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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. Awithdrawal 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
Carisoprodol (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 speciallyapproved 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.
recognized because reports of misuse appeared in the literature
within 2 years of being placed on the market.
4
The chemical
nomenclature suggests that carisoprodol is structurally related
to meprobamate. Meprobamate and carisoprodol differ only by
the substitution of a hydrogen atom for an isopropyl group on
one of the carbamyl nitrogens. Carisoprodol itself may also
activate GABA
A
receptors
5
; therefore, carisoprodol has po-
tential for being abused.
Carisoprodol has been scheduled as a controlled substance
in several US states. In 1996, the US Drug Enforcement Ad-
ministration (DEA) recommended scheduling at the federal
level, but the US Food and Drug Administration (FDA) Drug
Advisory Committee concluded that there was insufficient
evidence
6
; however, since that time, additional information led
the DEA to alter this conclusion.
Carisoprodol Abuse
Numerous reports describe more than 30 individuals abusing
carisoprodol under various conditions.
7Y19
Carisoprodol has been
abused (usually in amounts much larger than the recommended
daily dosage) for its sedative and relaxant effects. It has been used
to augment or alter the effects of other drugs (eg, to increase the
sedating effects of benzodiazepines or alcohol, prevent jitteriness
during cocaine consumption, and help calm individuals after an
episode of cocaine use). Some patients have substituted car-
isoprodol for opiates or benzodiazepines when those substances
were not available. Others have combined carisoprodol with other
drugs to intentionally produce a synergistic effect, resulting in
significant relaxation and euphoria. Abuse has involved the
planned procurement of carisoprodol and other noncontrolled
medications because of the ease (as compared with controlled
substances) of obtaining prescriptions. A concise overview of
reports of carisoprodol abuse and withdrawal is available.
20
Reeves and colleagues surveyed 40 carisoprodol users
and found that among those with a history of substance abuse
(n = 20), 40% used carisoprodol in larger than prescribed
amounts: 30% to obtain an effect other than that for which it
was prescribed, 10% to augment the effect of another drug, and 5%
to counteract another medication.
21
Twenty percent attempted to
obtain extra carisoprodol by prescription and 10% obtained it by
means other than a legal prescription. Owens and colleagues
reviewed 2005 Idaho Medicaid claims and surveyed pharmacies
filling prescriptions for long-term carisoprodolusers (N = 340).
22
Patients prescribed carisoprodol used opioids and other drugs
more frequently, and 80% of patients continued to pay out of
pocket for carisoprodol when Medicaid coverage ended.
Prisoners in Norway taking 700 to 2100 mg/day of car-
isoprodol for at least 9 months and then withdrawing from the
drug reported anxiety, insomnia, irritability, cranial and mus-
cular pain, and anergy.
23
Withdrawal symptoms occurred in 2
patients following cessation of doses as low as 4 to 8 tablets
daily.
16
More severe symptoms occurred in 5 patients who
stopped daily intake of 2100 to 4200 mg.
24
Carisoprodol withdrawal syndrome was described in
2004
25
by a 43-year-old man taking more than thirty 350-mg
carisoprodol tablets per day. Within 48 hours of cessation he
developed anxiety, tremors, muscle twitching, insomnia, hal-
lucinations, and bizarre behavior, peaking on the fourth day. He
was treated with olanzapine and lorazepam. Four other cases
were subsequently described.
26Y28
They shared similar char-
acteristics: cessation from daily intake of 12 to 25 carisoprodol
tablets followed by anxiety, tremulousness, insomnia, psy-
chomotor agitation, hallucinations (auditory and/or visual),
and paranoia. Treatment involved benzodiazepines and/or
antipsychotics until withdrawal symptoms resolved, typically
within 4 to 6 days. The likely mechanism for carisoprodol
withdrawal syndrome is withdrawal from meprobamate accu-
mulated with intake of excessive carisoprodol, although the
capacity of carisoprodol to modulate GABA
A
function also
may contribute to withdrawal symptoms.
26Y28
It is not known
whether carisoprodol has cross-tolerance with other sedative
drugs, although case reports of patients substituting car-
isoprodol for benzodiazepines and opiates suggest the possi-
bility of this substitution. Another case report noted that the
benzodiazepine antidote flumazenil reversed carisoprodol in-
toxication in a 52-year-old woman,
29
suggesting similarities in
the actions of carisoprodol and benzodiazepines.
Animal studies support the development of tolerance and
withdrawal from meprobamate and carisoprodol. Hyperexcit-
ability was shown to be detectable in mice 4 to 8 hours after
drug withdrawal following chronic administration of mepro-
bamate. This excitation subsides within 28 hours.
30
In another
study, mice were administered carisoprodol (0, 100, 200, 300,
or 500 mg/kg) for 4 days.
