This blog follows the story of cannabis from human's first contact with the plant and its medicinal uses, to the discovery of the endocannabinoid system in the 1990s. Cannabis was first referenced around 12,000 years ago near the Altai Mountains in Central Asia, and since then, cannabis seeds have followed the migration of nomadic groups.The structure of the main psychoactive cannabinoid, tetrahydrocannabinol (THC), was discovered in Israel by Mechoulam and Gaoni in 1964. This opened the gate for many further developments in the ﬁeld of endocannabinoid system (ECS) research. Once the ECS became a topic of research and curiosity, research into the other elements of the plant gained strong momentum.
Contrary to a first impression, this is not a sensational news item about an adventurous tourist facing a prison sentence far away from home, but a scholarly archeological report about the excavation of the grave of a 45-year old male of high social status, probably a shaman, buried around 750 bc.1 The tomb was associated with the Tocharian culture, a nomadic population speaking a now extinct Indo-European language, depicted as blue-eyed and fair-haired in ancient Chinese records.
Classical records of the medicinal and psychoactive properties of cannabisThe common name for hemp and cannabis in China is Má, and this character can appear in word compositions meaning numbness or anesthesia. The topical application of cannabis for inflammation is mentioned in the Ebers papyrus, written in Egypt in about 1500 bc.
Herodotus (c. 484-c. 425 bc) describes how Scythians, after a King’s burial, prepare small chambers that are hermetically closed with woolen blankets laid on three posts sloping toward each other.11 The participants crawl under the blankets and throw hemp seeds (κάνναβις) on red hot stones and are “delighted” (ἀγάμενοι) by the fragrant smoke. Herodotus remarks that hemp either grows spontaneously or is sown and cultivated by the Scythians.
The first Golden Age of medical cannabis
The discovery of the endocannabinoid system, and the renewed debate on cannabis liberalizationMore than 100 cannabinoids have been isolated from cannabis; the two significant compounds are cannabidiol (CBD) and Δ 9 -THC. CBD was first isolated from marijuana in 1940, and its structure was reported in 1963.26 However, since CBD was not psychoactive, it was neglected and eclipsed by THC.
A singularity of the ECS is retrograde signaling, ie, the signaling initiates in postsynaptic neurons and acts upon presynaptic terminals. AEA and 2-AG are produced in the postsynaptic neuron and released into the synaptic space, then travel in a retrograde direction to the presynaptic terminal to interact with CB 1 Rs, which leads to a decrease in neurotransmitter release by the presynaptic neuron.
The conclusion of the 2017 report from the US National Academy of Medicine on “The Health Effects of Cannabis and Cannabinoids—The Current State of Evidence and Recommendations for Research” confirmed the limitation of scientific knowledge.35 The National Academy of Medicine report stated that conclusive or substantial evidence that cannabis or cannabinoids are effective is limited to only three domains. The recognized therapeutic uses were as follows: (i) alleviation of chronic pain in adults (cannabis); (ii) as antiemetics in the treatment of chemotherapy-induced nausea and vomiting (oral cannabinoids); and (iii) the improvement in patient-reported multiple sclerosis spasticity symptoms (oral cannabinoids).
At a time of cannabis liberalization, essential unsolved questions persist. For instance, we know little about the psychotomimetic effect of THC, even in persons without a history of mental disorders. Although considered a congener of heroin by the 1961 UN Single Convention, cannabis naturally belongs to the class of substances such as tobacco, alcohol, and caffeine, which are used regularly by all humanity. Mechoulam’s milestone discovery that Δ 9 -THC is the primary psychoactive principle, and the ensuing elucidation of the ECS, opened the gate for a new era in cannabis history.
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