In 1963, a 33-year-old Israeli chemist at the Weizmann Institute of Science obtained five kilograms of Lebanese hashish from the Israeli National Police. He signed for it. He carried it to his laboratory. He and his colleagues began the work of isolating, for the first time in the history of pharmacology, the precise chemical compounds within the cannabis plant responsible for its documented effects. The Israeli police had no objection. The Israeli government had no objection. The plant had been used as medicine for five thousand years and its chemistry had never been systematically studied. Raphael Mechoulam intended to change that. He did not know, in 1963, that what he was beginning would take sixty years, span the discovery of an entirely new biological system within the human body, and produce findings that would eventually make every major cannabis prohibition law on earth scientifically indefensible. He knew only that the chemistry had not been done and that it needed to be.

Raphael Mechoulam biography Hebrew University Jerusalem Israeli chemist cannabis THC CBD isolation pharmacology

Raphael Mechoulam was born in Sofia, Bulgaria, in 1930. His father was a physician and the head of a Jewish hospital. In 1944, the family was deported to a labour camp as part of the Nazi occupation of Bulgaria. They survived. In 1949, Mechoulam emigrated to Israel and enrolled at the Hebrew University of Jerusalem, where he would spend the majority of his professional life. He studied chemistry and later earned his doctorate at the Weizmann Institute. By the early 1960s, he was a young researcher interested in the chemistry of natural products, specifically in the isolation and characterisation of the active compounds in plants that had long been known to produce physiological effects.

What struck him about cannabis, he said in numerous interviews across his career, was its anomalous position in pharmacology. Every other major plant-derived medicine, from morphine to aspirin to digitalis, had had its active chemistry identified and understood. Cannabis had not. It had been used as medicine for five thousand years, documented in the Ebers Papyrus, the Vedas, the Chinese pharmacopoeia, and the work of Dioscorides. It had appeared in the British Pharmacopoeia from 1850 to 1932. Queen Victoria's physician, Sir Russell Reynolds, had prescribed it for her menstrual cramps. And yet, in 1963, nobody knew which molecule in the plant produced which effect, or why. The chemistry was a blank. Mechoulam intended to fill it.

CBD cannabidiol isolation 1963 Mechoulam Shvo Weizmann Institute cannabis pharmacology non-psychoactive

Working with his colleague Yechiel Gaoni at the Weizmann Institute, Mechoulam published the first complete isolation and structural characterisation of cannabidiol, known as CBD, in 1963. CBD is the second most abundant cannabinoid in most cannabis varieties and the most abundant in hemp. It is non-psychoactive, meaning it does not produce the altered state of consciousness associated with cannabis use. Its pharmacological profile, which Mechoulam and subsequent researchers would spend decades exploring, includes anti-inflammatory, anticonvulsant, anxiolytic, and neuroprotective properties.

The 1963 isolation of CBD was a technical achievement of considerable precision. Mechoulam and Gaoni used nuclear magnetic resonance spectroscopy and other analytical techniques to determine, for the first time, the precise three-dimensional molecular structure of a major cannabis compound. The paper was published in the Journal of the American Chemical Society. It attracted limited attention at the time. The scientific community had not yet understood that this was the beginning of a series of discoveries that would eventually require a complete rethinking of human neuroscience.

THC tetrahydrocannabinol isolation 1964 Mechoulam Gaoni Journal American Chemical Society psychoactive cannabis compound

In 1964, Mechoulam and Gaoni isolated and characterised delta-9-tetrahydrocannabinol, the compound universally known as THC. This was the molecule responsible for the psychoactive effects of cannabis, the compound El Guindy had been describing in his 1925 Geneva speech without knowing its name, the compound the 1961 UN Single Convention had classified as dangerous without knowing its mechanism. Mechoulam now knew its structure. He knew its molecular weight. He knew how it was arranged in three-dimensional space. And he could now, for the first time, begin to ask the question that would define the next three decades of his research: what does this molecule actually do in the human body, and how does it do it?

The 1964 paper, published again in the Journal of the American Chemical Society, is one of the most significant publications in the history of pharmacology. It established the chemical identity of the primary active compound in the world's most widely used illegal substance and the world's oldest continuously documented medicine. It was the necessary precondition for every subsequent advance in cannabis science. Without knowing what THC was, no researcher could study how it worked. Mechoulam had provided the key. The lock would take another twenty-four years to find.

CB1 cannabinoid receptor discovery 1988 Allyn Howlett William Devane endocannabinoid system THC receptor binding site

The discovery of the cannabinoid receptor in 1988 was not made by Mechoulam directly. It was made by Allyn Howlett and William Devane at the St Louis University Medical School. But it was the direct consequence of Mechoulam's 1964 isolation of THC, which gave Howlett and Devane the molecular tool they needed to search for the receptor. Their method was elegant: they created a radioactively labelled version of THC and used it to find the protein on the surface of brain cells to which THC bound. When THC bound to a cell receptor, the radioactive label lit up. In 1988, they found it. They named it the CB1 receptor. It was concentrated in the brain, particularly in areas associated with memory, coordination, pain processing, and appetite.

