The medicinal benefits of natural cannabinoids like tetrahydrocannabinol (THC) and cannabidiol (CBD) are widely known, but so are the dangers of synthetic cannabinoids (SCs). SCs are not natural. They are created using chemistry and have been linked to very serious and potentially fatal side effects. Despite the many health risks involved with consuming SCs, they are one of the fastest-growing groups of psychoactive substances available today.
Fortunately, researchers are working on this growing problem. After seeing success with immunopharmacotherapeutics against powerful drugs like opioids, cocaine, and methamphetamine, a new study [1] analyzed the effectiveness of creating vaccines that broadly neutralize SCs. The goal was to test the designs of 10 different haptens for creating antibodies that could be used for two classes of SCs. Haptens are molecules that stimulate antibody production when linked to a carrier molecule.
SCs are structured “into four regions: core, linker, head, and tail. The most popular SCs are continuously composed of (1) an indole or indazole core; (2) a flanking carbonyl, amide, or ester linker; (3) a relatively conserved tail group largely limited to pentyl, fluoropentyl, benzyl, and cyclohexyl methyl; and (4) a more variable head moiety typically consisting of derivatives of naphthyl and valine.”
The haptens for this study were designed by adjusting their locations at one of the four regions, primarily the head and tail positions, while also giving attention to the importance of the linker position, as this determines how immune cells approach the hapten.
Study models of vaccines against SCs traditionally use a drug administration route of injection, but researchers also included vaping as a route of drug administration to create more realistic models, mimicking how SCs are most commonly consumed. The experiment used animal models, where locomotion, body temperature, and pharmacokinetics were measured to determine how successful each hapten was in sequestering SCs.
There were twenty-two targeted SC molecules used in formulating the experimental vaccines, each of which was “proportionately distributed among three classes: indole carbonyl (Class I), indazole amide (Class II), and indole ester (Class III).” Half of the SCs were included in the first two classes as indole naphthyl and indazole valine derivatives, making these the “primary vaccine targets”. [1]
After identifying these targets, haptens and combinations of haptens called admixture vaccines, were tested with variations in the core, linker, head, and tail positions. These variations and combinations were tested for efficacy in broadly neutralizing SCs. In doing so, researchers successfully discovered three haptens showing potential in broadly neutralizing SCs within the two main drug classes studied. They also noted an admixture vaccine that broadened the targeting spectrum of the vaccine to more than 10 SC drugs. [1]
Having vaccines that broadly neutralize SCs is important because SCs are usually consumed as a mixture of many drug compounds, which is one attribute that makes them so dangerous, and another great reason research like this is being conducted.
References:
- Lin M, et al. Broadly neutralizing synthetic cannabinoid vaccines. JACS Au. 2021;1(1):31-40. Impact Factor: 12.350; Times Cited 0.
