Carisoprodol, sold under the brand name Soma among others, is an oral medication used for

musculoskeletal The human musculoskeletal system (also known as the human locomotor system, and previously the activity system) is an organ system that gives humans the ability to move using their muscular and skeletal systems. The musculoskeletal system provid ...

pain. Effects generally begin within half an hour and last for up to six hours. Common side effects include headache, dizziness, and sleepiness. Serious side effect may include

addiction Addiction is a neuropsychological disorder characterized by a persistent and intense urge to use a drug or engage in a behavior that produces natural reward, despite substantial harm and other negative consequences. Repetitive drug use can ...

allergic reaction Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allergy, food al ...

s, and

seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

s. In people with a sulfa allergy certain formulations may result in problems. Safety during

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

and

breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...

is not clear. How it works is not clear. Some of its effects are believed to occur following metabolic conversion into

meprobamate Meprobamate—marketed as Miltown by Wallace Laboratories and Equanil by Wyeth, among others—is a carbamate derivative used as an anxiolytic drug. It was the best-selling minor tranquilizer for a time, but has largely been replaced by the benz ...

, carisoprodol's main active metabolite. Carisoprodol was approved for medical use in the United States in 1959. Its approval in the European Union was withdrawn in 2008. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

. In 2019, it was the 343rd most commonly prescribed medication in the United States, with more than 800thousand prescriptions. In the United States, it is a Schedule IV controlled substance.

Medical uses

Carisoprodol is meant to be used along with rest,

physical therapy Physical therapy (PT), also known as physiotherapy, is a healthcare profession, as well as the care provided by physical therapists who promote, maintain, or restore health through patient education, physical intervention, disease preventio ...

and other measures to relax muscles after strains, sprains and muscle injuries. It comes in tablet format and is taken by the mouth three times a day and before bed.

Side effects

The usual dose of 350 mg is unlikely to engender prominent side effects other than

somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling aslee ...

, and mild to significant

euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...

dysphoria Dysphoria (; ) is a profound state of unease or dissatisfaction. It is the semantic opposite of euphoria. In a psychiatric context, dysphoria may accompany depression, anxiety, or agitation. In psychiatry Intense states of distress and uneas ...

, but the euphoria is generally short-lived due to the fast metabolism of carisoprodol into meprobamate and other metabolites; the euphoria derived is, according to new research, most likely due to carisoprodol's inherent, potent anxiolytic effects that are far stronger than those produced by its primary metabolite, meprobamate, which is often misblamed for the drug-seeking associated with carisoprodol, as carisoprodol itself is responsible for the significantly more intense central nervous system effects than meprobamate alone. Carisoprodol has a qualitatively different set of effects to that of meprobamate (Miltown). The medication is well tolerated and without adverse effects in the majority of patients for whom it is indicated. In some patients, however, and/or early in therapy, carisoprodol can have the full spectrum of sedative side effects and can impair the patient's ability to operate a firearm, motor vehicles, and other machinery of various types, especially when taken with medications containing

alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

, in which case an alternative medication would be considered. The intensity of the side effects of carisoprodol tends to lessen as therapy continues, as is the case with many other drugs. Other side effects include:

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a ...

, clumsiness,

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

, fast

heart rate Heart rate is the frequency of the cardiac cycle, heartbeat measured by the number of contractions of the heart per minute (''beats per minute'', or bpm). The heart rate varies according to the body's Human body, physical needs, including the nee ...

upset stomach Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Since the abdomen contains most of the body's vital organs, it can be an indicator of a wide variety of diseases. Given th ...

vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...

and

skin rash A rash is a change of the skin that affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked ...

. There are 368 drugs known to interact with carisoprodol including 28 major drug interactions. The interaction of carisoprodol with essentially all opioids, and other centrally acting analgesics, but especially codeine, those of the codeine-derived subgroup of the semisynthetic class (ethylmorphine, dihydrocodeine, hydrocodone, oxycodone, nicocodeine, benzylmorphine, the various acetylated codeine derivatives including acetyldihydrocodeine, dihydroisocodeine, nicodicodeine and others) which allows the use of a smaller dose of the opioid to have a given effect, is useful in general and especially where skeletal muscle injury and/or spasm is a large part of the problem. The potentiation effect is also useful in other pain situations and is also especially useful with opioids of the open-chain class, such as methadone, levomethadone, ketobemidone, phenadoxone and others. In recreational drug users, deaths have resulted from combining doses of hydrocodone and carisoprodol. Another danger of misuse of carisoprodol and opiates is the potential to asphyxiate while unconscious. Meprobamate and other muscle-relaxing drugs often were subjects of misuse in the 1950s and 60s. Overdose cases were reported as early as 1957, and have been reported on several occasions since then. Carisoprodol is metabolized by the liver and excreted by the kidneys, so this drug must be used with caution with patients that have impaired hepatic or

renal function Assessment of kidney function occurs in different ways, using the presence of symptoms and signs, as well as measurements using urine tests, blood tests, and medical imaging. Functions of a healthy kidney include maintaining a person's flu ...

