Appendix C: Cannabis
History and Terminology
Updated date
The evolution of cannabis goes back 28 million years to the Eastern Tibetan Plateau[McPartland_2019]. The original strains appear to have been more hemp than marijuana. Chinese farmers used cannabis for oil, rope, clothing, and paper four thousand years ago[History_of_cannabis_2020]. Two thousand seven hundred years ago, shamans were using cannabis to get high[Russo_2008].
The Historic Rise and Fall of Cannabis
Cannabis in the form of hemp cloth existed in the British Isles in the fourth century BC[princess]. Knowledge of medical cannabis came to Europe in the 19th century, mainly through the efforts of Sir. William Brooke O'Shaughnessy. He observed its use in India, did experiments, published his research, brought quantities of Cannabis indica specimens and seeds to Briton, and inspired pharmacies to carry cannabis products such as "hemp resin" [Neenan_2016][Mukherjee_2017].
Cannabis, including industrial hemp, was effectively driven underground in the United States in 1937 by the Marihuana Tax Act[Marihuana_Tax_Act_of_1937]. The act was primarily the brainchild of Harry Anslinger, the founding commissioner of the Federal Bureau of Narcotics. He sold the idea with purported cases of stoned black men raping young white women and the like[Anslinger_2020].
Time Out for Some Terminology
Cannabis is both a species and a genus. The species
contains three well-known wild varieties: Cannabis sativa, Cannabis indica,
and Cannabis ruderalis. They all readily interbreed. Standard botanical
conventions force them into the same species
The term hemp has typically been associated with Cannabis sativa used to make industrial products[webster_hemp]. The Mexican Pharmaceutical Academy introduced the term marijuana in 1846 as a synonym for Cannabis indica used for intoxication[webster_marijuana].
In 1937, nobody knew about CBD and THC. There was no firm distinction between hemp and marijuana, so the Marijuana Tax Act drove both underground.
Roger Adams and colleagues first extracted CBD from cannabis in 1940. Loewe, Wollner, Matchett, and Levine extracted THC from cannabis in 1942[Pertwee_2006].
The official boundary between hemp and marijuana was set in 2018 by the 2018 farm bill. Cannabis strains with less than 0.3% THC are hemp, and the others are marijuana. This distinction is now universal among growers, merchants, and users.
Today, “marijuana” is still a dirty word to many. There is a trend to use "cannabis” as a polite synonym for marijuana even though hemp plants are cannabis plants.
Modern Research and Repression
Dr. Raphael Mechoulam first determined the structure of THC in 1964. Israel awarded him the state's highest cultural honor for his cannabis research in 2001 — the Israel Prize[Pertwee_2006][Wilcox_2016]. The twenty years following Dr. Mechoulam's achievement led to many discoveries, including the ability of cannabis to stimulate appetite, dampen nausea, quell seizures, relieve pain, and even stop an asthma attack in seconds rather than minutes.
Dr. Mechoulam is thought to have coined the word cannabinoid in 1967. It's meaning has grown over the years. Today, cannabinoids are chemicals that are either structurally similar to THC or that bind to cannabinoid receptors[cannabinoid_webster]. CBD qualifies as a cannabinoid through its structural similarity to THC. The terpene β-caryophyllene qualifies as a cannabinoid because it binds strongly to CB2 receptors.
cannabinoid_webster. Cannabinoid. Definition. Unattributed. Merriam-Webster. Updated 2022 March 12.
In the meantime, the U.S. Congress replaced the Tax Act with the Controlled Substances Act of 1970. This act banned cannabis altogether[Controlled_Substances_Act], and the era of mass incarceration began[Anonymous_2016]. In 1988, a new three-strikes law mandated life imprisonment for chronic cannabis users. At that time, all government-funded cannabis research was devoted to substantiating the adverse effects of marijuana[Lee_2013].
Some of this government research led to a significant breakthrough in 1988. Working in Dr. Allyn Howlett’s laboratory at the St. Louis University Medical School, a graduate student, William Anthony Devane, discovered cannabinoid receptors — cell membrane receptors activated by THC[Mo_2019][Devane__1988][Deutsch_2018]. The discovery of cannabinoid receptors inspired new research the world over. Investigators learned that most cannabinoid receptors were of two types, CB1 and CB2[Cannabinoid_receptor].
CB1 is found mainly in the central nervous system and the lungs, liver, kidneys, and white blood cells. CB2 is located in the immune system, the red bone marrow that produces blood cells, and the peripheral nerve terminals, where its activation relieves pain. CB2 is also found throughout the gut.
Researchers wondered why brains and bodies should have receptors for THC and other cannabinoids. They guessed there had to be as yet undiscovered internally created cannabinoids whose purpose was to bind to the cannabinoid receptors. In other words, there had to exist endocannabinoids. The first such was discovered in 1992 by chemists Ondřej Hanuš and William Anthony Devane. They named it anandamide after the Sanskrit word for bliss[Hanuš_2020].
