Designer drugs, which are sold openly and legally, are often marketed as "not for consumption" or "for research purposes only."KELLEY MCCALL/AP

O

ne of Max’s friends taught him an easy way to buy shady drugs. What he learned almost killed him, and it opened my eyes to a hiding-in-plain-sight source of dangerous drugs that is amplifying the opioid epidemic.

When Max (not his real name) developed pancreatitis a decade ago, his physicians prescribed opioids to ease his extreme pain. When he experienced anxiety between episodes of pancreatitis, his physicians prescribed a benzodiazepine.

Benzodiazepines are used to treat anxiety and insomnia, symptoms they can effectively resolve, at least in the short term. Textbooks euphemistically call these drugs anxiolytics and hypnotics. An estimated 1 in 20 Americans use them each year. When taken long term, benzodiazepines can cause physical dependence. Their sudden discontinuation can be lethal.

The combination of opioids and benzodiazepines is common — the CDC estimates that between 12 percent and 19 percent of patients who are prescribed an opioid are also prescribed a benzodiazepine. It is also dangerous, since both drugs increase the risk of slowing or stopping breathing. In fact, benzodiazepines are involved in 31 percent of overdose deaths attributed to prescription drugs.

As Max’s body became accustomed to the effects of the opioid-benzodiazepine combination, his doctors increased the doses of these drugs. When they eventually refused to further boost their doses, Max bought the drugs from dealers. Then a friend introduced him to Domestic RCs (DRC), an online company selling compounds that have never been approved for human use but that are so similar to existing drugs they attract users like Max seeking an alternative to doctors and dealers. (A pre-admission disclaimer on the company’s website says that all products it sells “are for the purposes of research only.”)

For the six months before I met Max, he bought drugs from DRC. Doing so required no waiting room, no insurance card, no physical exam, and no doctor. Buying these drugs required no dim alley, no scuffed bills, no threatening transaction with a dealer. Max simply shopped online for designer benzodiazepines. He could choose liquids, pills, powders, and pellets of substances with names that sounded like real drugs — clonazolam, diclazepam, etizolam, and flubromazolam — but weren’t.

He usually picked clonazolam. The name is a mashup of two FDA-approved benzodiazepines — clonazepam and alprazolam — that his physicians had prescribed for him.

At the DRC checkout, Max paid with a credit card or Bitcoin. Days later, a package of clonazolam arrived at his home, labeled “not for human consumption” and “research chemical.”

Experts use the term “new psychoactive substances” for clonazolam and other compounds sold by DRC and related companies. Some of these chemicals are close cousins of FDA-approved drugs, or active metabolites of them. Some were synthesized decades ago but never rigorously studied. None have been approved for human use. What makes them new is that, in our knowledge economy, they can be compounded, marketed, and delivered to people who want them.

DRC and companies like it sideline the doctor, the pharmaceutical industry, and its regulators from the patient-physician relationship.

Over the last few years, the use of new psychoactive substances has increased dramatically. They may represent the future of medicine: the patient-chemical relationship.

That worries me. When I form a clinical relationship with a patient, I have ethical responsibilities to know which medications he or she is taking. A prudent physician reviews these medications at every encounter and considers their effectiveness, possible interactions with other drugs, and possible adverse side effects. If I want to understand more about a medication, I can read reference materials about it. If I want to know if a patient is comprehensively reporting the medications he or she is taking, my state of Colorado, like most states, has an online registry in which I can review the prescription medications with high abuse potential — like benzodiazepines — that are being dispensed to patients.

When Max was hospitalized on our service with recurrent depression last month, we asked him about the substances, prescribed and otherwise, he was taking. He told us about the three psychoactive medications he took each day, all prescribed by his doctors. We confirmed these medications in the electronic health records maintained by his outpatient physicians and in our state’s online registry. They included the combination of buprenorphine and naloxone (Suboxone), which is commonly prescribed to chronic pain patients like Max who have become dependent on opioids, and also the benzodiazepine clonazepam. Max was physiologically dependent upon these medications.

Recognizing that he was at risk for withdrawal, we prescribed all three at the same doses he had been taking at home while we began treating his depression.

Despite our efforts at prudent prescribing, Max’s health began to decline. By the fifth day of his hospitalization, his thinking had become muddled, his memory faltered, and his attention fluctuated. He slid into delirium, a disturbance of consciousness with multiple causes.

To treat delirium, you need to identify its cause. We interviewed Max, examined him, and ordered the relevant lab and imaging studies. Our efforts revealed no apparent cause for his delirium.

As Max continued to decline, our fear increased. About 1 out of every 3 patients who develops delirium will die in the following year.

Our team made an educated guess that Max was experiencing benzodiazepine withdrawal delirium and decided to treat him for it. To the verified dose of his clonazepam, we added another benzodiazepine commonly used for detoxification. By the next morning, Max was thinking clearly enough to speak for himself. He expressed surprise at his delirium and ignorance at its cause, but later admitted that he had been taking clonazolam, which he told us he had ordered from DRC, in addition to the clonazepam his doctor had prescribed.

After taking clonazolam, “I felt like I was totally free from my anxiety,” Max told me, “but I was probably just high. The anxiety always came back afterwards.”

Clonazolam is not recorded in online registries for controlled substances. It is not detected in the routine lab studies that look for substance use. It barely appears in the medical literature that physicians rely upon for information. When clonazolam does appear in the literature, the limited nature of our knowledge about it is embodied in phrases about its “proposed elemental composition” and “postulated chemical structure.” After Max told me about clonazolam, I learned more from Reddit’s research chemicals forum than from any textbook or medical journal.

The opioid epidemic has taught us that doctors and dealers are both capable of dispensing lethal drugs. Max taught me that companies like DRC are a dark partner in the addiction epidemic, delivering dangerous drugs directly to my patients’ homes.

Max told me that he will never again order drugs from DRC or similar companies, saying, “I see where it got me.” Today, he is gradually being weaned off benzodiazepines in an outpatient substance treatment program.

DRC, however, is still open online. The company claims that it screens for fraud. Yet I recently created an account, listed 1600 Pennsylvania Ave. as my address, and filled an online shopping cart with $50,000 of clonazolam, the drug that nearly killed Max, without triggering any fraud warnings.

As we fight the opioid epidemic, physicians and patient advocates must sound their own warnings about it. But it is also time for the actual occupants of 1600 Pennsylvania Ave. to shine a light on the online retailers selling designer benzodiazepines.

Abraham M. Nussbaum, M.D., is the chief education officer at Denver Health, an associate professor of psychiatry at the University of Colorado School of Medicine, and the author of a memoir, “The Finest Traditions of My Calling: One Physician’s Search for the Renewal of Medicine” (Yale University Press, 2016).