Cocaine Addiction
What is Cocaine Addiction? Cocaine Addiction and crack addiction is a complex illness. It is characterized by compulsive, at times uncontrollable drug craving and seeking. Cocaine addiction also is characterized by use that persists even in the face of extreme negative consequences. For many people, cocaine drug addiction becomes chronic, with relapses possible even after long periods of abstinence. The path to cocaine addiction begins with the act of taking cocaine the first time, probably at the prompting of a friend. Over time, a person's ability to choose not to take cocaine can be compromised. Cocaine addiction and seeking becomes compulsive and obsessive in large part as a result of the effects of prolonged drug use on brain functioning.
Compounds Show Strong Promise For Treating Cocaine Addiction
NIDA-supported animal research is finding a number of compounds that show particular promise as treatment medications for cocaine addiction. The compounds significantly reduce the amount of cocaine animals will give themselves, sometimes for long periods of time. The research is furthering the Institute's wide-ranging quest for a viable cocaine treatment medication.
One of the most promising of these compounds is GBR 12909. Synthesized in the late 1970s, GBR 12909 was tested initially in Europe as a potential antidepressant. In 1989, Dr. Richard Rothman, then at the National Institute of Mental Health, and colleagues proposed that GBR 12909 and related compounds might be useful medications for treating cocaine addiction.
In 1995, Dr. John Glowa, then at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), studied the effects of GBR 12909 on cocaine self-administration by rhesus monkeys. In these NIDA-funded studies, Dr. Glowa found that an injection of GBR 12909 could substantially decrease cocaine self-administration by the monkeys.
An injection of GBR 12909
can substantially decrease
cocaine self-administration
by monkeys.
"Under the right conditions, we completely eliminated cocaine-seeking behavior for about 2 hours without affecting food-seeking behavior," says Dr. Glowa. This suggests that GBR 12909 reduces cocaine craving while not suppressing normal desires such as hunger. This selectivity is desirable for potential treatment medications.
More recently, Dr. Rothman proposed a long-acting derivative of GBR 12909. The derivative, called compound 5, subsequently was developed by Dr. Kenner Rice and colleagues at NIDDK and then tested by Dr. Glowa, now at the Louisiana State University Medical Center in Shreveport. The derivative is formulated to be released slowly into the blood over several weeks. In a NIDA-funded study, Dr. Glowa determined that compound 5 could substantially reduce cocaine self-administration by monkeys for nearly a month with only one injection. At the highest dose tested, a single injection reduced cocaine self-administration by nearly 75 percent for 24 days without affecting food-seeking behavior.
Studies have shown that both GBR 12909 and cocaine inhibit the action of a protein called the dopamine transporter. By inhibiting the transporter, both GBR 12909 and cocaine elevate the levels of the pleasure-inducing chemical messenger dopamine outside the nerve cells, a process that increases and prolongs dopamine's pleasurable effects. However, according to Dr. Rothman, who is now in NIDA's Division of Intramural Research, GBR 12909 acts more slowly and elevates dopamine levels less than does cocaine.
"Cocaine causes a huge spike of dopamine that goes up to a very high level, which you can think of as a burst of pleasure," explains Dr. Rothman. "GBR 12909, on the other hand, produces a relatively modest and long-lasting increase in dopamine, which may not cause the same degree of euphoria but might be good for treating cocaine craving." By attaching to the dopamine transporter, GBR 12909 also blocks cocaine from binding there, he adds. "GBR 12909's affinity [chemical attractiveness] for the transporter is 500 times that of cocaine, so it binds to the transporter and stays there for a long time. While it's sitting on the transporter, cocaine has no access to the transporter, so the cocaine can no longer act to induce euphoria," says Dr. Rothman.
Dr. Srihari Tella, a NIDA grantee at Georgetown University in Washington, D.C., has discovered that prolonged treatment with GBR 12909 might actually reverse the addiction process. In Dr. Tella's study, rats that were allowed to self-administer cocaine for about 3 weeks had significantly increased dopamine transporter levels in several areas of the brain. According to Dr. Tella, the brain increases dopamine transporter levels to compensate for cocaine inhibiting the activity of the existing transporters. Because of the increased transporter levels, dopamine levels outside nerve cells were reduced, creating a dopamine "deficit." This deficit might be responsible for the feelings of depression and craving that cocaine abusers often describe. When the animals were switched from cocaine to water, the dopamine transporter levels stayed elevated, but if they were switched instead to GBR 12909, their transporter levels returned to normal.
"This benefit for patients may come only with prolonged treatment with GBR 12909. Prolonged treatment would be necessary to give the medication time to bring the dopamine transporter levels back to where they were before the patient started taking cocaine," says Dr. Tella.
