Short history of cannabinoids
Short history of cannabinoids

Throughout recorded history, and even before it, humans have used plants as medicine. Ancient cultures created organized lists of various plants and their medicinal properties[1]. We now know that the healing properties of plants come from the active substances within them. Over hundreds of millions of years, plants evolved to create a large number of diverse natural substances with different biological properties.

The first successful attempt to chemically isolate active substances from a plant, took place in the beginning of the 19th century (1805)[2]. Chemists isolated alkaloids, among them codeine and morphine, from the opium poppy. These breakthroughs laid down the foundation for plant-based drug discovery. Two hundred years later, more advanced technologies and modern separation techniques have made this process routine. The medicinal and psychoactive properties of cannabis have been documented since at least the second millennium BC when the plant was used by cultures stretching from the Middle East to China.


When scientists started to research the plant, they wanted to find out which substances were responsible for its psychoactive properties. This research discovered that there are actually dozens of chemicals in the plant with closely related structures and physical properties, specific to the species. These are called cannabinoids. As scientific techniques improve, researchers have been able to isolate and study more and more cannabinoids.

Timeline of major cannabinoid discoveries

1899 - Isolation of the first plant cannabinoid (phytocannabinoid), Cannabinol (CBN)[3].

Its structure was later discovered between 1932-1940[4],[5];


1940 - Isolation of Cannabidiol (CBD)[4]. Its structure was later discovered in 1963[6];






1963 - Isolation of Tetrahydrocannabinol (Δ9-THC), the active substance responsible for the psychotropic effect of cannabis[7].


Since the 1960s researchers have discovered many more phytocannabinoids. And they’ve also discovered how and why these chemicals interact wdith our bodies the way they do. They discovered what we call the endogenous cannabinoid system.

Timeline of major discoveries about the endogenous cannabinoid system

1988 - Discovery of the cannabinoid receptor type 1 (CB1) receptor[8] and its cloning in 1990[9];


1992 - Isolation and structure elucidation of the endogenous cannabinoid anandamide[10];

1993 - Discovery of the Cannabinoid Receptor type 2 (CB2)[11];


1995 - Isolation and structure elucidation of the endogenous cannabinoid 2-AG[11],[12].

Bibliography

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2. Hamilton GR and Baskett TF: In the arms of Morpheus the develop- ment of morphine for postoperative pain relief. Canadian journal of anaesthesia = Journal canadien d'anesthesie 47: 367-374, 2000. 

3. Wood TB, Spivey WTN and Easterfield TH: Cannabinol. Part I. J Chem Soc 75: 20–36, 1899. 

4. Adams R: Marihuana. Harvey Lectures. 37 168–197: 1941–1942. 

5. Cahn RS: Cannabis indica resin, Part, III The constitution of Cannabinol. J Chem Soc 1342–1353, 1932. 

6. Mechoulam R and Shvo Y: Hashish. I. The structure of cannabidiol. Tetrahedron 19: 2073-2078, 1963. 

7. Gaoni Y and Mechoulam R: Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish. Journal of the American Chemical Society 86: 1646-1647, 1964. 

8. Devane WA, Dysarz FA, 3rd, Johnson MR, Melvin LS and Howlett AC: Determination and characterization of a cannabinoid receptor in rat brain. Molecular pharmacology 34: 605-613, 1988. 

9. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC and Bonner TI: Struc- tre of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346: 561-564, 1990. 

10. Devane WA, Hanus L, Breuer A, et al: Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science (New York, NY) 258: 1946-1949, 1992. 

11. Munro S, Thomas KL and Abu-Shaar M: Molecular characterization of a peripheral receptor for cannabinoids. Nature 365: 61-65, 1993. 

12. Mechoulam R, Ben-Shabat S, Hanus L, et al: Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to canna- binoid receptors. Biochem Pharmacol 50: 83-90, 1995. 

13. Sugiura T, Kondo S, Sukagawa A, et al: 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochemical and biophysical research communications 215: 89-97, 1995.