A concise history tracing cannabis from 12,000-year-old Central Asian origins through ancient medicine, 19th-century rediscovery, 20th-century prohibition, and the molecular discoveries that finally explained why the plant works.
Read this if you want the complete narrative arc of cannabis and humans — from nomadic shamans to Mechoulam's lab — in one sitting.
12,000 years of cannabis use, 3,500 years of medical documentation, 60 years of molecular science — and only 3 confirmed therapeutic indications
The Backstory
In the Turpan Basin of northwestern China, near the Flaming Mountains of the Xinjiang-Uighur autonomous region, archaeologists opened a 2,750-year-old tomb and found a man buried with approximately 800 grams of cannabis.
He was about 45 years old, likely a shaman, and of high social status. The cannabis was not hemp — not fiber, not rope, not food. Botanical and phytochemical analysis confirmed it had been cultivated specifically for elevated THC content. Male plant parts had been selectively removed because they produce less psychoactive resin. Whoever prepared this burial stash knew exactly what the plant did and wanted the strongest possible material.
That was 750 BCE. Cannabis had already been accompanying humans for more than 11,000 years by then.
In 2020, French psychiatrist Marc-Antoine Crocq published what may be the most elegant short history of that 12,000-year relationship — tracing the plant from Central Asian nomads through ancient pharmacies, Scythian rituals, Islamic scholars, Victorian physicians, twentieth-century prohibition, and finally to Raphael Mechoulam's laboratory in Israel, where science finally caught up with what humans had known empirically since the last ice age.
12,000 Years in One Timeline
Research Timeline
Cannabis and Humans: A 12,000-Year History
Crocq (2020), Dialogues Clin Neurosci 22(3):223-228
The Ancient Pharmacy
Cannabis appears in the medical records of nearly every major ancient civilization — always for the same core indications: pain, inflammation, nausea, and anxiety. The consistency across cultures that had no contact with each other is striking.
China (~2,000 BCE)
The BenCao compendium lists cannabis among 365 fundamental herbs. The Chinese character Ma (麻) means both 'hemp' and 'numbness/anesthesia' — the plant's medical identity is embedded in the language itself. The Han dynasty surgeon Hua Tuo reportedly performed surgery under general anesthesia using wine mixed with herbal extracts possibly containing cannabis.
The word for the plant IS the word for anesthesia
Egypt (~1,500 BCE)
The Ebers papyrus — one of the oldest surviving medical documents — prescribes topical cannabis for inflammation. Egyptian cannabis preparations later appeared in Homer's Odyssey, when Helen served Greek soldiers a drug called nepenthes ('no-grief') from Egypt to quiet their pain from the Trojan War.
Topical anti-inflammatory use 3,500 years ago
Mesopotamia (~1,000 BCE)
Assyrian clay tablets reference cannabis (azallu in Akkadian) for medicinal use, apparently including treatment of depression — possibly the oldest documented psychiatric indication for any drug.
Earliest psychiatric indication on record
Rome (1st-2nd century CE)
Pliny the Elder documented cannabis root decoction for arthritis and gout. Dioscorides confirmed anti-inflammatory properties. Galen noted that Italians served cannabis-infused cakes for dessert, producing warmth and, in large quantities, a toxic vapor affecting the head.
Cannabis cakes at Roman dinner parties
Crocq (2020), Dialogues Clin Neurosci 22(3):223-228
The point is not that ancient people were sophisticated pharmacologists. They were not — they had no concept of receptors, molecules, or dose-response curves. The point is that the therapeutic profile they observed empirically — pain, inflammation, nausea, appetite, anxiety — maps almost exactly onto what we now know the endocannabinoid system regulates. They found the signal without knowing the mechanism. It took another 3,500 years to find the mechanism.
The Scythian Ritual and the Sanskrit Connection
One of the most vivid scenes in ancient historical writing comes from Herodotus, writing around 450 BCE. He describes Scythian post-burial purification rituals:
They set up three sticks leaning together, stretch woolen blankets over them, crawl underneath, and throw hemp seeds onto red-hot stones. The seeds produce such smoke that no Greek vapor-bath could surpass it. The Scythians, delighted (agamenoi), howl with pleasure.
