Cannabidiol or CBD (Figure 1) is one of the most popular cannabinoids out there on the market. While it has some supported health benefits, the aim of this article is to also take a look at the history and the science behind its use.

Figure 1. The chemical structure of Cannabidiol (CBD)

A BRIEF HISTORY OF CBD

Long before the compound was discovered, cannabis has been used for thousands of years. It is widely agreed upon that Cannabis Sativa was one of the first plants to be cultivated in the early years of agriculture. It was used for many things such as food, clothing, religious ceremonies, and even medicine (1).

In the United States, hemp was a profitable industrial crop and cannabis was being explored for any potential therapeutic applications but as anti-marijuana movements gained traction in the 1930s, the Marihuana Tax Act of 1937 (2) was passed putting high taxes on the import of cannabis. Eventually, hemp was also associated with cannabis and the profitability of the industrial crop declined (3). While the price of importing hemp and cannabis increased, scientific research was still underway and it was in 1940 that the CBD was partially isolated and named by Roger Adams, Madison Hunt, and J.H. Clark (4) and in 1963, was further isolated, synthesized, and the structure was discovered by Rapahel Mechoulam and Yehiel Gaoni (5). The Marihuana Tax Act of 1937 was repealed in 1969 as a part of the ruling of the U.S Supreme Court Case of Leary vs. United States (6) but was quickly replaced with the Controlled Substances Act of 1970 and as anti-marijuana movements grew more and more popular, research slowed down drastically as hemp got lumped in with all the anti-drug rhetoric (7). Since 2018, the Hemp Farming Act has legalized hemp on a federal level under the restriction that the total THC content (combined THCA and THCD9) must be less than 0.3% on a dry weight basis (8), and as of 2022, 37 states and territories have legalized medicinal cannabis use, 18 have legalized recreational cannabis, and 27 have decriminalized cannabis (Figure 2).

Figure 2. Map of the legality of cannabis in the United States (accessed 08 March 2022)

THE CHEMISTRY OF CBD

CBD is a phytocannabinoid which are cannabinoids that are made in plants like Cannabis Sativa (9). Without overcomplicating it, there are precursor molecules that undergo various chemical changes to make the progenitor cannabinoid, Cannabigerolic Acid or CBGA, then with the appropriately named CBDA synthase enzyme, is converted into Cannabidiolic Acid or CBDA (Figure 3).

Figure 3. The CBDA synthase mechanism

While CBDA is in this acid form, it does not interact with the body as well as CBD because of the carboxylic acid (COOH) attached to the molecule lowering the affinity or strength to bind to the appropriate receptor sites in the body (10). The molecule needs to go through a process called decarboxylation where through heat and light, removes that carboxylic acid in the form of carbon dioxide (CO2) (Figure 4) and converts CBDA into the more active CBD form that interacts with the body (11).

Figure 4. The decarboxylation of CBDA

Once decarboxylated, CBD has a greater affinity for the binding sites in the body and interacts with the endocannabinoid system to produce the effects on the body. In the endocannabinoid system, there are receptors in the nerves that can be activated by CBD such as the CB2 receptors which are mainly located throughout the body such as the liver and the lungs compared to the CB1 receptors which are mainly found in the brain (12). CBD acts as a partial antagonist with the CB1 receptor, binding and inhibiting the receptor from activating, and acts as an agonistwith the CB2 receptor, binding to the receptor and producing an effect on the body (13). While CBDA can pass through some of the same membranes, it does not bind to the CB receptors as well as CBD does due to that carboxylic acid, but it can bind to the 5-HT1a receptor better than CBD (14,15). These effects of binding to the receptors can range from pain relief, helping with anxiety and depression, to even protecting and preserving nerves against damage.

THE EFFECTS OF CBD

Studies have shown that taking CBD has supported potential benefits but research is still being performed to confirm any of the claims products will have. There are supported studies that show that CBD can reduce inflammation and reduce both acute and chronic pain with the best results for pain relief being a combination of CBD and THC (16,17). Some studies suggest that CBD can help with anxiety and depression by being an agonist to the 5-HT1a receptor which normally binds with serotonin to activate (18). And some studies suggest that CBD can have neuroprotective properties by activating various mechanisms in the central nervous system and CBD has even been shown to have anticancer properties by decreasing tumor growth, inhibiting angiogenesis, and decreasing metastasis (19,20,21).

TESTING CBD PRODUCTS

CBD is not regulated by the Food and Drug Administration (FDA) and it’s important to know what exactly is in the products that are on the market (22). When purchasing a CBD product, make sure that there is a Certificate of Analysis (COA) from an accredited third-party laboratory associated with that specific product, meaning that if the label claim is 1500mg per bottle, the COA will confirm that the label is correct. These COAs are usually found as a scannable QR code on the product itself or on the distributor/manufacturer’s website. Shopping for CBD products can also be overwhelming with everything out there, some things to avoid are any label claims of being able to cure or prevent anything. Know that there is still research being done to learn more about any potential health benefits CBD can provide and that these supposed benefits are not backed by the FDA.

Here at Ionization Labs, our Cannabinoid Testing Services are able to test the potency of CBD in products you develop or buy from a manufacturer. You can get verified and accurate results in as little as 24 hours!

Any comments or questions about testing can be directed to labservices@ionizationlabs.com or call us at 737-231-0772. In addition to our Cannabinoid Testing Services, we also offer CannID, an in-house testing solution for quality assurance/quality checks during the product development cycle for our customers that manufacture their own products.

References:

1. A History of CBD and Cannabis - both Controversial and Cool.
2. The Marihuana Tax Act of 1937 - Full Text of the Act
3. Did You Know... Marijuana Was Once a Legal Cross-Border Import?.
4. Structure of Cannabidiol, a Product Isolated from the Marihuana Extract of Minnesota Wild Hemp. I | Journal of the American Chemical Society
5. Hashish—I : The structure of Cannabidiol
6. Leary v. United States :: 395 US 6 (1969)
7. 1236 PUBLIC LAW 91-513-OCT. 27, 1970 [84 STAT. Public Law 91-513 Be it enacted by the Senate and House of Representatives
8. 115th Congress (2017-2018): Hemp Farming Act of 2018
9. Phytocannabinoids: Origins and Biosynthesis: Trends in Plant Science
10. In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa
11. Decarboxylation: What Is It and Why Is It Important?.
12. The Endocannabinoid System
13. Psychology blog: Agonists and antagonists - Pamoja.
14. Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses).
15. Agonistic properties of cannabidiol at 5-HT1a receptors
16. Pharmacotherapeutic considerations for use of cannabinoids to relieve pain in patients with malignant diseases
17. Cannabidiol (CBD) as a treatment of acute and chronic back pain: A case series and literature review
18. Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa
19. Cannabidiol as a Therapeutic Target: Evidence of its Neuroprotective and Neuromodulatory Function in Parkinson's Disease
20. Anticancer mechanisms of cannabinoids
21. Definition of angiogenesis - NCI Dictionary of Cancer Terms
22. FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD) | FDA