History of cannabis and the endocannabinoid system

Abstract

This article retraces the story of cannabis from the earliest contacts of humans with the plant to its subsequent global expansion, its medicinal uses, and the discovery of the endocannabinoid system in the 20th century. Cannabis was attested to around 12 000 years ago near the Altai Mountains in Central Asia, and since then, cannabis seeds have accompanied the migration of nomadic peoples. Records of the medicinal use of cannabis appear before the Common Era in China, Egypt, and Greece (Herodotus), and later in the Roman empire (Pliny the Elder, Dioscorides, Galen). In the 19th century, orientalists like Silvestre de Sacy, and Western physicians coming into contact with Muslim and Indian cultures, like O’Shaughnessy and Moreau de Tours, introduced the medicinal use of cannabis into Europe. The structure of the main psychoactive phytocannabinoid, tetrahydrocannabinol (THC), was determined in Israel by Mechoulam and Gaoni in 1964. This discovery opened the gate for many of the subsequent developments in the field of endocannabinoid system (ECS) research. The advances in the scientific knowledge of the ECS place the debate on cannabis liberalization in a new context.

Polypharmacological Approaches for CNS Diseases: Focus on Endocannabinoid Degradation Inhibition

“…Furthermore, FAAH has cellular localization in the large neurons postsynaptic to CB 1 receptors [57,62]. Neurochemical studies in FAAH-knockout mice showed that endogenous concentrations of AEA and other N-acylethanolamines increased 10-15 times in several brain regions including cerebellum, hippocampus, and cortex [35,38]. Fascinatingly, these elevated levels of FAA in the CNS correlated well with the CB 1 receptordependent anxiolytic and analgesic effects [60,63,64].…”

“…They have closely related structures and physical properties, which make their separation difficult. In 1964, the active ingredient delta-9tetrahydrocannabinol (Δ 9 -THC) was isolated for the first time [38]. Surprisingly, although most phytocannabinoids have now been identified and their structures are chemically related, the only major mood-altering constituent is Δ 9 -THC.…”

Cannabinoids and Neurogenesis: The Promised Solution for Neurodegeneration?

“…Cannabis sativa plants contain different chemical species and more than 60 belong to the group of terpenophenolic compounds of cannabinoids [ 7 ]. The beneficial properties of C. Sativa are not a mystery, since historians found evidence of the use of this plant several centuries before Christ as painkiller or in shamanic rituals [ 8 ]. Cannabinoids that can be extracted directly from the plant fall under the name of phytocannabinoids, where Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD) are the major and most famous: THC is known for being psychoactive, while CBD does not possess any psychotropic effect and therefore, it represents a better candidate for medical use [ 9 ].…”

“The Two Sides of the Same Coin”—Medical Cannabis, Cannabinoids and Immunity: Pros and Cons Explained

“…The relationship between man and the Cannabis plant reaches back thousands of years; its first known use is as early as 10,000 years ago and as far back as the Stone Age [1]. The first historical evidence for the spiritual and medical uses of cannabis is from central Asia, India, and China, where its primary use was in treating rheumatic pain, malaria, beriberi, and gynecological disorders [2].…”