Mithridate, Universal Antidote or the Ultimate Hoax?

Mithridate was one of the most complex and highly sought-after preparations during the Middle Ages and Renaissance era. This somewhat mythical, ancient tonic which contained more than 60 ingredients, was used for centuries, particularly in Italy and France as an antidote. Petrus Andreas Matthiolus, naturalist and personal physician to various European royalty, considered it more effective against poisons than Venice treacle - and easier to make! The term now refers to any all-purpose antidote to poison.

This astonishing cure was not invented by a doctor but by Mithridates VI Eupator Dionysus, also known as Mithridates the Great, who was born in 135 BC and king of Pontus until 63 BC.

Mithridates was a prince of Persian and Greek ancestry. He claimed lineage from many revered warriors - Cyrus the Great, the family of Darius the Great, as well as Alexander the Great. He has been called the greatest ruler of the Kingdom of Pontus. Under his leadership, Pontus expanded to absorb several of its small neighbors and he briefly contested Rome’s control in Asia Minor.

The Tragic Early Life of a Great King

In his early teens, Mithridates' mother poisoned his father at a lavish banquet. Upon his death, she became regent of Pontus until a male heir was of age. Mithridates, however, was not the only competitor for the throne, as his brother was favored by their mother. When he experienced pain during meals, which he suspected was brought on by slow poisoning by his own mother, he fled into the wilderness.

We cannot know who Mithridates met while in hiding or how he came by the knowledge, but it is said he consumed non-lethal levels of poisons and mixed these into a tonic to make him immune. He invented an intricate "universal antidote" against poisoning. 

Mithradates VI Eupator on a silver coin of Pontus, 2nd–1st century BCE (Yale University Art Gallery)

Mithridates emerged from hiding and returned to Pontus between 116 BC and 113 BC. He had grown to become a man of considerable stature and physical strength. He overthrew his mother and brother, imprisoning both, and became the sole ruler of Pontus. His mother died in prison of natural causes, while his brother may have been tried for treason and executed. Mithridates gave both royal funerals. 

Mithridates first married his younger sister Laodice, who was 16 years old. He wanted to solidify his claim to the throne and ensure the succession of his legitimate children by preserving the purity of their bloodline. In total, he had at least six wives, numerous mistresses, and several children.

All his life, Mithridates worried that he was the target of assassination attempts. Since royal court intrigues were relatively common, his concerns were justified. Legend has it he was guarded in his sleep by a horse, a bull, and a stag, which would make a terrible racket whenever anyone approached the royal bed. He exercised to increase his strength, carried a weapon, and continued studying toxicology by researching and examining all known toxins. Supposedly he tested potential remedies on prisoners and his work paid off.

While Mithridates was a man of great stature and physical strength, a brave fighter, and a keen hunter, ruthless and often cruel, he was also a polyglot. According to Pliny the Elder's writings, Mithridates could speak the languages of all the 22 nations he governed.

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The Kingdom of Pontus at its height: before the reign of Mithridates VI (dark purple), after his early conquests (purple), and his conquests in the first Mithridatic wars (pink) (Public Domain)

He is remembered as one of the Roman Republic’s most formidable and successful enemies, fighting some of the most spectacular battles in ancient history. He even threatened to invade Italy itself. In 88 BC, he organized the slaughter of over 100,000 Roman and Italian non-combatants in a single day. He managed to evade capture and intimidated the Romans when he kept coming back for more, even after heavy losses. He foiled assassination attempts and eliminated rivals.

Mithridates treated Greek, Roman, and Asian alike and all were welcome at his court provided they could be of use to him, but he trusted no one. His grand attempts at building an empire and his aggressive foreign policy ensured his place in history, but his constant paranoia and obsession with toxicology has ensured that his name is forever linked to poison.

The Irony of Mithridates’ Death

After Pompey defeated him in Pontus, Mithridates fled to the lands north of the Black Sea in the winter of 66 BC. Not many years later, the nobles there rebelled against his rule. Left with nowhere else to go, legend states that Mithridates took out the poison that he always carried next to his sword. Perhaps it was the only poison without a cure, or a dose big enough to kill him. Two of his daughters asked him to let them have some of the poison first. It killed them at once but had no effect on him. Was this because he had taken his antidote for so many years, or because there was not enough poison left to kill the powerfully built king?

One account states that in desperation he asked his Gallic bodyguard and friend to kill him using a sword. The Romans recorded an alternate history reporting that while Mithridates was weak from the poison ingested, assassins stabbed him to death.

Mithridates, who had lived a most remarkable life, even experienced an extraordinary end, “partly by poison and partly by the sword he was at once self-slain and murdered by his foes.” Mithridates' body was buried in the royal sepulcher at Sinope, the Pontic capital, alongside his ancestors. 

How Mithridate Was Made

After his death in 63 BC, the recipe for Mithridates’ antidote was found in his cabinet and taken to Rome. It was translated into Latin and later improved upon by physicians to Nero and Marcus Aurelius. It had likely undergone considerable alterations since the time of Mithridates.

The mithridate was said to contain up to 65 ingredients (Tryfonov / Adobe Stock)

All versions listed many ingredients as well as the required quantities which were then "pounded and taken up in honey. A piece the size of an almond is given in wine. In other affections an amount corresponding in size to an Egyptian bean is sufficient."

