MurphyClox
Bluelighter
- Joined
- Mar 26, 2008
- Messages
- 1,416
It was speculated numerous times if JWH-018 and its close congeners (in particular 015 and 073) could act as cancerogenics. See e.g. this thread (JWH-018-related; very lenghty) and this thread (JWH-073-related).
To repeat the mentioned arguments in short:
For JWH-015 it was shown (using fractions of liver microsomes, to emulate the metabolic environment of the rat liver) that certain pathways of the compounds metabolism included epoxide-intermediates, which are quite infamous for causing cancer, similar to benzen's metabolism. The respective reference is Analytical and Bioanalytical Chemistry 2006, 386(5), p.1345.
Because in particular JWH-018 is structurally very close related to JWH-015, it was assumed by some folks (incl. me) that JWH-018, a very popular 'legal' cannabinoid, is potentially harmful.
Of course, one has to add to the discussion the numerous by-products of the synthesis, which were not removed lege artis in the first batches (...which were orange coloured), but this should not be part of this thread and is another topic.
This discussion was, of course, quite speculative due to the lack of appropriate metabolism studies with JWH-018 and lots of people disagreed with the cancerogenity-proposal.
Now I have found novel evidence that the doubts over JHW-018's benignity were justified. (Thx to Vecktor, who posted the resp. link elsewhere, where I now found the info). I quote:
So what's the message?
The usual metabolic pathway to aromatic hydroxy-functions goes via epoxides!!!
Therefore I conclude that the fear for the potential cancerogenity of the JWH-compounds, in particular those with a very low sustitution pattern, were justified. I don't say this is THE evidence, but the new info definitively speaks against the presumable benignity of these compounds.
- Murphy
To repeat the mentioned arguments in short:
For JWH-015 it was shown (using fractions of liver microsomes, to emulate the metabolic environment of the rat liver) that certain pathways of the compounds metabolism included epoxide-intermediates, which are quite infamous for causing cancer, similar to benzen's metabolism. The respective reference is Analytical and Bioanalytical Chemistry 2006, 386(5), p.1345.
Because in particular JWH-018 is structurally very close related to JWH-015, it was assumed by some folks (incl. me) that JWH-018, a very popular 'legal' cannabinoid, is potentially harmful.
Of course, one has to add to the discussion the numerous by-products of the synthesis, which were not removed lege artis in the first batches (...which were orange coloured), but this should not be part of this thread and is another topic.
This discussion was, of course, quite speculative due to the lack of appropriate metabolism studies with JWH-018 and lots of people disagreed with the cancerogenity-proposal.
Now I have found novel evidence that the doubts over JHW-018's benignity were justified. (Thx to Vecktor, who posted the resp. link elsewhere, where I now found the info). I quote:
(highlights added by me)Studies on the metabolism of JWH-018 and of a homologue of CP 47,497, pharmacologically active ingredients
of different misused incense (“Spice”) using GC-MS and LC-MSn techniques
T. Kraemer, K.Y. Rust, M.R. Meyer, D.K. Wissenbach, D. Bregel,
M. Hopf, H.H. Maurer, J. Wilske
(Institute of Legal Medicine, Saarland University, 66421 Homburg,
Germany; Experimental and Clinical Toxicology, University of Saarland,
66421 Homburg, Germany)
Introduction: In the last few months, a new drug has conquered the cannabis market: different types of incenses (trade names “Spice”, “Smoke”, “Sence” and others) have widely been misused by smoking these blends of herbs. Recently, artificial endocannabinoid receptor agonists (JWH-018 and a homologue of CP 47, 497) have been found to be the pharmacologically active principles in these blends. Unfortunately, little is known about these substances.
Aim: The aim of this study was to elucidate the metabolism of JWH-018 and of a homologue of CP 47,497 (CP47).
Methods: Ethanolic extracts were prepared from incenses containing JWH-018 and CP47, respectively. After removal of the ethanol the residues were given to Wistar rats by gastric intubation and urine was collected over 24 hours. For identification, the metabolites were isolated after enzymatic or acidic cleavage of conjugates by liquid-liquid extraction (LLE) or solidphase extraction (C18 ) followed by acetylation and GC-MS analysis. For LC-MS the underivatized extracts were used. Metabolites were identified by interpretation of the EI mass spectra (GC-MS) and enhanced product ion (EPI) scan mass spectra (LC-MS). MS3 experiments allowed differentiation of isomeric metabolites.
Results: The parent compounds JWH-018 and CP47 could be found in the urine extracts. For JWH-018, the N-dealkyl metabolite could be detected as well as the hydroxylated metabolite. The highest signals could be observed for the hydroxylated N-dealkyl metabolites. Hydroxylation took place in the side chain and in both aromatic systems, the naphthalene and the indol part, which could be shown by mass shift of the corresponding fragments and by MS3 experiments. For CP47, several hydroxylated metabolites could be identified. Aliphatic hydroxyl groups could be differentiated from aromatic hydroxyl groups by different fragmentation patterns (loss of water/acetic acid for aliphatic hydroxyl groups).
Conclusion: JWH-018 and CP 47 are extensively metabolized in rats. According to our experience similar metabolic patterns can be expected in humans. Therefore, screening procedures for these drugs in urine should include not only the parent compound but also the corresponding metabolites.
So what's the message?
The usual metabolic pathway to aromatic hydroxy-functions goes via epoxides!!!
Therefore I conclude that the fear for the potential cancerogenity of the JWH-compounds, in particular those with a very low sustitution pattern, were justified. I don't say this is THE evidence, but the new info definitively speaks against the presumable benignity of these compounds.
- Murphy
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