Non-Dopamine Genes

Many genes not associated with dopamine may be involved in addiction. Following are some examples.

People who are born with a high tolerance to drugs are suspected to have a higher risk of addiction than those who have normal tolerance. Dr. Ulrike Herberlein from the University of California, San Francisco, studies addiction using fruit flies. She discovered what she calls a “cheap date” gene, which makes some flies more susceptible to the effects of alcohol than others. One fruit-fly gene controls the stimulation of a chemical messenger called cyclic AMP (or cAMP, pronounced “see-amp”). This gene was knocked out of fruit flies to test the effect of a lack of cAMP. The result was that the flies got intoxicated faster than the other flies.1

Although fruit flies aren’t people and no “cheap date” gene has been discovered in humans (yet), all mammals use cAMP messengers. Dr. Ivan Diamond, vice-chair of neurology at the University of California, San Francisco, demonstrated that brain cells exposed to alcohol in a lab dish developed higher levels of cAMP, and that prolonged exposure changed the way cAMP worked within the cells.2

Sociological research has supplemented genetic studies in showing that people who had a high tolerance to alcohol were more likely to become addicted to it. University of California, San Diego, researchers conducted an experiment involving 400 men in their 20’s, all of whom had alcoholic fathers. They were given the equivalent of three to five drinks and tested to see how tolerant they were. Ten years later they were interviewed and 60% of the men with high tolerance had become alcoholics themselves.3

Another genetic variation being studied involves an opioid receptor gene which binds with opiates and alcohol. A gene mutation causes an enhanced ability to bind and thereby increases the resulting euphoria. Male rhesus monkeys with the variant gene doubled their alcohol intake and drank on 30% of testing days, while monkeys without the variation drank on only 8% of testing days. Alcohol-dependent subjects with the mutation also had better therapeutic response to drugs that block opioid receptors.4 Human heavy drinkers with this genetic variation experience greater cravings for alcohol than those with the more common form and thus find it harder to resist the urge to drink.5

Another potential genetic target also involves the opioid system. Those with naturally low levels of beta-endorphins, a type of opioid, are especially susceptible to addiction. The University of Granada in Spain studied 200 families with at least one chronic alcoholic parent in each family. Children with two alcohol-abusing parents had the lowest levels of beta-endorphins, while those with one abusing parent had higher levels, but still less than a control group with no alcohol-abusing parents. Researches suggest that low levels of beta-endorphin may be a biological marker that can be used to identify those at risk of addiction.6

A different potential genetic contributor to addiction involves a monoamine oxidase A (MAOA) gene involved in metabolizing stress-related neurotransmitters. Girls with a low-activity variant of the gene who suffered childhood sexual abuse were more likely to become addicts later in life than those with the high-activity variant. Similarly, boys with the low-activity type were more likely to develop behavioral problems than their high-activity peers.7

There are also genetic variations relating to how drugs are metabolized that impact the risk of addiction. For example, a large minority of Asians (as many as 40%) carry genes which quicken alcohol’s metabolism by as much as 200 times faster than people without this gene variant. Accelerated alcohol break-down overwhelms the body’s ability to cope with toxic byproducts, resulting in feeling uncomfortable even after ingestion of small amounts of alcohol. The same gene has been found in Afro-Trinidadians and a large percentage of Jews. Those with this genetic variant have very low risk of alcoholism.8

For the next article in the Genetic and Environmental Components of Addiction series click here.

To go back to the Addiction Science Menu click here.

1. A Serious Buzz; San Francisco Magazine, Oct. 2000.
2. A Serious Buzz; San Francisco Magazine, Oct. 2000.
3. A Serious Buzz; San Francisco Magazine, Oct. 2000; Study Advances Evidence For Receptor’s Role In Alcohol Pleasure And Problems,, March 10, 2007.
5. G Allele Of The Mu-Opioid Receptor Gene Linked To Craving,, January 7, 2007.
6. Alcohol Abuse Is Hereditary;, Jul. 5, 2007.
7. Gene Variation Increases Risk for Alcoholism Following Childhood Abuse;, Jul. 1, 2007.
8. Genetics and Alcohol Consumption;, May 19, 2007;  A Form of the Alcohol Dehydrogenase Gene May Protect Afro-Trinidadians From Developing Alcoholism,, Jan. 30, 2007.


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