The manufacture of mithridate continued into the nineteenth century. Ephraim Chambers, in his 1728 Cyclopaedia, wrote: "Mithridate is one of the capital Medicines in the Apothecaries Shops, being composed of a vast Number of Drugs.”

As noted in the British Journal of Clinical Pharmacology, “Mithridatium and the related product Theriac were both regarded from the time of their original formulations … until the mid 18th century as universal panaceas. Any failure of these products to achieve the desired therapeutic result was attributed to defective composition or manufacture. As a result, measures were introduced to ensure the quality of ingredients used in these products...” A decision was made in 1799 for a committee of eminent physicians to scrutinize all new products prior to their launch to the public. This formed the basis of modern medicine regulation.

For centuries doctors and scientists have attempted to discover Mithridates’ exact panacea and versions of the elixir have existed for thousands of years. But was Mithridates’ theriac really an antidote or a cure? Unfortunately, the original recipe is now hopelessly lost.

Mithridate - a Showy Parade of the Art, and a Colossal Boast of Science

In the Middle Ages, mithridate was used as part of a treatment to ward off threats of plague. It’s said that Oliver Cromwell took a large dose of mithridate as a precaution and found it cured his acne.

Working plague doctor (Andrey Kiselev / Adobe Stock)

Pliny the Elder, whom it must be noted was a Roman and could have been biased, was skeptical of mithridate with its numerous ingredients: “The Mithridatic antidote is composed of fifty-four ingredients, no two of them having the same weight, while of some is prescribed one sixtieth part of one denarius. Which of the gods, in the name of Truth, fixed these absurd proportions? No human brain could have been sharp enough. It is plainly a showy parade of the art, and a colossal boast of science.”

While many sought to rediscover Mithridates’ life-saving potion, few took the time to question boastful claims made by Mithridates and ancient authors. Mithridates spoke openly about his love for toxicology and his antidote. He is said to have publicly ingested fatal doses of poison to prove his invention’s worth, but we have no proof whether he took poison or a harmless substance that looked similar.

Perhaps it was only an elaborate ruse meant to persuade his enemies that any poisoning attempts were going to fail. Had there really been such a fantastic medicine, many would have tried stealing the formula to leave him vulnerable or use it themselves as Mithridates had a tendency to poison his enemies. The next best thing to having a complicated, miraculous cure is to publicly lie about having a complicated, miraculous cure.

These are not the only holes in the myth of Mithridates. In order to build immunity against certain poisons, he reportedly included small amounts of arsenic and possibly venoms into his almond-sized tablets, and while this could work in theory, the results would probably have been disastrous when mixed by someone unskilled. Mithridates would likely have killed himself while experimenting in the wilderness as a young teen. Even surviving experimentation and adjustments of dosage, the effect on his body after years of ingesting toxins would have been severe. Yet he died at the great age of 71 years, fit and healthy.

Famous Poisoners of Ancient Times

Of course, King Mithridates was not the only ancient who studied toxicology. In ancient Rome, poisoning became a favorite of those who wanted to kill without a trace when murder needed to be discreet. It was not always reliable. 

in the 1 ^st century Locusta was a famous poison maker in the Roman Empire. She supposedly took part in the murder of Emperor Claudius by supplying a poison to his wife, the empress Agrippina the Younger. When this poison failed, a doctor assassinated Claudius with a poisoned feather put down his throat to induce vomiting. Locusta advised Agrippina to use  Atropa belladonna, which was commonly used in ancient Roman murders.  

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Locusta testing in Nero's presence the poison prepared for Britannicus, painting by Joseph-Noël Sylvestre, 1876 (Public Domain)

Locusta was a favorite of emperor Nero (Agrippina's son) for several years. In AD 55, she was asked by Nero to concoct a poison to murder Claudius' sons, Britannicus. When this poison was slow to work, she was flogged and threatened with immediate execution. She then supplied a quicker-acting poison that succeeded. Nero rewarded Locusta with a full pardon and large country estates where he sent pupils to learn from her.

The popular story of Cleopatra’s death was most likely untrue. Cleopatra, like Mithridates and Locusta, knew about poisons. The Roman historian Cassius Dio wrote that she died a "quiet and pain-free death", which she would not have had, had she been bitten by the asp. One theory states that Cleopatra used a mixture of hemlock, wolfsbane and opium. The last would have allowed her to fall into a deep, calm sleep before dying.

The death of Cleopatra by Reginald Arthur (1871-1934) (Public Domain)

Even though doubts remain that Mithridates the Great ever invented a truly effective and universal panacea, it does not mean that he did not experiment or take precautions against poisonings. He was fascinated by toxicology, and there were undoubtedly a few known cures for certain ancient poisons, but the field of study was unsophisticated at the time. Perhaps the king who devoted time to his research discovered a few basic remedies.

While Mithridates no doubt took some sort of tablet daily, this may have been nothing more than a modern-day version of a health boost. Someone as paranoid as Mithridates probably continuously research in a desperate attempt to find a universal cure. In the meantime, by bragging that he had already come up with marvelous remedy, he managed to ward off successful assassination by poison. And thanks to his complex list of plants, poisons and venoms, as well as the doses he recorded, we now have medicine regulations.

Top image: Apothecary vintage set of bottles, herbs and mortar Source: Kiryl Lis/ Adobe Stock

By Michelle Freson