. Because of potential for more severe side effects, this drug is on the list to avoid for elderly people.

Withdrawal

Carisoprodol, meprobamate, and related drugs such as tybamate, have the potential to produce physical dependence of the barbiturate type following periods of prolonged use. Withdrawal of the drug after extensive use may require hospitalization in medically compromised patients. In severe cases the withdrawal can mimic the symptoms of

alcohol withdrawal Alcohol withdrawal syndrome (AWS) is a set of symptoms that can occur following a reduction in or cessation of alcohol use after a period of excessive use. Symptoms typically include anxiety, shakiness, sweating, vomiting, fast heart rate, a ...

including the potentially lethal

status epilepticus Status epilepticus (SE), or status seizure, is a medical condition with abnormally prolonged seizures. It can have long-term consequences, manifesting as a single seizure lasting more than a defined time (time point 1), or 2 or more seizures over ...

. Psychological dependence has also been linked to carisoprodol use although this is much less severe than with meprobamate itself (presumably due to the slower onset of effects). Psychological dependence is more common in those who use carisoprodol non-medically and those who have a history of substance use (particularly

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...

s or alcohol). It may reach clinical significance before physiological tolerance and dependence have occurred and (as with

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

s) has been demonstrated to persist to varying degrees of severity for months or years after discontinuation. Discontinuation of carisoprodol, as with all GABA-ergics, can result in cognitive changes which persist for weeks, months, or rarely even years including greatly increased anxiety and depression, social withdrawal, hair-trigger agitation/aggression, chronic

insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

, new or aggravated (often illogical)

phobias The English language, English suffixes -phobia, -phobic, -phobe (from Ancient Greek, Greek φόβος ''phobos'', "fear") occur in technical usage in psychiatry to construct words that describe irrational, abnormal, unwarranted, persistent, o ...

, reduced IQ, short term and long-term memory loss, and dozens of other sequelae. The effects, severity, and duration appear to be slightly dose-dependent but are mainly determined by the patients pattern of use (taken as prescribed, taken in bulk doses, mixed with other drugs, a combination of the above, etc.), genetic predisposition to substance use, and a history of substance use all increase the patients risk of persistent discontinuation syndrome symptoms. Treatment for physical withdrawal generally involves switching the patient to a long-acting benzodiazepine such as

diazepam Diazepam, sold under the brand name Valium among others, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is used to treat a range of conditions, including anxiety disorder, anxiety, seizures, alcohol withdrawal syndr ...

or clonazepam then slowly titrating them off the replacement drug completely at a rate which is both reasonably comfortable for the patient but rapid enough for the managing physician to consider the rate of progress acceptable (overly rapid dose reduction greatly increases the risk of patient non-compliance such as the use of illicitly obtained alternative sedatives and/or alcohol).

Psychotherapy Psychotherapy (also psychological therapy, talk therapy, or talking therapy) is the use of Psychology, psychological methods, particularly when based on regular Conversation, personal interaction, to help a person change behavior, increase hap ...

and

cognitive behavioral therapy Cognitive behavioral therapy (CBT) is a form of psychotherapy that aims to reduce symptoms of various mental health conditions, primarily depression, PTSD, and anxiety disorders. Cognitive behavioral therapy focuses on challenging and chang ...

have demonstrated moderate success in reducing the rebound anxiety which results upon carisoprodol discontinuation but only when combined with regular and active attendance to a substance use support group. Carisoprodol withdrawal can be life-threatening (especially in high dose users and those who attempt to quit " cold turkey"). Medical supervision is recommended, with gradual reduction of dose of carisoprodol or a substituted medication, typical of other depressant drugs.

