Why the Federal Government Must Remove Cannabinoids from Schedule I
The legal status of cannabis in the United States over the past century has created a black hole in our collective scientific and medical knowledge. Most of the world can agree that cannabis extracts, and CBD in particular, possess strong potential as therapeutic agents for a wide variety of diseases and disorders1. The Federal Government of the United States, however, still considers cannabis and CBD both to be Schedule I2.
Schedule I compounds are narcotics and drugs that are supposedly deemed by the medical community to have no accepted medical uses AND to have a high potential for abuse3. So, here we are, one of the most advanced nations in the world, and our cannabis policy is so far behind the times that it contradicts scientific evidence presented by major organizations and universities throughout the country and the world. It may soon reach the heights of hypocrisy and even contract itself, if the FDA actually approves Epidiolex (pure CBD) for the treatment of seizures.
How could we, as a group, have ceded the responsibility of cannabinoid research to other countries? A simple search of the literature reveals where the current centers for cannabidiol research are: Brazil, Italy, and Israel. The governments of those countries don’t necessarily have laxer laws with regards to recreational cannabis use. They do, however, allow universities and research organizations to obtain and study cannabis. They understand the distinction between illegalizing a substance and studying it. Because even if you don’t believe it has therapeutic properties—against all evidence to the contrary—there is at least a strong interest in understanding its physiological activity and mechanism of action.
More critically, important discoveries made about cannabinoids are going untested and unnoticed. An Italian group in 2008 made important discoveries regarding the potential of cannabinoid antibiotic therapy4. They found that the five major cannabinoids in C. sativa all show remarkable activity against several different strains and classes of antibiotic-resistant bacteria. Their high potency suggests a specific, but yet not understood, mechanism of activity. Even though the dire need for new antibacterial pharmacophores is widely known5, the study was not followed up on once in the ten years since it was published. Presumably this was due to the terrible difficulty in obtaining permission to source research-grade cannabinoid in the United States.
Cannabinoids are interesting therapeutic molecules because they do not act the same as most pharmaceutical drugs. Rather than strongly binding to a single target in the body, many cannabinoids only weakly connect with targets, or affect receptors in a process called allosteric regulation. They also reinforce each other’s behavior, with the presence of one cannabinoid causing increased sensitivity to the activity of another6. There is still so much we do not understand about them, and the reason for that cannot be because we are just afraid of misuse.
One of the things most people don’t realize about the drug discovery process is that a compounded goes through many changes before its final form. Compounds are screened for potential activity in simple assays at high compound concentrations in a process called lead generation. Once leads have been identified and characterized, they undergo structure-activity relationship (SAR) studies. Medicinal chemists go about synthesizing a variety of compound analogues. When tested against the same assay as the natural compound, they probe the relationship between structural components and the activity of the compound in the assay.
SAR allows scientists to edit a molecule to increase activity and to reduce unwanted side effects. More often than not, drugs going into human trials look nothing like the natural compounds from which they were derived. Many of the topical anesthetics available today are designed based around the active pharmacophore present in cocaine (Lidocaine, benzocaine, etc.). Their development would not have been possible if the DEA had stonewalled cocaine’s medicinal research.
Rescheduling cannabinoids from Schedule I is, I believe, the minimum in policy reevaluation that must occur. Even if the federal government insists on labeling cannabis a controlled substance, there is truly no reason why its pharmacology could not be exploited to do good. We will never know the full potential of cannabinoids as long as the DEA maintains cannabis at Schedule I.
References
- Cannabidiol (CBD) Pre-Review Report. Expert Committee on Drug Dependence. World Health Organization. Thirty Ninth Meeting, Agenda Item 5.2. November 6-10, 2017.
- 21 C.F.R. § 1308.11(d)(23,31,58)
- Schedules of Controlled Substances – 21 U.S. Code § 812.
- Appendino et al. Antibacterial Cannabinoids from Cannabis sativa: A Structure-Activity Study. J Nat Prod 2008;71:1427–1430.
- The need for new antibiotics. Clin Microbiol Infect 2004 Nov;10 Suppl 4:1-9.
- Gallily et al. Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol. Pharmacology & Pharmacy 2015;6:75‐
