By Roger Chriss, PNN Columnist

Drug decriminalization and legalization have become hot topics in the U.S. and around the world. Some states have legalized recreational cannabis and a handful of cities have decriminalized psilocybin, a hallucinogen found in some mushrooms. Countries like Portugal have decriminalized all drugs.

The arguments in favor of legalization seem reasonable, from harm reduction and de-stigmatization to access to a well-regulated supply of substances that people are going to use regardless of whether they are legal or not.

But rarely are questions asked about the drugs that haven’t been invented yet. Debate about legalization usually centers on popular but controversial substances like cannabis, with no mention of novel fentanyl analogs or other new psychoactive substances.

Novel opioids appear on the dark web regularly. For instance, the potent synthetic opiod isotonitazene is now being sold online, even though a team of international researchers said it “represents an imminent danger.”

Public health officials in the U.S. also recently warned about isotonitazene in the journal NPS Discovery, after the drug was identified in blood samples from eight overdoses deaths in Illinois and Indiana.

“Pharmacological data suggest that this group of synthetic opioids have potency similar to or greater than fentanyl based on their structural modifications,” they warned. “The toxicity of isotonitazene has not been extensively studied but recent association with drug user death leads professionals to believe this new synthetic opioid retains the potential to cause widespread harm and is of public health concern.”

Similarly, there are reports on overdoses with cyclopropylfentanyl, a chemical cousin of fentanyl that first appeared in Europe in 2017.

“The constantly growing diversity of NSO (new synthetic opioids) still poses a high risk for drug users and can be a challenging task for clinicians and forensic toxicologists. Clinicians treating opioid overdoses should be aware of the potentially long lasting respiratory depression induced by fentanyl analogs,” German researchers said.

Novel Substances

This problem is not limited to illicitly manufactured fentanyls and other opioids. Novel synthetic cannabinoids also pose risks. Such compounds include JWH-018 and AKB48, both known to be dangerous.

And the world of hallucinogens, amphetamines and other psychoactive substances is evolving, too. Psilocybin can now be harvested from bacteria and over 150 synthetic cathiones-- amphetamine-like psychostimulants -- have been identified in clandestine drug markets.

“Over the past hundred years or so, humankind has learned to synthesize the active chemicals in laboratories and to manipulate chemical structures to invent new drugs—the numbers of which began growing exponentially in the 2010s,” Ben Westoff notes in Fentanyl, Inc.

Further, drug consumption technology is changing rapidly. Just as the hypodermic syringe forever changed the risks of heroin, vaping devices are having similar effects. They allow for high-intensity consumption of nicotine, THC, and other drugs that contain unknown contaminants, as seems to have happened with vitamin E acetate in the recent outbreak of lung illnesses associated with vaping.

Lastly, there are risky interactions that can occur with the use of novel substances. The American Council of Science and Health points to the particularly important issue of drug-drug interactions. The world of street drugs now involves so many adulterants and contaminants that, when combined with novel substances, drug-drug interactions are potentially more dangerous than ever.

Historically, legalization of drugs has not led to a net public health benefit. And that was when “drugs” consisted of plant matter or distilled liquids. Modern technology means we can do much better, which in turn means we may be facing far worse.

The greatest risks arguably come from the drugs that have yet to be invented and the interactions that have not been discovered. Any discussion of full drug legalization needs to consider such possibilities.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.