Non-medical use

Combining a muscle relaxant like carisoprodol with opioids and benzodiazepines is referred to as "The Holy Trinity" as it has been reported to increase the power of the "high". Recreational users of carisoprodol usually seek its potentially heavy sedating, relaxant, and

anxiolytic An anxiolytic (; also antipanic or anti-anxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxie ...

effects. Also, because of its potentiating effects on

narcotic The term narcotic (, from ancient Greek ναρκῶ ''narkō'', "I make numb") originally referred medically to any psychoactive compound with numbing or paralyzing properties. In the United States, it has since become associated with opiates ...

s, it is often used in conjunction with many

opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...

drugs. Also it is not detected on standard

drug test A drug test (also often toxicology screen or tox screen) is a technical analysis of a biological specimen, for example urine, hair, blood, breath, sweat, or saliva, oral fluid/saliva—to determine the presence or absence of specified parent ...

ing screens. On 26 March 2010 the DEA issued a Notice of Hearing on proposed rule making in respect to the placement of carisoprodol in schedule IV of the

Controlled Substances Act The Controlled Substances Act (CSA) is the statute establishing federal government of the United States, federal drug policy of the United States, U.S. drug policy under which the manufacture, importation, possession, use, and distribution of ...

. The DEA ended up classifying it under schedule IV. Carisoprodol is sometimes mixed with date rape drugs.

Overdose

As with other GABAergic drugs, combination with other drugs that depress the respiratory system, such as alcohol, sedatives and opioids possess a significant risk to the user in the form of overdose. Overdose symptoms are similar to those of other GABAergics including excessive sedation and unresponsiveness to stimuli, severe

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

amnesia Amnesia is a deficit in memory caused by brain damage or brain diseases,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be temporarily caused by t ...

confusion In psychology, confusion is the quality or emotional state of being bewildered or unclear. The term "acute mental confusion"

, agitation, intoxication and inappropriate (potentially violent) behavior. Severe overdoses may present with

respiratory depression Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (''hypo'' meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapni ...

(and subsequent

pulmonary aspiration Pulmonary aspiration is the entry of solid or liquid material such as pharyngeal secretions, food, drink, or stomach contents from the oropharynx or gastrointestinal tract, into the trachea and lungs. When pulmonary aspiration occurs during ea ...

coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to Nociception, respond normally to Pain, painful stimuli, light, or sound, lacks a normal Circadian rhythm, sleep-wake cycle and does not initiate ...

, and

death Death is the end of life; the irreversible cessation of all biological functions that sustain a living organism. Death eventually and inevitably occurs in all organisms. The remains of a former organism normally begin to decompose sh ...

. Carisoprodol is not detected on all toxicology tests which may delay diagnosis of overdose. Overdose symptoms in combination with opiates are similar but are distinguished by the presentation of normal or pinpoint pupils, which are generally unresponsive to light. Carisoprodol (as with its metabolite meprobamate) is particularly dangerous in combination with alcohol. Flumazenil (the benzodiazepine antidote) is not effective in the management of carisoprodol overdose as carisoprodol acts at the barbiturate binding site. Treatment mirrors that of

barbiturate overdose Barbiturate overdose is poisoning due to excessive doses of barbiturates. Symptoms typically include difficulty thinking, poor coordination, decreased level of consciousness, and a decreased effort to breathe ( respiratory depression). Complic ...

s and is generally supportive, including the administration of mechanical respiration and pressors as indicated and, in rare cases, bemegride. Total amnesia of the experience is not uncommon following recovery. In 2014 actress Skye McCole Bartusiak died of an overdose due to the combined effects of carisoprodol,

hydrocodone Hydrocodone, also known as dihydrocodeinone, is a semi-synthetic opioid used to treat pain and as a cough suppressant. It is taken by mouth. Typically, it is dispensed as the combination acetaminophen/hydrocodone or ibuprofen/hydrocodone fo ...

and difluoroethane. In 1999 actress Dana Plato died after taking carisoprodol (Soma) along with a few doses of a hydrocodone / acetaminophen painkiller (Lortab), in an overdose that was ruled a suicide.

Pharmacology

Pharmacodynamics

Carisoprodol, has a chemical structure similar to

glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

, a neurotransmitter, and dimethylglycine. Carisoprodol's structural similarity to

indicates GABAergic activity, including GABA_A agonism, similar to the mechanism of benzodiazepines. This will allow for further muscle relaxation and anxiety reduction. Therefore, carisoprodol, at low to moderate dosages, may be clinically indicated for absent seizures, yet exacerbate tonic-clonic seizures.

Pharmacokinetics

Carisoprodol has a rapid, 30-minute onset of action, with the aforementioned effects lasting about two to six hours. It is metabolized in the liver via the

cytochrome P450 oxidase Cytochromes P450 (P450s or CYPs) are a superfamily of enzymes containing heme as a cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for example, they have not been found in ''Escherich ...

isozyme In biochemistry, isozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. Isozymes usually have different kinetic parameters (e.g. di ...

