Eric Whitney, MD, MSEd. Clinical Instructor, Child and Adolescent Psychiatry Fellow, NYU Grossman School of Medicine. New York, NY. Deepti Anbarasan, MD. Associate Professor, Psychiatry & Neurology, New York University. New York, NY.
Dr. Whitney and Dr. Anbarasan have no financial relationships with companies related to this material.
Some teens view over-the-counter (OTC) substances as safe or non-addictive (Levine DA, Curr Opin Pediatr 2007;19(3):270–274). In 2020, the National Institute on Drug Abuse reported that 3.2%–4.6% of high schoolers nationwide reported misusing OTC cough and cold medicines in the prior year (www.tinyurl.com/mwpke3js). Below, we will review several commonly misused, legally available substances.
Dextromethorphan (DXM) is the active ingredient in hundreds of OTC cough and cold products, including Coricidin HBP, Robitussin DM, and Delsym, and combined with bupropion in a recently released antidepressant with purportedly rapid effect. Adolescents misuse this drug for its euphoric, stimulant, and dissociative effects. DXM is metabolized by CYP2D6 with a half-life of two to four hours, and its psychoactive properties are based on dosing. In adults, it works as a cough suppressant at doses of 15–30 mg. At 100–200 mg, DXM has a stimulant-like effect, while doses over 200 mg produce intoxication with slurred speech, hallucinations, and impaired memory (Levine, 2007).
DXM toxicity causes various symptoms depending on dose, from flushed skin and tachycardia to hallucinations, ataxic gait, and agitation (Boyer EW, Pediatr Emerg Care 2004;20(12):858–863).
Chronic use of DXM is associated with psychosis and cognitive impairment. Cessation of DXM in chronic users causes non-life-threatening withdrawal symptoms: restlessness, insomnia, muscle aches, dysphoria, and intense cravings (Boyer, 2004). Patients on serotonergic medications who also use DXM are at risk for developing serotonin syndrome.
The US began efforts to curb adolescent misuse of DXM in 2021. Today, 21 state governments prohibit the sales of DXM to those under 18 years old.
First-generation antihistamines are usually used to treat allergy symptoms (eg, runny nose, sneezing) or motion sickness. Commonly misused agents that cross the blood-brain barrier include diphenhydramine (Benadryl), doxylamine (found in NyQuil), and dimenhydrinate (Dramamine). Adolescents use antihistamines in low doses for sedating and anxiolytic effects, or in higher doses for stimulant-like effects.
Antihistamine toxicity causes symptoms such as delirium, hallucinations, seizures, psychosis, tachycardia, dry mouth, blurry vision, constipation, and urinary retention. Use of antihistamines also causes QT prolongation, increasing the risk of dangerous arrhythmias (www.tinyurl.com/ymrdahvh). Withdrawal symptoms after chronic use include cravings, runny nose, nausea, diarrhea, cramping, irritability, restlessness, and insomnia.
The 2020 “Benadryl Challenge” dared people to ingest large amounts of diphenhydramine and post their experiences on the social media platform TikTok. This coincided with increased diphenhydramine-related emergency department visits in adolescents, including one reported death, followed by a warning from the US Food and Drug Administration (www.tinyurl.com/3sw5xz7p). To date, no laws limit access to antihistamines.
Pseudoephedrine is a nasal decongestant often packaged with antihistamines, DXM, acetaminophen, or NSAIDs (eg, Sudafed, Comtrex, Dristan, Entex). Usual daily pseudoephedrine doses are 15–60 mg in immediate-release form and 120–240 mg in extended-release form.
Teens misuse pseudoephedrine for its stimulant properties, hoping to boost athletic and academic performance while suppressing appetite and sleep. Toxic effects include hypertension, tachycardia, dizziness, seizures, and psychotic symptoms (Gunn VL et al, Pediatrics 2001;108(3):e52). Withdrawal symptoms include dysphoria, restlessness, and abnormal perception (Schifano F et al, Front Psychiatry 2021;12:657397).
Pseudoephedrine interacts with monoamine oxidase inhibitors (MAOIs) such as selegiline and can induce a hypertensive crisis. Counsel your patients on MAOIs about the risks of hypertensive crisis and the interaction between MAOIs and pseudoephedrine.
Federal law limits daily sales of pseudoephedrine to 3.5 g and monthly sales to 9 g per person. Iowa, Mississippi, and Oregon have age restrictions for purchasing pseudoephedrine.
Kratom is an herbal extract from Mitragyna speciosa and acts on opioid receptors. It is sold as a tea, capsule, or powder in vape shops or via the internet. Sales of kratom exceeded $1.13 billion in 2016. Most toxic exposures to kratom in 2011–2017 were among adolescents (Eldridge W, J Pediatr Pediatr Med 2019;3(1):1–5; Sharma V et al, J Adolesc Health 2021;70(4):677–681).
Kratom causes stimulant effects at low doses and euphoria at higher ones. Toxicity causes tachycardia, hypertension, altered mental status, abdominal pain, and seizures. Regular use can create dependence and withdrawal symptoms similar to opioids (anxiety, gastrointestinal symptoms, headache, runny nose, watery eyes, and sweating). Withdrawal can be treated in the same way as opioid withdrawal.
Kratom is illegal in Alabama, Arkansas, and Indiana as well as some cities, such as San Diego and Sarasota. Most states do not regulate it. Advocacy groups and policymakers have stymied efforts to regulate kratom, arguing that it may be beneficial for managing pain and reducing opioid addiction.
Tianeptine is a tricyclic antidepressant that binds to opioid receptors. It is prescribed outside of the US but sold as a supplement in the US without restrictions. It produces euphoria and is energizing but has rapid withdrawal symptoms similar to opioids.
Tianeptine is banned in Alabama, Georgia, Indiana, Michigan, Minnesota, and Tennessee.
Talking with teens and parents
Here are some recommendations for discussing substance use with patients and families:
Since there is little research on treating misuse of legal substances, we recommend general approaches like motivational interviewing and cognitive behavioral therapy (www.tinyurl.com/yc3ekdb4).
Ask about use of legal substances. Intoxication with any of these can lead to dangerous side effects requiring scute management. Counsel teens about the dangers of using legal substances. While the evidence base is sparse, psycho-therapy and behavioral approaches can be useful in treatment.
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