevard
San Diego, CA 92128
USA
E-Mail: Kristen.Morris@elan.com

Douglas Taren received his doctoral degree in nutritional sciences from Cornell University in 1986. After serving on the faculty at the University of South Florida College of Public Health from 1987 to 1992, he joined the University of Arizona College of Medicine in 1996. His work has focused on women’s health and the prevention of preterm infants, the development of educational programs, the improvement of dietary assessment methods, and child nutrition. He has undertaken projects in Central and Latin America, Africa, China and Nepal. Author of two textbooks, numerous book chapters, and more than 60 published papers, Dr. Taren is currently an Associate Professor of Public Health in the Mel and Enid Zuckerman Arizona College of Public Health where he chairs the Master of Public Health Program.

Douglas L. Taren Ph.D
Associate Professor of Public Health; Chair MPH
2231 E. Speedway Blvd
Campus Mail PO Box 245158
Tucson, AZ 85719
(520) 321-7777 x17
taren@email.arizona.edu