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Gabapentinoids are \u03b3\u2010aminobutyric acid analogues that produce their therapeutic effects by inhibiting voltage\u2010gated calcium channels and decreasing neurotransmitter release. Recently gabapentinoid prescribing and use have increased tremendously. Although traditionally thought to possess a favorable safety profile, gabapentinoid misuse has also risen significantly. Gabapentinoid misuse generally occurs in combination with other substances, most notably opioids, and may be for purposes of eliciting euphoric effects, enhancing the effects of other substances, or self\u2010treating conditions such as withdrawal, pain, anxiety, or insomnia. Given its faster onset, increased bioavailability and potency, and nonsaturable absorption, pregabalin's pharmacokinetics theoretically enhance its misuse liability versus gabapentin. However, gabapentin can produce similar euphoric effects, and epidemiologic studies have identified higher rates of gabapentin misuse in the United States, likely because of greater availability and less regulated prescribing. Although adverse events of gabapentinoid\u2010only ingestion are relatively benign, a growing body of evidence indicates that gabapentinoids significantly increase opioid\u2010related morbidity and mortality when used concomitantly. In addition, significant withdrawal effects may occur on abrupt discontinuation. As a result of these trends, several US states have begun to further regulate gabapentinoid prescribing, reclassifying it as a controlled substance or mandating reporting to local prescription drug\u2010monitoring programs. Although increased regulation of gabapentin prescribing may be warranted, harm reduction efforts and increased patient and provider education are necessary to mitigate this concerning gabapentinoid misuse trend.<\/jats:p>","DOI":"10.1002\/jcph.1833","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T06:34:25Z","timestamp":1629095665000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Gabapentinoid Pharmacology in the Context of Emerging Misuse Liability"],"prefix":"10.1002","volume":"61","author":[{"given":"Kirk E.","family":"Evoy","sequence":"first","affiliation":[{"name":"The University of Texas at Austin College of Pharmacy  Austin Texas USA"},{"name":"University Health System  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa M.","family":"Peckham","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Northeastern University  Boston Massachusetts USA"},{"name":"Department of Pharmacy, Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan R.","family":"Covvey","sequence":"additional","affiliation":[{"name":"Duquesne University School of Pharmacy  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"Tidgewell","sequence":"additional","affiliation":[{"name":"Duquesne University School of Pharmacy  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,15]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.21897"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2018.5705"},{"key":"e_1_2_12_4_1","unstructured":"Drug Enforcement Administration Department of Justice.Schedules of controlled substances: placement of pregabalin into Schedule V. 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