The Rise of Designer Synthetic Cannabinoids, By Dr. Leonard Sowah

Addiction and Substance Abuse Cannabis environment and health illigal Drug Trade International trade in illicit drugs Mental health Synthetic Cannabinoids

Sometime in the 1990s a Harvard educated chemist funded by the National Institute of Drug Abuse worked with his colleagues to synthesize compounds that could stimulate the endocannabinoid system. John William Huffman and his colleagues were trying to find an effective cannabinoid that stimulates cannabinoid receptors better than THC (Tetrahydrocannabinol) the active euphoria creating hallucinogen in marijuana. This research it was hoped will help in understanding the effects of the cannabinoid receptors and possibly develop a drug that could treat pain, modulate appetites or cure some diseases. Huffman and his team synthesized more than 400 different compounds which were mostly given names like JWH-001, JWH-002 etc. based on order of synthesis.

The substances synthesized by Huffman and his team helped researchers better understand the mechanisms of the endocannabinoid receptors, but unfortunately no FDA approved drug was developed from this research. Huffman like all basic science researchers who create a new chemical patented his synthetic cannabinoids. Many of the chemicals created by Huffman and his team just disappeared into the ether of the numerous patents that had no commercial use. Or so they thought!

Screen Shot 2019-09-18 at 6.34.24 AM
John Huffman at his home in Sylva, N.C.

It is very unlikely that in Huffman’s wildest dreams one of his chemicals which he named JWH-018 (1-Pentyl-3-(1-naphthoyl)indole) was going to become an international sensation. After these studies Huffman went on to other things until a German blogger,  sent him a news article describing a new drug one man had smoked. It was called K2, the active compound: JWH-018

In an interview with the Washington Post Huffman was quoted as saying he was surprised at the popularity of this compound, however on much thought believed the secret to the popularity of K2 lay in the ease of synthesis from easily available compounds.

Chemical structure of cannabinoids  – Source: Adams AJ et al. N Engl J Med 2017;376:235-242

Somehow black market chemists had managed to use his patents filings to engineer his cannabinoid JWH-018 and with the assistance of labs in China were producing his compound for commercial gain as a “legal” alternative to marijuana. The chemical was being sold around the world as a supposedly “harmless” alternative to cannabis and had the advantage of not being detectable using commercially available controlled substances testing kits.

In the United States this has been sold as K-2, Spice, Fake Pot, Potpourri, Bath Salts etc and was very popular in convenience stores and gas stations as a safe legal hallucinogen. The advent of synthetic cannabinoids in the around 2008 all but evolved before the legalization of cannabis across many states in the US.

Synthetic marijuana products

The belief that K-2 and its sister synthetic hallucinogens were a safer option could however be as far from the truth as one could imagine. These compounds have been linked to numerous cases of drug overdoses which initially perplexed many physicians on account the inability to identify a causative agent using routine methods. In many overdose victims conditions similar to seizures as well as catatonic states have been seen. Several victims have sustained injuries inflicted by others on account of the significant paranoia induced by these drugs and its resulting acts of aggression against others. These synthetic cannabinoids stimulate the cannabinoid receptors at levels that could be tens to hundreds of times more potent than Cannabis and produce a dangerous easily addictive high. There have been multiple fatal overdoses and many cases of kidney failures and heart attacks from K-2 and similar compounds.

Currently JWH-018 and similar analogues are classified as Schedules I (controlled substances with no known medical use) but chemists quickly develop analogues with similar characteristics creating a game of wakamo with regulatory authorities. Current DEA law has imposed a blanket ban on all K-2 like agents but this has not stemmed the tide of illegal importation of these chemicals from labs in China and other foreign sources. US federal authorities worked collaboratively with China to achieve some form of control over this illicit market, however so far all these efforts have not put any dent on this trade. We must all learn to appreciate a few simple facts related to these chemicals

  1. These synthetic marijuana products are not as safe as some may have you believe, in most cases on account of their potency at the cannabinoids receptors  they are far more dangerous than herbal marijuana.
  2. They are not herbs at all, though they may be marketed as such, the street product is a random herbs infused with synthetic agents that act like cannabis only more potent.
  3. It is very easy to overdose on these agents leading to severe psychotic reactions, loss of consciousness, heart and kidney related issues to name just a few.
  4. Some overdoses have resulted in deaths including several still under investigation.
  5. These drugs are not easily detected by our current available drug testing screens. There are however ways to detect them using a method called chromatography.

So while the DEA and FDA continue to strive to control these agents we should all be watchful and keep our families safe from this onslaught.

Dr. Leonard Sowah is an internal medicine physician in Baltimore, Maryland

Photo Credit

John Huffman photo

Courtesy of John Fletcher, Jr./The Washington Post


A physician providing primary medical care to patients across the lifespan