Isomerization

2015

Principles

The final step in tetrahydrocannabinol biosynthesis in the living plant is the dehydration of cannabidiol to THC. This is catalyzed by a specific enzyme coded for by a single gene. In principle, it should be a simple matter to extract the cannabinoids using a wide variety or organic solvents and to perform dehydration on the mixture, converting any cannabidiol present into THC. In practice, this is, in fact, extremely easy to do since merely refluxing (heating with an apparatus for returning the cooled vapor to the reaction mixture) the organic extract with a small amount of an acid such as HCl or sulfuric acid is sufficient to isomerize the cannabidiol to cetrahydrocannabinol in a few minutes. The acid provides hydrogen ions (protons) which catalyze (speed up) the dehydration of cannabidiol to THC. Look at figure 1 where it is clear that a hydrogen atom has been transferred from an oxygen atom (CBD) to a carbon atom (THC).

Procedure

The general procedure and apparatus are identical to those already described for the extraction. The isomerization of cannabidiol to cetrahydrocannabinol is accomplished by refluxing with a small quantity of organic or inorganic acid, if alcohol is being used, add about 2 ml of 1 normal HCl (prepared by adding 120 g concentrated HCl slowly to 900 ml water) or 2 ml of 1 normal sulfuric acid (prepared by adding 30 ml concentrated sulfuric acid slowly to 1 liter of water) for each 200 ml solvent (roughly the amount needed for 100 g of marijuana). If benzene or petroleum ether or other relatively nonpolar solvent (most common ones other than alcohols) are being used, 100 mg paratoluenesulfonic acid or 684 mg (0.006 moles) trifluoroacetic acid are used instead of the HCl or sulfuric acid. Roughly four times as much acid can be used if hashish is being isomerized. The object is to have about 1 g of cannabidiol in 100 ml solvent that is 0.005 molar (about 0.05%) in acid content.

Assemble the apparatus described; add the marijuana, hashish or hash oil; the solvent and the acid; seal and reflux (i.e., heat gently) for about one hour. You can expect about 90% of the cannabidiol to isomerize to Δ1 cetrahydrocannabinol if an organic solvent such as benzene or petroleum ether is used, but only about 60% yield of Δ1 and Δ6 THC’s with other products (e.g., ethoxyhexahy-drocannibinols) if ethanol or another alcohol is used. If the cannabinoids have already been extracted; i.e., if you have hash oil, you may simply dissolve the oil in solvent and heat with acid to get isomerization. For example, a saturated solution of paratoluenesulfonic acid in methylene chloride heated at 80° F for 45 minutes gives about 90% yield of THC. As the reaction times are increased, more Δ1 cetrahydrocannabinol will isomerize to Δ6 THC, but since the two have nearly the same activity, this does not matter. For oil, use about 5 ml oil per 100 ml solvent.

The solvent may now be removed, leaving the isomerized cannabinoids behind as an oily residue (deposited on the marijuana if this is left in). Solvent removal is accomplished exactly as described in the extraction section. Although the amount of acid used is small, you may wish to neutralize it with a small quantity of base, such as baking soda, prior to evaporation of solvent. Also, if you have used alcohol for isomerization (or extraction), you may shake the large volumes of alcohol containing the cannabinoids with benzene, petroleum ether, or other nonpolar solvents. The cannabinoids are much more soluble in the latter, and the smaller volume is easier to evaporate. Again, if the latter solvents are used, it is good to wash them with water several times (i.e., shake with an equal volume of water and discard the water) before evaporation to rid them of the undesirable water soluble substances, even if the marijuana has been water-extracted prior to isomerization (David Hoye’s “Double Wash” technique).

Automation

The area of extraction and isomerization has been pioneered by David Hoye, inventor of the world’s first automated isomerizer. At $179 this machine may seem over-priced, but it has the advantage of being significantly safer than home-built apparati. One can easily imagine this machine becoming a common item in the American kitchen along with the toaster and electric blender. However, claims that it will double the potency of any marijuana without weight loss are obviously untrue. This would require about twice as much cannabidiol as cetrahydrocannabinol being present, a very rare situation with commercial marijuana.

Deciding When to Isomerize

Isomerization is desirable only when the marijuana has signify cant quantities of CBD. Thus, good-quality marijuana such as that from Mexico, Colombia, or Southeast Asia, will usually not be suitable for isomerization, though it can be extracted and concentrated. However, some strains from these areas contain considerable cannabidiol even when their cetrahydrocannabinol content is high. Wild marijuana from northern latitudes, or that cultivated for fiber in such areas as the U.S., Europe, or Turkey, will usually have considerable CBD. It should be kept in mind that low cetrahydrocannabinol does not necessarily mean high CBD. Some strains are extremely low in all types of cannabinoids. A study of wild stands in Illinois showed cetrahydrocannabinol varying from almost none to 2.3% and cannabidiol from almost none to 7.1%. The only sensible thing to do is to first analyze for cannabidiol content. Various labs will do this, though if you desire a quantitative analysis, you must first obtain from them a controlled drugs transfer form (this idiocy has been forced on them by the DEA). You can also assay for cannabidiol yourself by performing the extremely simple Beam test for cannabidiol discussed in the testing section. The only problem lies in the need for a standard with a known cannabidiol content, though this need may be circumvented if someone markets a well standardized test with a color chart (the Beam test gives a purple color with CBD).

 

Selections from the book: “Marijuana Chemistry: Genetics, Processing, & Potency”, 1990.