This was not medicine. This was ritual — grief processing, purification, and, frankly, getting high together after burying the dead. The Scythians were Central Asian nomads, exactly the population that had been traveling with cannabis seeds for thousands of years.
Twenty-five centuries later, when William Devane isolated the brain's own cannabis-like molecule in Mechoulam's laboratory, the team needed a name. They chose anandamide — from the Sanskrit word ānanda (आनंद), meaning bliss, happiness, or pleasure. The same word that could describe what the Scythians experienced howling over their hot stones.
The naming was deliberate. The molecule that your brain produces to regulate mood, pain, and pleasure was named after the same experience that humans have been seeking from cannabis since prehistory. Neuroscience looped back to the Scythians.
West Meets East: The 19th Century Rediscovery
For centuries, European medicine had largely forgotten cannabis. It was the encounter with Islamic and Indian cultures that brought it back — through three remarkable individuals.
William Brooke O'Shaughnessy (1809-1889) was born in Limerick, Ireland, trained in medicine at Edinburgh, and relocated to Calcutta. There he encountered a plant whose intoxicating effects were "then unknown in Europe" — except among youth experimenting with "hasheesh" in Marseilles, where Napoleon's soldiers had brought it back from their Egyptian campaign.
O'Shaughnessy made a critical observation: the cannabis growing in India was fundamentally different from the hemp growing in Europe. Though the plants looked identical, the Indian varieties produced a "resinous secretion" — what we now know as THC-rich trichomes — that European hemp lacked, "likely attributable to climatic differences." He was the first Western physician to document the relationship between growing conditions and psychoactive potency.
He published his results in 1839, describing traditional Indian preparations: Gunjah (dried flowers), Bang (leaf preparations), and Majoon — a green, buttery electuary made by boiling cannabis in fat and adding sugar. The name derives from the Arabic Ma'jūn (kneaded). His publication introduced cannabis therapeutics to Western medicine and triggered the first golden age of medical cannabis in Europe.
Jacques-Joseph Moreau de Tours, a French psychiatrist and student of the great Esquirol, traveled the Middle East from 1836 to 1840. He encountered dawamesk — cannabis leaves and flowers boiled in butter, flavored with rose, jasmine, or honey — essentially the same preparation O'Shaughnessy had documented as majoon.
But Moreau had a different agenda. He was not looking for a medicine. He was looking for a model of madness.
He experimented with dawamesk himself, observing that it produced "pure bliss alongside idea disorganization and temporal distortions." He shared it with Parisian poets and novelists, including Théophile Gautier, creating what became the famous Club des Hashischins. But behind the literary glamour, Moreau was conducting the first systematic study of drug-induced altered states as a window into psychiatric illness.
He documented cannabis-induced psychoses and abulia (inability to make decisions or act) — observations that remain clinically relevant today in the study of cannabis-induced psychosis. Moreau de Tours was, in a sense, the first psychopharmacologist.
The First Golden Age — and Why It Ended
Myth vs. Reality
Emperor Shennong first documented cannabis as medicine in 2737 BCE, making it one of humanity's oldest medicines with nearly 5,000 years of continuous medical use.
The Shennong Bencao Jing was not written in 2737 BCE. It is attributed to the mythical emperor Shen Nong but was actually compiled during the Han dynasty (221 BCE - 220 CE) from older oral traditions. The '2737 BCE' date appears in popular histories but has no archaeological support. The oldest verified physical evidence of medicinal/psychoactive cannabis use is the Xinjiang shaman burial (~750 BCE) and the Ebers papyrus (~1500 BCE). Cannabis use is genuinely ancient — but the popular 5,000-year claim inflates the documented record.
The Evidence
Crocq notes the Shennong attribution is 'likely exaggerated' and dates the actual written BenCao to the Han dynasty. Archaeological and textual scholars place the compilation between 300 BCE and 200 CE.
