Synthetic Cannabinoids are Here to Stay

Synthetic cannabinoids were designed and synthesized in the beginning as molecular probes that would provide the characterization and activities of relationships as well as to clarify the pharmacological properties along with the biological basis of the contents found in cannabis. The studies compiled the chemical structure of the plant as mainly a psychoactive compound known as Δ9-THC along with the same after synthesis. Two synthetic annabinoids formulas Marinol and Cesamet did receive licensing and was marketed for therapeutic benefits; however since the chemical brought about effects to the nervous system, abuse possibilities, and the FDA scheduling the chemical as controlled substances, the usage was quite limited. Due to this, chemical research remained in creating chemicals that offered better therapeutic possibilities while decreasing the bad side effects on the central nervous system.

Central Pfizer Pharmaceuticals during the 1980’s conducted a medicinal study and synthesized a large series of strong synthetic cannabinoids. One of these was CP 55,94o which was 100 fold stronger than Δ9-THC in creating canabinoid receptor effects when used on animals. This synthetic chemical when readiolabeled showed that it was easier to absorb high affinity binding sites which are the CB1 and CB2 receptors that was localization, signal transduction and activation that could be correlated with the effects of cannabimimetic. The earlier research by Pfizer started other studies that resulted in deviation of the molecular structures of the template of Δ9-THC. Due to this, the chemical class of the CB receptor agonists with better efficiency, high affinity, binding and aviation of the CB receptors that were discovered which produced pharmacological effects of a stronger therapeutic interest. The problem was that even the new agonists created canabimimetic activity that could not be detach the desirable clinicially effects.

The intoxicating effects as well as the liability of abuse of the CB receptor agonists were thought to be unpleasant for therapeutic purposes, therefore those with less dignified goals realized that synthetic cannabinoids based on non-THC structure could allowed to be distributed or used for recreation purposes without prosecution and penalty under laws and international scheduling.

In the early 21st century chemical compounds that were originally created from Sterling-Winthrop, Central Pfizer, and other independent researchers such as CP 47,497, WIN 48,098, JWH 018 and AM2201, were discovered in formulations of herbal designer drugs. In most cases all of these designer drugs were normally labeled incense and had directions that they were not to be used by humans, and in several cases contained often more than one synthetic cannabinoid.
Due to the fast response and use of synthetic cannabinoids, law enforcement agencies around the world started controlling the most common version and even prosecute distributors, manufacturers and users. This is normally the case with all designer drugs; however, once one is banned a new one is created to replace the chemical entities just as fast the government is banning, identifying, and detecting the older ones.

Since synthetic cannabinoids are associated with the effects often produced by phytocannabinoids, they are often assumed to be safer than other designer drugs. There is evidence that adverse effects including death has been increased with time. The adverse effects of the primary chemical found in cannabinoids as well as the uncontrolled way in which manufacturers formulate the chemical compound it can affect the purity, identity, strength and of stability, which may lead to exposure to a variety of other chemicals. When purchasing these drugs users could be exposed to several different chemicals such as thermolysis products or chemical degradants. Examples of these are AM2201 and JWH 018 and were then banned by the DEA along with other chemicals that had pentylindole as a core and linked via a ketone to a tetramethylcyclopropyl ring instead of the prototypical naphthalene ring, which was found in many new designer drugs.

When designer drugs such as XLR11, UR-144 and other analogs with tetramethylcyclopropyl ring systems if not stored correctly such as at room temperature it can cause ring opening. RTI International laboratories conducted studies along with Cayman Chemical to show that heating or combusting the chemicals will speed up the process which will lead to fast and complete conversion of UR-144 and XLR11 into their ring open forms. In addition, in vitro studies it was shown that the ring open degradants a high affinity and increases efficacy at the CB1 receptor along with a greater strength over the non-degraded forms in animals used in laboratory testing assays selective for cannabimimetics. Exposure to such strong synthetic cannabinoid chemicals as those mentioned above may create more pronounced dependence as well as withdrawal or be responsible for increase in panic attacks, other adverse effects and death according to recent reports.

In the continental United States between January and May of 2015, The poison control centers received 3,572 calls that were all related to the use of synthetic cannabinoid which was a huge increase over the figure seen during the same time of the year in 2014 which was 1,085. The most calls were received in April which included 15 deaths but only five deaths were reported in 2014.

Even though the harm that has been proven with the usage of synthetic cannabinoid chemicals the abuse is still happening, mainly seen in military personnel, athletes, employees that are subject to drug testing and others that want to get high without being detected in the blood. Even though, all the health risks have been published and documented, the long term effects at this time are completely unknown and may not even be known for several years or generations. This was seen with thalidomide and diethylstilbestrol.

Further investigation of newer synthetic cannabinoids that have been found in materials seized by the authorities like MN-18, MN-39, MN38, and NNEI contained a substitute known as amide-linked naphthylamine which may be linked to carcinogens in the bladder.