The discovery of the CB1 receptor was immediately significant and immediately puzzling. The brain had evolved a specific receptor that fit THC like a key fits a lock. But evolution does not produce receptors for compounds that exist only in external plants. The existence of the CB1 receptor could mean only one thing: the brain produced its own molecule, chemically similar to THC, that normally occupied this receptor and performed some essential biological function. The receptor existed before cannabis existed. Cannabis had simply evolved a compound that happened to fit it. Mechoulam understood this immediately. He set about finding the brain's own molecule.

anandamide isolation 1992 Mechoulam Devane Sanskrit bliss endocannabinoid brain molecule cannabis receptor natural

In 1992, Mechoulam and his colleagues, working with William Devane who had now joined his laboratory in Jerusalem, isolated the brain's own THC-like molecule. They found it in pig brain tissue. It was a fatty acid neurotransmitter that bound to the CB1 receptor with similar affinity to THC. They needed a name for it. Mechoulam, characteristically, chose to look to the oldest human knowledge of the cannabis plant for guidance. He named the molecule anandamide, from the Sanskrit word ananda, meaning bliss or joy. The name was precise and deliberate. The Sanskrit tradition had named cannabis among the five sacred plants of the Vedas. The ancient Indian physicians had documented its therapeutic properties for three thousand years. And now a 62-year-old Israeli chemist, in a laboratory in Jerusalem in 1992, named the brain's own version of its active compound after a Sanskrit word. The circle of knowledge, across three millennia and three continents, was complete.

Anandamide is produced by the body on demand. It does not sit in a storage vessel waiting to be released the way most neurotransmitters do. It is synthesised by the neuron exactly when it is needed, released across the synapse, binds to the CB1 receptor on the adjacent neuron, produces its effect, and is then broken down by an enzyme called FAAH (fatty acid amide hydrolase). The entire transaction takes milliseconds. And its function, as Mechoulam and subsequent researchers would document, is the regulation of homeostasis: the brain's mechanism for maintaining its own biochemical balance. When the brain is over-excited, anandamide acts to calm it. When the brain is under-stimulated, anandamide acts to engage it. It is the body's own regulator of its own equilibrium. Cannabis works because it mimics this endogenous regulator. The plant did not introduce a foreign chemical into the human body. It introduced a compound that speaks the language the body was already using.

endocannabinoid system CB1 CB2 receptors anandamide 2-AG homeostasis 600 million years evolution vertebrates human body

The discovery of anandamide in 1992 established that the human body contained a complete biological system built around cannabis-like molecules. Subsequent research identified a second endocannabinoid, called 2-arachidonoylglycerol or 2-AG, which bound to both the CB1 receptor and a second receptor, CB2, concentrated in the immune system. Together, the CB1 receptors, the CB2 receptors, the endocannabinoids anandamide and 2-AG, and the enzymes that synthesise and break them down constitute what is now called the endocannabinoid system.

The endocannabinoid system is not a peripheral curiosity of human biology. It is one of the most ancient and widespread regulatory systems in the animal kingdom. Research published across the 1990s and 2000s established that the endocannabinoid system is present in all vertebrates and in many invertebrates. Its evolutionary origin is estimated at approximately 600 million years. It predates the cannabis plant by a considerable margin. The co-evolution of the cannabis plant with the endocannabinoid system, producing compounds that interact with a biological system present in virtually every animal on earth, is not an accident of chemistry. It is the result of a relationship between a plant and its animal environment that stretches across hundreds of millions of years of biological history.

The UN Single Convention of 1961 placed cannabis in Schedule IV on the basis that it had no medical value and high abuse potential. The endocannabinoid system was discovered in 1988. The UN Commission on Narcotic Drugs did not reclassify cannabis until December 2020, thirty-two years after the discovery of the CB1 receptor made the Schedule IV classification scientifically untenable. Thirty-two years. Every arrest, every prosecution, every provisional charge, every year served in prison for cannabis in every signatory nation between 1988 and 2020 occurred after the scientific basis for the prohibition had been destroyed, and before the international legal framework acknowledged it.

cannabis endocannabinoid system prohibition law Schedule IV UN 1961 reclassification 2020 scientific evidence ignored Mechoulam

Mechoulam was not an activist. He was a scientist, and he described himself as such throughout his career. He gave interviews. He spoke at conferences. He published papers. He did not campaign for legalisation. But in his later years, he became increasingly direct about the consequences of what his science had established. In an interview given to the Israeli newspaper Haaretz in 2012, he said: "I think the field of medicine has suffered tremendously by not using the cannabinoid system. It is a very important system that is still not utilised." In a 2021 interview with the Israeli news site Walla, he said: "Cannabis is not a dangerous drug. It is a drug that has been kept illegal for political reasons, not medical ones."

