Be alert to the signs of dextromethorphan abuse

May 2007

Dextromethorphan is a common ingredient in many over-the-counter (OTC) cough and cold products.

It is included in these products as a cough suppressant, and is the most commonly used cough suppressant available OTC. Recent studies, however, have shown that dextromethorphan is increasingly being abused for its euphoric effects at high doses. This month’s Pharmacology Consult will review the epidemiology and pharmacology of dextromethorphan abuse.

Dextromethorphan is chemically similar to codeine, as it is the d-isomer of the codeine analog methorphan. However, dextromethorphan has no analgesic or addictive properties at therapeutic doses, and it does not interact with mu, kappa or delta opioid receptors. Dextromethorphan’s efficacy as an antitussive in children is controversial, with few data from controlled trials of children demonstrating effectiveness. Pharmacology texts state dextromethorphan is an effective antitussive agent in adults. Dextromethorphan is metabolized by the hepatic cytochrome P450 system of enzymes, specifically 2D6. It is metabolized to dextrorphan (an active metabolite), the d-isomer of levorphanol (an opioid analgesic agent). Despite its chemical similarities to levorphanol, dextrorphan has no analgesic activity. The isoenzyme 2D6 exhibits genetic polymorphism and approximately 10% of the Caucasian population does not significantly express 2D6 activity. At therapeutic dosing, dextromethorphan is safe, with a low toxicity profile. Higher doses, however, produce significant adverse effects. At higher doses, dextrorphan antagonizes NMDA (N-methyl-d-aspartate) receptors for gluatmate, similar to ketamine or phencyclidine. This affects excitatory neurotransmitter actions, resulting in the symptoms seen with dextromethorphan abuse.

Dextromethorphan became widely available for OTC use in the late 1950s, and abuse of dextromethorphan has been known for the past 40 years. Changes in pharmaceutical dosage forms, with an increase in non-liquid dosage forms, in part, may be responsible for the increasing popularity of dextromethorphan abuse. While liquid cough preparations containing dextromethorphan continue to be available, the amount of liquid that must be ingested is relatively large (eg, 8 ounces or more). Ingestion of such a large volume of liquid, which many consider not very palatable, often leads to nausea or vomiting, thus reducing the ability to abuse the product. With the more recent availability of tablet or capsule dosage forms, some of which contain a relatively large dose of dextromethorphan (as compared to the amount available in liquid products), abuse of commonly available OTC products has become easier and more widespread.

Prevalence

There are recent data describing the prevalence of dextromethorphan abuse. The Monitoring the Future Survey has measured drug, alcohol and cigarette use among adolescents since 1975. Conducted by researchers from the University of Michigan, the Monitoring the Future survey is one of the major national surveys of youth behaviors. This survey is unique as it is the first national survey to include non-medical use of cough/cold products. Students (n=48,460) from 410 public and private schools in eighth, tenth and twelfth grades were surveyed in 2006. This survey reveals that, during the past year, 4.2% of eighth grade students, 5.3% of tenth grade students, and 6.9% of twelfth grade students reported using dextromethorphan to get high.

Bryner and colleagues reviewed six years of retrospective drug data on dextromethorphan abuse from three sources: the California Poison Control System, American Association of Poison Control Centers, and the Drug Abuse Warning Network (DAWN), a program of the Substance Abuse and Mental Health Services Administration. All dextromethorphan abuse cases reported to these centers were analyzed. The authors of this study sought to assess the trend of dextromethorphan abuse in California and to compare it to national trends.

During the six-year study period (1999-2004), 1,382 cases reported to the California Poison Control Center were identified. During this time period, the frequency of occurrence of dextromethorphan abuse cases increased 10-fold. Increases in case reports of dextromethorphan were also seen in the comparative national databases, although they were not as large. Of the cases reported in California, nearly 75% occurred in adolescents aged 9 to 17 years. Increases in dextromethorphan abuse increased by 15-fold in this age group during the study. The ages most commonly abusing dextromethorphan were 15 to 16 years. Most cases resulted in minor or moderate outcomes, and 0.5% resulted in major outcomes. No deaths were reported. The most commonly abused dextromethorphan dosage form was Coricidin HBP Cough and Cold Tablets (contains 30 mg dextromethorphan). Smaller surveys have also been conducted and their results published.

