Posted by Michael D on November 20, 2002, at 11:25:23
http://www.cannabisculture.com/articles/2527.html
"Researchers at the University of California speculate that THC and other cannabinoids may be useful in the treatment of schizophrenia.
Some forms of schizophrenia are believed to be caused by a hyperactive dopamine system, and dopamine is regulated by anandamide, a chemical similar to THC but produced naturally in the body. Analysis of the cerebro-spinal fluid extracted from schizophrenics in Germany found levels of anadamide twice as high as a normal person's.
Daniele Piomelli, who heads the research team, speculates that the higher anadamide levels are "the brain's response to bring this dopamine activity down, but the brain cannot keep the amount of anandamide high enough." This might explain why schizophrenics use marijuana at higher rates than the general population.
THC and anandamide both bind to the brain cannabinoid receptor CB1, which is mostly found in regions of the human brain that have been implicated in schizophrenia, including prefrontal cortex, basal ganglia and hippocampus."
http://www.newu.uci.edu/archive/1999-2000/spring/000529/n-000529-medicine.html
"Medicine: UCI researchers have developed a marijuana-like chemical for treating mental disorders.
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By Andreas von Bubnoff
Staff Writer
Most of us have heard of these disorders: schizophrenia, Tourette's Syndrome or Attention Deficit Hyperactivity Disorder. They all seem to have only one thing in common: they are all mental disorders.But there is something else they have in common: all of them show hyperactivity of the neurotransmitter dopamine in some area of the brain."
...
""[Dopamine] receptor blockers are all there is [for such disorders like] schizophrenia [and] Tourette's Syndrome, and they have a lot of side effects."
The reason for these side effects, said Piomelli, is that in patients with these disorders, only a subset of dopamine receptors in the brain are hyperactivated, but that the currently available drugs block all of them.
Now Piomelli and his research team have developed a chemical called AM404 which could form the basis for a new class of drugs to treat these disorders more selectively, with fewer side effects.
AM404 does not block dopamine receptors. Instead, it blocks the inactivation of the neurotransmitter anandamide.
Anandamide is similar to marijuana's active ingredient, THC and belongs to a class of neurotransmitters called endogenous cannabinoids since it is naturally produced by some of the brain's nerve cells.
It is produced only by nerve cells whose dopamine receptors are activated, Piomelli said.
Anandamide in turn binds to cannabinoid receptors and thereby inhibits the effects of dopamine.
"[It is] kind of a negative feedback," Piomelli said.
Like most neurotransmitters, anandamide is inactivated soon after it has been released. "It is taken up by [the] cells so it [gets] inside the cell where an enzyme destroys it," Piomelli said.
In their most recent paper, published in the May issue of the Journal of Neuroscience, Piomelli's group has shown that AM404 inhibits this inactivation of anandamide.
The researchers showed that AM404 treatment leads to an accumulation of anandamide, but only outside of nerve cells that are already activated by dopamine. Anandamide then inhibits the effects of dopamine in these cells by binding to cannabinoid receptors.
Thus, Piomelli pointed out, AM404 should act more selectively than dopamine receptor blockers, because it only inhibits dopamine activity in nerve cells or brain areas that are already activated by dopamine.
PiomelliÕs group tested this by injecting AM404 into the brain of rats treated with anandamide.
Anandamide alone, which inhibits dopamine action, had similar effects on the animals as drugs blocking the dopamine receptor. "One of [these effects] is a profound inhibition of locomotor activity," Piomelli said, "so the animals donÕt move very much."
This effect, similar to the side effects observed in humans treated with drugs blocking the dopamine receptor, was not observed anymore after injecting AM404 into the brains of these rats as well.
The researchers also injected AM404 into the brains of mutant rats that are hyperactive and these rats behaved normally again.
These results suggest that AM404 may inhibit dopamine hyperactivity without showing many of the side effects of the drugs currently used.
Will patients with schizophrenia soon be able to take AM404 as a drug with fewer side effects than the drugs currently available? "We are still far [away from a drug], but we are closer than before," Piomelli said.
One problem, he said, is that AM404 is not a very potent drug, so more of it is necessary to achieve an effect. "We don't know if it has other side effects in the body," Piomelli said. "If you keep taking it for two or three weeks, it could accumulate in the liver, you have no idea [what it does]."
"We have been trying very hard to find more potent drugs, and so far we haven't succeeded," he said.
Until then, patients will have to put up with the side effects of current drugs.
Many patients suffering from schizophrenia smoke marijuana, Piomelli said, adding that this is not the treatment of choice.
One reason is that, according to Piomelli, marijuana has side effects because its active ingredient-THC-binds to all cannabinoid receptors and not just the ones on nerve cells with too much dopamine activity.
Piomelli added that "there is evidence that marijuana is a risk factor for worsening the symptoms."
The reason, he said, is that smoking marijuana reduces the number of available cannabinoid receptors.
"The [cannabinoid] receptor shuts off as a result of the activation [by marijuana]," he said.
"Now all of a sudden, [by smoking marijuana] you have shut off all your receptors."
As a result, smoking more marijuana doesn't have any effect anymore.
"You are eliminating the one brake mechanism that you had [against the symptoms]," Piomelli said."
poster:Michael D
thread:128458
URL: http://www.dr-bob.org/babble/20021116/msgs/128458.html