Salvia is best known as somewhat of a meme—the goofy, over-the-counter psychedelic prevalent in head shops, notorious for its uncomfortable, short-lived hallucinogenic trip. Pretty much harmless, but a way that many young psychonauts get their toes wet. But the herb Salvia divinorum carries great cultural significance in some parts of the world, and research into the plant can teach us a lot about the psychedelic mind and potentially unlock new drugs.
Some early studies in rats and mice suggest salvia could work as a potent antidepressant. Most recently, researchers synthesized an analog of salvinorin A—the active chemical in salvia—and hypothesized it could be developed into painkillers without the risk of addiction or deadly overdose. A study published this year explored another salvia-related chemical, mesyl salvinorin B, which may be effective at treating alcohol addiction, at least in rodent models.
Given mainstream media’s hysteric approach to salvia, it’s a little bizarre that a drug as powerful and otherworldly as salvia could potentially reveal numerous medical applications. Nor is the drug worth dismissing as little more than a party favor—like many entheogens, for some it holds great value for its spiritual and cultural use.
Before we dive in, let’s explore what makes salvia such a unique entheogenic substance.
What Is Salvia?
There are many plants in the salvia family, but S. divinorum is special. Sometimes known as “Diviner’s Sage” or “Magic Mint,” salvia is an herb native to a cloud forest in Sierra Mazateca, a mountainous area in Oaxaca, Mexico, where Mazatec Shamans have used the plant for centuries. It may have even been used by Aztecs. They used it to treat anemia, diarrhea, headache, and rheumatism.
They took between 20 and 80 leaves of what they called “hierba Maria” and either chewed them or crushed them into juice, unlike the highly concentrated headshop blends that are smoked. It wasn’t until the early ‘90s, however, that the plant’s unique pharmacology really began to unravel.
Despite the trip generally being challenging or uncomfortable (it’s described as dysphoric in contrast to euphoric), salvinorin A (SA) is not very toxic or addictive. Still, the hallucinations it can give are vivid and synesthetic, meaning you can hear colors or taste sounds. The intense effects peak at about two minutes, which users often compare to dreams or trance-like states.
Weight for weight, SA is one of the most potent naturally-occurring psychedelics known to man. LSD, for example, is so potent that a dose the size of a grain of salt can give a strong effect. Salvia is also active in the microgram range, with around 200 to 500 μg producing effects. Oddly, at high doses such as 10 milligrams, the drug seems to have no effect.
Salvinorin A has only a short duration in the body before it breaks down, which is why trips typically last 20 to 30 minutes. Strangely, SA does not bind to the 5-HT2A receptor, which is a serotonin receptor that the majority of psychedelics activate. This makes it quite a unique psychedelic. Instead, salvinorin A shows high preference for the kappa opioid receptor (KOR), which is found throughout the spine and brain.
Of course, like other opioid receptors, the KOR is related to analgesia, or pain relief. But it is also involved with balancing mood, stress and even urine regulation. Certain agonists at this site, like salvinorin A, can also cause potent psychomimetic hallucinations.
Because so many painkillers target the mu-opioid receptor instead, there is great interest in looking at one of the other three opioid receptors, including KOR. That makes SA analogs an attractive candidate for painkillers and other drugs that have less side effects than current pharmaceuticals.
Think about opium. It’s been used for all of recorded human history, but once morphine was isolated from the poppy plant in the early 19th century, it led to an explosion of analgesic drugs, essentially launching the pharmaceutical industry and forever changing the way we do medicine. Trust me, you wouldn’t want surgery without a morphine analog.
We could be on the cusp of another painkiller revolution, one without highly addictive drugs like fentanyl or oxycodone that can cause deadly overdose. And perhaps salvia will lead the way.
“The future of the [salvinorin A] scaffold is bright,” a March report concluded. Researchers at The Scripps Research Institute in La Jolla, California cataloged literally dozens of salvinorin analogs, which opens the door for more research, including clinical tests.
We still have a long way to go—we don’t even have a decent binding or predictive model for these drugs yet, as the researchers note—but perhaps the strange, powerful little psychedelic known as salvia still has more to teach us.