Potentiation of the Effect of Buprenorphine/Naloxone With Gabapentin or Quetiapine

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.