Active Ingredient in OTC Inhaler a 'New' Drug of Abuse

Fran Lowry

December 19, 2019

SAN DIEGO ― The active ingredient in an over-the-counter nasal decongestant appears to be re-emerging as a "new" drug of abuse, addiction experts warn.

Propylhexedrine (multiple brands) is indicated for relief of nasal congestion from colds, allergic rhinitis, and sinusitis. Previously considered to have low potential for abuse, new research suggests the opposite may be true.

Dr Nikhil Teja

"Propylhexedrine carries significant abuse potential and health risks, and its use may be on the rise as part of a bigger, growing problem of methamphetamine abuse," said study investigator Nikhil Teja, MD, Dartmouth Hitchcock Medical Center, Hanover, New Hampshire.

The findings were presented here at the American Academy of Addiction Psychiatry (AAAP) 30th Annual Meeting.

Amphetamine Analogue

In the United States, propylhexedrine is available as an inhaler for relief of nasal congestion due to colds, allergic rhinitis, and sinusitis under the trade name Benzedrex. In Europe, it is available in oral form and is marketed as an appetite suppressant under the trade name Obesin.

When used in doses of 100 to 300 mg, the drug can produce psychoactive effects that are similar to those of amphetamines, including stimulant-induced psychosis, which can include paranoia, hallucinations, delusions, and agitation.

In addition, it can cause a myriad of physical symptoms, such as tachycardia, hypertension, arrhythmias, pupil dilation, vasoconstriction, and others.

Historically, propylhexedrine has been viewed as a nonaddictive, nonabusable substance that had a good safety profile, Teja told Medscape Medical News.

"It was developed in the 1940s in response to abuse and deaths from amphetamines extracted from inhalers. It is not a scheduled substance, yet it is a structural analogue of amphetamine and has similar properties," Teja said.

Recently, two patients presented at Dartmouth-Hitchcock Medical Center with propylhexedrine toxicity, prompting the investigators to take a closer look at this readily available substance.

Dr Cornel Stanciu

These two patients, said study coinvestigator Cornel Stanciu, MD, were young individuals who resorted to propylhexedrine as a way of achieving a stimulant high while avoiding a positive result on a drug screen.

"One patient was under legal monitoring by his probation officer, and the other was enrolled in a Suboxone [buprenorphine and naloxone] clinic where he could not test positive," said Stanciu.

A Growing Threat

To gain a better understanding of the extent of propylhexedrine abuse, Teja and Stanciu conducted a literature review. They searched databases for studies published in English between 1970 and 2019 and supplemented their review with data from online user forums. They found 28 case reports that cited propylhexedrine toxicity.

The first case of propylhexedrine abuse that was reported occurred in 1970 in New Zealand and involved acute psychosis. Numerous case reports emerged in the US literature in the 1970s and 1980s. In 2011, there was a death that involved propylhexedrine in combination with mitragynine, the active ingredient in kratom, Teja said.

Nasal decongestant inhalers are the most common source of propylhexedrine.

Users crack open the encasing to obtain propylhexedrine by use of a cotton swab. The cotton swab can then be cut into pieces and ingested. It can also be placed in an acidic liquid, such as soda or lemon juice, for an extended period to extract the drug.

This extract is then injected, smoked, or insufflated. The most dangerous delivery method is intravenous injection, Teja noted.

"Anyone can go and buy a relatively small amount, crack the inhaler open, and inside there's about 250 mg of propylhexedrine, which is enough to induce psychoactive effects," he said.

"It's readily available; it's extremely cheap, $4 or $5 at your local pharmacy. I think that with the Internet and YouTube, there's been a resurgence in the knowledge base on how to abuse this substance," Teja added.

Teja and Stanciu believe propylhexedrine should be deemed a controlled substance and should be regulated.

"We want increased awareness among the physician community. This substance has huge potential for abuse and is readily available. There are extensive user forums discussing its abuse potential, yet the darker side of this seemingly innocuous substance is rarely covered in medical education.

"We feel the gravity of the complications with propylhexedrine abuse warrants consideration of regulating this drug, and policy makers should be aware of the threat it poses," Teja said.

Commenting on the findings for Medscape Medical News, Anil Thomas, MD, Icahn School of Medicine at Mount Sinai, New York City, said he had not heard of propylhexedrine abuse before this study was presented.

This research, said Thomas, highlights the need for physicians to ask patients who potentially have problems with substances about propylhexedrine abuse, and physicians should be aware that any potential physical or mental symptoms may be due to propylhexedrine toxicity.

Also commenting, Jonathan Lee, MD, Farley Center, Williamsburg, Virginia, said he had not encountered any patients who had used it, "but I agree that physicians need to be aware of its abuse potential."

Teja, Stanciu, Thomas, and Lee report no relevant financial relationships.

American Academy of Addiction Psychiatry (AAAP) 30th Annual Meeting: Abstract 5. Presented December 8, 2019.

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