Promising Cocaine Treatment Compound Blocks Cocaine's Action
Cocaine causes a large spike in the levels of the chemical
messenger dopamine outside the nerve cells in the brain,
which cocaine users experience as euphoria. The graph at
top shows this dopamine increase in rats when they are
administered cocaine. The graph at bottom shows that
treatment with the compound GBR 12909 reduces this dopamine
increase caused by subsequent cocaine use and thus dampens
cocaine's euphoric effects.
Based on this and other research, Dr. Rothman concludes that GBR 12909 is the best candidate so far for treating cocaine addiction. "If you survey the animal literature, I don't think you'll come up with anything that looks as good as GBR 12909," says Dr. Rothman. "It just eliminates cocaine taking without any side effects."
Dr. Frank Vocci, acting director of NIDA's Medications Development Division, agrees that GBR 12909 is a promising compound. He also notes that in tests using nondrug- abusing human volunteers, doses of GBR 12909 in the range that might be given to cocaine-abusing patients did not cause behavioral symptoms such as those of cocaine, which suggests that GBR 12909 does not have the abuse potential that cocaine does. Dr. Vocci adds that NIDA will continue to support research on several other compounds that act on the dopamine transporter.
One of these is PTT, which is being studied by Dr. Michael Nader at Wake Forest University in Winston-Salem, North Carolina. Dr. Nader found that a single injection of PTT could significantly reduce cocaine self-administration by rhesus monkeys for more than 4 hours. PTT appears not to have abuse potential, as indicated by the fact that the monkeys will not self-administer it more than a few times. "When you give the animals almost unlimited access to PTT, they don't take very much of it," says Dr. Nader. He calls PTT "an excellent candidate" for treating cocaine dependence.
GBR 12909, compound 5, and PTT are currently undergoing toxicity testing to determine if they would be safe for humans. GBR 12909 was previously tested in humans in connection with its possible use as an antidepressant, but further safety testing is considered necessary. If no safety issues arise with these compounds, the next step will be to test them in clinical trials with cocaine abusers.
The compulsion to use cocaine can take over the individual's life. Cocaine addiction often involves not only compulsive cocaine use but also a wide range of dysfunctional behaviors. This can often interfere with normal functioning in the family, workplace and community. Cocaine addiction also can place people at increased risk for a wide variety of other illnesses. These illnesses can be brought on by the addiction type behaviors, such as poor living and health habits that often accompany the lifestyle of an addict and the toxic effects of the cocaine itself.
Nearly all individuals suffering from cocaine addiction believe in the beginning that they can stop using drugs on their own, and most try to stop without treatment. However, most of these attempts result in failure to achieve long-term abstinence. Research has shown that long-term drug use results in significant changes in brain function that persist long after the individual stops using drugs. These cocaine induced changes in brain function may have many behavioral consequences besides just addiction, including the compulsion to use drugs despite adverse consequences the defining characteristic of cocaine addiction.
Understanding that cocaine addiction has an important biological component may help explain an individual's difficulty in achieving and maintaining abstinence without treatment. Psychological stress from work or family problems, social cues, such as meeting individuals from one's cocaine addiction history, or the environment, such as encountering streets, objects, or even smells associated with drug use can interact with biological factors to hinder attainment of sustained abstinence and make relapse more likely. Research studies indicate that even the most severely individuals with cocaine addiction can participate actively in treatment and active participation is essential to good, positive outcomes.
Because cocaine addiction has so many dimensions and disrupts so many aspects of an individual's life, treatment for this illness is complex. Cocaine addiction drug treatment must help the individual stop using cocaine and maintain a drug-free lifestyle, while achieving productive functioning in the family, at work, and in society. Effective drug abuse and cocaine addiction treatment programs typically incorporate many components, each directed to a particular aspect of the illness and its consequences. Of course, not all cocaine addiction and abuse treatment is equally effective.
Recovery from cocaine and crack cocaine addiction is considered a long term rehab process. There are several different levels of treatment, also known as rehab. Inpatient, residential, partial and outpatient are the standard modalities. For the greatest chance at success, most cocaine and crack cocaine addicts should begin the recovery process on a full-time, residential rehab basis. This is usually done in a licensed accredited rehab, treatment facility. The classic 28 days of cocaine and crack cocaine rehab treatment can sometimes be enough time to absorb the knowledge necessary to step down into a lesser level of care. This can be partial day rehab treatment or Intensive outpatient rehab and treatment. Many people make the mistake of believing they are cured after completing their initial phase of cocaine or crack cocaine rehab treatment. This erroneous type of thinking has lead many people back into using cocaine or crack cocaine after a relatively short period of abstinence. The duration of time at any one level of rehab treatment varies depending on a variety of factors. Funding will often dictate the length of rehab stay and usually is the biggest concern in attending treatment and rehab. Insurance is the first thing to consider for rehab. Some insurance will not support full-time, inpatient treatment and rehab for cocaine crack cocaine addiction because, right or wrong, detox for cocaine and crack cocaine is not considered a medical procedure.
Sources
http://www.drugabuse.gov
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