Anandamide binds to the same CB1 and CB2 receptors as THC. CBD and THC raise anandamide levels[Elmes_2015]. Another endocannabinoid goes by the name 2-AG[Lu_2015]. It also binds to both CB1 and CB2.
Can anandamide get people high? No, it is metabolized so quickly that nobody will get high on it. However, some people have less of the FAAH enzyme that degrades anandamide. Such people have a gene variant that causes lower levels of FAAH to be produced, resulting in higher levels of anandamide. We know anandamide is an upper because this gene variant is more prevalent in countries with happier people. This key to happiness counts even more than having a great climate, which is also valuable[Minkov_2016][MacRae_2016].
World Cannabis Legality
In 2022, recreational cannabis was still illegal in most of the world[Legality_of_cannabis].
References
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History_of_cannabis_2020. Ancient uses [in History of cannabis]. Full text. WikiProject Cannabis. Wikipedia. Updated 2020 June 22.
Russo_2008. Phytochemical and genetic analyses of ancient cannabis from Central Asia. Full text. Russo E, Jiang H, Li X, et al. Journal of experimental botany. Online 2008 November 01.
Neenan_2016. Sir\. William Brooke O’Shaughnessy - Medical Cannabis Pioneer. Essay. Neenan B. medium.com. 2016 June 12.
webster_hemp. History and Etymology for hemp. Etymology. Unattributed. Merriam-Webster. Updated 2022 March 27.
princess. A Brief History of Hemp in the UK. Exposition. Unattributed. UK Hemp Association. Publiished 2017 February 14.
Mukherjee_2017. W\. B\. O'Shaughnessy and the Introduction of Cannabis to Modern Western Medicine. Essay. Mukherjee S. The Public Domain Review. 2017 April 19.
webster_marijuana. History and Etymology for marijuana [in Merriam-Webster.com Dictionary]. Etymology. Unattributed. Merriam-Webster. Updated 2022 March 23.
webster_species. Species. definition. Unattributed. Merriam-Webster. Updated 2022 March 28.
Marihuana_Tax_Act_of_1937. Marihuana Tax Act of 1937. Full text. WikiProjects Cannabis, Drug Policy, Law. Wikipedia. Updated 2020 June 25.
Anslinger_2020. Harry J\. Anslinger. Full text. WikiProjects Pennsylvania, Biography, Cannabis. Wikipedia. Updated 2020 July 3.
Pertwee_2006. Cannabinoid pharmacology: the first 66 years. Full text. Pertwee R. British journal of pharmacology. Published 2006 January.
Wilcox_2016. The Guy Behind The High: Meet The Father Of THC. Full text. Wilcox A. Herb. Online 2016 February 23.
Controlled_Substances_Act. Controlled Substances Act. Full text. WikiProjects Cannabis, Politics, United States. Wikipedia. Updated 2020 July 10.
Anonymous_2016. American History, Race, and Prison [in Reimagining Prison Web Report]. Full text. Unattributed. Vera Institute. Online 2016 September.
Lee_2013. The Marijuana Miracle: Why a Single Compound in Cannabis May Revolutionize Modern Medicine. Full text. Lee M. The Nation. Online 2013 November 18.
Mo_2019. Why did it take scientists so long to discover the endocannabinoid system? Full text. Mo M. momjmd.com. 2019 August 13.
Devane__1988. Determination and Characterization of a Cannabinoid Receptor in Rat Brain. Abstract. Devane W, Dysarz F, Johnson M, Melvin L, Howlett A. Molecular pharmacology. Published 1988 Novmber.
Deutsch_2018. IN MEMORIAM: William Anthony Devane. Full text. Deutsch D. The International Cannabinoid Research Society. Posted 2018 October 15.
Cannabinoid_receptor. Cannabinoid receptor. Full text. WikiProjects Molecular and Cell Biology, Cannabis, Pharmacology. Wikipedia. Updated 2020 June 29.
Hanuš_2020. Lumír Ondřej Hanuš. Full text. WikiProjects Biography, Czech Republic. Wikipedia. Updated 2020 February 24.
Elmes_2015. Fatty Acid-Binding Proteins (FABPs) Are Intracellular Carriers for Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD). Full text. Elmes M, Kaczocha M, Berger W, et al. The Journal of biological chemistry. Online 2015 February 9.
Minkov_2016. A Genetic Component to National Differences in Happiness. Abstract. Minkov M, Bond M. Journal of Happiness Studies. Online 2016 January 12.
MacRae_2016. Do YOU have the happiness gene\? It may depend where you live: Sweden and Ghana have lots of cheery DNA, but it's bad news for the Chinese and Jordanians. Full text. MacRae F. Daily Mail Online. Updated 2016 January 14.
Legality_of_cannabis. Legality of cannabis. Full text. WikiProjects Cannabis, Law. Wikipedia. Updated 2022 February 5.
Lu_2015. An introduction to the endogenous cannabinoid system. Full text. Lu H-C, Mackie K. Biological psychiatry. Online 2015 October 30.