Crocq (2020), Dialogues Clin Neurosci 22(3):223-228
The genuine golden age of Western medical cannabis came in the late 19th century. Queen Victoria used cannabis for menstrual pain. Empress Elisabeth (Sissi) of Austria used it for cough — and preferred it precisely because it was a natural remedy in an era when she distrusted synthetic medicines.
But the most important figure was J. Russell Reynolds, appointed in 1878 as Queen Victoria's household physician-in-ordinary. In 1890, he published a summary in The Lancet of more than 30 years of clinical experience with cannabis. His documented indications — facial neuralgia, migraine, dysmenorrhea, numbness and limb paresthesiae in gouty patients — are recognizably the same pain conditions that dominate modern medical cannabis registries, where pain syndromes account for 42.4% of all cases.
Reynolds also identified the two problems that would haunt cannabis medicine for the next 130 years:
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Standardization was impossible. "Hemp grown during different seasons, and in different places, varies in the amount that it contains of the therapeutic agent." He could not isolate the active ingredient — that would take until 1964.
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Dosing was unpredictable. Without knowing the active compound or its concentration, Reynolds could only use careful titration — tinctures with cautiously increased doses administered via drops on sugar or bread.
These problems remain partially unsolved today. The standardization challenge is exactly why pharmaceutical cannabinoids (Marinol, Sativex) were developed — and why whole-plant cannabis products vary so dramatically in quality and effect.
The Dark Century
The golden age ended not because cannabis stopped working but because better-characterized alternatives arrived (aspirin, barbiturates, opioids) and because political forces turned against the plant:
- 1937: The US Marihuana Tax Act effectively criminalized cannabis
- Within years: Cannabis was removed from the American pharmacopeia
- 1961: The UN Single Convention on Narcotic Drugs placed cannabis under Schedule IV — the strictest international control — alongside heroin
- 1970: The US declared cannabis Schedule I, defined as having "no accepted medical use and a high potential for abuse"
Crocq notes the irony: the UN placed cannabis — a substance with at least 3,500 years of documented therapeutic use — in the same category as heroin. The scheduling made cannabis research "practically impossible" in the United States for decades. Scientists could study heroin more easily than cannabis.
The Israeli Breakthrough
In 1964, a chemist who had survived the Holocaust as a child in Bulgaria changed everything. Raphael Mechoulam, working at the Weizmann Institute in Israel, obtained 5 kilograms of seized cannabis from the police — reportedly carrying it on a public bus — and set about separating its chemical components using column chromatography.
He and Yechiel Gaoni identified the structure of delta-9-tetrahydrocannabinol: the molecule that explained 12,000 years of human experience with cannabis.
To confirm they had the right compound, they fed cake containing the isolated THC to healthy volunteers — fellow researchers and their wives. The results were dramatic and personality-dependent: some laughed, some experienced panic attacks, some became unusually open in conversation. One researcher's wife reportedly talked non-stop for hours and then baked a cake, insisting the experience was wonderful.
Mechoulam's discovery was not just a chemical identification. It was the key that unlocked an entire biological system. Once you know the molecule, you can find the receptor. Once you find the receptor, you can find the body's own version of the molecule. The entire cascade — CB1 in 1990, anandamide in 1992, CB2 in 1993 — flows from that afternoon in the Weizmann Institute.
The System Revealed
The endocannabinoid system that emerged from Mechoulam's discovery has a unique feature that Crocq highlights: retrograde signaling. Unlike almost every other neurotransmitter system in the brain, endocannabinoid signals travel backward.
In conventional neurotransmission, a presynaptic neuron releases a chemical that activates the postsynaptic neuron. In the endocannabinoid system, it's reversed: the postsynaptic neuron produces anandamide or 2-AG, releases them backward across the synapse, and they act on CB1 receptors on the presynaptic terminal — turning down future neurotransmitter release.
