CB1 Antagonist for dieting?

Rimonabant (aka SR141716), a CB1 receptor antagonist, is being investigated as a diet drug. This is disturbing to me because of the significant acute effects of cannibinoids on cognitive function.

Note also that the function of endocannabinoids is a mystery but it is a hot area of research right now and they have been implicated in, amongst other things, plasticity. I am already aware of at least one study implicating Rimonabant in changes in cognitive function (the study; press release). (in addition to emotional function; the drug trials revealed an increased incidence of depression amongst Rimonabant users as compared to placebo).

I’m not saying that this is definitely not a good diet drug. The cognitive changes could be minor, or they be beneficial, or they could be outweighed by the weight loss effects. But the cognitive effects might also be subtle and hard to detect. I just hope the patients understand that drug affects the brain in unknown and possibly significant ways. I feel that people should take the decision to chronically consume this drug as seriously as they would consider chronically consuming marijuana (a CB1 agonist).

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8 thoughts on “CB1 Antagonist for dieting?

  1. While your concerns are reasonable, no acute or chronic effects on cognitive function have been reported to be of greater prevalence in rimonabance treated vs control subjects after 2 years. In addition, since cannabis and cannabinoids impair several aspects of learning and memory, you might expect some cognitive enhancement, which should not often be looked at as an adverse effect 🙂

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  2. CB1 receptor ANTagonist, meaning it blocks the recetor….not stimulates as marijuana would do. It is the opposite of marijuana. If you dont like it, use diet and excercise (as everyone SHOULD do), instead of popping a pill. (i.e. put down the coke and get off the computer)
    Thanks, your freindly pharmacist

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  3. Brian: That would be cool 🙂

    A Dogg: We know it’s an antagonist; my reasoning was just that if a cannabinoid agonist affects cognitive processing seriously enough that people are afraid of it, then an antagonist of the same receptor may have equally profound effects, although perhaps harder to detect, and therefore people should treat it with caution.

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  4. A further clarification: A CB1 antagonist will not *necessarily* have the “opposite” effect of marijuana/THC (a CB1 receptor agonist). This is a bit of a incorrect, “textbook neuroscience” view but undoubtedly a common one. There are several reasons to doubt this statement. First and foremost, the logic is wrong: if you modulate a receptor EITHER WAY (increase or decrease activity) which has been implicated in cognitive modulation that you will do precisely that. That is, if THC, which increases CB1 activation, has cognitive side-effects, it would be very difficult to believe that a CB1 antagonist will not have cognitive side-effects.

    There are other, more technical reasons that we would want to consider too… In the case of THC, it is a broad spectrum agonist for several receptors, including CB2 (and I’m sure other cannabinoid receptors that I’m not aware of). Surely, a CB1 antagonist will not be able to account for all of the diverse phenomena that THC produces. Also, the binding constants governing the receptor-ligand interaction matter enormously. For example, the CB1 antagonist might not bind the receptor as strongly as THC. Even though THC is an agonist, the receptors are only the first step in a complex signalling cascade. Low levels of antagonist action and high levels of agonist action might result in the same downstream effects. (Wasn’t there some LTP paper that showed that low levels of cytosolic Ca++ and high levels of Ca++ resulted in LTP but medium levels resulted in LTD?)

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  5. Neville,

    If you want to know all about calcium’s effects on synapse dynamics in the hippocampus, your going to want to check out the stuff by Malenka and Nicoll but I think maybe the paper you were thinking of was the Sabatini & Svoboda Neuron paper a couple of years back (PMID 11832230)???? Just a guess…

    Regarding the original posting, it seems like SR141716 is a pretty sloppy antagonist (at least judging from the Nicoll and Algers papers). I would be very surprised if it makes it past phase III. I wonder when the public is going to catch on to the fact these magic little pills perscribed by their Doctor is just some scientists half assed attempt to get rich quick…

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  6. Sure, any drug that works in the CNS has the potential of causing some issues with cognition, but are we talking inprovement are decline?????. (Please refer to Beta agonists/antagonists, quite opposite effect on cognition if you ask me). I didn’t want to get very technical with the drugs (perhaps you could verse me on the post receptor events involving CB1 agonists); I just wanted to make the point that if you want to lose weight a pill is not your answer. Weight loss is a huge industry (look at Anna Nicole), and if there is money to be made making a pill….someone will do it. And if there are cognitive effects (+/-) that are subtle and/or hard to detect, I’ll betcha Phase III trials wont catch it. Furthermore, the people who use it wont care about cognitive effects if it works. Sad but true.

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  7. Pingback: neurodudes » Blog Archive » CB1 antagonist seems to cause depression

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