Cocaine Addiction --a Ray of Hope : Scientists Are Encouraged by Studies of Medications to Treat Dependency
Before comedian John Belushi died from an overdose of cocaine and heroin, before cocaine killed basketball player Len Bias, before cheap, smokable “crack” appeared on the scene, cocaine was considered a recreational drug.
Nose candy for the chichi, it was celebrated in rock music and spoofed in movies.
Few patients queued up at drug-treatment centers seeking help for their coke habits. And until recently, neither drug experts nor psychiatrists classified cocaine as truly addictive.
Heroin Treatment
Methadone, a synthetic opiate that replaces the addict’s craving for heroin, had been available for treatment since the 1960s. But no equivalent drug existed to treat the cocaine-dependent patient.
All that has changed.
At research centers throughout the United States, scientists are finding out how cocaine works and what can be done to break the addiction it causes. At Yale University here, hopes have been raised by trials of two medications ordinarily used to treat depression and schizophrenia. At Columbia University in New York, work continues on a third.
Doctor Encouraged
The Yale research into the benefits of an antidepressant called desipramine is “by far the best work in the field looking for pharmacologic strategies” for cocaine addiction, said Dr. Richard A. Rawson, who was involved in early trials of the drug at a California drug-treatment clinic.
Yale’s work is led by Dr. Frank H. Gawin, an assistant professor of psychiatry at the university’s School of Medicine. This year, in February and April, respectively, Gawin outlined the results of his work with desipramine and an injectable antidepressant, flupenthixol decanoate, in two articles published in the Archives of General Psychiatry.
Desipramine, also known by the trade name Norpramin, is one of a class of drugs known as tricyclic antidepressants. It is taken orally.
Gawin (pronounced GAV-in) and associates from Yale’s medical school and the APT Foundation, a New Haven drug-treatment center, enrolled 72 cocaine users into a six-week study of desipramine. The group was divided into three equal parts. One group got the antidepressant; another was given lithium, a drug used to treat manic-depression; and the third was given a placebo, a bogus medicine containing no active ingredients. The patients did not know which of the three they were getting.
The study found that 59% of those taking desipramine were able to kick their cocaine habits for three to four consecutive weeks, compared with 17% on the placebo and 25% taking lithium.
Preliminary trials on other tricyclics are going on around the nation.
A study using imipramine, conducted at the Columbia University College of Physicians and Surgeons, showed a 30% reduction in craving among patients on the drug, while none on the placebo improved.
Bahamas Study
The injectable drug flupenthixol was subject to a less scientific study in the Bahamas among 10 crack users. Flupenthixol acts more quickly and showed good results in preliminary trials with that harder-to-treat addiction.
Intended for a younger population, crack sells on the street for $10 to $20 for a “rock”--enough for one euphoric high--compared with the $80 to $100 per quarter-teaspoon that crystalline cocaine fetches, said Paul McLaughlin, director of the Hartford Dispensary, a drug-treatment center in Hartford, Conn.
Snorted cocaine is usually “cut,” or diluted, but crack, which is smoked in a pipe, can be as much as 90% pure, delivering a euphoric rush similar to that of heroin and almost as potent in its addicting ability.
Studies of crack addicts at the Veterans Administration Hospital in Philadelphia have yielded a two-pronged theory of dependency.
Subtle cues--a certain smell, the consumption of alcohol, an argument, even getting a paycheck on Friday, Gawin said--can provoke acute surges that lead the abuser to go on daily “four-hour binges.” The recreational cocaine user who snorts, by contrast, can cope for a few days between “hits,” or episodes of use.
The crack user is “reminded in a vivid way” of the rewards that come from cocaine, Gawin said.
Another more intense consequence of crack withdrawal is anhedonia, or the inability to feel happiness or satisfaction. That period is marked by major depression and feelings of intense boredom and loneliness, said Gawin, who directs the treatment and research of stimulant abuse at Yale and the APT Foundation.
Interfering with crack addiction is ‘a much more difficult battle” than cocaine dependency alone, he said. Between the cravings and the depression, the chances of a relapse are overwhelming.
Desipramine takes 10 days to start working, and two weeks to show a reduced craving.
But flupenthixol is ideally suited to crack users in treatment, who, Gawin said, often “leave the steps of a clinic and face a dealer.” The temptation to resume a crack habit is almost irresistible in such situations. Many addicts in conventional “talking” therapies quit the program in the early stages of treatment.
Injection Lasts 2 Weeks
Flupenthixol does not require the daily administration of a pill. One injection lasts two weeks, and it takes three to five days to begin working. Addicts receiving flupenthixol show a measurable drop in craving in one week, he said.
Although it is used in Western Europe and Latin America, flupenthixol is not yet approved for use in the United States.
Desipramine and flupenthixol treatments are meant to be short-term, lasting six to eight weeks. They are incorporated into a program of psychotherapy designed to keep the addict off cocaine once the medication is ended.
Further studies of desipramine are going on at Yale, the University of Pennsylvania and UC San Francisco. And Gawin has asked the National Institute for Drug Abuse for about $800,000 to launch a wider study in the United States.
Gawin said that he is bolstered by the results using desipramine and flupenthixol. “But I’m more optimistic about where we’re going to be in five years than satisfied about where we are today.”
Effect on Brain
Cocaine--whether inhaled, injected or smoked--works by traveling to a region of the brain where sensations of pleasure are recorded.
Throughout the nervous system, nerve signals are carried by traces of chemicals that ferry between nerve cells called neurons. Called neurotransmitters, the chemicals conduct the charges from one neuron across a minuscule space called a synaptic cleft or gap to the next neuron, where they relay their message. The neurotransmitters then return to the original neuron, where they go through a process of reabsorption or “re-uptake.”
In the brain, one of those neurotransmitters, dopamine, governs the perception of pleasure and produces feelings of happiness and satisfaction. Other neurotransmitters affected by cocaine are norepinephrine, which regulates the body’s “fight-or-flight” reflex, and serotonin, which governs anxiety and energy levels and the need for sleep.
Cocaine works by interfering with the neurotransmitters’--especially dopamine’s--absorption by the receiving neuron, as well as its re-uptake after being relayed back to the sending cell.
As a result, dopamine accumulates in the synaptic gap, overstimulating the nervous system and producing the high, the intense feeling of pleasure associated with cocaine.
But when the drug wears off, so do the dopamine levels in the synapses. They drop to lower-than-normal levels that cause the high to end abruptly. The brain-reward system works less effectively, plunging the habitual cocaine user into cycles of depression and feelings of hopelessness and even thoughts of suicide.
External Reminders
The crack user is particularly primed to respond to cues, those external reminders that provide a link for the user to the experience of the high.
Unfortunately, Gawin said, the associations are only pleasant. “They don’t remind you of how cocaine has messed up your life,” he said.
The antidepressants studied boost the levels of neurotransmitters in the synapse by dampening the re-uptake mechanism or making the receptors less sensitive.
Flupenthixol zeroes in on dopamine, while the drugs desipramine and imipramine, also known by the trade name Tofranil, activate norepinephrine levels.
As a result, the wide swings in mood associated with the wearing off of the cocaine high are moderated. Users are better able to resist cravings and hold onto their resolve to not get high again.
Patients taken into treatment report feeling better, Gawin said. The chronic swings in euphoria flatten out, and patients express hope that they will be able to beat their addictions.
Gawin described the medications as effective tools in a broad strategy for breaking cocaine addiction.
“It’s still possible to relapse. None of the tools are magical at erasing the craving. But the battle is not as bad,” he said.
