Cannabinoid Pharmacology: The First 66 Years — A Field's History Told by Someone Who Lived It
Cannabinoid pharmacology: the first 66 years
In 2006, Roger Pertwee — who had been working in cannabinoid pharmacology since 1968 — published a concise historical narrative of the entire field, from the first cannabinoid isolation in 1940 through six decades of receptor discoveries, endocannabinoid identification, and therapeutic development.
In 2006, a pharmacologist at the University of Aberdeen sat down to write a history of his field. It began in 1940, with the first isolation of a cannabinoid from cannabis. It ended in 2006, with selective receptor drugs entering clinical trials and an entire signaling system mapped across the body.
Sixty-six years. And Roger Pertwee had been in the field for thirty-eight of them.
This wasn't a historian reviewing archives. It was a builder surveying the house he helped construct — from a postdoc extracting cannabinoids from legal cannabis tincture in 1968 Oxford, to a co-founder of the field's professional society, to the developer of one of its most important research tools. When Pertwee wrote the history, he was writing partly from memory.
The Man in the Story
Roger Pertwee holds three degrees from Oxford — a BA in biochemistry, a DPhil in pharmacology, and a DSc in physiological sciences. He entered cannabinoid research in 1968, four years after Mechoulam characterized THC, as a postdoctoral researcher in Sir William Paton's pharmacology laboratory at Oxford.
When Pertwee began his work, cannabis tincture was still a legal medicine in the United Kingdom. His early research used THC and CBD extracted directly from pharmaceutical-grade cannabis tincture — a supply chain that would be unimaginable in most countries just a few years later as drug scheduling tightened worldwide. He worked with the crude plant material before most of the synthetic tools that define modern cannabinoid pharmacology existed.
His initial contributions included demonstrating that CBD potently inhibits liver enzymes (hepatic microsomal enzymes) and developing the "ring immobility test" — a behavioral assay for measuring cannabinoid effects in rodents that is still used today, over fifty years later.
In 1974, Pertwee moved to Aberdeen, where he would spend the rest of his career. And it was in Aberdeen that he made his most lasting methodological contribution — by borrowing a tool from another field entirely.
Hans Kosterlitz's laboratory at the University of Aberdeen was famous for opioid pharmacology — Kosterlitz had co-discovered the endogenous opioids enkephalins. His lab used the mouse isolated vas deferens as a standard bioassay for opioid receptor agonists: apply the compound, measure the inhibition of electrically-stimulated muscle contractions.
Pertwee realized this same tissue preparation might work for cannabinoids. He was right. The mouse vas deferens turned out to be an extraordinarily sensitive and quantitative functional bioassay for CB1 receptor agonists — far more precise than behavioral tests. It became the gold standard for measuring cannabinoid receptor activation and was used by labs worldwide for over two decades.
The connection between opioid and cannabinoid research tools, forged in the same Aberdeen corridor, would prove symbolically appropriate: the two systems would later be found to interact extensively in pain processing.
In 1990, at a scientific meeting in Kolympari, Crete, Pertwee was among a small group of cannabinoid researchers who decided to formalize their community. They founded the International Cannabinoid Research Society (ICRS) — the field's first dedicated professional organization. Pertwee would serve as its president twice.
A year later, at a 1991 conference in Palm Beach, Florida, Pertwee met Raphael Mechoulam. Mechoulam's lab had just discovered anandamide. Using his vas deferens bioassay, Pertwee and his colleague Graeme Griffin provided the first functional evidence that anandamide doesn't just bind the cannabinoid receptor — it activates it. Binding had been shown in the original 1992 paper. Functional activation was Pertwee's contribution.
66 Years in Nine Pages
The review itself is concise — nine pages in the British Journal of Pharmacology. But it covers six and a half decades of discovery with a clarity that only a participant could achieve. Where Pacher's 74-page review mapped diseases and Piomelli's review mapped mechanisms, Pertwee mapped time. The field as a narrative, each chapter building on the last.
A Chain of Dependencies
The review's most important insight isn't any single discovery — it's the structure of how the field developed. Each breakthrough depended specifically on the one before it. You couldn't skip steps.
This chain explains something that frustrates cannabis advocates: why did it take so long? The answer isn't politics (though that didn't help). It's science. Each step required specific technical capabilities that didn't exist until the previous step was completed. You couldn't discover anandamide in 1964 because the receptor hadn't been found yet. You couldn't find the receptor in 1940 because pure THC didn't exist. The 66 years weren't wasted time — they were the minimum path through a chain of dependencies.
The Tools He Built
Pertwee's personal contribution to this chain was primarily methodological. He didn't discover a molecule or clone a gene. He built tools — ways to measure what cannabinoids do, precisely and reproducibly.
Without tools like these, the discoveries in the timeline above couldn't have been made — and the therapeutic applications couldn't have been explored. The glamorous history is the discoveries (THC! receptors! anandamide!). The enabling history is the tools. Pertwee understood this better than most because he was, fundamentally, a tool-builder.
Where History Stood in 2006
The review was published at a specific moment: the endocannabinoid system was fully characterized, selective drugs existed for both receptors, and therapeutic applications were entering clinical trials. Rimonabant had just been approved in Europe. FAAH inhibitors were in development. The field felt like it was on the verge of delivering medicines.
38
years of personal involvement in the field (1968-2006) by the time Pertwee wrote this review. He started when cannabis tincture was still a legal UK medicine. He wrote the history at the moment the field pivoted from discovery to application.
Of the 66 years covered, Pertwee was an active researcher for more than half. He's not reviewing history — he's recounting it.
University of Aberdeen faculty profile; Pertwee (2006)
What the review couldn't know was what would happen next. Rimonabant would be withdrawn within two years due to psychiatric side effects. A FAAH inhibitor trial would cause a death in 2016. CB2 drugs would fail Phase 2. The therapeutic promise would prove harder to fulfill than anyone in 2006 imagined.
But the basic science — the 66 years of pharmacology Pertwee documented — held firm. Every receptor, every endocannabinoid, every enzyme, every signaling pathway he described has been confirmed and extended. The foundation was solid. Only the translational path was harder than expected.
Pertwee continued active research for years after the review, eventually receiving the ICRS Lifetime Achievement Award in 2018 — recognizing more than half a century of contributions to a field he helped build from nearly the beginning.
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Cite this study
Pertwee, R G. (2006). Cannabinoid pharmacology: the first 66 years. British Journal of Pharmacology, 147(S1), S163-171. https://doi.org/10.1038/sj.bjp.0706406