This week in New Haven, Connecticut, emergency services responded to a mass of K2 (or 'synthetic marijuana') overdoses in a public park. At least 85 people are thought to have overdosed on the drug. Regrettably, this isn't the first time this has happened. This story from August 2017 highlights the dangers of K2 - and points towards a solution. - Editor

In just 3 days in early July, 102 people in Pennsylvania’s Lancaster County were treated for marijuana overdose. By the end of the week, 158 patients had been admitted to the hospital with symptoms ranging from vomiting, blackout, dangerously low blood pressure, and kidney failure. No deaths occurred, but the severity of symptoms raised alarm.

What’s going on?

Your struggle to recall a previously reported case of cannabis toxicity is justified. It doesn’t happen. In fact, the Lancaster County case doesn’t argue against the safety of marijuana, but supports its full legalization.

The 158 patients who overdosed in Lancaster County had consumed what’s known as K2, a synthetic version of cannabis that, for the time being, is legal. Synthetic cannabis (i.e., cannabinoids that are created in the lab) is gaining popularity in regions where recreational cannabis remains illegal or procuring medicinal cannabis is prohibitively challenging. The problem is that it’s extremely dangerous.

Synthetic cannabis is sold in gas stations, in smoke shops, and of course, on the internet. You can find it under a variety of brand names such as Spice, K2, and Kronic with a label reading, “not for human consumption”. But despite the warning, many still chose synthetic cannabis because it’s legal, it doesn’t turn up in a urine analysis, and it’s cheap.

The Origin of Synthetic Weed

Spice, the first of the synthetic cannabinoids to hit the streets, has innocent origins. Its inventor, Dr. John W. Huffman, was a biochemist at Clemson University studying the body’s cannabinoid system, particularly THC’s actions on CB1 receptors. He received federal grants from the National Institute of Drug Abuse to synthesize compounds that similarly activate the CB1 receptor. Over the years, these compounds have greatly improved our understanding of how CB1 receptors function.

Dr. Huffman’s numerous compounds were named with his initials (JWH) followed by a number, indicating its effect on the CB1 receptor, and not its ability to mimic cannabis’ psychotropic effects. In 1994, he published a paper titled, “Design, Synthesis and Pharmacology of cannabimimetic Indoles” which was intended to help scientists better study and understand the body’s cannabinoid system. Instead, it became a cookbook for amateur chemists.

In 2008, JWH-018 surfaced in Germany. It was the active compound in what is now known as Spice (note: Spice is now a combination of evolving synthetic cannabinoids). Serious side effects were soon reported -- and a few deaths. In a 2015 interview with The Washington Post, Dr. Huffman describes the fear he felt when he realized that someone had opened Pandora’s Box. His compounds were never intended for human use. But for chemists with a criminal mind, they were a quick way to make loads of money.    

Why Synthetic Cannabis Is Dangerous

Even though the synthetic compound acts on the same CB1 receptor as THC, there are several reasons that make it especially dangerous. Synthetic marijuana is essentially just a combination of various synthetic compounds that act similarly to THC, but not exactly like THC. For instance, synthetic cannabis has a far greater affinity for CB1 receptors, meaning that it’s more likely to bind to CB1 receptors than THC. It also acts as a full agonist at CB1 receptors, whereas THC acts only as a partial agonist. This means that actions of synthetic cannabis are substantially stronger than that of THC. In fact, synthetic cannabis compounds have been reported to be between 2 and 100 times more potent than THC. Therefore, the synthetic cannabis’ effects are for more intense than anything you could smoke from an actual plant.

Furthermore, in real cannabis, there are numerous additional cannabinoids such as cannabidiol and cannabidivarin that can counteract THC’s effects. Without these additional cannabinoids, the chemical reaction of the synthetic cannabis goes unchecked, leading to a stronger response.

Even individuals who are heavy cannabis users are at risk when using the synthetic version. There are reports that even brief use of synthetic cannabis can induce psychosis in regular cannabis users. This likely stems from the extreme potency of the synthetic compounds for the CB1 receptor coupled with the absence of additional cannabinoids.

But there’s an additional reason why synthetic cannabis is so dangerous.

Synthetic Cannabis Is Poison

Dr. Brian Thomas, an analytical chemist at the Research Triangle Institute presented data at June’s International Cannabinoid Research Society meeting in Montreal that should raise fear in any synthetic user. His research team found that smoking synthetic cannabis is poisonous. While these studies have yet to clear peer review, he suggests that combusting synthetic cannabinoids, such as K2 in the Lancaster County case, releases naphalene, the active ingredient in mothballs, and cyanide. Ingesting naphalene and cyanide could contribute to the acute effects experienced with synthetic marijuana, such as nausea and vomiting, and lead to severe long-term health risk such as liver failure and death with prolonged use.

Given all the harmful health effects associated with synthetic cannabinoids, which seem to be worse than those derived from the plant, how can synthetic cannabis be legal while the cannabis plant is not? Basically, it’s because the government can’t keep up. In the United States, the government’s policy regarding drugs and other chemicals is that they’re legal until proven otherwise (note: Different regulations apply to pharmaceuticals, or drugs that are intended for human consumption, but synthetic cannabis has the warning that it’s not intended for human use). If the chemical composition of the synthetic cannabinoid differs from that of THC, it’s technically federally legal until proven that it has THC-like effects. Once proven to have similar effects as THC by the National Institute of Drug Abuse, that synthetic cannabinoid becomes illegal. Then chemists tweak the chemical composition slightly, and… voilà, legal!

Spice today isn’t what it was a few years ago. New synthetic cannabinoids replace old ones made illegal and classified as Schedule I substances. But Spice, like the other synthetics, remains dangerous and the effects on the brain and body are largely unknown. The federal government isn’t going to win the battle over synthetic cannabis without making sweeping legal changes. Instead, by legalizing plant-derived cannabinoids, the government could undermine the synthetic cannabis market. No longer would people need to circumvent the law by using synthetic weed. No longer would cash-strapped individuals be forced to buy synthetic products to avoid the ballooning costs of black-market cannabis.

So if you’re deciding between synthetic versus real cannabis, learn from the lessons of Lancaster County, and put your health first.