Cannabeginners: What Are Synthetic Cannabinoids?

Some are legal, some are dangerous—learn the difference.

Synthetic cannabinoids – they’re known by many names around the world, spice and K2 are the most common, but in Japan the street name is “dappou herb.” Simply put, these are man made chemicals that interact with the body’s endocannabinoid system in a similar way to phytocannabinoids or endocannabinoids. Unfortunately, in many ways they are cannabinoids in name only and the effects are often unpredictable and can even be deadly. 

What Are Synthetic Cannabinoids?

Synthetic cannabinoids generally act as agonists (causing an interaction) with the CB1 receptor rather than antagonists (blocking an interaction). According to the National Institute on Drug Abuse (NIDA) , “synthetic cannabinoids are sometimes misleadingly called synthetic marijuana [and] marketed as safe, legal alternatives to that drug,” but the more accurate way to refer to them is new psychoactive substances (NPS). “NPS are unregulated mind-altering substances that … are intended to produce the same effects as illegal drugs,” but NIDA says they do not actually produce the same effects, and “may affect the brain much more powerfully.” The Centers for Disease Control and Prevention (CDC) adds that “Synthetic cannabinoid products can be toxic. As a result, people who smoke these products can react with rapid heart rate, vomiting, agitation, confusion, and hallucinations.”


The History of Synthetic Cannabinoids

The earliest synthetic cannabinoid developed was Nabilone, a synthetic version of THC, back in the 1970s by Lilly Research. The 1980s brought a boom in research on these chemicals with the creation of CP 47,497 by Pfizer, followed soon by Marinol in 1985, HU-210 in 1988 (created by Professor Raphael Mechoulam), and the JWH series in 1995 (created by Professor John W. Huffman). 

It took about another decade for herbs sprayed with synthetic cannabinoids sold as spice to hit the market in Europe in 2004 and then in the United States four years later being marketed as “incense” to avoid regulation. The packaging never disclosed what synthetic cannabinoids were used or the amount used, which contributed to the unpredictable effects noted by the CDC and NIDA. Though the DEA used emergency powers in 2010 to try and control these new drugs, followed by a federal law in 2012, chemists just tweaked the molecules into new synthetic cannabinoids to evade the law and the DEA, which has continued to the present. With every new generation of synthetic cannabinoids that was released, the effects became more unpredictable as they were less well researched.

Common Synthetic Cannabinoids

While CP 47,497 was one of the pioneering synthetic cannabinoids, it has not seen widespread use in spice, instead the main ones being used are HU-210, the JWH series (generally JWH-018), and a relatively newer one 5F-ADB. 

HU-210 was named after Hebrew University, where Professor Raphael Mechoulam conducted his research before he passed. The DEA notes that while there are legal research uses for HU-210, it “is in schedule I of the U.S. Controlled Substances Act,” because of its illegal use in spice production. Compared to some other synthetic cannabinoids, the negative impacts of HU-210 appear to be relatively benign. A 2007 study found that it could cause “spatial memory deficits” but “had no effect on working or short-term memory.” One of the more shocking findings about HU-210 came from a 2014 study, which observed a “long duration of action and apparent slow rate of dissociation from cannabinoid receptors” which could result in a “pseudo-irreversible” interaction with the endocannabinoid receptors. Thankfully, a recent study has shown that HU-210 does not “significantly impact adult anxious- or depressive-like behaviors.”

Out of the JWH series of molecules, according to the United Nations Office on Drug and Crime, JWH-018 is “arguably the most widely known synthetic cannabinoid” and “considered to be three times as potent as THC.” That potency has made JWH-018 a Schedule I drug and popular for use in spice, despite some major health risks. A 2011 study found that “Ingestion of JWH-018 can produce seizures and tachyarrhythmias,” which could be what contributed to the death of a college athlete that same year.

The synthetic cannabinoid 5F-ADB is also commonly known as 5F-MDMB-PINACA, and no matter what it is called, it is a Schedule I drug in the United States. This may be the deadliest synthetic cannabinoid that has been identified by researchers, it was actually first discovered from an autopsy in Japan, one of nearly a dozen deaths there. In addition to those deaths in Japan, there have been another two dozen in Germany and the United Kingdom caused by “confirmed exposure to 5F-MDMB-PINACA.” Beyond deaths, 5F-ADB has also been shown to cause “confusion (possibly even psychosis), collapse, loss of consciousness, unsafe driving style or changing moods.”

Marinol / Shutterstock

Unlike JWH, 5F-ADB, and HU-210/211, Marinol (Dronabinol) and Nabilone (Cesamet) are synthetic versions of a naturally occurring cannabinoid – specifically, THC. Interestingly, while they are both synthetic versions of the same molecule, Nabilone is a Schedule II drug whereas Marinol is just Schedule III. These drugs are nothing like what GW Pharmaceuticals did with Epidiolex, which is actually derived from cannabis plants and contains real phytocannabinoids, rather than synthetics.

1 comment

    Nabilone was NOT the first synthetic cannabinoid developed, in fact Dr Roger Adams (the discoverer of cannabidiol) synthesized a whole variety of THC derivatives in the 1940s and proved their THC mimicking cannabinoid activity by administering them to dogs.
    Among these was a compound now called Hexahydrocannabinol (HHC), one of ‘hemp derived’ apparently federally legal compounds now being sold in disposable vapes in the USA (U.S.Patent 2419937(A) 1947-05-06).

    Roger Adams also synthesized what is now known as DMHP (Dimethylheptylpyran) which is from memory ~200 times the potency of THC (Adams R, Harfenist M, Loewe S (1949). “New Analogs of Tetrahydrocannabinol. XIX”. Journal of the American Chemical Society. 71 (5): 1624–1628.).
    He was the first researcher to synthesize and test (in dogs) THC analogs with modified hydrocarbon chains at position 3 of the THC molecule – discovering that lengthening the chain increases potency up to a point and that replacing THC’s five carbon chain (pentyl) with a branched 1,2-dimethylheptyl group achieves the greatest potency molecule.

    Marinol (generic Dronabinol) is NOT a synthetic version of naturally occurring THC, but is absolutely identical to the main isomer of THC naturally found in the Cannabis plant i.e. (−)-trans-Δ9-tetrahydrocannabinol. It is synthesized in a laboratory for pharmaceutical use by a number of companies, but could also actually just be extracted from the cannabis plant – the two reasons that this is not being done are (1)separating it from all the other cannabinoids in cannabis (including other THC isomers) is very laborious, thus not being ‘commercially viable’, and (2)apparently the DEA would then consider it a federally illegal cannabis derivative!?

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