THC Derivatives and Their Creation Process

As cannabis legalization continues to spread, more data is constantly being collected about the compounds found within the cannabis plant and THC derivatives.

Apart from hundreds of cannabinoids, there is a giant variety of terpenes, flavonoids along with other compounds. Even the primary psychoactive ingredient, the phyto-cannabinoid tetrahydrocannabinol (THC), is now more understood and scientists and cannabis manufactures are continuously improving extraction and purification procedures.

Nowadays many THC derivatives have been developed to create new synthetic products or to make in the laboratory related cannabinoids found in the plant in traces.

The Progenitor of THC and All THC Derivatives (THCA)

Tetrahydrocannabinolic acid (THCA) is the precursor of THC. THCA does not bond to cannabinoid receptors, making it the only form of THC that is not psychoactive. In terms of extraction, THCA has a major advantage over other forms of THC. [1] Stems, leaves, and roots all provide an abundant quantity of THCA. [2] THCA can be obtained in crystalline form and it can reach a purity of around 99%. [3]

To produce this concentrated form, it is essential to avoid heat in the extraction process, which means that it relies primarily on solvent based extraction. [4] Cannabis plant material is first mixed with a solvent like hexane, and the solution is placed it in some kind of rotary vessel. [5]

The kinetic motion separates the cannabinoid from the solvent, which then evaporates away. Chromatography is then used to remove any other impurities, which involves adding additional chemicals like silica or alumina and repeating the process in the rotary vessel. [6] This isolates the THCA into chemically bonded crystals with exceptional purity.

The Primary Form of THC (Delta 9 THC)

When THC is described, usually they are referring to delta-9-tetrahydracannabinol (THC). Though it will vary by strain, THC tends to make up approximately 30% of the cannabinoids in cannabis. [7] This means that THC is the primary psychoactive ingredient. THC can be isolated using various methods.

One of them is known as supercritical extraction, which employs solvents at the supercritical state such as carbon dioxide (CO2) among others in order to selectively extract the desired cannabinoid or cannabis constituent. [8] The yields of the extraction are similar to other methods, but supercritical extraction is safer by comparison. By releasing the pressure in the extraction chamber, the carbon dioxide evaporates as a gas, leaving only the THC extract.

Ethanol can also be used as a solvent for a chemical based extraction, but instead of relying on pressure, heat is the primary driver. [9] This is because ethanol has a significantly lower boiling point than THC.

Finally, another THC derivatives production method is called isomerization. [10] This has the regulatory advantage of being derived from CBD, but it is chemically complicated as it requires the cannabinoids be dissolved in an acidic solvent like battery acid, muriatic acid, or vinegar. The procedure itself is simple: the solution sits for 24 hours before filtering out the acid and any contaminants. Owing to the nature of the solvents, though, there is a higher potential for error.

The Cannabidiol Derived Cousin (Delta 8 THC)

While slightly milder in potency than THC-9, Delta-8 tetrahydrocannabinol (THC-8) is derived from a complementary cannabinoid: cannabidiol (CBD). CBD is not psychoactive, but THC-8 is. Because of this, D8 falls into a legal loophole, as CBD products are legal in the United States while Delta-9 THC is still federally illegal. [11]

The THC-8 psychoactive effects are similar to that of THC-9, but with less paranoia. [12] There are still some remaining concerns about THC-8, revolving around how it is extracted. THC-8 does occur naturally in cannabis, but in traces. The conversion of CBD to THC derivatives -8 can be done with the isomerization process. [13]

By mixing CBD with various acids, this can lead to a lot of byproducts, many of which are not found in cannabis at all. One study found that up to 47% of D8 products may consist of largely harmful materials, and many other contain ingredients where the effects on humans are unknown. [14] The amount of byproducts varies by brand and methods of isomerization.

Because THC-8 is unregulated, there is very little testing on what may be contained in these products, and none of them have been approved by the FDA. Because of this, THC-8 may pose a greater risk to consumers than other THC derivatives, and as a response, several states have chosen to criminalize THC-8 until more data emerges about the safety regarding human consumption.

THC Derivatives: the Synthetic Alternative (THCO)

Numerous synthetic cannabinoids have been developed, but one of the most closely related to the original organic compound is tetrahydrocannabinol acetate (THCO). THCO is produces by taking THC-8 derived from CBD, and going one step further by adding acetic anhydride. [15] THC derivatives -O have multiple advantages over THC-8 and THC-9 that is isomerized from CBD.

By becoming THCO, terpenes and other cannabis compounds are stripped from the original product. Arguably, this may be a way to remove some harmful byproducts associated with THC-8 synthesis, but this has not been definitively proven.

Additionally, some evidence suggests that THCO may be 3x more potent than THC-9. [16] THCO is not completely risk-free, though. This compound should only be synthesized in a certified laboratory with experienced professionals, as acetic anhydride is highly flammable.[17] Additionally, there is some evidence that vaping THCO may lead to long-term lung damage, but more data is needed to confirm this connection. [18]

The Most Potent THC Derivative (THCP)

Discovered accidentally in 2019, tetrahydrocannabiphorol (THCP) is a cannabinoid with a longer alkyl side chain that allows it to bond 33 times more effectively to CB1 receptors than Delta-9 THC. [19][20] This makes THCP the most potent cannabinoid derivative, but owing to its recent discovery the least understood. Another reason for this lack of knowledge is because it also only appears naturally in trace amounts.

Because of this, it is only realistically obtained through extraction procedures, specifically those relying on CBD derivation similar to Delta-8 THC isomerization. There is hope that THCP may provide a safer option for consumers, as the extraction method also goes through a dewaxing and chromatography procedure that may provide a purity of up to 95%.[21]

Because this compound is so new, it is difficult to determine both how effective this procedure is, and what any long term consequences it may have for users. An initial study on zebrafishes found that exposure to THC derivatives -P may have detrimental neurological effects, but the same study was not repeated on humans. [22]

The Cannabinoid Alternative to Stimulants (THCV)

By hampering appetites and providing an energizing boost, tetrahydrocannabivarin (THCV) is often described as having an effect similar to stimulants. This THC derivative may provide a mitigating effect to some negative consequences of THC-9 consumption. [23] This is because THCV can help to limit connections of THC to CB1 receptors, creating a milder psychoactive experience overall. [24]

The downside to this derivative is that it is typically found in significantly lower amounts than THC. Because of this, users may need to take it in larger amounts compared to THC, which can also mean it becomes more expensive to extract a large amount to provide a noticeable response. [25]

Similar to THC-9 extraction, one of the most effective extraction methods is supercritical extraction using either carbon dioxide or ethanol. [26] While the effects of THC derivatives -V may be promising, its availability on the market is still limited, despite studies that indicate it is safe for consumption. [27]

References: 

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