The Dayton Area Drug Survey assessed teen drug abuse among junior through high school-aged students in 15 Dayton, Ohio school districts in 2006 (Falck). Use of dextromethorphan for getting high was assessed in eleventh and twelfth-grade students (n=4176). Among these students, 2.4% and 3.7%, respectively, reported abusing dextromethorphan within the previous 12 months; 33.9% and 55% of reported users, respectively, had used dextromethorphan more than three times.

Dosing and effects

The doses of dextromethorphan used for non-medicinal purposes are substantially greater than therapeutic doses. Therapeutic dosing of dextromethorphan for children 12 years of age and older and adults includes 10 to 20 mg every 4 hours or 30 mg every 6 hours.

The effects, or high, which are seen with higher doses vary, depending upon the dose taken. The effects are often referred to as “plateaus.” The first plateau results in a mild stimulant effect. Hallucinations may occur with the second plateau, or effects similar to use of ethanol and marijuana together. The third plateau can be described as an “out-of-body,” or dissociative state. The fourth plateau is a more intense dissociative state. These latter two states may be similar to effects produced from dissociative agents, such as ketamine. Euphoric effects may persist for up to six hours. Dosing for these plateaus may vary for an individual, but they are often described as 100 to 200 mg for the first plateau; 200-400 mg for the second plateau; 300 to 600 mg for the third plateau; and 600 to 1,500 mg for the fourth plateau. Thus, approximately 10 to 20 Coricidin HBP Cough and Cold tablets (30 mg per tablet) would need to be taken to reach the third plateau. If a maximally concentrated liquid product were used (eg, Robitussin Maximum Strength Cough, 15 mg/5 ml), 3- to 7 ounces would need to be taken. Case reports have included adolescents taking up to 50 Coricidin tablets (Kirages).

Other effects may also include tachycardia, lethargy, hypertension, mydriasis, agitation, or nausea/vomiting. Deaths of adolescents believed to be due to toxicity from dextromethorphan abuse have been reported. Complicating these effects are other symptoms, which may result from additional ingredients in abused products. Many OTC cough/cold products containing dextromethorphan also include an antihistamine, decongestant, or analgesic, such as acetaminophen. Ingestion of multiple doses of a dextromethorphan-containing product, which also includes acetaminophen, may potentially result in acetaminophen-induced hepatic damage. For example, the most concentrated tablet dosage forms, Coricidin HBP Cough and Cold and Coricidin HBP Maximum Strength Flu tablets contain 30 mg and 15 mg of dextromethorphan, respectively, and 4 mg chlorpheniramine, and 2 mg chlorpheniramine/500 mg acetaminophen, respectively.

Internet

The Internet is a powerful source of information on numerous topics, and it is unfortunate that one can find much information on how to abuse dextromethorphan, including how to obtain dextromethorphan in powder form, what dose to take to reach the different effect plateaus, and what OTC products to take to most effectively produce euphoric effects. Several Internet sites specify what products or how much to use (“…make sure that DXM is the ONLY active ingredient…”). Slang terms for dextromethorphan include: triple C, red hots, skittles, robo, dex or tussin.

Conclusion

Although dextromethorphan has been abused for more than 40 years, the prevalence of abuse has increased sharply in recent years. Taken in large enough doses, dextromethorphan, and the coingredients often included in OTC products, can produce significant toxicity, including death. Clinicians providing care for adolescents should be aware of the magnitude of dextromethorphan abuse, and should educate parents and adolescents on the dangers of abusing dextromethorphan-containing products.

For more information:

• Edward A Bell, PharmD, BCPS, is a Professor of Pharmacy Practice at Drake University College Pharmacy and a Clinical Specialist at Blank Children’s Hospital, Des Moines, Iowa.
• 2006 Monitoring the Future Survey. www.drugabuse.gov/DrugPages/MTF.html
• Bryner JK. Dextromethorphan abuse in adolescence. Arch Pediatr Adol Med. 2006;160:1217-1222.
• Falck R. The prevalence of dextromethorphan abuse among high school students. Pediatrics. 2006;118:2267-2269.
• Kirages TJ. Severe manifestations of Coricidin intoxication. Amer J Emer Med. 2003;21:473-475.
• Boyer EW. Dextromethorphan abuse. Pediatr Emer Care. 2004;20:858-863.
• Schwartz RH. Adolescent abuse of dextromethorphan. Clin Pediatr. 2005;44:565-568.