To the Editor: Although it is an effective treatment for opioid dependence, buprenorphine/naloxone may be misused. We report here a case of potentiation of buprenorphine/naloxone with gabapentin and quetiapine.
“Mr. A,” a 38-year-old man, began misusing heroin and prescription opioids in his late twenties. After being arrested for drug possession, he completed a treatment program and was placed on probation that stipulated periodic drug screens. He was prescribed buprenorphine (8 mg)/naloxone (2 mg), two films sublingually as a single daily dose. He initially appeared to do well. After presenting to his probation officer in an apparently intoxicated state, he was taken back into custody. His urine drug screen was negative.
Mr. A admitted he had been misusing buprenorphine/naloxone in conjunction with other prescription medications as a partial substitute for illicit opiates. He wanted to maintain negative drug screens but also “still get high.” He described taking buprenorphine/naloxone simultaneously with up to 1,000 mg of quetiapine or with up to 2,400 mg of gabapentin. With buprenorphine/naloxone and either additional medication, he experienced a relaxed euphoric state that was not as intense as with illicit opiates but was still quite desirable. He entered another drug treatment program to address this problem.
In a survey carried out in substance misuse clinics, 22% of respondents admitted abusing gabapentin or pregabalin, and of these, 38% abused gabapentanoids to potentiate the high obtained from methadone (1). The possible mechanism of action for the potentiation of an opiate high may be related to gabapentin’s ability to increase the analgesic effect of opiates. Opiates act by bonding to opioid receptors, opening G protein-coupled potassium channels, and closing voltage-dependent calcium channels, thus preventing the release of excitatory amino acids in the spinal cord (2). Gabapentin selectively inhibits voltage-gated calcium channels, increases GABA transmission, and modulates excitatory amino acids at N-methyl-d-aspartic acid receptor sites (3). Thus opiates and gabapentin have certain shared mechanisms affecting analgesia. It has also been hypothesized that an increased analgesic effect of gabapentin and morphine may be contributed to by an increase in gabapentin serum concentration that results from the two medications being given together (2). Gabapentin has demonstrated usefulness in preventing opioid withdrawal, probably by modulating excitatory amino acids, which are increased during withdrawal (3). The interactions of quetiapine’s effects on serotonergic, dopaminergic, and other receptor systems with opiate effects, and possibly nonopiate effects, are speculative.
Clinicians treating opiate-dependent individuals should be aware that some patients may attempt to covertly potentiate the effects of buprenorphine/naloxone by abusing drugs such as gabapentin or quetiapine.