Gabapentin, originally an antiepileptic medication, has been increasingly explored for its potential use in treating alcohol and substance use disorders.
This article provides a comprehensive review of the evidence supporting the use of gabapentin for alcohol use disorder, opioid use disorder, cocaine use disorder, and cannabis use disorder.
| Potential Mechanism | Description |
|---|---|
| Modulation of calcium channels | Gabapentin binds to the α2δ subunit of voltage-gated calcium channels, which may inhibit neurotransmitter release related to substance abuse behaviors. |
| GABAergic effects | Gabapentin may mimic GABA and increase GABAergic neurotransmission, reducing dopamine release in areas associated with addiction. |
| Glutamatergic effects | Gabapentin may inhibit glutamate synthesis and glutamate synaptic release, normalizing glutamate homeostasis altered by chronic drug use. |
| Anti-craving | Gabapentin may reduce drug cravings and the rewarding effects of abused substances by inhibiting dopamine pathways. |
Alcohol Use Disorder
The rationale for using gabapentin in alcohol use disorder is to counteract the kindling process, which involves compounded neurotoxicity and subsequent withdrawal effects in patients with alcohol use disorder.
Gabapentin has been shown to be as effective as lorazepam in reducing withdrawal symptoms, except seizures and delirium tremens, in the outpatient setting. Moreover, it has the added benefit of being less sedating compared to benzodiazepines.
In 2018, the APA guidelines included gabapentin as a third-line option for alcohol use disorder patients who either failed naltrexone or acamprosate or could not take them for some reason. Studies have shown that gabapentin increases the mean percentage of days abstinent from alcohol and decreases the percentage of heavy drinking days compared to placebo. However, evidence remains limited due to the small sample sizes of the available studies.
Opioid Use Disorder
Gabapentin’s potential for treating opioid withdrawal symptoms is hypothesized to be related to its ability to suppress overall excitation in the central nervous system. While the literature supporting gabapentin’s use in this population is limited and mixed, a few pilot trials have shown promising results.
| Potential Mechanism | Summary |
|---|---|
| Modulating dopamine | May reduce dopamine release in the nucleus accumbens, decreasing rewarding and reinforcing effects of opioids. |
| Increasing GABA | Mimics GABA effects, which may reduce opioid-associated dopamine release and regulate reward pathways. |
| Glutamate regulation | May counteract opioid-induced glutamate deficits in areas like the nucleus accumbens. |
| Anti-hyperalgesia | May prevent opioid tolerance and hyperalgesia through effects on calcium channels. |
Cocaine Use Disorder
Chronic cocaine use disrupts GABA functioning, leading to disinhibited dopamine transmission. The rationale for using gabapentin in cocaine use disorder is to restore balance in the GABAergic system and thereby reduce dopamine disinhibition. However, a systematic review of antiepileptics for treating cocaine dependence found no significant change in cocaine use with gabapentin treatment.
Cannabis Use Disorder
Withdrawal symptoms of cannabis, such as anxiety and agitation, are thought to be related to dysregulated corticotropin-releasing factor (CRF) in the amygdala. Preclinical evidence suggests that gabapentin normalizes CRF release and can help with anxiety and agitation symptoms in patients withdrawing from cannabis.
MD, PhD. Physical Medicine & Rehabilitation Physician from São Paulo - Brazil. Pain Fellowship in University of São Paulo.