Depending on where you live, scoring actual marijuana can be difficult and risky. But you can get synthetic cannabinoids at your local gas station. You see them packed into small foil pouches, touting a legal reproduction of a natural high. Local and federal municipalities have taken lengths to remove many from sale, but more continue to pop up.


Why have some of these substances been deemed illegal? Are they as safe as marijuana? Also, is there an ingredient missing from these packages that would normally be a very active constituent of marijuana? Find out the truth about synthetic cannabis below.

Top image: Kronic, a synthetic pot substitute, via News.com.au.

The origin of retail synthetic cannabinoids

Modern retail synthetic cannabinoids originated in Europe sometime around 2004, They were initially a product of the now defunct UK company Psyche Deli, a company that dabbled in the legal sale of Psilocybe cubensis mushrooms for recreational use in the years prior. The Spice "generabrand" and the number of lookalikes it spawned were cheap and convenient substitutes for marijuana - they cost about 30 to 35 US per 3 gram pack, enough for several uses, and could even be bought at a gas stations and convenience stores in some countries.




One researcher's inadvertent contribution

John W. Huffman, a research professor at Clemson University, is forever tied to synthetic cannabinoids, due to his academic research and through the use of compounds he synthesized that are now available for retail sale. Huffman inadvertently lent his initials, JWH, to one of the most common synthetic cannabinoids distributed for sale. Per typical organic chemistry nomenclature, when you synthesize a new molecule, you tab it with your initials and the reaction number, so JWH-018 was likely the 18th reaction Huffman set up on this endeavor.

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Huffman's academic research centered on synthesizing small molecules that could be applied as new pharmaceutical analgesics, particularly molecules that bind to the cannabinoid brain (CB1) and peripheral (CB2) receptors, receptors found in the brain and spleen. It is thought that binding the CB1 receptor in the human body simulates the calming effect of cannabis.

With the rise in synthetic cannabinoid blends made available for retail sale, Huffman has turned an eye toward examining these blends, in particularly the presence of compounds he synthesized within the blends. Huffman's research has shown that JWH-018 binds the receptor CB1 four times tighter than THC and binds CB2 ten times tighter, with this increased binding affinity hypothesized to lead to substance dependence amongst blends that is not observed in marijuana use. Analogues of JWH-018 (and thus, THC) are continually being created, with many on par with the binding of THC, but few exceeding the binding affinity of JWH-018.


Batch to batch variations

Analysis of several synthetic cannabinoid blends has shown a concentration variation of cannabinoids within the same batch of a particularly product, and, in many cases, a lack of stated ingredients. The packets are essentially vegetable fibers sprayed with one or a mixture of synthetic cannabinoids, with the amount of synthetic active ingredient varying from foil package to foil package. These blends are not regulated, and are essentially homemade in a small manufacturing plant with little or no quality control.


A large amount of tocopherol (a Vitamin E analogue) has also been detected in packages of cannabinoid blends. Tocopherol thought to be added in order to hamper drug testing, however, tocopherol is a blood thinner, and would only hamper blood-based drug tests (which are rarely used). JWH-018 and several analogues of the molecule used in cannabinoid blends were recently made schedule one controlled substances in the United States, placing their illegality on par with heroin and LSD. Analogues of these molecules, due to their commercial appeal, will continue to be synthesized, making legality a moving target for synthetic cannabinoids. Image: Diane Machen, a criminalist with the Washoe County Sheriff's Office, holds samples of synthetic cannabinoids that she is helping to outlaw in Carson City, NV. Photo by Cathleen Allison/AP.


What's in marijuana that might be missing in synthetic cannabis?

Marijuana, when smoked, contains a large number of active ingredients, with this being one of the reasons marijuana, as a plant, has never been approved for medical use by the FDA. FDA requirements call for a single, reproducible formulation, a situation that will not happen with a plant. The concentration of ingredients literally changes from leaf to leaf, with the main active constituent being THC, however, other molecules play a role.


One molecule that plays a role in marijuana that is absent from these blends is cannabidiol, a sedative and anti-anxiety agent. Synthetic blends are giving you part of the main ingredients, but not the whole set, and that could greatly influence how some behave after using them.

Cognitive dissonance


Synthetic cannabinoids aim to take a natural plant product and produce a derivative of one of the constituent ingredients, in order to commercialize (and, at times, legalize) a substance that yields a similar effect. Image via AP.

Huffman, when asked about the unintended uses of his research, said:

We had no idea that anyone would be stupid enough to use it […] If you want to get high, marijuana is easily available.


Huffman has been besieged with e-mail and phone calls in the past couple of yearsfrom individuals that tried to synthesize JWH-018 with terrible results. One thing people often forget is that organic molecules go through several purification steps , steps which decrease the mass, but purify the desired molecule if the steps are performed properly. It might be legal, but do you want to be a guinea pig for untested synthetic analogues a guy made in his basement?