31
The loss of righting reflex (a mea-
sure of coordination) was measured 20 to 30 minutes following
each administration. On day 4, 20 mg/kg bemegride (a drug
not used clinically in humans that antagonizes the effects of
barbiturates), 20 mg/kg flumazenil, or vehicle was administered
following carisoprodol, after which withdrawal signs were
measured. Separate groups of mice receiving the same treatment
were tested for spontaneous withdrawal at 6, 12, and 24 hours
following the last dose of carisoprodol. The first administration
of carisoprodol produced a substantial dose-dependent loss of
motor coordination as measured by the loss of righting score. A
75% to 100% decrease in the impairment of the righting reflex
occurred during the 4 days of exposure, indicating the devel-
opment of tolerance to carisoprodol. Withdrawal signs were not
observed with carisoprodol cessation; however, bemegride and
flumazenil each precipitated withdrawal within 15 to 30 minutes
of administration. Carisoprodol administration resulted in tol-
erance and antagonist precipitated withdrawal, suggesting sig-
nificant potential for addiction.
Carisoprodol and Public Safety
Carisoprodol may impair a person’s ability to drive, as
reported by Logan and colleagues, who investigated drivers in
whom carisoprodol or meprobamate was detected following
Reeves et al &Carisoprodol: Update on Abuse Potential and Legal Status
620 *2012 Southern Medical Association
Copyright © 2012 The Southern Medical Association. Unauthorized reproduction of this article is prohibited.
accidents or arrests for impaired driving.
32
In 21 cases, no other
drugs were detected. Signs of intoxication occurred in some
patients, even when combined serum concentrations of car-
isoprodol and meprobamate were within the therapeutic range.
Bramness and colleagues reviewed 62 cases of drivers in whom
carisoprodol and meprobamate were the only drugs identi-
fied.
33
Impaired drivers (73%) had higher blood carisoprodol
concentrations than unimpaired drivers, but no difference in
blood meprobamate concentration was found for all drivers
reviewed together. Thus, carisoprodol alone can have an
impairing effect at higher blood levels. An obvious concern is
the degree of impairment that could occur when carisoprodol
and alcohol are combined; however, the impact of combining
alcohol and carisoprodol on driver performance has not been
formally investigated.
Hoiseth and colleagues assessed the impact of the
scheduling of carisoprodol in Norway.
34
Driving under the
influence cases involving carisoprodol dropped 7% to 8% from
2004 to 2006, 5% in 2007, and 1% in 2008. Detection of the
drug during autopsies dropped 3% from 2004 to 2006, 2.5% in
2007, and 0.6% in 2008. Poison control contacts regarding
carisoprodol decreased from 1% between 2004 and 2006, to
0.8% in 2007, and 0.3% in 2008. Zacny and colleagues ad-
ministered subjects 0, 350, and 700 mg of carisoprodol. For the
next 6 hours they administered a battery of tests at fixed
intervals to assess subjective and psychomotor effects.
35
The
therapeutic dose (350 mg), although producing few or mild
subjective effects, still produced psychomotor impairment,
leading to concern that patients prescribed carisoprodol may
feel normal and engage in tasks such as driving that could place
themselves and others at risk. The same researchers showed
that the administration of oxycodone and carisoprodol within
60 minutes of each other produced effects that are of concern
for abuse liability and public safety.
36
Evidence of Increasing Carisoprodol Misuse
The Drug Abuse Warning Network reports a steady in-
crease in emergency department visits involving carisoprodol.
Carisoprodol-related visits more than doubled, from 6569 visits
in 1994 to 14,376 in 2004 and more than doubled to 29,980 by
2009 (Fig.).
37,38
National Survey on Drug Use and Health data
from 2002Y2005 demonstrated that incidences of misuse of
carisoprodol were approximately equal to those of clonaze-
pam.
39
The 2008 annual report of the American Association of
Poison Control Centers reported 2632 intentional carisoprodol
exposures requiring medical treatment.
40
The 2009 Monitoring
the Future national survey on drug use showed an annual
prevalence of carisoprodol abuse by high school seniors of
1.3% in 2007 and 1.4% in 2008; these rates are higher than
those for lorazepam and clonazepam.
41
Carisoprodol abuse is common in the southern United
States, and in 1991 the Mississippi Board of Pharmacy issued a
warning that carisoprodol abuse was increasing. Two phar-
macists in the state were fined and given probation after 71,000
doses of the drug were discovered missing. An investigation
showed that certain patients may have taken Q20 carisoprodol
tablets daily.
42
Theft or loss of carisoprodol also was reported in
neighboring Louisiana and Alabama. In Alabama, pharmacists
were sanctioned by their licensing boards for personal misuse
of the drug.
42
Davis and Alexander performed a retrospective
study on deceased individuals who were examined at the Jef-
ferson County (Alabama) medical examiner’s office from
January 1, 1986 to October 31, 1997 and reported that car-
isoprodol was detected in 24 cases.
43
They concluded that
carisoprodol was ‘‘probably responsible, in part, for those
deaths.’’ Texas poison control centers received 936 car-
isoprodol-related calls from 1998 to 2003.
44
It was reported
that for many years carisoprodol distributed under the brand
name Somacid could be obtained easily in large quantities (up
to several thousand pills at a time) in Mexican pharmacies near
the US border and transported into the United States.
45
A study of the Norwegian Prescription Database revealed
that in 2004, 83,713 individuals were prescribed car-
isoprodol.