CYP2C19 Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some ...

, excreted by the kidneys and has about an eight-hour half-life. In patients with low levels of CYP2C19 (poor metabolizers), standard doses can lead to increased concentrations of carisoprodol (up-to a four-fold increase). A considerable proportion of carisoprodol is metabolized to

, which is a known addictive substance; this could account for the addictive potential of carisoprodol (meprobamate levels reach higher peak plasma levels than carisoprodol itself following administration). It is slightly

soluble In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution. The extent of the solubi ...

water Water is an inorganic compound with the chemical formula . It is a transparent, tasteless, odorless, and Color of water, nearly colorless chemical substance. It is the main constituent of Earth's hydrosphere and the fluids of all known liv ...

and freely soluble in

ethanol Ethanol (also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound with the chemical formula . It is an Alcohol (chemistry), alcohol, with its formula also written as , or EtOH, where Et is the ps ...

chloroform Chloroform, or trichloromethane (often abbreviated as TCM), is an organochloride with the formula and a common solvent. It is a volatile, colorless, sweet-smelling, dense liquid produced on a large scale as a precursor to refrigerants and po ...

and

acetone Acetone (2-propanone or dimethyl ketone) is an organic compound with the chemical formula, formula . It is the simplest and smallest ketone (). It is a colorless, highly Volatile organic compound, volatile, and flammable liquid with a charact ...

. The drug's solubility is practically independent of pH.

History

In June 1959, several American pharmacologists convened at

Wayne State University Wayne State University (WSU) is a public university, public research university in Detroit, Michigan, United States. Founded in 1868, Wayne State consists of 13 schools and colleges offering approximately 375 programs. It is Michigan's third-l ...

Detroit, Michigan Detroit ( , ) is the List of municipalities in Michigan, most populous city in the U.S. state of Michigan. It is situated on the bank of the Detroit River across from Windsor, Ontario. It had a population of 639,111 at the 2020 United State ...

to discuss a newly discovered structural analogue of

. The substitution of one

hydrogen Hydrogen is a chemical element; it has chemical symbol, symbol H and atomic number 1. It is the lightest and abundance of the chemical elements, most abundant chemical element in the universe, constituting about 75% of all baryon, normal matter ...

atom with an isopropyl group on one of the carbamyl

nitrogen Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...

s was intended to yield a drug with new pharmacological properties. It had been developed by Frank Berger at Wallace Laboratories and was named carisoprodol. Building on

's pharmacological effects, carisoprodol was intended to have better muscle relaxing properties, less potential for addiction, and a lower risk of overdose. Carisoprodol's effect profile did indeed turn out to differ significantly with respect to meprobamate, with carisoprodol possessing stronger muscle relaxant and

analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...

effects.

Usage and legal status

Norway

Reports from Norway have shown carisoprodol has addictive potential as a prodrug of

and/or potentiator of

oxycodone Oxycodone, sold under the brand name Roxicodone and OxyContin (which is the extended-release form) among others, is a semi-synthetic opioid used medically for the treatment of moderate to severe pain. It is highly addictive and is a commonly ...

codeine Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...

, and similar drugs. In May 2008 it was taken off the market in Norway.

European Union

In the EU, the European Medicines Agency issued a release recommending member states suspend marketing authorization for this product in the treatment of acute (not chronic) back pain. As of November 2007, carisoprodol has been taken off the market in Sweden due to problems with dependence and side effects. The agency overseeing pharmaceuticals considered other drugs used with the same indications as carisoprodol to have the same or better effects without the risks of the drug.

United States

In December 2011, the

Drug Enforcement Administration The Drug Enforcement Administration (DEA) is a Federal law enforcement in the United States, United States federal law enforcement agency under the U.S. Department of Justice tasked with combating illicit Illegal drug trade, drug trafficking a ...

(DEA) issued the final ruling placing carisoprodol on Schedule IV of the

(CSA). The placement of carisoprodol on Schedule IV was effective in January 2012.

Canada

Federally, carisoprodol is a prescription drug (Schedule I, sub-schedule F1). Provincial regulations vary. It is no longer readily available.

Indonesia

* In September 2013, carisoprodol was taken off the market due to problems with diversion, dependence and side effects. * In September 2017, one child died and 50 had seizures when PCC, which stands for "Paracetamol Caffeine Carisoprodol" was mixed (probably illicit) into children's drinks in elementary and junior high schools in Kendari.