Wednesday, October 10, 2012

Omega-6: Obesity and addiction

So Derek Lowe recently wrote in his medicinal chemistry blog 'In the Pipeline' about a new interest from pharmaceutical companies in cannabinoid receptor 1 (CB1). CB1 was the target of the (successful) obesity drug rimonabant. Successful until it was withdrawn from the european market for the side effects of depression and suicidal thoughts. Now people are however trying to make drugs that also target CB1 but without the ability to enter the brain from the blood. And it will of course be interesting to see how that plays out.
Why is this interesting? Well, rimonabant is an inverse agonist of CB1 which means that it blocks the action of the agonist as well as removes the spontaneous signalling through CB1 that occurs even without an agonist. And the agonists of CB1 are THC from cannabis (of course) and the neurotransmitters anandamide and 2-arachidonoylglycerol (2-AG). And those two agonists produced naturally by the body are made from omega-6 fatty acids. I actually got to the point, hurray!
So what do these agonists and inverse agonists do? Well, THC increases appetite and decreases short-term memory. It also makes mice more sensitive to reward from sugar water. Inverse agonists however decrease appetite, improves memory in mice, and makes giving up cigarettes easier. And cause depression, anxiety, and make you want to kill yourself. In addition the cannabinoid system is involved in a shitload of other things as well - I think it's better to leave that whole bag of rats alone (on the other hand a drug is definitely preferable to the current standard of care - a ridiculously dangerous operation that permanently changes the gastrointestinal layout and still isn't effective without lifestyle changes). However, I don't see why you would take a drug to reduce this signalling without first trying to reduce your amounts of the signalling molecule. Unfortunately, it would be quite hard to figure out if a lifestyle change to reduce the intake of omega-6 would be effective against obesity because of the elimination of excess omega-6 or because of the necessary reduction in junk food intake to reach that goal.

tl;dr The human equivalent to pot is made from omega-6 fatty acids. It is better for you to eat an amount of omega-6 that is natural (not much actually). I don't care if you get high, I just think it's fucking stupid to do the equivalent of taking just enough to not get high every single day of your life.

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