Cannabidiol: Cannabis for Medicine

An old plant, a new medicine

Cannabis has been used in traditional medicine for thousands of years, but its chemistry was a mystery until the twentieth century. The plant makes more than a hundred related compounds called cannabinoids. In 1940 the American chemist Roger Adams isolated one of them, cannabidiol (CBD), from wild hemp, but he could not determine its complete structure.

In 1963 the Israeli chemist Raphael Mechoulam and his colleague Yuval Shvo, at the Hebrew University of Jerusalem, published the structure of CBD, and in 1964 Mechoulam and Yehiel Gaoni isolated THC (Δ⁹-tetrahydrocannabinol) and showed that it, not CBD, is responsible for the “high” of cannabis.

Same formula, different molecules

CBD and THC have exactly the same molecular formula, $\ce{C21H30O2}$: they are isomers. In CBD, the benzene ring carries two –OH groups and is joined to a separate six-membered ring. In THC, one of those –OH groups has formed an ether link to the other ring, closing an extra ring. This small change alters the molecule’s shape and how it binds to cannabinoid receptors in the brain: THC strongly activates the CB1 receptor and is intoxicating, whereas CBD is not.

Epidiolex

Some children have rare, severe forms of epilepsy, such as Dravet syndrome and Lennox–Gastaut syndrome, in which seizures happen many times a day and standard medicines often fail. Reports from families using cannabis extracts led the British company GW Pharmaceuticals to develop Epidiolex, a purified, standardized CBD solution. In three randomized, placebo-controlled trials with more than 500 patients, it reduced seizure frequency. On 25 June 2018 the US FDA approved it for patients two years and older: the first FDA-approved medicine containing a purified substance from the cannabis plant.