The tetrahydrocannabinol (THC) molecule exists as several separate isomers, however two in particular – delta-9-THC and delta-8-THC – have proven to be the most dynamic and prevalent of all. Nearly identical in structure, these two distinct compounds provide two somewhat different experiences for the consumer. But how are these two isomers similar and different analytically and what if any other isomers besides delta-8 and delta-9 are on the rise?
Double bond location and classification
Most cannabinoids have a 21-carbon atom structural feature, with possible variations in the length of their side chains attached to the aromatic ring. [1] The main difference between delta-9 and delta-8 is the location of the double bond (which gives these compounds the delta name itself) in the molecular structure of each. When this double bond is found between carbons 9 and 10, the molecule is classified as delta-9-THC. Conversely, when the double bond is found between carbons 8 and 9, it is deemed naturally occurring delta-8-THC.
This minor difference in the double bond position found in cannabis is very significant for how it changes the properties of both delta-8 and delta-9. Delta-8 has shown to be somewhat less intoxicating (about two-thirds of D9) than delta-9 due to its reduced affinity for the CB1 receptor. [1]
It is important to note that in this instance above, we discussing the naturally occurring delta-8 isomer that occurs in low concentrations in the mature cannabis plant rather than the delta-8 end products available on the consumer market that come about as a result of extracting dried cannabidiol (CBD) flower and subsequent chemical syntheses to transform CBD into delta-8-THC.
How THC isomers are analyzed
The processes of high performance liquid chromatography (HPLC), gas chromatography, and mass spectrometry provide the ability to separate and analyze each isomer individually. [2] In the case of HPLC, one can turn to chiral stationary phases to separate out isomers. Briefly, chiral molecules are asymmetric and are not superimposable (e.g., mirror images). A stationary phase is typically comprised of very small silica particles that have different chemical groups attached that interact with the sample to varying degrees, resulting in some molecules being more attracted to those chemical groups than others, thus enabling the separation.
Also interesting to note is the method of nuclear magnetic resonance (NMR) instruments that can show researchers only certain atoms and their placements in a particular molecule. Thus, the method can unveil how atoms are arranged in molecules, elucidating molecular structures. NMR analysis is not typically used in conjunction with cannabis testing (the instruments are traditionally very expensive, but Nanalysis has made a benchtop unit), but when it was used in one particular analysis, it was able to recognize the presence of another isomer – delta-10 – within extracted cannabis biomass.
Delta-10 & Delta-6
Through methods such as NMR analysis and reverse engineering, specific radically-initiated, catalytic reactions can create large yields of delta-10 crystals or isolates similar to how a chemical synthesis is necessary to give us the delta-8 end products that we are familiar with in the consumer marketplace. As scientific research efforts emerge on delta-10, potential medicinal and intoxicating effects will being determined, but anecdotal reports indicate a focused and euphoric experience in comparison to traditional delta-9-THC.
Delta-6 is another THC isomer that we are learning more about and it is also found in trace amounts within cannabis flower. Delta-6 can also be formed from CBD or D9-rich flower by altering its molecular structure similar to how D8 end products are produced. Reported effects include a more intense experience and Dr. Raphael Mechoulam’s group found anticonvulsant properties in the late 1980s. [3]
One of federal cannabis prohibition’s main drawbacks – amongst numerous others – is how it slams the door shut on proper study and grant money regarding possible therapeutic benefits of the plant and cannabinoids therein that have yet to be discovered. That said, researchers are still doing whatever is within their abilities to unlock the potential of rarer cannabinoids and isomers and their interactions with the human endocannabinoid system.
We can look forward to more regular breakthroughs by science in the ways these compounds can help our minds and bodies medicinally while further establishing cannabis and its polypharmacy as a most-dynamic, non-addictive medicine that can be utilized for a variety of ailments.
References
[1] Hollister LE, Gillespie HK. Delta-8-and Delta-9-tetrahydrocannabinol; Comparison in man by oral and intravenous administration. Clin Pharm. 1973;14(3):353–7. [journal impact factor = 2.61; times cited = 63][2] Santos NA, Tose LV, Silva SR, Murgu M, Kuster RM, et al. Analysis of isomeric cannabinoid standards and cannabis products by UPLC-ESI-TWIM-MS: A comparison with GC-MS and GC×GC-QMS. Journal of the Brazilian Chemical Society. 2018;30:60-70. [journal impact factor = 1.838; times cited = 22]
[3] Consroe P, Mechoulam R. Anticonvulsant and neurotoxic effects of tetrahydrocannabinol stereoisomers. NIDA Res Monogr. 1987;79:59-66. [journal impact factor = N/A; times cited = 8]
