- By Jorrit
- 2 comments
3. A BRIEF HISTORY OF CANNABIS RESEARCH

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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 19402,3. 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.
Contemporary Trends
Legalisation of the plant in recent years in Canada and USA helped this process, as cannabis became more available to research teams. Not surprisingly, this reflects today in the amount of publications on cannabis, where North-American countries are currently leading in the field (Figure 2). Countries such as France, Germany, Italy and the Netherlands are also making important contributions to this field in the old continent. Overall, research on cannabis is more prevalent in the western world, highlighting how legalisation efforts go hand in hand with increased knowledge about this plant. This interest in research comes also from an increase in the total estimated value of cannabis market. For instance, it is estimated that cannabis sales in the United States increased from $5.7 billion in 2015 to $7.1 billion in 20168.
Today, cannabis research embraces many other fields than chemistry and pharmacology. The changing legal status of the plant around the world favoured research on the effects of cannabis, both from a medical and social point of view. As shown in Figure 3, topics such as “Substance Abuse”, “Addiction” as well as “Schizophrenia” and “Psychosis” appear today among the topics most often connected to cannabis-related studies, with “Cannabinoids” and “Cannabidiol” closely following behind. The mechanisms through which cannabis excerts its effects remain a focus for research today; our understanding of them being enriched by technological advances in both analytical chemistry, biomedical sciences and neuroscience. This trend is understandable, as comprehending the effects that the plant has on consumers has the interest of both research teams as well as cannabis producers and regulators (local governments for instance). In 2018, research on the harmful effects of cannabis in the USA has received twice as much funding as research on cannabinoids therapeutic and other applications of the plant9. Nonetheless, interest into the underlying chemistry and biology of the plant is still alive. This is motivated by, for instance, the many applications that knowledge about the chemistry that underlies smell and taste of cannabis, or about the nuances that distinguish strains for instance, can have in the cannabis industry and beyond10.
The increase in legality helps with access to cannabis in many regions of the planet, allowing researchers to learn more and more about this plant! Within this context, the Adriaan van Royen Institute wants to establish itself as a promoter of scientific knowledge about cannabis. In the coming edition of the newsletter, we will cover advances in cannabis chemistry, biology, pharmacology, societal impact and more. Stay tuned!
Sources
- On the Preparations of the Indian Hemp, or Gunjah (Cannabis Indica), Their Effects on the Animal System in Health, and Their Utility in the Treatment of Tetanus and Other Convulsive Diseases. Br Foreign Med Rev 10, 225-228 (1840).
- Adams, R., Hunt, M. & Clark, J.H. Structure of Cannabidiol, a Product Isolated from the Marihuana Extract of Minnesota Wild Hemp. I. Journal of the American Chemical Society 62, 196-200 (1940).
- Wood, T.B., Spivey, W.T.N. & Easterfield, T.H. III.—Cannabinol. Part I. Journal of the Chemical Society, Transactions 75, 20-36 (1899).
- Gaoni, Y. & Mechoulam, R. Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish. Journal of the American Chemical Society 86, 1646-1647 (1964).
- Pain, S. A potted history. Nature 525, S10-S11 (2015).
- Pertwee, R.G. Cannabinoid pharmacology: the first 66 years. Br J Pharmacol 147 Suppl 1, S163-71 (2006).
- Crocq, M.A. History of cannabis and the endocannabinoid system Dialogues Clin Neurosci 22, 223-228 (2020).
- National Academies of Sciences, E. et al. The National Academies Collection: Reports funded by National Institutes of Health. in The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research (National Academies Press (US)
- O’Grady, C. Cannabis research data reveals a focus on harms of the drug. Science 369, 1155-1155 (2020).
- Aliferis, K.A. & Bernard-Perron, D. Cannabinomics: Application of Metabolomics in Cannabis (Cannabis sativa L.) Research and Development. Frontiers in Plant Science 11(2020).



Sources
- On the Preparations of the Indian Hemp, or Gunjah (Cannabis Indica), Their Effects on the Animal System in Health, and Their Utility in the Treatment of Tetanus and Other Convulsive Diseases. Br Foreign Med Rev 10, 225-228 (1840).
- Adams, R., Hunt, M. & Clark, J.H. Structure of Cannabidiol, a Product Isolated from the Marihuana Extract of Minnesota Wild Hemp. I. Journal of the American Chemical Society 62, 196-200 (1940).
- Wood, T.B., Spivey, W.T.N. & Easterfield, T.H. III.—Cannabinol. Part I. Journal of the Chemical Society, Transactions 75, 20-36 (1899).
- Gaoni, Y. & Mechoulam, R. Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish. Journal of the American Chemical Society 86, 1646-1647 (1964).
- Pain, S. A potted history. Nature 525, S10-S11 (2015).
- Pertwee, R.G. Cannabinoid pharmacology: the first 66 years. Br J Pharmacol 147 Suppl 1, S163-71 (2006).
- Crocq, M.A. History of cannabis and the endocannabinoid system Dialogues Clin Neurosci 22, 223-228 (2020).
- National Academies of Sciences, E. et al. The National Academies Collection: Reports funded by National Institutes of Health. in The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research (National Academies Press (US)
- O’Grady, C. Cannabis research data reveals a focus on harms of the drug. Science 369, 1155-1155 (2020).
- Aliferis, K.A. & Bernard-Perron, D. Cannabinomics: Application of Metabolomics in Cannabis (Cannabis sativa L.) Research and Development. Frontiers in Plant Science 11(2020).
2 Comments
Giovanni
Very interesting, keep up the good work! Looking forward to reading about the scientific research aspect of cannabis!
Tim
Really informative and well-written. Thank you for sharing!