Law360 (January 13, 2020, 5:49 PM EST) —
Original article: https://www.law360.com/articles/1232597/the-evolving-legality-of-lesser-known-cannabis-compounds One may be forgiven for being unaware of cannabinoids other than THC and CBD. THC is famous, of course, for providing the intoxicating effect of marijuana, whereas CBD has bloomed in popular awareness following passage of the 2018 Farm Bill, which removed hemp-derived CBD from the Controlled Substances Act. With more than 120 identified cannabinoid compounds found in the plant genus Cannabis, it’s all but certain that products based on cannabinoids other than THC and CBD will become better-known. The two most likely contenders are cannabigerol, or CBG, and cannabinol, or CBN.
The U.S. Food and Drug Administration continues to explore potential pathways for various types of CBD products to be lawfully marketed. In the wake of new warning letters sent to 15 CBD companies that were issued on Nov. 25, 2019, the FDA has announced that it “plans to provide an update on its progress regarding the agency’s approach to these products in the coming weeks.” Similar to CBD, the question of the extent to which CBG and CBN are legal for use in consumer products will evolve over time.
CBG is the nonacidic form of cannabigerolic acid, the parent molecule from which most cannabinoids are synthesized. During growth, most of the plant’s CBG is converted into other cannabinoids, primarily THC and CBD. Adult cannabis plants typically contain 1% or less CBG concentration, so plants must be harvested early to produce pure CBG before it synthesizes into other cannabinoids.
Very little clinical research has been conducted on CBG’s effects in humans. Current research is under way to explore CBG’s pharmacological properties and effectiveness as a medication for various diseases. Animal studies have indicated that CBG may assist with modulating pain, regulating blood pressure and reducing inflammation. CBG also may have neuroprotective qualities and antibacterial properties. CBG also is being studied for its potential support of sleep and appetite regulation.
There are a number of CBG products available on the market, but CBG is not yet widely produced at scale and remains prohibitively expensive to produce compared with CBD. CBG products are therefore currently much more expensive than comparable CBD products.
CBN is a cannabinoid found only in trace amounts in most cannabis varieties and is primarily found in aged cannabis. It is the degraded product of THC. Degraded cannabis products that have been oxidized with age tend to be high in CBN.
Few studies of CBN in humans have been conducted. It is believed, however, to have immunosuppressive qualities and antifungal properties as well as anticonvulsant effects. It also may stimulate appetite. CBN is most commonly sold today as a sleep aid, though additional study on its effectiveness for sleep is needed.
Are CBG and CBN Legal?
Neither CBG nor CBN is listed as a controlled substance under the CSA or the United Nations Single Convention. Like CBD, however, if CBG or CBN are derived from marijuana, they fall within Schedule I of the CSA. If the cannabinoid is derived from properly sourced industrial hemp, it should fall outside the CSA. CBG may be extracted from hemp, but CBN is the degraded product of THC such that it is not practical to cost-effectively derive CBN from hemp.
Regardless of how it is derived, because CBN is the degraded product of THC, some commentators have questioned whether CBN may be treated as an illegal controlled substance under the Federal Analog Act, which allows any chemical “substantially similar” to a controlled substance in Schedule I to be treated as if it were listed in Schedule I. This hypothesis has never been tested through any reported prosecution or in court.
Under food and drug laws, the analysis for CBG and CBN is similar. As an initial point, it should be understood that the FDA has never affirmatively permitted any cannabinoid in food or supplements. CBG and CBN nevertheless fall into a regulatory gray area that provides potential protections not afforded to CBD.
With respect to CBD, the FDA has relied primarily on its drug exclusion rule. Because the FDA previously authorized investigation of CBD as a new drug — for which substantial clinical research already had been conducted and made public — CBD products are considered drugs and require FDA approval under the Food, Drug and Cosmetics Act. The new drug approval process is exorbitantly expensive. In 2016, the Journal of Health Economics estimated the average cost per approved drug at well over $1 billion.
The drug preclusion rule should not apply at the present time to either CBG or CBN, for which no substantial clinical research has been conducted and made public. After such research occurs, an exception exists if the substance was marketed as a food or supplement prior to the clinical research. In the absence of the drug preclusion rule, the question of whether CBG or CBN may be marketed as food, a food additive or a dietary supplement is discussed below.
CBG and CBN as Food
Under the FDCA, food generally is defined as any item consumed primarily for taste, aroma or nutritive value. It is doubtful that any cannabinoid would satisfy this test.
CBG and CBN as Food Additives
Every ingredient in a food sold in interstate commerce is a food additive and subject to FDA preapproval requirements, unless an exception applies. Prior to adding a new food additive to a conventional food, one must obtain approval through a food additive petition, which can take years to complete. The primary exception is for a substance that is generally recognized as safe, or GRAS. A substance is generally recognized as safe if it is shown to be safe using scientific procedures or if it were used in food before Jan. 1, 1958, and shown to be safe through “experience based on common use in food.”
Although GRAS determination has been made in the case of hulled hemp seeds, hemp seed protein and hemp seed oil, the FDA concludes further research is needed for CBD and presumably for other cannabinoids including CBG and CBN to be determined GRAS.
CBG and CBN as Dietary Supplements
One could potentially market a dietary supplement containing a cannabis-based new dietary ingredient, including CBG or CBN, if there were a history of use or other evidence of safety establishing that when used according to the direction in its labeling, the ingredient will reasonably be expected to be safe. One first must submit a new dietary ingredient notification at least 75 days before introducing the supplement to market. The FDA may send a no-objection letter, but in the absence of a response from the FDA, one may legally market the dietary supplement after the 75-day notification has expired. There is substantial risk in attempting to market any dietary supplement through this route without reliable scientific evidence of safety.
Of course, it goes without saying that one should not make any unapproved health or disease claims when marketing any CBG or CBN product because doing so would cause the product to become an impermissible drug under the FDCA.