For hundreds of years, the Mazatec people of Oaxaca in southern Mexico have conducted rituals that combine their own ancient beliefs with those of Catholicism. Healers use herbs and other plants, incense, and chanting in order to learn the cures for illness, seek out lost objects and people, and travel to spiritual or astral dimensions. The most famous component of their rituals is the “magic” mushroom, which contains the psychedelic chemical psilocybin. Another tool in the Mazatec healing toolbox is “divine sage,” Salvia divinorum, which is said to belong to the Virgin Mary and the leaves of which are consumed for their physical and spiritual healing powers. If the patient has prepared their body and mind properly beforehand, if patient and healer are both able to sing well enough during the ceremony, and if the Catholic Saints and indigenous spirits are amenable, a ritual involving the use of Salvia can purportedly lead to profound healing.

One of the most intriguing reasons to participate in these Salvia rituals is for the healing of substance abuse and dependence. We have traveled to Oaxaca to learn from the healers and villagers about the history of Salvia and its uses. The results of our fieldwork with the Mazatec will be published later this year and can be followed here. The Mazatec employ Salvia as an effective treatment for arthritis and inflammation, headaches, gastrointestinal and other problems. Oaxacan villagers also told us of Salvia helping to cure people of addictions to alcohol, inhalants, and stimulants such as cocaine. They believe that the feminine entity that inhabits the plant heals the body, teaches the patient what causes and sustains the addiction, and guides the patient on the road to recovery and a balanced life.

Scientists are beginning to uncover what may be happening during these rituals, as outlined in a recently published review paper. Salvia alters dopamine levels in ancient parts of the brain responsible for motivation, reward, and the internal sense of what is going on in our bodies. The Mazatec use Salvia as part of a larger ritual and worldview that cannot be reduced to a single pharmacological mechanism. However, by studying Salvia, we may be able to better understand the addiction process in the brain and devise new treatments for stimulant-use disorders. Western medicine has developed pharmacological treatments for the abuse of opioids, alcohol, and tobacco, but not for psychostimulant abuse. Increasing our understanding of Salvia and the brain may help us to reduce the suffering of those who abuse and are dependent upon cocaine and other stimulants.

Salvia leaves contain over a dozen unique chemicals, including salvinorin-A, which is the most potent naturally occurring psychedelic substance known. It is about 10 times more potent than psilocybin, for instance. Salvinorin A is a selective kappa opioid receptor agonist, which is unlike any other psychoactive substance. Drugs like psilocybin, LSD, and MDMA produce their psychedelic effects by activating part of the serotonin system. Salvia does not affect the serotonin system — and LSD, psilocybin, and all the rest do not affect the kappa opioid system in any way.

Salvinorin-A seems to disrupt many of the effects of cocaine and the addiction cycle. For instance, rats tend to move about more frequently when given cocaine compared to placebo. Rats given salvinorin-A and then cocaine do not display this cocaine-induced hyper-locomotion. Salvinorin-A is not a general sedative though, as rats on salvinorin-A do move about as normal in an open field. Rats trained to push a lever to give themselves cocaine will do so rather frequently when they have nothing else to do. Rats given salvinorin-A will push the cocaine lever much less frequently, but will push a lever for sugar water just as frequently as usual. Salvinorin-A does not seem to suppress movement, lever pushing, or motivation for stimuli. Instead, it seems to suppress only cocaine-related behaviors and motivation.

These anti-addiction effects are likely due to salvinorin-A’s influence on kappa receptors, and how the kappa system affects dopamine. Dopamine receptors and kappa receptors act in opposite and complementary ways in order to maintain balance. The first thing a stimulant like cocaine does is hijack the brain’s natural reward circuitry by increasing dopamine levels in the basal ganglia. Increased dopamine feels good. It is euphoric, and it can lead to impulsive and frequent drug use. Salvinorin-A, in contrast, reduces dopamine levels in parts of the basal ganglia. This leads to what is termed “dysphoria”, the opposite of the euphoria that cocaine elicits. Dysphoria is not uncontrollable sadness, weeping, and gnashing of teeth. It is more of a dissociation from the warmth and familiarity of the body and human connections. One of my research participants said they were aware of everyone and everything in the room as if through a tunnel or a long cardboard tube. You become distanced from being a body, and you can even lose connection with the body entirely.

Another factor in salvinorin-A’s anti-addiction effects is interoception, a term that refers to both the internal state of the body at any given time, as well as the emotional response to the body. At any given time, our bodies are giving off hundreds of signals about our muscles and skin and organs and orientation and location in space. All these signals come up into the brain where they are collected in the insular cortex, which is right next to, and connected with, the basal ganglia and is also densely packed with kappa receptors.

Over time, cocaine subtly but substantially alters one’s sense of interoception. When a rat or a human impulsively takes cocaine, the insular cortex compares the internal milieu of “body before drug” with that of “body on drug”, finds the “body on drug” milieu to be the more pleasurable of the two, and initiates more impulsive drug use. Later, the insula compares “body on drug” to “body after drug”, again finds “body on drug” more pleasurable, and initiates compulsive drug seeking and use. Over time, cocaine causes the insular cortex to devalue what used to be rewarding stimuli. Things that used to be pleasurable are not any more. The drug becomes the only thing that is pleasurable, that leads to that dopamine release. However, the addiction process is not as simple as reducing interoceptive input to the insula. Pleasurable signals are blunted, but unpleasable signals are enhanced. Aches and pains are magnified, so that a person with a long-term substance use disorder feels bad things very clearly and frequently, and feels good things very rarely, unless it is the drug.

Human studies show salvinorin-A profoundly alters interoception. We recently published a study in which we had healthy adults inhale vaporized salvinorin-A. We found that low doses of salvinorin-A increased interoception, meaning that subjects experienced their own bodies as safe and trustworthy. In contrast, high doses of salvinorin-A increased dissociation and decreased interoception, meaning that subjects lost both the ability to sustain and control attention to body sensations as well as awareness of the connection between body sensations and emotional states. These findings are in line with a study one of us conducted showing that salvinorin-A affected perception of the body.

The Mazatec have used Salvia to treat addiction for hundreds of years as part of a cultural and religious tradition that is quite outside Western pharmacology. They cultivate the plant in secret places and collect fresh leaves the day of the ritual. Patients must maintain a strict diet, abstaining from sex, alcohol, and certain foods for several weeks. Ceremonies are held at night in complete darkness and may last three to four hours. The distinction between self and other, between the internal and external worlds, breaks down during these complex rituals. The healer mediates between the patient and the spirits, asking for health and wellness. After the ceremony, the healer prepares an amulet of plant leaves and spices for the patient to carry in order to complete the ritual. We owe it to the Mazatec people that this plant has survived until now. By the cultivation of cuttings in their homes and lands over the centuries, the Mazatec have made it possible for Western science to begin to uncover its medicinal properties. We feel that this plant, the people who live with it, have more to teach us still.