Gabapentin

Gabapentin, first approved in 1993, is one of the most widely prescribed medications in the U.S., used for epilepsy, post-herpetic neuralgia, restless legs syndrome, and off-label for anxiety, fibromyalgia, and alcohol-use disorder. It belongs to a class called gabapentinoids alongside pregabalin. Its very wide prescribing and easy availability — it is not federally scheduled and in most states does not require prescription-monitoring reporting — have made it a growing subject of misuse and diversion concern, particularly in combination with opioids.

Despite being named after GABA, gabapentin does not bind GABA receptors or alter GABA uptake in a simple way. Its main action is on the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system, where it reduces the release of excitatory neurotransmitters. This dampening of nerve signaling underlies its effects on seizures and neuropathic pain. The net effect is a calming of overactive nerve transmission rather than the direct GABA-A potentiation seen with benzodiazepines or barbiturates.

At therapeutic doses gabapentin commonly causes drowsiness, dizziness, and fluid retention. When misused at higher-than-prescribed doses, users report sedation, mild euphoria, and dissociative effects. Tolerance can develop, and people who misuse it often do so to enhance the effects of other drugs, especially opioids. The subjective 'high' is generally milder than that of benzodiazepines, which is part of why its abuse potential is lower — but not zero.

The most serious risk highlighted by the FDA is respiratory depression: in December 2019 the FDA required new warnings on gabapentinoids after reports of serious, life-threatening, and fatal breathing problems, especially when gabapentin is combined with opioids, other CNS depressants, or in people with reduced lung function. Misuse and dependence risk is low in people without a substance-use history but rises sharply in those with opioid use disorder. Stopping gabapentin abruptly after regular use can cause withdrawal, and it should be tapered gradually; the label also carries warnings about suicidal thoughts and behavior. Because it is easy to obtain, it is increasingly diverted and co-used with other depressants, which is where most of its danger concentrates.