Introduction
In recent years, notable progress has been made in identifying the evolving generations of synthetic cannabinoids such as JWH-018 and their corresponding metabolites. However, two areas remain relatively unexplored: the toxicity and mechanism of toxicity of the parent drugs and their metabolites and identification of common pyrolytic products and their toxicity. The latter is critical, given that the most common mode of ingestion of synthetic cannabinoids is smoking or heated vapor inhalation. These compounds mimic Δ9-tetrahydrocannabinol (THC), the active ingredient of cannabis. The additional effects, referred to as the “cannabinoid tetrad” include hypothermia, analgesia, catalepsy and uppression of locomotor activity. The tetrad test is a series of behavioral paradigms in which rodents treated with cannabinoids such as THC show effects. It is widely used for screening drugs that induce cannabinoid receptor-mediated effects in rodents. The four behavioral components of the tetrad are spontaneous activity, catalepsy, hypothermia, and analgesia. To date, few pyrolytic products have been identified with only two being observed in toxicological matrices, UR-144 and XLR-11 degradants. As a result, realistic and reproducible simulation of ingestion by smoking is difficult. Furthermore, there is no way to establish what compounds produced by smoking remain in inhaled air for delivery to the lungs and absorption into the bloodstream. In light of these considerations, exhaustive sampling and collection methods are a reasonable alternative as a starting point. The analytical method was optimized using replicate and duplicate analyses, starting with herbal mixtures without cannabinoids. These experiments established compounds that would be expected to arise from the substrate and to differentiate these from compounds arising from the synthetic cannabinoids. Using the optimized experimental procedures, each synthetic cannabinoid was characterized. The results were used to identify common pyrolytic pathways and to develop methods that will allow for prediction of pyrolytic products of new cannabinoids. In this article, you can read about heating process and thermal decomposition of substances while smoking.
Fig. 1 Breakdown chart of JWH-018 to its observed pyrolytic products; (*) unique products
Synthetic JWH-018 pyrolysis
The pyrolysis trials of the synthetic cannabinoids yielded 14 pyrolytic products, and each was found to have presence in the smoke as detected in either the tube or solvent samples, with little to none detected left behind in the quartz/ashes sample. The unique products might be exploitable as additional markers of synthetic cannabinoid use, even when the parent compound is not detected. You have to pay attention and take this information into account. Police can figure out what are you smoked before. Figure 1 outlines an example breakdown of JWH-018 parent to pyrolytic products.
Figure 1 further illustrates examples of three common breakdown tendencies across the pyrolysis of synthetic cannabinoids. The first is a break on either side of the central carbonyl group, commonly present in synthetic cannabinoids. This breakdown trend produces pyrolytics such as indole or naphthalene products. The second trend, predictable due to the weak C–N bond, is the loss of the substituent group bonded to the nitrogen of the indole or indazole ring structures. An example of this in Figure 1 is 3-naphthoylindole. The majority of synthetic cannabinoids have either an indole or indazole ring structure, and with the pyrolytic ring size increase, they convert to a quinoline or cinnoline ring structure, respectively. These breakdown or conversion trends can be used for a prediction model for the thermal degradation of the continually evolving generations of synthetic cannabinoids. The detection of these products could not be used to indicate the use of synthetic cannabinoids in general or possibly limit the search to a structural class such as naphthoylindoles, indazoles or tetramethylcyclopropyls. Figure 2 shows an example breakdown of the different parent synthetic cannabinoids that produced the pyrolytic, quinoline. It can be noted that each parent compound includes an indole group, and this type of trend could be exploited to limit a search to those with an indole moiety if quinoline was detected during analysis if additional information points toward synthetic cannabinoid use.
Figure 1 further illustrates examples of three common breakdown tendencies across the pyrolysis of synthetic cannabinoids. The first is a break on either side of the central carbonyl group, commonly present in synthetic cannabinoids. This breakdown trend produces pyrolytics such as indole or naphthalene products. The second trend, predictable due to the weak C–N bond, is the loss of the substituent group bonded to the nitrogen of the indole or indazole ring structures. An example of this in Figure 1 is 3-naphthoylindole. The majority of synthetic cannabinoids have either an indole or indazole ring structure, and with the pyrolytic ring size increase, they convert to a quinoline or cinnoline ring structure, respectively. These breakdown or conversion trends can be used for a prediction model for the thermal degradation of the continually evolving generations of synthetic cannabinoids. The detection of these products could not be used to indicate the use of synthetic cannabinoids in general or possibly limit the search to a structural class such as naphthoylindoles, indazoles or tetramethylcyclopropyls. Figure 2 shows an example breakdown of the different parent synthetic cannabinoids that produced the pyrolytic, quinoline. It can be noted that each parent compound includes an indole group, and this type of trend could be exploited to limit a search to those with an indole moiety if quinoline was detected during analysis if additional information points toward synthetic cannabinoid use.
Fig. 2 Chart displaying each parent synthetic cannabinoid that produced quinoline.
There is lacking data on the majority of products’ volatility, but a few, where there is, indicate the ability of the reported methodology to collect products across the volatility range. A few high volatile product examples are indole, quinoline and naphthalene whose vapor pressure levels are on the order of ~10−2 mm Hg. On the other side of the spectrum, low volatile parent compounds such as JWH-018 and JWH-073 whose vapor pressure is on the order of ~10−10 mm Hg were also collected (the lower the vapor pressure, the less volatile the compound). The constructed apparatus demonstrated the ability to produce a “smoking-like environment”, which is important as synthetic cannabinoids are often smoked using a herbal matrix laced with the compound of interest. Six common herbal materials were pyrolyzed to determine background products to differentiate from those pyrolytics of synthetic cannabinoids, and 10 consistent products, which were tentatively identified, were detected and consistent with previous pyrolysis studies on plant material demonstrating the methodology was fit for pyrolytic analyses.
Conclusion
Pay attention to note that when laboratory are examining urine or blood, toxicological laboratories can track the use of JWH-018 for a long time by pyrolysis products and their metabolites (substances that are formed in the body after consumption). The pyrolysis trials of JWH-018 produced 14 pyrolytic products. Six of these products were unique to a particular parent cannabinoid compound, whereas the remaining 8 were shared by multiple parent compounds. The unique pyrolytics are important, as they may serve as additional toxicological markers and indicate use of a specific synthetic cannabinoid without detection of the parent or metabolic compound. The shared pyrolytic products are not an indication of a specific cannabinoid, but are a useful suggestion of synthetic cannabinoid use. Upon analysis of the studied cannabinoids, three major thermal degradation trends were apparent, including: (1) a break on either side of the central carbonyl; (2) loss of the indole/indazole N-bonded substituent group and (3) a ring size increase from indole/indazole to quinoline/cinnoline, respectively. These trends may be used as a predictive model for other synthetic cannabinoids not studied here, not yet seen in casework, or for future generations yet to be synthesized.
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