How Salvia Produces a High

The hallucinogen has been all over the news lately after Miley Cyrus' now infamous video. But how exactly does it work?

THE GIST

A new study of salvia finds the hallucinogen kicks off an unusually intense and short-lasting high, with no obvious ill effects.

While the study can't vouch for the safety of salvia, the results lend some hard science to the current legislative fray around the substance.

Shamans in Mexico have been chewing the leaves of the hardy mint relative for centuries.

Researchers are closer to understanding how a bong packed with leaves of Salvia divinorum gave Smiley Miley the giggles.

Although shamans in Mexico have been chewing the leaves of the hardy mint relative for centuries (and without any prompting from an infamous YouTube video of Miley Cyrus smoking it), little is known about what the plant's psychoactive substance, salvinorin A, actually does to humans -- despite its increasing popularity as a recreational drug.

A new study provides some data: The hallucinogen kicks off an unusually intense and short-lasting high, with no obvious ill effects, researchers report in an upcoming Drug and Alcohol Dependence paper.

"This is a landmark paper because it's the first paper in which authentic salvinorin A was administered to human volunteers under controlled conditions, and it was shown to be hallucinogenic," says psychiatrist and pharmacologist Bryan Roth of the University of North Carolina at Chapel Hill, who was not involved in the research. "All we had before were anecdotal reports, where people had bought salvia extract from their local smoke shop."

While the study is small and can't vouch for the safety of salvia, the results lend some hard science to the current legislative fray around the substance, which is criminalized in some states but not regulated federally.

"A lot of folks don't know what to do with this," says study coauthor Matthew W. Johnson, an experimental psychologist at Johns Hopkins University School of Medicine in Baltimore. "So we were trying to study this thing that is really uncharacterized under any formal conditions."

Johnson and his colleagues recruited four volunteers who had used hallucinogens such as LSD or psilocybin in the past. Over 20 sessions, the participants inhaled various doses of highly purified salvinorin A or a placebo while researchers monitored their vital signs and queried them about their experiences.

The effects of the salvinorin A were remarkably strong, consistent and fast-acting, peaking about two minutes after inhalation, and nearly disappearing by 20 minutes.

As doses increased across sessions, volunteers reported stronger and stronger hallucinations, which included cartoonlike images, revisiting childhood memories and contact with an entity. "With this drug, at its peak intensity, people describe popping out and visiting a completely different world. Some people say it seems like another dimension or maybe the spirit world," Johnson says. "They report these very profound experiences in these highly altered states of consciousness."

The researchers saw no changes in blood pressure or heart rate, even at the highest doses of salvinorin A. Other hallucinogenic compounds, such as LSD and psilocybin, moderately raise blood pressure and heart rate, Johnson says. But because the study used a small number of healthy volunteers, it can't make broad statements about the overall safety or the long-term effects of the substance. The team is currently expanding the numbers of participants.

Studies in animals have shown that salvinorin A acts on molecules in the brain called kappa-opioid receptors. These receptors are part of the pain-dulling opioid system but are not the same receptors that addictive opiates target.

Most of the evidence so far suggests that salvinorin A is not likely to hopelessly hook its users, Johnson says. "There's more work that needs to be done, but it's not looking like this is going to be the next cocaine or methamphetamine or heroin in the sense of a highly reinforcing, highly addicting new drug."

Researchers think the kappa-opioid receptor is important for a type of chronic pain, so understanding salvinorin A's effects on the receptor might lead to better pain treatments. What's more, tweaking the kappa-opioid receptor with salvinorin A-like compounds might one day treat neurological disorders in which a person's view of reality is altered, such as schizophrenia, depression or Alzheimer's disease.

"It's clear that when you give this compound to humans, it transports them to an alternative reality," Roth says. "So what that suggests to me and to others is that this receptor is very important for consciousness and how we view reality."