This post title is very misleading. You’re comparing activities for (-)-trans-D9-THC to (+)-cis-D9-THC. The stereochemistry around the 6a,10a positions will have an effect on binding affinity that is not dependent on if it is synthetic or isolated from natural sources. Additionally the JNP paper cited states that the cis diastereomers were found in a scalemic mixture with the (-)-cis-D9-THC being more prominent and having more activity than the (+)-cis-D9-THC enantiomer. As expected, these cis diastereomers both bind to CB1 and CB2 weakly when compared to the (-)-trans-D9-THC stereoisomer which is in higher natural abundance in cannabis.
I also find the statement about an uncited study on formation of the (+) and (-)-trans enantiomers forming in a ratio of 5:1 confusing. Starting from what, under what conditions?
CBD isolate under numerous reaction conditions has been shown to produce the (-)-trans-THC stereoisomers and any (+) stereoisomer cis/trans produced is likely from an impurity.
I did acknowledge that it was a misleading title based on the original study I provided, and I apologize for that. However, I do believe the broad statement remains true because of the attached study confirming the ratio of enantiomers in synthetic conversion samples.
The enantiomeric ratios I referenced come from a senior thesis study where chiral separation of Δ9-THC was performed using HPLC equipped with a Daicel CHIRALPAK ID column. The study analyzed both known plant-derived extracts and known synthetic conversion samples (CBD-to-Δ9-THC) to determine enantiomeric composition. However, the exact reaction conditions (acid type, solvent, temperature, time) for the synthetic samples were not disclosed in the study (as these were commercially obtained distillates of known synthetic origin).
Results showed that synthetic conversion samples exhibited scalemic mixtures with (−):(+) enantiomeric ratios ranging from 5.6:1 to 15.3:1, whereas plant-derived samples contained exclusively the natural (−)-Δ9-THC (100:0). All synthetic samples also contained Δ8-THC and Δ8-iso-THC, supporting the synthetic origin.
I don’t believe the study has been published yet, as it’s part of a larger ongoing project. However, here is the senior thesis submitted and presented by Martyna Berto, a recent graduate from Lake Superior State University: LSSU Senior Thesis- Cannabinoid Chirality Analysis.pdf (320.5 KB)
If you want to to jump way ahead in the Pharmacology of (+) enantiomeric THC. That lab needs.to just report on some ROSIN guy taking two or three enormous bong hits of the (+) enantiomeric THC in purified form. There are numerous people here that would test and give you a professional answer. I see that @Phytochem17 points out that (+)-cis-D9-THC and (-)- cis D9 THC only show weak binding activity when compared to (-)-Trans-D9 THC on CB1. A big hit may not be such a “treat”.?
While I’m not sure we’ll be handing out bong hits of purified (+)-THC anytime soon, it would definitely be interesting to see whether consumers could differentiate between the various stereoisomers of Δ9-THC if each were isolated and consumed individually. There’s a study I referenced earlier that compared the (+)-trans stereoisomer of Δ9-THC in animal behavioral models, which gives some insight into the potential effects. Theoretically, we’d expect to see similar outcomes in human trials if the study were repeated with that specific comparison in mind.
I appreciate the link to the thesis with the data. Their approach to the analysis was a good first step but I see some issues that could cause issues with the conclusions.
The only tool for identification past UV was NMR to identify other possible cannabinoids in these mixes. With many of the protons of these compounds coalescing it’s going to be easy to miss some of the lower level concentration impurities. It’s great that they identified D8-iso-THC as a fingerprint for conversion, but that’s only one of four total possible iso-THC stereoisomers that have been identified in conversion products. Additionally exo-THC is another possible isomer commonly seen. The thesis didn’t state that the HPLC methods were checked for coelution with these other contaminants to avoid misidentification as the proposed enantiomer.
All of these THCs look essentially the same by UV. LC-MS is another tool that would have allowed for identification as the enantiomer as the fragmentation for (-) and (+)-trans would be the same but different for cis and the other isomers I’ve mentioned, but it doesn’t appear that was utilized.
Finally, it’s not clear if these synthetic samples are from CBD isolate or synthetic CBD. This is becoming an issue as the starting materials for making CBD synthetically are becoming cheap enough to compete with the time and investment to grow, harvest and isolate CBD from cannabis. Synthetic CBD will have a different impurity profile relative to that of CBD isolate even if both show purities >99.9%.
I want to commend the study and say it’s asking important questions but recommend the scientists at LSSU to keep going to answer these questions.
Based on the University you posted you are not too far from me! If you need volunteer(s) who already consume heavy amounts of THC per day (750mg-3 gramsHD9/ND9) then I know a group of legal (if you gift the THC) lab rats prepared to test said differences! Personally, I have found in my previous consumptions of HD9 that it is typically more intoxicating.