Synthetic cannabinoid Receptor Agonists

Synthetic cannabinoid Receptor Agonists are also known as spice. These are a collection of herbs or plant material which has been sprayed with synthetic cannabinoid receptor agonists, often referred to as synthetic cannabinoids, producing a cannabis-like effect when smoked. Today there are more than one type of cannabinoids that have been identified but they are all active as they mimic the psychoactive effects of THC (tetrahydrocannabinol), the active principle in cannabis. Most compounds come from the JWH chemical family, such as JWH-018.

For emphasis it is good to repeat that these synthetic cannabinoids are functionally similar to tetrahydrocannabinol often shortened as THC. THC is the most active principle of cannabis. Like THC, they bind to the same cannabinoid receptors in the brain and other organs as the endogenous ligand anandamide. More correctly designated as cannabinoid receptor agonists, they were initially developed over the past forty years as therapeutic agents, often for the treatment of pain. However, it proved difficult to separate the desired properties from unwanted psychoactive effects.

In the past years especially in the late 2008, several cannabinoids were detected in herbal smoking mixtures and incense as well as room odorisers. Typical of these were Spice Gold, Spice Silver and Yucatan Fire, but many other products later appeared. They do not contain tobacco or cannabis but when smoked, produce effects similar to those of cannabis. These products are typically sold via the Internet and in ‘head shops’. The spices are therefore as dangerous as cannabis and so should be avoided.

The fact that these spices are referred to as synthetic cannabinoids does not mean that they are similar to the real cannabinoids in all aspects in fact most of these synthetic cannabinoids are not related to the real cannabinoids in structure and hence though they can mimic the activities of the cannabinoids but they may work in a way that will cause more harm. The cannabinoid receptor agonists form a diverse group, but most are lipid soluble and non-polar, and consist of 22 to 26 carbon atoms. This therefore means that they would therefore volatilize readily when smoked. A common structural feature is a side-chain, where optimal activity requires more than four and up to nine saturated carbon atoms. The synthetic cannabinoids can be classified into seven major structural groups. These groups are;

• Naphthoylindoles (e.g. JWH-018, JWH-073 and JWH-398).
• Phenylacetylindoles (i.e. benzoylindoles, e.g. JWH-250).
• Cyclohexylphenols (e.g. CP 47,497 and homologues of CP 47,497).
• Classical cannabinoids (e.g. HU-210).

Other cannabinoid receptor agonists include substances such as oleamide. Oleamide is an endogenous substance that is also used in plastics manufacture. Another one is methanandamide. Oleamide and methanandamide are both related to anandamide in structure. Despite the similarities in structure with the anandamide the activities of these two synthetic cannabinoids have been questioned. It is thought that neither methanandamide nor other arachidonyl derivatives related to anandamide would be sufficiently volatile to be smoked. Certain fluorosulfonates exhibit agonist activity at cannabinoid receptors, as does naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone, but the latter appears not to be psychoactive, at least when administered orally.

Physical state

Most of these synthetic cannabinoids are either solids or oils as they exist in pure state. Smoking mixtures are usually sold in metal-foil sachets, typically containing 3 g of dried vegetable matter to which one or more of the cannabinoids have been added. Typically, a solution of the cannabinoids has been sprayed onto the herbal mixture to give it the drug effect. Just like any other business oriented producer you will find a number of plants listed on the packaging but the plants mentioned on the packaging may not even be present. This is utmost dangerous as you may be using these spices thinking you are safe based on the ingredients wrote on the packaging while in real sense you are using substances you do not even know. These spices are often sold while containing high amounts of Vitamin E which is purported to be used in masking the analysis of the most active cannabinoids. The producers of these spices will put more cannabinoids in the samples to confound the forensic chemical detection.

The cannabinoid receptor agonists mimic the effects of THC and anandamide by interacting with the CB1 receptor in the brain. Several research studies have shown that some synthetic compounds bind more strongly to this receptor than THC as measured by the affinity constant Ki. All of the cannabinoids found in smoking mixtures have, like THC (Ki = 10.2nM), high affinity to the CB1receptor although small variations in Ki values occur between different publications. The substance HU-210 has a particularly low value of Ki (0.06nM), and it binds over 100 times more tightly to the CB1 receptor than THC.

However, little is known about the detailed pharmacology and toxicology of the synthetic cannabinoids and few formal human studies have been published. It is possible that, apart from high potency, some cannabinoids could have particularly long half-lives potentially leading to a prolonged psychoactive effect. In addition, there could be considerable inter-and intra-batch variability in smoking mixtures, both in terms of substances present and their quantity. Thus, there is a higher potential for overdose than with cannabis.

Finally, Dr. Dalal Akoury (MD) is an experienced doctor who has been in the frontline fighting drug addiction. He runs a website that equips readers of better ways to overcome not only drug addiction but also serious health problems that have caused nightmares to the world population. Get in touch with her today and learn more.

Synthetic cannabinoid Receptor Agonists

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