The emergence of new pills to treat alcohol addiction.
A new study has identified the molecular reasons why alcoholism and other drug addictions are so difficult to quit. This could point the way to new pharmaceuticals for alcoholism and thus help addicts overcome their illness.
Scientists have known for years how excessive alcohol and drug use acts on the brain’s reward centres to induce dependence. New research, including a study published in November in JAMA Internal Medicine and early-stage drug trials at the US National Institute on Alcohol Abuse and Alcoholism, is revealing a more hidden side of how these substances affect the brain. By transforming its chemical architecture, alcohol and drug use triggers feelings of anxiety and tension that can only be relieved by further use.
“There have been a great many advances in understanding what drives alcoholism and makes it so difficult to stop,” says Barbara Mason, co-director of the Pearson Center for Alcoholism and Addiction Research at the Scripps Research Institute in La Jolla, California.
This hidden side has been documented in laboratory animals and in some human trials. Its validity in people was reaffirmed by the study recently published in JAMA. Led by Dr Mason, it indicates that a drug targeting the stressful effects of dependence helped people stop drinking. Its findings: around 45% of the 150 alcoholics who took the highest dose of the drug, known generically as gabapentin, either stopped drinking altogether or did so only occasionally.
In 2011, more than 21 million Americans needed treatment for an alcohol- or drug-related problem, according to the federal government’s most recent National Survey on Drug Use and Health. Many try to quit, but studies show that 60% or more of alcoholics and drug addicts relapse within the first year of trying to break their habit, addiction specialists say.
Support groups such as Alcoholics Anonymous and Narcotics Anonymous only work for a fraction of alcoholics and addicts, according to Michael Fingerhood, who heads the chemical dependency division at the Johns Hopkins University School of Medicine. The few pharmaceuticals for alcoholism often do not work, or addicts stop taking them before they reach recovery. Chemical replacement therapies such as methadone have proven effective at reducing pleasure and blocking cravings for certain opioids. But there is no effective prescription medication available to treat cocaine addiction.
So far, most research has focused on the pleasure provided by drug use or drinking—that is, studying how neurotransmitters such as dopamine help reward and provide pleasure, which encourages use. But drug abuse can compromise this reward system, researchers say, requiring the production of ever greater amounts of dopamine to achieve the same feeling. This is called tolerance.
More recent research is showing that the brain’s stress response also contributes to dependence. Years of alcohol or drug use remodel the circuitry around a part of the brain known as the amygdala, where these feelings of anxiety are triggered, says George Koob. He pioneered the study of this dark side of addiction. The brain’s stress system becomes impaired.
The result: constant feelings of tension that alcohol or drugs temporarily ease, but that worsen in the long term. “You’re fixing one hole by digging another hole,” says Dr Koob, a Scripps scientist who is the incoming director of the National Institute on Alcohol Abuse and Alcoholism. One molecule found when the brain is under stress is known by the initials CRF (corticotropin-releasing factor).
In effect, the brain remembers that substances relieve stress, says Paul Kenny, who studies the molecular basis of addiction at the Icahn School of Medicine at Mount Sinai. CRF is sometimes referred to as a “misery neurotransmitter”, as it is believed to cause the anxiety addicts feel, which ends when they get temporary relief by drinking again or taking drugs.
The NIAAA, part of the National Institutes of Health, is conducting early-stage trials in alcoholics with two experimental drugs aimed at stopping CRF in the brain’s stress centres, says Markus Heilig, the agency’s clinical director. The NIAAA is also testing a third drug in alcoholics and heroin addicts. It blocks another neurotransmitter involved in the stress response, called neurokinin 1.
Nora Volkow, director of the National Institute on Drug Abuse, says successful addiction treatment will likely require a combination of behavioural and cognitive counselling, along with the prescription of multiple medications and pharmaceuticals for alcoholism, tailored to the stage of recovery and targeting both the light and dark sides of dependence. “These two systems interact very, very clearly with each other,” says Dr Volkow.
