Drug Enforcement Administration
Diversion Control Division
Drug & Chemical Evaluation SectionCYCLOBENZAPRINE(Brand Name: Flexeril®, Amrix®)
March 2020

Introduction:
Cyclobenzaprine is a central nervous system(CNS) muscle relaxant intended for short-term use
in the treatment of pain, tenderness and limitation ofmotion caused by muscle spasms. Cyclobenzaprine
may enhance the effects of other CNS depressantsincluding alcohol, barbiturates, benzodiazepinesand narcotics and anecdotal reports indicate it isused non-medically to induce euphoria andrelaxation.

Illicit Uses:
Anecdotal reports found on the Internet suggestthat individuals are taking cyclobenzaprine alone orin combination with other illicit drugs to produce orenhance psychoactive effects. Individuals havereported taking cyclobenzadrine both orally andintra-nasally at doses ranging from 10 mg to 60 mg.
Sedation, relaxation and increased heart rate werethe most common effects reported. Euphoria wasreported by a smaller number of individuals.

Licit Uses:
Cyclobenzaprine hydrochloride is approved foruse in the United States as a muscle relaxant. It ismarketed under the brand names Flexeril® andAmrix® and as generic formulations in 5, 7.5, and 10mg tablets intended for short-term (2 to 3 week) oral
administration. The usual starting dose is 5 mg,three times per day. The maximum recommended
dose is 10 mg, three times daily. IQVIA™ reports
28.4 million total prescriptions of cyclobenzaprinedispensed in the U.S. in 2017; with 26.9 millionprescriptions actually being sold or picked-up by
patients and 26.7 million prescriptions being
sold/picked-up for 2018 and 2019.

Illicit Distribution:
Several indicators suggest that cyclobenzaprineis being intentionally misused or abused. According
to the American Association of Poison Control
Centers, 10,615 case mentions and 4,444 single
exposures were associated with cyclobenzaprine in2016, resulting in 75 major medical outcomes andfour deaths among single substance exposures. In
2017, there were 10,429 case mentions, 4,248
single exposures, 97 major medical outcomes, andone death.
For emergency department (ED) visits, there
were an estimated 12,411 emergency room visits
associated with cyclobenzaprine in 2010, a
statistically significant increase of 101% from 6,183
visits in 2004 from the Drug Abuse Warning Network
Emergency Department visits, DAWN ED; thatceased data collection in 2011.
According to the National Forensic Laboratory
Information System (NFLIS), there were 1,142
cyclobenzaprine reports from federal, state and local
forensic laboratories in 2016 and 995 reports in2017. For 2018 and 2019, preliminary reporting
indicates an estimated 883 and 527 reports ofcyclobenzaprine identified, respectively.

Chemistry and Pharmacology:
Cyclobenzaprine hydrochloride is a white
crystalline tricyclic amine salt that is freely soluble inwater or alcohol. Cyclobenzaprine has been shown
to reduce or abolish skeletal muscle hyperactivity. It
is thought to act within the CNS at the brain rather
than the spinal cord, although action at the spinal
cord may contribute to some of its skeletal muscle
relaxant action. Pharmacological studies in animals
have shown a similarity between the effects of thestructurally-related tricyclic antidepressants andcyclobenzaprine. The most frequently encounteredadverse effects of cyclobenzaprine include theanticholinergic effects, such as, drowsiness, drymouth and dizziness. Other CNS effects include
blurred vision, confusion, anxiety, agitation,psychosis, abnormal thinking, and hallucinations.
Cardiovascular effects include increased heart rateand palpitations. The induction of these effects isdose-dependent. Nausea, headache and malaise
may be experienced upon abrupt termination ofprolonged use.

Control Status:
Cyclobenzaprine is not currently controlled
under the Controlled Substances Act.

Comments and additional information are welcomed by the Drugand Chemical Evaluation Section; Fax 571-362-4250,
Telephone 571-362-3249, or Email DPE@usdoj.gov.