This makes the endocannabinoid system a braking system for the brain. It doesn't initiate signals — it modulates them. It says "that's enough" to neurons that are firing too much. Pain signals, stress responses, inflammatory cascades — the endocannabinoid system regulates them all by providing retrograde feedback.
This is why cannabis affects so many different functions: pain, mood, appetite, memory, inflammation, sleep. It's not that cannabis is a wonder drug. It's that cannabis hijacks a system whose job is to regulate everything else.
And it's why the Scythians howled, why Helen's soldiers forgot their grief, why Queen Victoria's cramps eased, and why modern patients report relief from the same conditions documented on Assyrian clay tablets 3,000 years ago. One system. One plant. 12,000 years.
Where 12,000 Years Led
After all of that history — after Shennong and Herodotus and Pliny and O'Shaughnessy and Queen Victoria and Mechoulam — what does modern science actually confirm?
Conclusive/Substantial Evidence
- Chronic pain in adults (cannabis)
- Chemotherapy-induced nausea and vomiting (oral cannabinoids)
- Multiple sclerosis spasticity symptoms (oral cannabinoids, patient-reported)
Three indications — exactly the conditions ancients documented
Moderate Evidence
- Short-term sleep improvement (cannabinoids, in pain patients)
- Limited evidence for many other conditions
- Ongoing research in dozens of areas
Still building the evidence base
What We Still Don't Know
- Optimal dosing for any indication
- Long-term safety of chronic use
- Whether CBD protects against THC's psychotomimetic effects
- Cannabis-induced psychosis risk in general population
- Cognitive effects during neurodevelopment
12,000 years of use, decades of prohibition, fundamental questions unanswered
US National Academy of Sciences (2017); Crocq (2020)
Crocq frames this as the central paradox of cannabis history. We have 12,000 years of human experience, 3,500 years of medical documentation, 60 years of molecular science, an entire endogenous signaling system named after the plant — and we can only confirm three therapeutic indications with high confidence. Not because the plant doesn't work, but because decades of prohibition made the research practically impossible.
The three confirmed indications — chronic pain, chemotherapy nausea, and MS spasticity — are, as Crocq notes, almost exactly the same conditions documented by Reynolds in 1890, by Pliny in 70 CE, and in the Chinese BenCao two millennia ago. Science has confirmed what empirical observation established thousands of years earlier — but it has not yet expanded much beyond it.
Key Takeaways
Related Research
The Discoveries That Explained 12,000 Years
Each pillar study below represents a moment when science caught up with what humans had observed empirically about cannabis. Together, they form the molecular explanation for 12,000 years of history.
Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish
Gaoni & Mechoulam (1964)
The structure of THC — the molecule that explained what the Scythians were inhaling and what Queen Victoria was taking
Structure of a cannabinoid receptor and functional expression of the cloned cDNA
Matsuda et al. (1990)
CB1 — the receptor that THC activates, found primarily in the brain and explaining the psychoactive effects
Isolation and structure of a brain constituent that binds to the cannabinoid receptor
Devane et al. (1992)
Anandamide — the brain's own cannabis, named from the Sanskrit word for bliss, connecting neuroscience back to the Scythians
Molecular characterization of a peripheral receptor for cannabinoids
Munro, Thomas & Abu-Shaar (1993)
CB2 — the immune receptor, explaining cannabis's anti-inflammatory effects documented since the Ebers papyrus
Cannabinoid pharmacology: the first 66 years
Pertwee (2006)
Pertwee's own 66-year history — the scientific complement to Crocq's cultural one
Is it true that cannabis has been used as medicine for 5,000 years?
The popular claim traces to Emperor Shennong and a date of 2737 BCE, but this is misleading. The Shennong Bencao Jing was actually compiled during the Han dynasty (roughly 300 BCE - 200 CE) from older oral traditions — the 2737 date has no archaeological support. The oldest verified physical evidence of psychoactive cannabis use is a burial in Xinjiang, China (~750 BCE), and the oldest surviving medical text mentioning cannabis is the Egyptian Ebers papyrus (~1,500 BCE). Cannabis use is genuinely ancient — at least 3,500 years of documented medicine, and 12,000 years of human-plant coexistence — but the "5,000 years" figure overstates the documented record.
