Several persistent researchers finally have proof for a theory they have held for more than a decade, despite dissent from the larger scientific community: Morphine occurs naturally in the human brain.

Most scientists have been skeptical of the claim, saying previously studied samples were likely contaminated with morphine molecules. But a paper published in the Sept. 21 issue of the *Proceedings of the National Academy of Sciences * seems to put the question to rest.

Meinhart Zenk and his colleagues at Martin-Luther-University Halle-Wittenberg in Germany found that human cells grown in a dish synthesized morphine.

"Without doubt, human cells can produce the alkaloid morphine," Zenk wrote in the paper. "The studies presented here serve as a platform for the exploration of the function of 'endogenous morphine' in the neurosciences and immunosciences."

In other studies, researchers had found trace amounts of morphine in human and other animal tissues, but only a handful of believers thought morphine occurred naturally in the brain. Most assumed it came from foods like hay, lettuce, milk and rabbit feed that contain the chemical.

If Zenk's paper finally convinces scientists that morphine is as natural a presence in the brain as serotonin or dopamine, it will open new doors for looking at the treatment of pain, addiction and other health issues, said George Stefano, director of the Neuroscience Research Institute at the State University of New York at Old Westbury.

Stefano also has a paper coming out in the Oct. 5 Neuroendocrinology Letters showing that animal neural tissue can synthesize morphine.

Instead of pumping patients full of morphine, Stefano said, doctors could instead give a morphine precursor – a molecule that would set off a chain reaction eventually resulting in increased morphine production in the brain. Stefano, who has championed the existence of morphine in the brain for years, published proof of such a precursor, called reticuline, in the journal Molecular Brain Research in 2003.

The approach could circumvent dependency because it would increase an individual's own morphine levels instead of replacing natural morphine with a synthetic version. Similarly, a drug called levodopa, a precursor to dopamine, is commonly used to treat Parkinson's disease.

The discovery could also explain why some people are more susceptible to addiction – they may have a morphine deficiency.

"All of a sudden," Stefano said, "(morphine-deficient individuals) take this compound (and) it really makes them feel not only good but normal."

A morphine deficiency could also be the cause of some chronic pain, Stefano said.

The researchers believe morphine is created by neurons in the brain, but much about the production remains mysterious. They found morphine in the limbic center, which is involved with emotions.

"That puts this new signaling molecule in a very crucial part of the brain," Stefano said. "If morphine's there, it's involved with subjective thinking."

Stefano hopes that the realization that morphine is endogenous (meaning it's produced within an organism) will lessen morphine's association with abuse, and increase the amount of research on naturally occurring morphine. With only about 15 scientists concentrating on endogenous morphine, progress is slow going.

"In science, painstaking trial and error are big part of your life," he said. "But it's much harder when most people don't believe you."