DISCOVERY MAY END MARIJUANA HIGH TO HELP MEDICINAL USERS, ADDICTS
TORONTO - In a joint scientific effort, University of Toronto researchers have helped discover a human hormone that can eliminate the high caused by smoking pot.
The buzz-killing breakthrough - the result of an international collaboration - raises hopes for the creation of downer drugs that could control cannabis abuse and addictions and for the development of new, non-intoxicating compounds for medical marijuana users.
"The big deal in the paper is uncovering a whole new ( brain ) system that we didn't know was there," says Ruth Ross, head of pharmacology at the U of T and a key study author.
"The brain has and uses ( this system ) very carefully to control the effects of cannabis. The implications of that will be big."
The study was released Thursday by the journal Science.
In it, Ross and her colleagues described the previously unknown neural braking system, which is triggered by the presence in the brain of cannabis, in particular its active THC component.
The system centres on what's known as the type-1 can nabinoid receptor ( CB1 ) that's activated by THC.
This receptor, Ross says, is normally triggered by naturally occurring "cannabis-like" compounds in the brain that are involved in such things as food intake, memory and mood.
What her study revealed, however, was that the CB1 receptor also produces its own braking system when switched on.
In a feedback mechanism that helps rein in the physiological effects it creates, the receptor produces a type of steroid hormone, dubbed pregnenolone, that can turn it off.
"We've now added another whole layer onto our understanding of that ( CB1 ) system," Ross says.
Pregnenolone "is a kind of safety mechanism to switch it off again when it becomes active or overactive."
The hope, Ross says, is that this natural braking compound can be transformed into drugs that can be used to control the effects of marijuana such as euphoria, drowsiness and increased appetite - the munchies.
Researcher Pier Vincenzo Piazza, of France's INSERM ( Institut national de la sante et de la recherche medicale ) says that pregnenolone cannot be utilized as a treatment itself.
"Pregnenolone cannot be used ... because it is badly absorbed when administered orally and once in the blood stream it is rapidly transformed in other steroids."
However, he said in a media release that there is good probability that a usable synthetic form of the hormone can be created.
"We have now developed derivatives of pregnenolone that are well absorbed and stable," he said.
"They then present the characteristics of compounds that can be used as new class of therapeutic drugs. We should be able to begin clinical trials soon and verify whether we have indeed discovered the first pharmacological treatment for cannabis dependence."
Ross cautions that the research was conducted on rodents and that the effects of the mimicking compounds could differ in and among humans.
But Ross notes that the brain system that pregnenolone works on is essentially identical in people and mice.
"The inference from the research would be that certainly this would be something that would dampen or modulate a lot of the effects of cannabis."
In the study, mice and rats exposed to THC showed marked decreases in memory loss and hunger when injected with pregnenolone.
Ross says she doubts that the discovery will lead to such things as after-party pills that can sober pot smokers up before getting behind the wheel.
Rather, she says, new drugs would likely be aimed at people with serious cannabis abuse problems.
The discovery could also be useful in producing drugs that could control pain or tremors for medicinal marijuana users without the intoxicating side effects.
http://www.sciencemag.org/content/343/6166/94
TORONTO - In a joint scientific effort, University of Toronto researchers have helped discover a human hormone that can eliminate the high caused by smoking pot.
The buzz-killing breakthrough - the result of an international collaboration - raises hopes for the creation of downer drugs that could control cannabis abuse and addictions and for the development of new, non-intoxicating compounds for medical marijuana users.
"The big deal in the paper is uncovering a whole new ( brain ) system that we didn't know was there," says Ruth Ross, head of pharmacology at the U of T and a key study author.
"The brain has and uses ( this system ) very carefully to control the effects of cannabis. The implications of that will be big."
The study was released Thursday by the journal Science.
In it, Ross and her colleagues described the previously unknown neural braking system, which is triggered by the presence in the brain of cannabis, in particular its active THC component.
The system centres on what's known as the type-1 can nabinoid receptor ( CB1 ) that's activated by THC.
This receptor, Ross says, is normally triggered by naturally occurring "cannabis-like" compounds in the brain that are involved in such things as food intake, memory and mood.
What her study revealed, however, was that the CB1 receptor also produces its own braking system when switched on.
In a feedback mechanism that helps rein in the physiological effects it creates, the receptor produces a type of steroid hormone, dubbed pregnenolone, that can turn it off.
"We've now added another whole layer onto our understanding of that ( CB1 ) system," Ross says.
Pregnenolone "is a kind of safety mechanism to switch it off again when it becomes active or overactive."
The hope, Ross says, is that this natural braking compound can be transformed into drugs that can be used to control the effects of marijuana such as euphoria, drowsiness and increased appetite - the munchies.
Researcher Pier Vincenzo Piazza, of France's INSERM ( Institut national de la sante et de la recherche medicale ) says that pregnenolone cannot be utilized as a treatment itself.
"Pregnenolone cannot be used ... because it is badly absorbed when administered orally and once in the blood stream it is rapidly transformed in other steroids."
However, he said in a media release that there is good probability that a usable synthetic form of the hormone can be created.
"We have now developed derivatives of pregnenolone that are well absorbed and stable," he said.
"They then present the characteristics of compounds that can be used as new class of therapeutic drugs. We should be able to begin clinical trials soon and verify whether we have indeed discovered the first pharmacological treatment for cannabis dependence."
Ross cautions that the research was conducted on rodents and that the effects of the mimicking compounds could differ in and among humans.
But Ross notes that the brain system that pregnenolone works on is essentially identical in people and mice.
"The inference from the research would be that certainly this would be something that would dampen or modulate a lot of the effects of cannabis."
In the study, mice and rats exposed to THC showed marked decreases in memory loss and hunger when injected with pregnenolone.
Ross says she doubts that the discovery will lead to such things as after-party pills that can sober pot smokers up before getting behind the wheel.
Rather, she says, new drugs would likely be aimed at people with serious cannabis abuse problems.
The discovery could also be useful in producing drugs that could control pain or tremors for medicinal marijuana users without the intoxicating side effects.
http://www.sciencemag.org/content/343/6166/94
kind regards from guineapig 
My thoughts, exactly.