Why was cannabis placed in the same legal category as heroin?
The 1961 UN Single Convention on Narcotic Drugs classified cannabis under Schedule IV — the strictest control — based on perceived abuse potential rather than pharmacological evidence. This classification made research extremely difficult. As Crocq points out, cannabis more naturally belongs with substances like tobacco, alcohol, and caffeine — regularly used by humanity and potentially demonstrating less somatic toxicity than alcohol or tobacco. The scheduling reflected political and cultural attitudes of the mid-20th century more than scientific assessment.
What is retrograde signaling and why does it matter?
Most brain signaling goes in one direction: a sending neuron releases chemicals that activate a receiving neuron. The endocannabinoid system works backward — the receiving neuron produces endocannabinoids (anandamide and 2-AG) that travel back to the sending neuron and tell it to quiet down. This makes the endocannabinoid system a volume control for the brain, regulating how much activity occurs in pain circuits, stress responses, immune reactions, and more. It's why cannabis affects so many different body functions — it plugs into a system that regulates everything else.
What the researchers found
Cannabis use dates to approximately 12,000 years ago in Central Asia. Ancient medical texts from China, Egypt, Mesopotamia, Greece, and Rome all document cannabis for pain, inflammation, and nausea — the same conditions now known to be regulated by the endocannabinoid system. Mechoulam's 1964 identification of THC triggered the discovery of CB1 (1990), anandamide (1992), and CB2 (1993). Despite this 12,000-year relationship, only three therapeutic indications have conclusive evidence as of 2017.
Why it matters
Provides the most concise authoritative overview of the entire cannabis-human relationship, connecting ancient empirical observations to modern molecular discoveries. Frames the central paradox: 12,000 years of use but only three confirmed therapeutic indications, largely due to 20th-century prohibition.
The numbers in context
~12,000 years of cannabis-human coexistence. 800g cannabis in Xinjiang shaman burial (~750 BCE). 30+ years of clinical experience documented by Reynolds (1890). 3 confirmed therapeutic indications (2017 NAS). 42.4% of modern medical cannabis registry cases are pain syndromes.
How the study worked
Historical review article synthesizing archaeological, textual, and scientific sources across 12,000 years of human-cannabis interaction. Published in Dialogues in Clinical Neuroscience.
What this study cannot tell us
As a 6-page review, necessarily compressed. Some archaeological dates carry uncertainty. The '2737 BCE Shennong' claim is noted as exaggerated. Western-centric in its 19th-century coverage. Does not cover cannabis in sub-Saharan African or pre-Columbian American traditions in detail.
How to read the evidence
Historical review — not graded for evidence strength. Synthesizes archaeological, textual, and scientific primary sources. Published in a peer-reviewed clinical neuroscience journal.
When this study was published
Published in 2020. Covers history through the 2017 US National Academy of Sciences report on cannabis evidence.
The bigger picture
This review contextualizes the entire pillar study series within a 12,000-year narrative. Every molecular discovery profiled in earlier pillar studies — THC structure, CB1, anandamide, CB2 — appears here as the resolution of millennia of empirical observation.
Questions still open
- Why has 12,000 years of empirical use plus 60 years of molecular science produced only three confirmed therapeutic indications? Could earlier legalization have prevented the research gap? How does the endocannabinoid system's retrograde signaling explain the breadth of ancient therapeutic claims?
Common questions
Has cannabis really been used as medicine for 5,000 years?
Why was cannabis classified alongside heroin?
What is retrograde signaling in the endocannabinoid system?
Read the original research
History of cannabis and the endocannabinoid system
Dialogues in Clinical Neuroscience, 22(3), 223-228
Citation
Crocq, Marc-Antoine. (2020). History of cannabis and the endocannabinoid system. Dialogues in Clinical Neuroscience, 22(3), 223-228. https://doi.org/10.31887/DCNS.2020.22.3/mcrocq
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