Friday, December 16, 2005

Blocking the destruction of endocannabinoids

Ars Technica has a short article about URB597, a drug that prevents the enzyme fatty-acid amide hydrolase (FAAH) from working.

Well FAAH is the enzyme that degrades endocannabinoids (marijuana works by stimulating endocannabinoid receptors).  Blocking FAAH effectively amplifies the levels of naturally occurring endocannabinoids.  The increase caused by the drug should be proportional to what the body is already putting out.  This should give more gentle and targeted control than drugs like marijuana, which indiscriminantly stimulate all cannabinoid receptors.

A paper to be published in PNAS shows that URB597 is a potent antidepressant in several animal models, and that this is "prevented by the CB1 antagonist rimonabant" and "accompanied by increased brain anandamide levels" In plain English, it improves mood like marijuana, and is blocked by the same drugs that block other cannabinoids.  (It's usually impossible to tell which receptors a drug affects, so researchers administer known blockers and stimulators to find out by way of comparison.)

The abstract also says that the effects "are maintained upon repeated URB597 administration".  Good.  The drug doesn't "wear out" over time. Lots of good drugs crater because the body rapidly develops tolerance to them.

These results are of considerable interest to chronic pain patients.  Cannabinoids are known to affect pain, as shown by considerable anectdotal evidence and some controlled trials.  They are also famous for their ability to reduce nausea and increase appetite.  This is relevant to migraine because the disease process often has the opposite effect: spectacular nausea and food aversion (to the point that some sufferers need hospital treatment for dehydration).

The abstract for the paper also says "Unlike direct CB1 agonists, URB597 does not exert rewarding effects in the conditioned place preference test or produce generalization to the discriminative effects of Δ9-tetrahydrocannabinol in rats."  In plain English, it does not cause obvious addiction-related behavior in animals.  This is good because it means the prohibition industry might leave it alone.

The abstract mentions the drug rimonabant in passing. That's an interesting new drug that blocks CB1 receptors.  It seems to have some of the opposite effects as marijuana, in particular producing "anti-munchies". It therefore is promising for the treatment of obesity and diabetes.  I do worry that CB1 antagonism may have depressant side effects, which would be just terrible for folks who need to lose massive amounts of weight.


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