ABSTRACT
Unlike the opiates and many other medicinally used plant constituents, the cannabinoids were not identified before the twentieth century, which occasionally resulted in dosing problems of oral medicinal extracts which had been in use in the nineteenth century in Europe and North America. In the 1930s and 1940s, the chemical structure of the first phytocannabinoids had been successfully characterized (Loewe 1950), and the first synthetic derivatives of THC (parahexyl, DMHP) were successfully tested in clinical studies for epilepsy (Davis and Ramsey 1949), depression (Stockings 1947) and dependency to alcohol and opiates (Thompson and Proctor 1953). However, it was not until 1964 that Δ9-tetrahydrocannabinol (Δ9-THC, dronabinol), mainly responsible for the pharmacological effects of the cannabis plant (Dewey 1986; Hollister 1986), was stereochemically defined, and synthesized (Gaoni and Mechoulam 1964). Another scientific breakthrough in cannabinoid research was the detection of a system of specific cannabinoid receptors in mammals and their endogenous ligands within the past fifteen years. Both detections resulted in a considerable boost in research activities (see Figure 8.1). Dynamic of cannabinoid publications. Annual number of publications found in PubMed (<uri><a href="https://www.ncbi.nlm.nih.gov/PubMed/" target="_blank">https://www.ncbi.nlm.nih.gov/PubMed/</a></uri>) by using the keywords “cannabis, cannabinoids, THC, marijuana” between 1965 and 2002. https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9780203820803/946ca563-95be-452a-a87f-573ff13484ab/content/fig8_1_B.tif" xmlns:xlink="https://www.w3.org/1999/xlink"/>
