Scientists are taking a fresh look at salvia -- the controversial drug that can cause an intense psychedelic experience -- as a potential treatment for an array of neurological disorders, including addiction.
Smoking the herb, which is related to mint, has been chronicled in countless YouTube videos. Now, researchers at Johns Hopkins University Medical School say it could open the door to a whole new class of drugs that have powerful analgesic properties.
This is the first controlled study in humans on the effects of salvinorin A, the active ingredient in the plant salvia divinorum -- the most powerful hallucinogen in nature.
The study showed that the drug has no physically adverse effects on otherwise healthy people.
Lead researcher Matthew W. Johnson, a psychologist and assistant professor of psychiatry, said the study was an attempt to "put some rigorous scientific information into current concerns over the growing recreational use" of salvia.
The study findings are published online in the journal Drug and Alcohol Dependence.
"We did document the very intense nature of the drug, even among those who are used to strong hallucinogenic drugs," Johnson told ABCNews.com. "That in itself is an area of danger -- people can have accidents or do foolish things on the drugs."
"But it's a remarkably robust drug in terms of physiological safety," said Johnson. "But behavioral safety, that's another dimension."
Most of the understanding of salvia has come from YouTube videos and not scientific studies.
Johnson said learning about salvia's effects on the brain could lead to medical advances in the treatment of Alzheimer's disease, chronic pain and, though it seems counterintuitive, drug addiction.
"It might be a longer-acting version of the drug and one without the strong psychedelic effects, just the analgesic effects," he said. "We have done the first human study with the drug and it could be the first examination fo a whole new line of drugs that have a therapeutic potential."
Animal studies have shown that salvinorin A activates opioid receptors in the brain, which are responsible for the high a person gets from drugs like heroin and opium.
But addictive drugs work by stimulating what scientists call mu opioid receptors. Salvinorin A works on the kappa opioid receptors, which have a depressive effect if activated.
"Heroin, morphine, oxycontin, the traditional pain killers all hit the mu opioid," said Johnson. "But salvinorin A selectively hits the kappa receptors and it hits them more cleanly than any drugs have before."
The kappa receptors are associated with a strong analgesic response, but not the pleasure response that can cause addiction.
"It is the opposite of the addictive effect," he said. "Most animal models make it look like more of a punisher than a reinforcer."
In the study, humans, too, report that the drug is "too intense," according to Johnson. "It's bizarre, people say they just don't want to do it again."
The study was small and in a controlled medical environment. It involved four volunteers, two men and two women, who had experience with hallucinogens.
The participants, who were allowed to drop out of the study at any time, smoked the drug in 20 sessions over two to three months, inhaling a range of doses of the drug in its pure form and rating its strength.
None withdrew from the study, but they were allowed to take breaks from the drug when sessions were too intense.
When comparing saliva to other drugs, participants said they had an awareness of the external world with drugs such as LSD and psilocybin -- or so-called "magic mushrooms."
But with salvia, they said they had a feeling of "leaving this reality completely and going to other worlds or dimensions and interacting with entities," according to Johnson.
The participants, all of whom were healthy, showed no changes in heart rate or blood pressure.
Salvia is legal to buy, sell, and use in most parts of the United States. However, 13 states have adopted legislation banning or otherwise regulating its use. Legislators in a number of other states, as well as federal officials, are considering regulating the drug.
The DEA lists salvia, which is smoked, as a schedule 1 drug, like LSD and marijuana. Unlike LSD, a manmade hallucinogen that lasts about six hours, salvia's effects last an hour or so, peaking in about 20 minutes or less.
People who abuse salvia generally experience hallucinations or "psychotomimetic" episodes, a transient experience that mimics a psychosis, according to the National Institute on Drug Abuse. (NIDA)
Subjective effects have been described as psychedelic-like changes in visual perception, mood and body sensations, emotional swings and feelings of detachment.
Most concerning, according to drug experts, is the highly modified perception of external reality, leading to a decreased ability to interact with one's surroundings.
In a 2009 survey of first-time use among teenagers, 5.7 percent of high school seniors reported they had tried salvia in the past year -- a number greater than those who used ecstasy, according to NIDA.
"There is good news and bad news about salvia," said Dr. Byran Roth, a professor of pharmacology at the University of North Carolina, who discovered the mechanism of how salvia affects the brain in animal studies 2002.
Now, he has a National Institutes of Health grant to study medical applications of synthetic versions of the herb.
"In terms of its effects on humans, it's an extremely powerful hallucinogenic agent, and if people smoke it they basically are disassociated from reality," said Roth.
"The concern is that you don't want to drive a car," he said. "If you go on YouTube, there are frightening videos of people out of touch with reality."
Although there is no hard science on the long-term effects on the adolescent brain, which is still developing, there has been anecdotal evidence that it can have a prolonged and harmful effect on mood.
"It was becoming quite clear that adolescence is a time of remarkable change in the brain, and that the use, especially repeated, heavy use, of psychoactive drugs can have profound effects on the brain," said David P. Friedman, professor of physiology and associate dean for research at Wake Forest University School of Medicine.
"In the cases of alcohol and tobacco at least, we now know that adolescent use is more likely to lead to abusive use than if use is put off till the 20s," he said.
Traditionally, saliva has been ingested by chewing fresh leaves or by drinking their extracted juices. The dried leaves can also be smoked as a joint, consumed in water pipes, or vaporized and inhaled.
"The hopeful thing about it is emergency rooms are not inundated with people coming in with bad salvia reactions," Roth added. "It seems like the vast majority of people smoke it, had the experience and say they don't want to do it again. It's too frightening and intense and not what they are looking for."