Carbamazepine is for crack cocaine treatment



The use of cocaine drug in the form of "crack" has become widespread in the metropolitan Minneapolis-St. Paul area just as it has in the rest of the country. The latest drug abuse indicators for the Minneapolis-St. Paul metropolitan area as of December 1988 indicate that, while mention of heroin, morphine, and marijuana has remained relatively static during the last 4 years in emergency room documentation of illicit substances, cocaine use has increased by 300-400% in the last 24 months. Emergency room cocaine references indicate that in 1987 about 34% of drug-related contacts involved intravenous cocaine use and about 38% involved crack or smoked cocaine.

The use of cocaine drug in the form of "crack" has become widespread in the metropolitan Minneapolis-St.

Crack is the form of cocaine which can be smoked. It is a crystalline "rock" which is immediately ready for igniting in a pipe or smoking apparatus. The cocaine-rich vapors enter the pulmonary vascular bed directly, return to the left side of the heart and pumped immediately to the brain. It may be that laminar flow maintains a concentrated bolus of cocaine. The first pulse of euphoric central nervous system stimulation occurs within 7-10 s of the initial inhalation. By contrast, intravenous administration of cocaine requires 30-45 s for the initial CNS effects to be experienced by the user, because it must travel through the venous system, right heart, pulmonary bed, left heart, into the general arterial system, and up to the brain. Crack reinforcement can be so strong that the crack smoker becomes intensely involved in a ritualized ceremony of lighting and relighting the pipe every 2 to 3 min to attempt to sustain the original cocaine-induced euphoria.

From the point of view of the user, the advantages of purchasing crack are twofold. First, the cocaine rock is immediately able to be smoked without any extraction procedure ("freebasing"). Second, the unit price on the street has been dramatically lowered for the range of small ($10-$25) purchases. The advantage to the seller is that crack markedly inflates the milligram price of cocaine. For example, an ounce of cocaine powder may be purchased for approximately $2,000. This can be converted to over $6,000 street value of crack by freebase extraction which requires little more than the purchase of baking soda as an alkalinizing agent. When small units of cocaine powder are purchased on the street, they are usually adulterated with lactose, mannitol, or local anesthetics such as lidocaine or procaine. Although the crack cocaine addict is purchasing a much smaller amount of cocaine by weight, he is getting a purer product, immediately ready for use, with virtually instant euphorogenic properties. Hence, the crack epidemic.

Most experienced heavy cocaine users have a predominant route of administration. Drug abusers with extensive past IV drug experience generally prefer cocaine by the intravenous route. They claim more intense and prolonged euphoric experience. They also have more control of the process and repeatedly will draw blood back into the syringe to dilute remaining cocaine, creating several doses of diminishing intensity ("register" or "boot"). For most non-IV users, and for some IV users, crack smoking is the route of choice, and crack use becomes the compulsive center of their lives.

During the past year we have developed an experimental pharmacologic treatment for cocaine abusers based on the hypothesis that craving in humans may be the behavioral manifestation of the neurophysiological event of "kindling" which, in animals, can be caused by cocaine. The term "kindling" refers to the progressive facilitation of neuronal firing in discrete regions of the brain, elicited by temporally spaced exposure to specific consistent pharmacologic or electrical stimuli. Since 1929, cocaine has been shown to produce increasing psychomotor excitability with eventual seizures. The presence of seizures was the original meaning of kindling. Other psychomotor stimulants, local anesthetics, and electrical stimuli have similarly been found to produce kindling. Temporally spaced injections more than 24 h apart, of fixed sub convulsive doses of cocaine, were found to elicit major motor seizures as an endpoint in the kindling process, but with a variety of midstage kindling "behavioral" responses. The recognition of intermediate behavioral changes has given kindling a wider definition. Animals of all species studied developed specific stereotype and disruption of learned behavior before they progressed to major motor seizures. Limbic system structures, especially the amygdala and hippocampus, have been found to produce prominent activity in response to cocaine administration. Once the brain has been kindled by repeated exposure to cocaine, the neuronal sensitization persists for months after exposure to the drug.

Carbamazepine is a clinically useful anticonvulsant which affects temporal lobe dysfunction. In animals, carbamazepine selectively inhibits early, i.e., developmental, phases of pharmacological kindling induced by local anesthetics. It also blocks the late phases of electrically kindled seizures in animals. Based on these reverse effects on kindling, it was hypothesized by one of us (J.A.H.) before so many years that carbamazepine may efficiently treat cocaine abuse and mainly cocaine craving.

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