Gabapentin Therapy for Cocaine Cravings
To the Editor: A difficult aspect of treatment for cocaine addiction is the recurrent nature of cravings, even long after active use has ceased. Cravings can be controlled in the early stages of withdrawal, but pharmacological agents that can abate cocaine cravings beyond the withdrawal phase are still wanting. I report on two patients with a long history of cocaine addiction in whom cravings were greatly reduced by daily use of gabapentin.
Mr. A was a 42-year-old man with a history of cocaine addiction since the age of 17 and heroin addiction since age 28. After repeated attempts at detoxification and rehabilitation, he was able to forgo the use of cocaine, then heroin, and later methadone. During his 15 years of substance abuse treatment, he had received imipramine for depression at doses of 75–300 mg/day. During the year after his last use of methadone, Mr. A became increasingly engaged in restoring his relationship with his children and in computer training through a vocational program. The many difficulties and setbacks he faced often discouraged him; it was at these times that his cravings for cocaine returned. After a discussion about the experimental nature of gabapentin treatment, he agreed to a trial of gabapentin while continuing treatment with imipramine, 200 mg/day. His dose of gabapentin was increased to 400 mg b.i.d. over 1 week. His blood level of gabapentin at that dose was 12.4 mg/liter (>2 mg/liter is needed for seizure control). He reported that his cravings had completely disappeared within a month of reaching a dose of 800 mg/day.
Ms. B was a 31-year-old woman with a diagnosis of schizoaffective disorder and cocaine abuse. Her psychotic symptoms were well controlled with a bimonthly injection of 50 mg of fluphenazine decanoate. She required supplements of oral fluphenazine, up to 20 mg/day, to control auditory hallucinations immediately after she used crack cocaine, which she typically consumed night and day during binges lasting up to 10 days. Afterward she could be abstinent for several months. Her relapses usually coincided with returning to live with her mother in a crack-infested neighborhood, which would prompt strong cravings and vivid dreams about smoking crack. She began a course of oral gabapentin therapy, reaching a dose of 1200 mg b.i.d. At that dose, her blood level of the drug was 15.6 mg/liter. She reported a marked reduction in cravings, at times being able to live in the crack-infested neighborhood without relapsing. In the 9 months since she began gabapentin treatment, she has experienced one relapse, which consisted of smoking two crack cigarettes.
Frustration with the difficulty of treating cocaine cravings led me to an extensive review of the neuroanatomy of the ventral tegmental area, including the nucleus accumbens, which is thought to drive many aspects of addictive behaviors (1). Within the nucleus accumbens, a large number of γ-aminobutyric acid (GABA) neurons and axon fibers have been noted (2). Repeated cocaine use inhibits GABA release from nucleus accumbens axon terminals in the ventral tegmental area, where the mesolimbic dopaminergic neurons are located (3). This effect attenuates the GABA-mediated feedback inhibitory action of nucleus accumbens neurons onto ascending mesolimbic dopaminergic neurons, leading to increased activation of dopamine neurons projecting to the nucleus accumbens. Gabapentin increases brain GABA levels proportionally with dose, typically in the 800–2400-mg range (4). It was thus hypothesized that gabapentin restores the altered feedback inhibition from the nucleus accumbens. These neurobiological data, the excellent pharmacological profile of gabapentin, and a report about an addicted woman who noticed a decrease in her cravings for cocaine after she began taking 600–1500 mg/day of her husband’s gabapentin (5) prompted the trials described previously. Neither patient experienced significant side effects, such as sedation or ataxia, which are common with gabapentin therapy.
Should these findings be corroborated by further clinical observations and studies, gabapentin could become a safe, effective, and well-tolerated pharmacological agent to target this most vexing problem of recurrent cravings for cocaine.
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