Glutamate and gamma-aminobutyric acid (GABA) are the most common type of neurotransmitter, accounting for nearly half of all the brain’s neurotransmitters.1 Glutamate and GABA are opposing neurotransmitters. Glutamate acts as a general stimulant to nerve cells, while GABA inhibits them. Their balance is crucial to brain function. Too much glutamate can cause seizures while too little can cause coma.2
The glutamate/GABA system has been associated with alcohol withdrawal, particularly the susceptibility of detoxing alcoholics to delirium tremens (the DT’s) during withdrawal, which only some alcoholics get.3
Alcohol and cocaine abusers have less inhibitory GABA in their brains; medications that increase GABA have shown some promise in treating addiction. One, topiramate, has helped some addicts cut back on alcohol use. Another, baclofen, a muscle relaxant, has had the same effect for cocaine addicts.4 (For more, click on Treatment Drugs.)
One theory for why baclofen may work is that it latches onto GABA receptors. As a general inhibitor of neural activity, GABA may tamp down the dopamine system. Blocking GABA from its receptors could prevent the brain from “braking” dopamine.5
One remarkable patient turned up in a clinical trial of baclofen on cocaine addicts. Edward Coleman was a thirty-year-old paraplegic who took baclofen to counteract leg spasms. He conducted a private experiment with baclofen in relation to his cocaine use: “He had experimented with different doses and discovered that it would block his high if he took the baclofen too close in time to the time he took cocaine. He learned that the medication could reduce his craving when cocaine was unavailable. He also figured out that it quieted his craving for alcohol and cigarettes,” said researcher Dr. Rose Ann Childress. “In a way, he’s done my experiment for me.”6
Recent research into the subtle effects neurotransmitters have on each other has further complicated the picture. For example, in an experiment using rats given cocaine, it was found that a component of one dopamine receptor (called D2R) grabs onto a component of a glutamate receptor (dubbed NR2B), preventing activation of the glutamate receptor. Either activating the D2R receptor or inactivating the N2RB receptor in the rats’ brains resulted in cocaine-like behaviors such as hyperactivity and increased sniffing and biting.7
This kind of “cross-talk” may extend to other neurotransmitters: researchers believe alteration in one neurotransmitter is likely to involve repercussions in others, though how boosting or depressing one neurotransmitters affects another is not yet well understood. Therapies that target one neurotransmitter are likely to affect others, illuminating the difficulty of turning scientific discoveries into feasible treatments.
1. Targeting Depression, Wall Street Journal, December 14, 2006.
2. An Anti-Addiction Pill?, New York Times Magazine, June 25, 2006.
3. Both Genetics and Dopaminergic Neurotransmission Have A Role In Delerium Tremens, medicalnewstoday.com, January 30, 2007.
4. An Anti-Addiction Pill?, New York Times Magazine, June 25, 2006.
5. Genetic Studies Promise A Path To Better Treatment of Addictions, New York Times, November 14, 2000.
6. Genetic Studies Promise A Path To Better Treatment of Addictions, New York Times, November 14, 2000.
7. Interference In Neuronal Receiving Stations Cause Cocaine High,medicalnewstoday.com, December 11, 2006