Pubdate: Fri, 03 Jan 2014
Source: Guelph Mercury (CN ON)
Copyright: 2014 Metroland Media Group Ltd.
Contact:  http://www.guelphmercury.com/
Details: http://www.mapinc.org/media/1418
Author: Joseph Hall

DISCOVERY MAY CUT 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 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 cannabinoid 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.

Researchers from academic institutes in Spain, Scotland and the U.S.
were also involved in the study.  
- ---
MAP posted-by: Jo-D