My little aside about obesity as a disease reminded me of a story that illustrates just about everything that’s wrong with everything.
Back in the early aughts there was great hope for drugs called CB-1 receptor antagonists to treat obesity, notably one invented by Sanolfi-Aventis and called rimonabant. The idea was simple, or at least it was self-evident to anyone who might have smoked marijuana. The CB-1 receptor is stimulated by pot. (CB stands for cannabinoid; we have many different cannabinoid receptors in the brain, which is how pot does its thing.) Pot causes munchies. Therefore, if you block activity at the receptor, you can cause anti-munchies. Loss of appetite leads to less eating leads to weight loss, less diabetes and other metabolic diseases, and no more overflow on airplane seats. A win-win.
Except for one thing. On exactly the same logic, blocking cannabinoid receptors is going to cause anti-highness, or what the doctors like to call depression. I mean, it’s pretty obvious that a neural system that, when stimulated, makes you feel excellent is going to make you feel sort of lousy if it is suppressed. What were those scientists smoking when they forgot this?
And sure enough, although rimonabant was effective at making rats lose weight, and even some people, it also caused depressed mood with enough frequency and severity that the clinical trial was halted and the drug removed from the pipeline.
And here’s the funny part. In the wake of rimonabant’s demise there was a series of papers like this one offering solace to researchers by recounting what they had learned through the CB-1 antagonist adventure, and what other adventures lay in store. One of those suggested adventures was a foray into the world of depression treatment, once again on the same logic. As the scientists pointed out, “the reported clinical evidence that the CB1 antagonist rimonabant increases the risk of depression and anxiety, support the notion that the endocannabinoid system represents a novel target in the treatment of mood disorders.” Find a drug, in other words, that targets the cannabinoid receptors, and you might be onto something. You might discover a compound that makes people feel better, gives them pleasure even. I wonder what they’ll call it. Here’s my vote: marijuana.
