The United States has experienced a rapid increase in the use of prescription and non-prescription opioid medications since the beginning of the 1990s and their use has continued to increase over the last 25 years. As a result, this country has seen a rapid rise in opioid use disorder, opioid overdoses, and other adverse health effects of opioid use. [1] In 2016 over 60000 people died from drug overdoses, with opioids being responsible for nearly two-thirds of these deaths. [2] Opioids, which include oxycodone, hydrocodone, morphine, and more, interact with opioid receptors on nerve cells throughout the body and brain. The medication provides strong pain relief as well as euphoria. [3] The pleasure caused by the opioids’ activation of the central nervous system’s natural reward center promotes continued drug use. With chronic exposure, individuals develop dependence, leading to daily use to prevent withdrawal symptoms. Patients can also become addicted to the medication with long-term use due to cravings for the drug and its euphoric effects. [4] To combat the opioid crisis, providers are cutting back on opioids and prescribing non-opioid alternatives such as Gabapentin.
Gabapentin treats a range of conditions including neuropathic pain, postherpetic neuralgia, and partial seizures. The drug is a gamma-aminobutyric acid (GABA) analogue and binds to voltage-gated calcium channels, reducing calcium influx and neurotransmitter release. The mechanism of action is believed to contribute to its antinociceptive properties. [5] Although previously considered a safe alternative to opioids for pain relief, recent studies have indicated that this medication has increased risk of misuse and abuse, especially in those with a history of substance abuse. [6,7,8] The mechanism of abuse is not completely understood, but it is thought that the drug’s GABA-mimetic properties causes euphoric and dissociative effects. [5] A study of 503 adults in 2015 found that 15% of participants used the drug “to get high” and there was a 165% increase in recreational gabapentin use from the year prior. Multiple studies looking at gabapentin use in those with opioid use disorder found that 15-22% abused gabapentin. In the United States, the rate of misuse was comparable to clonazepam misuse and double that of amphetamines. [6]
Gabapentin may be abused alone or in combination with other drugs, including opioids, benzodiazepines, amphetamines, alcohol, and LSD. Gabapentin is thought to enhance the effect of other drugs. A 2017 study interviewed 30 heroin users in England and participants reported that gabapentin and related drugs “reinforced” the effects of heroin. [9] Multiple studies have also linked increased death rates with the combination of opioids with gabapentin. [9,10] After analyzing 1256 cases of opioid-related deaths, co-prescription of opioids and gabapentin was found to significantly increase the odds of opioid-related death. [10] The dose of gabapentin was also linked to increased death rates, with high dose gabapentin associated with close to 60% increase in the odds of opioid-related death compared to no gabapentin use. [10] Although the exact reason is unknown, the increased risk of overdose death is thought to be due to reversal of drug tolerance or an additive effect of the combined drugs on respiratory depression. [9]
The opioid epidemic has broadened the spectrum of gabapentin use. Although considered a safe alternative to opioids, recent studies have indicated the potential abuse and misuse of gabapentin as well as increased risk of death when combined with opioids. Further studies are needed to analyze the mechanism of abuse as well as the cause of increased death risk. Providers are trying to find safer medications to provide pain relief to suffering patients, however alternative medications like gabapentin carry their own risks. Before placing patients on gabapentin, providers should collect a thorough history, especially of substance use. Further studies are needed to clarify the role that gabapentin plays as a safe, effective pain management method.
1. National Academics of Sciences, Engineering, and Medicine. (2017). Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use. National Academies Press. Accessed from https://www.ncbi.nlm.nih.gov/books/NBK458662/.
2. Center for Disease Control. (2018). U.S. overdose deaths continue to rise; increase fueled by synthetic opioids. Accessed from https://www.cdc.gov/media/releases/2018/p0329-drug-overdose-deaths.html.
3. National Institute on Drug Abuse. Opioids Description. Accessed from https://www.drugabuse.gov/drugs-abuse/opioids
4. Kosten, T., George, T. (2002). The neurobiology of opioid dependence: Implications for treatment. Science & Practice Perspectives, 1(1):13-20.
5. Evoy, K.E., Morrison, M.D., Saklad, S.R. (2017) Abuse and Misuse of Pregabalin and Gabapentin. Drugs, 77: 403. https://doi.org/10.1007/s40265-017-0700-x.
6. Smith, R. V., Lofwall, M. R., Havens, J. R. (2015). Abuse and Diversion of Gabapentin Among Nonmedical Prescription Opioid Users in Appalachian Kentucky.The American7
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8. Baird, CR., Fox, P., Colvin, LA. (2014). Gabapentinoid abuse in order to potentiate the effect of methadone: a survey among substance misusers. Eur Addict Res, 20(3):115-118.
9. Lyndon, A., Audrey, S., Wells, C., et al. (2017). Risk to heroin users of polydrug use of pregabalin or gabapentin. Addiction, 112(9):1580-1589. doi: 10.1111/add.13843
10. Gomes, T., Juurlink, DN., Antoniou, T., et al. (2017). Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case-control study. PLoS Med, 14(10). doi: 10.1371/journal.pmed.1002396.
Arianna Cook is a member of the University of Arizona College of Medicine-Phoenix Class of 2019. She graduated from the University of Florida in 2015 with a Bachelor of Science in Nutrition and a Classical Studies minor. She hopes to match into anesthesiology. Outside of school, Arianna loves to cook Italian food and attend yoga and boxing classes.