46
Many patients used more carisoprodol than was
recommended in treatment guidelines. High carisoprodol use
was associated with high benzodiazepine and opiate use.
Patients abusing carisoprodol often received prescriptions from
doctors widely known to overprescribe. In Norway, the com-
pany that distributed carisoprodol agreed to withdraw mar-
keting authorization for carisoprodol-containing products.
47
Legal Status of Carisoprodol
Although evidence of abuse is widespread, legal action to
declare carisoprodol a controlled substance has occurred pri-
marily in Norway and the United States. In August 2007,
Norway reclassified carisoprodol to class A (their highest
scheduling level, in which opiates and amphetamines also are
classified). Carisoprodol was withdrawn from the market in
Norway on May 1, 2008, but, after application to the Norwe-
gian Medication Agency, could still be used by patients for
whom there were no alternative therapies.
34
In September
Fig. Emergency department (ED) visits related to carisoprodol
reported by the Drug Abuse Warning Network.
Review Article
Southern Medical Journal &Volume 105, Number 11, November 2012 621
Copyright © 2012 The Southern Medical Association. Unauthorized reproduction of this article is prohibited.
2007, the European Medicines Agency’s Committee for Me-
dicinal Products for Human Use concluded that carisoprodol’s
risks outweighed its benefits and recommended the suspension
of marketing authorization for carisoprodol-containing pro-
ducts in European Union member states.
48
To the best of the
authors’ knowledge, this action occurred only in Norway.
Abuse concerns have resulted in carisoprodol being
classified as a controlled substance in several US states. As
early as 1998, the drug was classified a schedule IV substance
in Alabama.
43
Fass showed that carisoprodol was classified a
schedule IV substance in 18 states (Alabama, Arizona, Arkansas,
Florida, Georgia, Hawaii, Indiana, Kentucky, Louisiana,
Massachusetts, Minnesota, Nevada, New Mexico, Oklahoma,
Oregon, Texas, Washington, and West Virginia) and was under
monitoring programs in North Dakota and Ohio.
6
Since then,
Tennessee (April 7, 2011),
49
Wyoming (July 1, 2011),
50
and
Mississippi (July 1, 2011)
51
have classified carisoprodol as
schedule IV.
After considerable debate, significant activity has occurred
at the federal level, including a ruling by the DEA to clas-
sify carisoprodol as a schedule IV controlled substance. The
December 12, 2011, issue of the Federal Register examines this
decision in detail.
52
Pertinent considerations included ‘‘car-
isoprodol possesses sedative properties that may underlie its
therapeutic usefulness and potential for abuse’’; ‘‘recent in vitro
studies demonstrated that carisoprodol possesses barbiturate-
like effects;’’ ‘‘carisoprodol’s discriminative stimulus effects
are similar to other Schedule IV drugs such as barbital, mep-
robamate, and chlordiazepoxide;’’ and ‘‘the record demon-
strates that excessive carisoprodol use creates toxicity and
withdrawal symptoms similar to other Schedule IV drugs.’’ The
FDA stated, ‘‘An evaluation of published case reports and case
series, the FDA Adverse Event Reporting System and the
SAMHSA DAWN databases, show that carisoprodol as cur-
rently used, raises concerns not only for the health and safety of
the users but also for the public because of exposure to those
who use carisoprodol.’’
With this ruling, the DEA placed carisoprodol, its salts,
isomers, and salts of its isomers into schedule IV of the Con-
trolled Substances Act, effective January 11, 2012. ‘‘Thereafter
any person who engages in the manufacture, distribution,
dispensing, importing, exporting, as well as any person who
possesses the drug will be subject to the provisions of the Act
and DEA regulations, including the Act’s administrative, civil,
and criminal sanctions which are applicable to Schedule IV
controlled substances,’’ including registration, disposal of
stocks, security, labeling and packaging, inventory, records,
and prescriptions. There is no definite gauge or way to predict
the impact that classifying carisoprodol as schedule IV at the
federal level will have on the use of the drug. Meprobamate was
used as a sedative hypnotic for many years after being
scheduled a controlled substance and is still available but
typically not prescribed. The decrease in use may have been the
result of concern about abuse and the drug’s essentially being
replaced by the increased use of benzodiazepines. What is
likely to happen with carisoprodol use in the United States is
uncertain, although the authors propose that some decrease in
both legal and illicit consumption as was seen in Norway may
be the most likely scenario.
In conclusion, carisoprodol is a schedule IV controlled
substance at the federal level in the United States, creating
applicable regulations, regardless of scheduling in individual
states. Carisoprodol has been classified as schedule A in
Norway and was removed from the market, but may still be
used by specially approved patients. The European Medicines
Agency has recommended similar actions by other European
countries, with action by these countries to be determined.
Clearly, clinicians should be aware of the abuse potential of
carisoprodol and exercise appropriate caution when prescrib-
ing the drug.
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Review Article
Southern Medical Journal &Volume 105, Number 11, November 2012 623
Copyright © 2012 The Southern Medical Association. Unauthorized reproduction of this article is prohibited.
