http://blog.wired.com/wiredscience/2007 … inoge.html
How Hallucinogenic Sage Works
August 27, 2007
By Aaron Rowe
Diviner's sage contains a powerful hallucinogen that may someday inspire a new class of depression, pain, and addiction medications. Now, researchers at Ohio Northern University have resolved a controversy about how the unique chemical works.
The potential therapeutic uses are very broad. After using some of the "Mexican-mint" sage from a mail order catalog, a woman managed to rid herself of depression. Tests on animals have shown that the Oxaccan plant, a relative of the culinary herb, can also control pain. However, no large pharmaceutical company would dare invest millions of dollars to win FDA approval for a drug that they can't patent and sell exclusively. To add insult to injury, it could someday be classified as a narcotic.
Research on hallucinogenic sage has been stop-and-go. In 2002, Bryon Roth and his research group explained how the potent drug plays games with the nervous system. Recently, some scientists cast doubt on his theory. Catherine Willmore and her colleagues have published a paper in the September issue of Neuropharmacology that not only proves the original conclusion, but also speculates about how the psychotropic agent may play a role in medicine.
The first step to understanding how a natural medication works is to determine where it strikes. Every drug has a target -- a molecule that it affects directly. Roth had indicated that Salvinorin A, the mind-altering molecule, activates a class of signal-sending proteins called kappa opioid receptors. Once triggered, those molecules initiate a series of events that results in an elevated mood and sometimes an out of body experience.
Willmore and her team trained rats to recognize the sensations caused by a well-understood drug that targets kappa opioid receptors. The rats were placed in a chamber with two switches. Each rodent learned to push the lever that was marked by a red light when it was feeling the effects of the drug. When they felt no unusual effects, the rodents would push a different lever that was marked with an amber lamp. Pressing the correct lever several times always earned them a 45 milligram food pellet as a reward.
It is impossible to know exactly how the rats felt during the test, but they could not tell the difference between the active chemical in sage and the one they had been trained to identify. Since the drugs feel the same, both of them must activate the same target.
The mystery of Salvinorin A is far from over. There are many different types of kappa-opioid receptors. Some control mood, while others regulate appetite, pain, and even addictive behaviors. The next step may be to find out which of these subtypes can be set off by the hallucinogenic molecule. Slight variations upon the natural chemical may become drugs that target only a single type of receptor and thus elegantly treat a single illness with a minimum of side effects.