Psychoactive compound activates mysterious receptor

Feb 12, 2009

(PhysOrg.com) -- A hallucinogenic compound found in a plant indigenous to South America and used in shamanic rituals regulates a mysterious protein that is abundant throughout the body, University of Wisconsin-Madison researchers have discovered.

The finding, reported in the Feb. 13 issue of Science, may ultimately have implications for treating drug abuse and/or depression. Many more experiments will be needed, the researchers say.

Scientists have been searching for years for naturally occurring compounds that trigger activity in the protein, the sigma-1 receptor. In addition, a unique receptor for the hallucinogen, called dimethyltryptamine (DMT), has never been identified.

The UW-Madison researchers made the unusual pairing by doing their initial work the "old-fashioned," yet still effective, way. They diagrammed the chemical structure of several drugs that bind to the sigma-1 receptor, reduced them to their simplest forms and then searched for possible natural molecules with the same features. Biochemical, physiological and behavioral experiments proved that DMT does, in fact, activate the sigma-1 receptor.

"We have no idea at present if or how the sigma-1 receptor may be connected to hallucinogenic activity," says senior author Arnold Ruoho, chair of pharmacology at the UW-Madison School of Medicine and Public Health. "But we believe that the National Institute on Drug Abuse (NIDA) may be interested in biological mechanisms underlying psychoactive and addictive drug action."

In addition to being a component of psychoactive snuffs and sacramental teas used in native religious practices in Latin America, DMT is known to be present in some mammalian tissues, and it has also been identified in mammalian blood and spinal fluid. Elevated levels of DMT and a related molecule have been found in the urine of schizophrenics.

Ruoho speculates that the hallucinogen's involvement may mean that the sigma-1 receptor is connected in some fashion to psychoactive behavior. When his team injected DMT into mice known to have the receptor, the animals became hyperactive; mice in which the receptor had been genetically removed did not.

"Hyperactive behavior is often associated with drug use or psychiatric problems," says Ruoho. "It's possible that new, highly selective drugs could be developed to inhibit the receptor and prevent this behavior."

The study revealed an additional neurologic link by confirming that the sigma-1 receptor and some compounds that bind to it inhibit ion channels, which are important for nerve activity. Work by many researchers — including some from UW-Madison — initially showed this relationship in earlier studies.

Some studies have also linked the receptor to the action of antidepressant drugs, and National Institutes of Health (NIH) scientists recently found that it appears to serve as a "chaperon," helping proteins to fold properly.

The Wisconsin researchers found that DMT is derived from the naturally occurring amino acid tryptophan and is structurally related to the neurotransmitter serotonin. This finding, Ruoho says, illustrates the mantra often used in the biological processing of natural molecules: Nothing goes to waste.

"Our findings support the idea that biochemical alterations of molecules such as tryptophan can produce simple compounds such as DMT that may target other regulatory pathways served by sigma-1 receptors," he says.

DMT may also reflect the presence of an even larger family of natural compounds that arise from other structurally related amino acids that may further regulate the receptor, Ruoho adds.

"It may well be that these different, naturally derived chemical forms regulate the sigma-1 receptor in tissue and organ-specific ways," he says.

Source: University of Wisconsin-Madison

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User comments : 15

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Honor
3.7 / 5 (3) Feb 12, 2009
give me some DMT
KBK
3.4 / 5 (5) Feb 12, 2009
If you bother to read the two books 'Journey of Souls', and 'Destiny of Souls' by Dr. Micheal Newton, you will soon understand that Schizophrenics are nearly 100% misdiagnosed, in a specific way. Just a bit of an esoteric note here, for those with the eyes to see. ;)
Mercury_01
3.7 / 5 (3) Feb 12, 2009
Eye have eyes, and I say beware messing around with peoples brains and this chemical. If you were to completely block it in the brain, you'd really throw a wrench into that persons very existence. Its importaince is net yet understood by science.
findingone
3 / 5 (2) Feb 13, 2009
Why is in important that it be best to not yet be understood by science?

Why?
Mercury_01
1 / 5 (2) Feb 13, 2009
re read. also, learn english.
Velanarris
5 / 5 (1) Feb 13, 2009
Eye have eyes

re read. also, learn english.

Likewise.
Mercury_01
3 / 5 (2) Feb 13, 2009
And you can learn to appreciate some literary license.

But really folks, DMT is an extremely important molecule. A little goes a long way, and plays a role in our spiritual development.
Velanarris
1 / 5 (2) Feb 13, 2009
And you can learn to appreciate some literary license.
Not if it muddles the point and causes confusion while you spew slander on someone without as strong a grasp of the terminology at play, but let's get away from this line of converse as it's a waste of both of our time and really, pretty silly.

But really folks, DMT is an extremely important molecule. A little goes a long way, and plays a role in our spiritual development.

Well not everyone values spiritual development, however, I'd be interested to see what role DMT plays in the development of spirituality.
Crucialitis
3 / 5 (2) Feb 13, 2009
Well not everyone values spiritual development, however, I'd be interested to see what role DMT plays in the development of spirituality.

----------------------------------------

Everyone needs a change of perspective every now and then to keep from flipping out on little things. Sometimes that change of perspective makes other little things into wonderful mysteries that make you appreciate life more as you stop to actually smell the roses for a change.

"You're so busy going from A to Z that you forget that there's twenty-four letters in between."
Mercury_01
5 / 5 (1) Feb 13, 2009
V, ...nevermind.
RolfRomeo
5 / 5 (1) Feb 15, 2009
I seem to remember having heard the brain releases DMT during birth and death, and possibly also during times of "near-death". Unfortunately I have no source for this.

As such some speculation even attributes the vision of a light at the end of a dark tunnel to this molecule. Recreational users on erowid.org also pretty consistently report encounters with angel-like beings.

DMT - the true gateway drug.
Gelvan_Tullibole_3rd
not rated yet Feb 15, 2009
Hi there Rolf Romeo, If you want to know about DMT and near death then read These two books.
DMT The Spirit Molecule by Rick Strassman, M.D.
and
The Cosmic Serpent by Jeremy Narby,
Both are currently available from Amazon new or secondhand.
Gelvan_Tullibole_3rd
not rated yet Feb 15, 2009
To fill in a few gaps meanwhile; Everything that has DNA has DMT it is essential to the functions of every living thing. To try to block it could be a really dumb idea; but then the lab-coats aren't going to try it themselves. Oops! "Ah well better luck next time" as the Doctor said.
Mercury_01
not rated yet Feb 15, 2009
"The real gateway drug" I like that. I also like erowid. They do a great service to the world of psychonautics.
Evan
not rated yet May 31, 2009
There is mistake in this article. The looked for elevated levels of DMT in schizophrenics but DID NOT find any such abnormal levels. They did, however, find elevated levels in stressed mice.
http://cottonwoodresearch.org/ is lab that will be examining the presence of endogenous DMT in humans. Check them out.