Conference Coverage

Synthetic drugs pose regulatory, diagnostic challenges



– Designer drugs, especially synthetic opioids and cannabinoids, are presenting increasing challenges to psychiatrists treating patients with overdoses or psychiatric adverse effects. In 2017, synthetic opioids caused more than 28,000 deaths in the United States, more than any other type. Some of these drugs are technically legal, because their modified chemical structures aren’t covered as legal definitions struggle to keep up with street drug identities.

From left: Brenna Rosenberg Emery, MD; Vanessa Torres-Llenza, MD; and Gowri Ramachandran, MD, participated in the general session at the APA on the growing problem of synthetic drugs. Jim Kling/MDedge News

From left: Brenna Rosenberg Emery, MD; Vanessa Torres-Llenza, MD; and Gowri Ramachandran, MD, participated in the general session at the APA on the growing problem of synthetic drugs.

“As psychiatrists, we should be looking at these newer drugs and how they may present in patients, especially in the young population ... people are using drugs and they don’t even know what they’re using,” Vanessa Torres-Llenza, MD, assistant professor of psychiatry at George Washington University, Washington, said in an interview. Dr. Torres-Llenza moderated a session on synthetic opioids at the annual meeting of the American Psychiatric Association.

Of particular concern is the synthetic opioid fentanyl, which has a potency about 50 times that of heroin, and 100 times that of morphine. It is a legal pharmaceutical drug for use in severe pain, but it can be made illicitly, and it is frequently mixed with heroin or cocaine and put into counterfeit pills. The user often is not even aware of its presence. Another derivative, carfentanil, is even more dangerous. Used as a large-animal tranquilizer, and illegal for human use, carfentanil is about 100 times more potent than fentanyl.

These developments may require reconsideration of treatment using the opioid antagonist naloxone and similar drugs. The current guidance for naloxone is a 0.4- to 2-mg dose, followed by repeat dose at 2- to 3-minute intervals as needed. Considering the increasing presence of more potent drugs, “there may not be time to wait,” Dr. Torres-Llenza said.

Another concern is illicit manufacturing: By making even slight modifications to legal drugs, illegal operations can stay a step ahead of regulators because these derivatives are completely legal until legislation is passed to ban them. Estimates peg the number of such new derivatives at about 250 per year.

The recent history of the Food Drug Administration’s regulation of synthetic opioids, presented during the session by Gowri Ramachandran, MD, a resident at George Washington University, illustrates the challenges. The Controlled Substances Act of 1970 assigned every regulated drug into one of five classes based on medical use, and potential for abuse and dependence. Schedule I substances are flagged for a high potential of abuse, having no medical use in the United States, and a lack of accepted safety data for use under medical supervision. Schedule II substances have accepted medical uses.

In 2012, the Synthetic Drug Abuse Prevention Act amended the earlier legislation, declaring that any chemical or related derivative with cannabimimetic properties, as well as some other hallucinogenic molecules and their close relatives, were included as schedule I controlled substances.

The amended legislation also extended the potential length of temporary schedule I status, from 1 year with a 6-month extension, to 2 years with a 1-year extension, to give regulators more time to catch up with both legal and illegal synthetic changes to determine if a drug should be schedule I or II.

A recent example of this problem is bath salts, which are far more powerful, synthetic versions of a stimulant derived from the khat plant that is grown in East Africa and southern Arabia. Bath salts can produce hallucinogenic and euphoric effects similar to methamphetamine and ecstasy, but they are readily available online and in retail stores, labeled as “not for human use” and marketed as “bath salts,” “plant food,” “jewelry cleaner,” or “phone screen cleaner.”

Another concern is synthetic cannabinoids, which resemble the 100 or so cannabinoids found in marijuana, tetrahydrocannabinol (THC), and cannabidiol (CBD) being the most well-known examples. These began to appear in recreational use in 2005, representing legal forms of marijuana and sold with names like K2, Spice, and Kronic. They are sold in tobacco shops, again labeled “not for human consumption,” trumpeted instead as a “harmless incense blend” or “natural herbs.” Manufacture and content of these derivatives are completely unregulated, according to Dr. Ramachandran.

Like other drug classes, synthetic cannabinoids – many related to THC – have been structurally altered in recent years, posing challenges to regulation and even detection. This is especially concerning because a synthetic cannabinoid product could contain a potpourri of other drugs such as opioids or herbs, leading to unpredictable effects. It’s also nearly impossible to identify everything in a patient’s system, Dr. Torrez-Llenza said.

That makes diagnosis challenging given that synthetic cannabinoids can cause a wide range of symptoms, commonly violence, agitation, panic attacks, hallucinations, hyperglycemia, hyperkalemia, and tachycardia.

Synthetic cannabinoids usually do not contain CBD, which has some antipsychotic and anxiolytic effects. Instead they are generally derived from THC, which is associated with psychosis, and they are 40-660 times more potent than natural THC. This suggests that synthetic versions may pose a greater psychosis risk than natural cannabis. However, only case reports have examined the existence of an association between synthetic cannabinoids and psychosis, and it is difficult to distinguish a toxic syndrome from exacerbation of a previous prodromal syndrome, or new-onset illness.

Acute reactions can occur within minutes of use and last 2-5 hours or more. But this is all very unpredictable as it depends on the specific mixture used.

In the emergency department, agitation, aggression, and impulsive behaviors may signal exposure to synthetic cannabinoids. Most patients can be treated in the ED with antipsychotics or benzodiazepines to manage symptoms. There could be regional toxidromes that arise from local distribution of specific synthetic cannabinoid combinations.

While testing for synthetic cannabinoids remains challenging, Quest Diagnostics has a urine-based panel that includes them, and the company says it is working with information from the National Forensic Laboratory Information System, the Drug Enforcement Agency, industry sources, and the scientific literature to periodically update its standard panel.

Dr. Torres-Llenza had no relevant financial disclosures.

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