What Mechoulam's science established, and what makes these statements not advocacy but scientific description, is the following. Every human being on earth has an endocannabinoid system. CB1 receptors in the brain, in concentrations highest in the areas governing memory, movement, pain, and appetite. CB2 receptors in the immune system. Anandamide and 2-AG produced by the body on demand to regulate these systems. The endocannabinoid system is not an optional feature of human biology. It is a fundamental regulatory system that has been present in vertebrates for 600 million years. A state that criminalises the external activation of this system is not criminalising a foreign intoxicant. It is criminalising the stimulation of a biological system that every citizen carries within their own body and that the body's own chemistry is designed to activate. This is what Mechoulam proved. He did not say it was unjust. The science says it for him.

Mechoulam Nobel Prize chemistry endocannabinoid system scientific achievement recognition cannabis research legacy

Raphael Mechoulam was nominated for the Nobel Prize in Chemistry on multiple occasions and was widely considered, by scientists in his field, to be one of the most significant figures in 20th century pharmacology. He did not receive it. The Nobel Committee has never offered a public explanation. The scientific community's view was expressed clearly by Leslie Iversen, Emeritus Professor of Pharmacology at the University of Oxford, who described Mechoulam's discovery of the endocannabinoid system as one of the most important discoveries in neuroscience in the second half of the 20th century.

Whether the Nobel Committee's reluctance was connected to the political sensitivity of cannabis science is a matter of speculation. What is not speculation is the asymmetry between the scale of the discovery and the recognition it received. The identification of a completely new regulatory system within the human body, present in all vertebrates, governing pain, memory, appetite, stress response, immune function, and neurological balance, and the isolation of the molecules and receptors through which it operates, is a body of work of the first order of scientific significance. It has been cited in thousands of subsequent papers. It has led directly to the development of FDA-approved medicines. It has changed the understanding of how the brain regulates itself. And its author received the Israel Prize and the Rothschild Prize, but not the prize that the scientific world reserves for its most consequential discoveries.

Mechoulam spoke about the Nobel Prize in his characteristically measured way. He said, in an interview with the Times of Israel in 2022: "I believe we have done important work. Whether it deserves the Nobel Prize is not for me to say." He died on 9 March 2023. The Swedish Academy has not explained its decision. The endocannabinoid system remains one of the most significant scientific discoveries of the 20th century. Its discoverer is not among the Nobel Laureates. This fact sits in the record alongside every other fact this edition documents: the science pointed clearly in one direction. The institutions pointed elsewhere.

endocannabinoid system Mauritius cannabis prohibition Dangerous Drugs Act 2000 science evidence pharmacology therapeutic

The Dangerous Drugs Act 2000 was passed in Mauritius one year after Kaya died in police custody. It placed cannabis in the most restrictive category of the Mauritian legal framework. In 2000, the endocannabinoid system had been known to science for twelve years. Anandamide had been known for eight years. The CB2 receptor had been known for seven years. 2-AG had been known for five years. Every Mauritian citizen had an endocannabinoid system. Every Mauritian citizen produced anandamide in their brain. The Dangerous Drugs Act 2000 criminalised the external activation of a biological system that every Mauritian citizen already carried within their own body and that Raphael Mechoulam had spent the previous four decades proving was fundamental to human health.

One in five Mauritians has type 2 diabetes. The endocannabinoid system is directly involved in the regulation of metabolic function, and THCV, one of the cannabinoids in the cannabis plant, has been studied as a potential treatment for diabetic neuropathy. One in ten Mauritians is estimated to suffer from chronic pain. The endocannabinoid system is the body's primary endogenous pain-modulation system. An unknown number of Mauritians suffer from PTSD, anxiety disorders, and treatment-resistant depression. The endocannabinoid system is centrally involved in the regulation of fear memory, stress response, and mood. The medicine the Dangerous Drugs Act 2000 makes a criminal offence is, at the biological level, the external activation of a regulatory system that the body of every Mauritian citizen already contains. Mechoulam proved this. The law has not yet acknowledged it.

This is the fourth article in The Colonised Plant: The Cannabis Edition, June 2026, and the first in Chapter Two: The Science. The next article examines the endocannabinoid system in detail: what it is, how it works, and why the body's production of its own cannabis-like molecules makes the "unnatural drug" argument scientifically unsustainable. The complete edition is published at themeridian.info/june-2026.