Carisoprodol: Update on Abuse Potential and Legal Status Roy R. Reeves, DO, PhD, Randy S. Burke, PhD, and Samet Kose, MD, PhD Abstract: Carisoprodol is a centrally acting skeletal muscle relaxant of which meprobamate, a controlled substance, is the primary active metabolite. The abuse of carisoprodol has increased dramatically in the last several years. A withdrawal syndrome occurs in some patients who abruptly cease carisoprodol intake. The symptoms of this syn- drome are similar to those seen with meprobamate withdrawal, sug- gesting that they may result from withdrawal from meprobamate accumulated with intake of excessive carisoprodol; however, car- isoprodol is capable of modulating GABA A function, which may contribute to its abuse potential. There has been considerable debate about whether carisoprodol should be considered a controlled substance. Carisoprodol was re- moved from the market in Norway on May 1, 2008, but may still be used by specially approved patients. Carisoprodol was classified as a controlled substance in several US states, and effective January 11, 2012, became a schedule IV controlled substance at the US federal level. This article updates the literature on abuse potential and ex- amines recent developments regarding the legal status of carisoprodol. Key Words: carisoprodol, controlled substances, substance abuse C arisoprodol (N-isopropyl-2 methyl-2-propyl-1,3-propanediol dicarbamate; N-isopropylmeprobamate; C 12 H 24 N 2 O 4 , mo- lecular weight 260.33) is a skeletal muscle relaxant available as 250- and 350-mg tablets with a recommended dosage of one tablet three to four times daily for both strengths. Carisoprodol is marketed in the United States under the brand name Soma (MedPointe Healthcare, Somerset, NJ), in the United Kingdom under the brand name Carisoma (Forest Laboratories UK Ltd, Kent, UK), and in other countries under the brand names Sonoma, Somadril, Somacid, Scutamil C, Relacton-C, Mio Relax and Relaxibys. Carisoprodol has been distributed in the United States under the brand names Rela and Soridol. 1 Carisoprodol is commonly prescribed for relief of pain associated with mus- culoskeletal conditions. A search of Intercontinental Marketing Services data from January 2003 to January 2004 showed that carisoprodol, cyclobenzaprine, and metaxalone represented more than 45% of all prescriptions for the management of musculoskeletal pain. 2 There has been concern and debate about whether car- isoprodol should be classified as a controlled substance because the drug acts centrally, causing sedation. 1 It is me- tabolized to meprobamate, which activates barbiturate-like GABA A receptors and is itself a schedule IV controlled sub- stance at the US federal level. Meprobamate was shown to have a risk of addiction similar to that of benzodiazepines, which are well known to be drugs of abuse. 3 Meprobamate is a carbamate derivative that is pharma- cologically similar to barbiturates, which was introduced as an antianxiety agent in 1955 and marketed under the brand names Miltown and Equanil. The drug was popular as a sedative- hypnotic, but was replaced by benzodiazepines. The potential for abuse and addiction related to meprobamate was quickly Key Points & Carisoprodol has potential for abuse for multiple reasons. The drug is metabolized to meprobamate, a controlled substance with proven abuse potential. Carisoprodol itself is capable of modulating GABA A function, which also may contribute to its potential for abuse. & Numerous case reports of carisoprodol abuse have been published. Some patients who abruptly cease intake of large amounts of carisoprodol have experienced a withdrawal syndrome consisting of insomnia, vomiting, tremors, muscle twitching, anxiety, ataxia, and sometimes hallucinations and delusions. & Carisoprodol has been withdrawn from the market in Norway, but may still be used in specially approved patients. The European Medicines Agency has recommended that carisoprodol- containing products be removed from the market in other European countries. Effective January 11, 2012, carisoprodol was classified as a schedule IV controlled substance at the federal level in the United States. & Clinicians should exercise appropriate caution when pre- scribing carisoprodol. Review Article Southern Medical Journal & Volume 105, Number 11, November 2012 619 From the G.V. (Sonny) Montgomery VA Medical Center, Mental Health Ser- vice, and the Department of Psychiatry, University of Mississippi School of Medicine, Jackson, Mississippi. Reprint requests to Dr Roy R. Reeves, Chief of Psychiatry (11M), VA Medical Center, 1500 E. Woodrow Wilson Dr, Jackson, MS 29216. Email: roy.reeves@va.gov The authors have no financial relationships to disclose and no conflicts of interest to report. Accepted June 8, 2012. Copyright * 2012 by The Southern Medical Association 0038-4348/0Y2000/105-619 DOI: 10.1097/SMJ.0b013e31826f5310 Copyright © 2012 The Southern Medical Association. Unauthorized reproduction of this article is prohibited.