Mechanism of Hallucinogen's Effects Discovered

[23smooches]

Thought this was interesting. Its a little old, but still breakthrough.
ScienceDaily (Feb. 2, 2007) — The brain mechanism underlying the mind-bending effects of hallucinogens such as LSD, mescaline, and psilocybin has been discovered by neuroscientists. They said their discoveries not only shed light on the longtime mystery of how hallucinogens work, but that the findings also offer a pathway to understanding the function of drugs used to treat neuropsychiatric disorders, which are now being used largely without an understanding of their fundamental mechanism.
Stuart Sealfon, Jay Gingrich, and colleagues published their findings in the February 1, 2007 issue of the journal Neuron, published by Cell Press.
Researchers have long known that hallucinogens activate specific receptors in the brain, called 5-HT2A receptors (2ARs), that are normally triggered by the neurotransmitter serotonin. Neurotransmitters are chemicals that one brain cell launches at receptors on another to trigger a nerve impulse in the receiving cell. However, a fundamental mystery has been why other compounds that activate the same receptors are not hallucinogenic.
In their studies, the researchers compared the differences between the effects of LSD and a nonhallucinogenic chemical that also activates 2AR receptors on the mouse neural machinery. Since the animals could not report the kinds of perception-altering effects that humans experience on hallucinogens, the researchers determined hallucinogenic properties by measuring a head twitch response the mice characteristically showed when under hallucinogens but not when under nonhallucinogens.
The scientists concentrated their studies on the cortex of the brain, which earlier studies had shown to be the center for action of the hallucinogens. Their analysis revealed that LSD produced genetic, electrophysiological, and internal cellular signaling responses that were distinctively different from those induced by a nonhallucinogenic compound.
They also explored whether 2ARs were central to the hallucinogenic effect of LSD by producing mice lacking the receptors, but in which receptor activity could be selectively restored in the cortex. The researchers found that mice without functioning receptors showed no hallucinogenic response to LSD, but restoring the receptors rendered LSD hallucinogenic in the animals.
The researchers wrote that "These studies identify the long-elusive neural and signaling mechanisms responsible for the unique effects of hallucinogens."
They also concluded that "The strategy we developed to elucidate [hallucinogen] action should be applicable to [central nervous system]-active compounds, with therapeutic potential in other disorders. Thus, our findings may advance the understanding of neuropsychiatric disorders that have specific pharmacological treatments whose mechanisms of action are not fully understood."

Reputation Comments on this post:

good read

[Panthers007]

A little old is right. But re-written with more esoteric language. Bet it got them a research grant - which might be a good thing. As long as they don't misuse it.

I see the use of psychedelics in medical applications taking off like the Wright Brothers plane from Kitty Hawk, North Carolina again. Slow and sputtering after a 40 year hiatus due to the grandstanding idiocy of a few blowhards (Leary, et al).

It's gonna take time, folks, it's gonna take time.

[23smooches]

Originally Posted by Panthers007

A little old is right. But re-written with more esoteric language. Bet it got them a research grant - which might be a good thing. As long as they don't misuse it.

I see the use of psychedelics in medical applications taking off like the Wright Brothers plane from Kitty Hawk, North Carolina again. Slow and sputtering after a 40 year hiatus due to the grandstanding idiocy of a few blowhards (Leary, et al).

It's gonna take time, folks, it's gonna take time.

Yes, it got them a grant, them and a few others at harvard can now study the effects of LSD on alchoholics, we can only hope it works out this time around.

[Zaprenz]

Very Interesting.

Psychedelic drug research almost follows a typical "new technology" enthusiasm curve. A good example being gene therapy when technology/investment/research suddenly took off and it was going to cure all the worlds diseases. Subsequently deaths occurred, safety problems hit home and everyone got out. Today's gene therapy research is leveling off at a more consistent and realistic level.

Anyway psychedelics caused such a huge storm when first introduced. Everyone pilled loads of research/investment/enthusiasm until problems occurred. [At which point people moved in to their respective psychedelics are GOOD, psychedelics are EVIL camps]. Possibly right now research is slowly building back up to a sustainable level [I.e a level government and tabloids will accept]

[Jatelka]

And for those that are interested in reading some papers... Here's what's in the archive (so far)...

http://www.drugs-forum.com/forum/local_links_search.php

[Zaprenz]

BTW would be interesting to know the structure of the chemicals which are 5-HT2A receptor agonists that DO NOT show hallucinogenic activity.

SWIM wonders whether their 5-HT2A agonist profile was determined in vivo or in vitro. Probably in vitro and if so how reliable is it to assume the substance passed the blood brain barrier in the animals used, doesn't get metabolised super fast etc etc.