What’s the Deal with H4 CBD?
While in the Netherlands this Spring I noticed cannabis products sold in smartshops (similar to smoke shops in the US) that contained the cannabinoid H4 CBD. I discussed these products with one smartshop owner, who informed me that sales of H4 CBD were increasing rapidly. Shortly afterwards, a client of mine who was also traveling in Europe for business said that he was negotiating an H4 CBD supply contract. Over the past two months I have begun to see products containing H4 CBD for sale in the US. So what’s the deal with H4 CBD? Is it lawful?
Hexahydrocannabidiol, commonly known as “H4 CBD”, is a synthesized form of CBD in which the two carbon-carbon double bonds on the cannabidiol (CBD) molecule are converted to single bonds by adding four hydrogen atoms. This is a common conversion, called “hydrogenation”, and it is widely used in foods. For example, margarine is created from vegetable oil by the process of hydrogenation. The cannabis plant does not naturally produce H4 CBD and it is only produced synthetically.
The legal status of H4 CBD, like all cannabinoids, is properly analyzed by reference to the Controlled Substances Act (CSA) and, when marketed for human or animal use, by the Food, Drug & Cosmetic Act (FDCA).
Part 1: The CSA
H4 CBD is not a controlled substance under the CSA. This was recently confirmed in a letter by the DEA that I wrote about here. In that letter, the DEA properly states: “Whether a cannabinoid product synthetically produced from non-cannabis materials is controlled depends on whether that product contains ‘any quantity’ of a synthetically produced tetrahydrocannabinol [(THC)].” Notably, the DEA does not address whether a cannabinoid product synthetically produced from cannabis materials is controlled or not. This is because the DEA has stated on numerous prior occasions that such a product is not controlled if its delta-9 THC concentrations do not exceed 0.3% by dry weight (ie, the legal definition of “hemp”.) Since pure H4 CBD does not contain any quantity of synthetically produced THC it is not controlled. Of course, if an impure form of H4 CBD, such as a distillate, contains trace amounts of synthetic THC it is controlled.
Part 2: The FDCA
If H4 CBD is marketed for use by humans or animals it is subject to the FDCA and is regulated by the FDA. Does the FDCA prohibit its use as a food ingredient or dietary supplement? This is more difficult to determine. On the one hand, the FDA could conclude that H4 CBD is really just a form of “CBD” and that it thus falls under the drug exclusion rule which prohibits it from being used as a food ingredient or marketed as a dietary supplement. That position would be clearly erroneous since CBD and H4 CBD are two separate cannabinoids with distinct molecular structures. In other words, they are not the same moiety (ie, substance) that was the subject of the Epidiolex clinical trials on which the FDA bases its position regarding the use of CBD in food and dietary supplements. (You can read more on this issue here and here.)
Regardless of whether or not H4 CBD is captured by the drug exclusion rule, it has not been marketed in the US prior to 1994 and is thus a “new dietary ingredient” (NDI) and subject to the rules regarding NDI. These rules include the requirement to submit a premarket notification to the FDA containing “information that is the basis on which you have concluded that a dietary supplement containing the new dietary ingredient will reasonably be expected to be safe.” With respect to H4 CBD, safety is the primary issue. H4 CBD has been touted as having 100 times more binding affinity to the CB1 receptors than CBD. Although this could potentially be helpful in certain circumstances, at least one clinical study states that there are, “clear differences between consumption of natural CBD, and two synthetic derivatives on ALT and AST levels.” (Note, ALT and AST are enzymes that the body uses to remove synthetic cannabinoids from the body.) The authors of this study contend that the elevated ALT and AST levels are due to the fact that, “[t]he human body is not equipped with the tools needed to catabolize synthetic cannabinoids.” While this may be an overstatement, their results in this specific trial did show heightened levels of these enzymes after consumption of H4 CBD. Another study concluded that H4 CBD has “no cardiac issues.“
Part 3- Summary
In summary, H4 CBD is an intriguing cannabinoid that is similar to CBD, though potentially much more potent. The fact that the cannabis plant does not naturally produce H4 CBD means that it can only arise as a synthetic compound. In and of itself, this may or may not be an issue. H4 CBD is not a controlled substance provided that it does not contain any quantity of synthetic THC. With respect to the FDCA as regulated by the FDA, H4 CBD also likely does not fall under the drug exclusion rule; however, since it is a new dietary ingredient it is important to follow NDI premarket requirements before marketing it. The crucial issue is its safety, which I hope will be the subject of future clinical trials.
August 3, 2023
Rod Kight is an international cannabis lawyer. He represents businesses throughout the cannabis industry. Additionally, Rod speaks at cannabis conferences, drafts and presents legislation to foreign governments, is regularly quoted on hemp matters in the media, and is the editor of the Kight on Cannabis legal blog, which discusses legal issues affecting the hemp industry. You can contact him by clicking here.