Recommendation (from TRS)
Substance identification
Carisoprodol (IUPAC name: 2-[(carbamoyloxy)methyl]-2-methylpentyl(1- ethylethyl)carbamate) is a centrally acting skeletal muscle relaxant sold as a single-ingredient preparation and in combination products. Carisoprodol is available as a pharmaceutical product in tablet form, has been detected in falsified pharmaceuticals and is also found as a white powder.
WHO review history
Carisoprodol was pre-reviewed at the 32nd ECDD meeting in 2000. At that time, the Committee did not recommend critical review, noting that sporadic nonmedical use of carisoprodol was not a new phenomenon and there was no indication of significantly increasing nonmedical use. A new pre-review was initiated in 2023 after an international agency provided information that suggested a significant increase in the reported number of trafficking cases and seizures involving carisoprodol. At the 46th ECDD meeting, increasing evidence of nonmedical use and public health harm led the Committee to recommend that carisoprodol be subject to a critical review.
Similarity to known substances and effects on the central nervous system
Carisoprodol is metabolized to meprobamate and has effects similar to those of other central nervous system depressants, such as meprobamate, phenobarbital, diazepam and chlordiazepoxide, which are listed under schedule IV of the Convention on Psychotropic Substances of 1971. Meprobamate is also a metabolite of carisoprodol. Although its exact mechanism of action is not known, its therapeutic effects appear to be due to modulation of γ-aminobutyric acid (GABA)-A, similar to the action of barbiturates. The sedative effects of carisoprodol can be potentiated when it is combined with benzodiazepines, opioids or alcohol.
Dependence potential
Tolerance and withdrawal have been documented in experimental animals, and potential dependence on carisoprodol is considered to be similar to that of barbiturates and benzodiazepines. In humans in the context of prolonged use, tolerance, withdrawal symptoms and craving have been documented. Increasing numbers of cases of carisoprodol dependence have been recorded in pharmacovigilance reporting systems and clinical settings.
Actual abuse and/or evidence of likelihood of abuse
In animal models of abuse liability, the effects of carisoprodol were similar to those of pentobarbital, chlordiazepoxide and meprobamate and were dose-dependent. In humans, in the context of its nonmedical use at high doses, carisoprodol produces central nervous system depressant effects, including drowsiness, sedation, confusion and coma.
Public health harm, including cases of driving under the influence of the drug and nonfatal and fatal intoxications, due to carisoprodol alone or in combination with other substances have been observed.
Nonmedical use of carisoprodol is widely documented in multiple countries and regions, including in combination with opioids and/or benzodiazepines. Increased restrictions on carisoprodol prescription or removal of the drug from the market in several countries have led to decreased incidences of poisoning and other types of public health harm. Seizures of carisoprodol have been reported in many countries in several regions.
Therapeutic use
Carisoprodol is a centrally acting muscle relaxant used in some countries in the short term as an adjunct in symptomatic treatment of acute musculoskeletal disorders associated with painful muscle spasms. It is not on the 2023 WHO Essential Medicines List or the WHO Essential Medicines List for Children. It has been withdrawn from therapeutic use in some countries because of concern about increased rates of diversion, nonmedical use, dependence, intoxication and psychomotor impairment.
Recommendation
There is increasing evidence that nonmedical use of carisoprodol in a number of countries constitutes a significant risk to public health. Carisoprodol is a medicine that has been shown to produce a state of dependence, central nervous system depression, and ill effects similar to those of other substances that are listed under Schedule IV of the Convention on Psychotropic Substances of 1971.
The Committee recommended that carisoprodol be added to Schedule IV of the Convention on Psychotropic Substances of 1971.