Using the query “Cannabis” in an academic search engine (PubMed; https://pubmed.ncbi.nlm.nih.gov) we find 29,898 publications spanning from 1840 to 2022. The oldest article available represents work by William O’Shaughnessy, an Irish physician¹. He studied applications of cannabis as a pain-relieving medication and as treatment for spasticity; he is largely credited with introducing cannabis to Europe and North America and for being the first physician to study the plant scientifically (Newsletter 1). One could think that scientific efforts to study this complex plant and its many facets proceeded steadily from the 1840s, but this is hardly the case. As Figure 1 shows, the number of publications containing the keyword “Cannabis” followed an interesting trend over the past 180 years. At the beginning, most of the research focused on the potential medical applications of the plant. It wasn’t until 1899 that the first cannabinoid compound was isolated, cannabinol (CBN), followed by cannabidiol (CBD) in 1940^2,3. Research efforts continued in the following years and culminated with the identification and characterization of tetrahydrocannabinol (THC), the main psychotropic cannabinoid, in 1964⁵. This discovery, combined with an increase in popularity of the recreational use of cannabis in Europe and North America during the 1960s and 1970s, favored a marked increase in publications investigating the pharmacological aspects of cannabis, as can be seen as a spike around 1970 (Figure 1).

Despite this academic interest, a series of increasingly strict legal measures tightened the regulations around cannabis, culminating in the UN Convention on Psychotropic Substances of 1971 that drastically restricted the possibility to carry out research⁵. Evidence was cumulating over those years about the existence of cannabinoids receptors, specific proteins that recognize the substances contained in cannabis and mediate their effects on the body. In the 1980s and 1990s, these receptors were identified and characterized, as well as their endogenous ligands⁶. The discovery of the endocannabinoid system, name given to the neuromodulatory system on which cannabinoids act, is an important landmark in cannabis research that renewed the interest into the therapeutic potential of cannabinoids. It also contributed to inform the debate about cannabis prohibition and pointed out the many unknowns about the actual risks associated with its use, as well pointing out the difference between recreational and medical use⁷. An important date in this sense is 1996, year in which the Compassionate Use Act approved the medical use of cannabis for patients in specific circumstances. From this moment onward the scientific interest about the plant, both from academia and industry, literally exploded.