Keywords

Cannabinoids · G-protein-coupled receptors · Cannabinoid 1 receptors ·

Cannabinoid 2 receptors · GRP55 · Palliative care · Signaling pathways ·

Apoptosis · Chemoresistance

12.1

Introduction

Cannabinoids are a group of alkaloids which are derived from the plant Cannabis

sativa. Their existence was first confirmed by China. Archaeological studies suggest

that C. sativa is cultivated for fibers since 4000 BC. The medical use of cannabis was

first mentioned in the Pen Ts’ao, a Chinese pharmacopeia (Read 1936). Later, Hua

T’o (AD 110–207), founder of Chinese surgery, used cannabis compound during

surgical procedures to anesthetize patients (Li and Lin 1974). Moreover, countries

like Nepal and India used the seeds of cannabis as spice and also for making cooking

oil (Touwn 1981). In India, cannabis seeds have been used for medicinal and

recreational purpose. Atharvaveda (Indian holy book) also mentioned cannabis use

against various diseases (Bowker 1997). In Indian traditional medicine, innumerable

functions of cannabis were identified such as analgesic, anticonvulsant, hypnotic,

tranquilizer, anesthetic, anti-inflammatory, antibiotic, antiparasitic, antispasmodic,

appetite stimulant, digestive, aphrodisiac, diuretic, and expectorant (Mikuriya 1969;

Aldrich 1997). Cannabis was considered sacred in Tibet and used to facilitate

meditation. However, over time, cannabis extracts have been explored worldwide.

In 1854, cannabis was included in the US dispensatory and was available in

pharmacies of western countries (Robson 2001). Meanwhile, at the same time,

recreational use of cannabis rapidly started spreading among the adult population

apart from its medicinal uses. Subsequently, possession or trading of cannabis

became an offense by law throughout the USA. As a result, cannabis extract and

its constituents were removed from the US pharmacopeia in 1942 and lost its

therapeutic legitimacy (Kandel 1984). In 1996, California was the first state to

pass Medical Marijuana Law (MML). As of January 2016, majority of US states

lifted the prohibition barriers and started considering outright legalization. As a

result, 25 additional states have legalized marijuana for medicinal use and 5 states

legalized for recreational use (Pacula and Smart 2017).

12.2

Discovery

A renewed interest in the studies about cannabis began in the late twentieth century.

Two researchers in 1964, Gaoni and Mechoulam, identified Δ⁹ THC as the major

psychoactive ingredient of C. sativa (Mechoulam and Gaoni 1965). This discovery

became the milestone toward identifying other compounds of cannabis. In 1987, two

new potent cannabinoid agonists HU-210 and desacetyl-L-nantradol were developed

(Melvin and Johnson 1987). The receptors on which they act are called the

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S. Singh et al.