Just to continue the spirit of skepticism and trepidation lurking around so many pharmaceutical programs these days, I noted something in the SFN abstracts that caught my eye vis-a-vis rimonabant. There was a paper that described HU-210 (a psychotropically active CB-1 and CB-2 agonist)as enhancing neurogenesis in the dentate gyrus--and a different CB-1 antagonist as reducing neurogenesis.
This raises an interesting (to me anyways) question about chronic use of a CB-1 antagonist like rimonabant: will it reduce neurogenesis? If so, one might wonder about longterm effects upon memory/learning, since neurogenesis is thought to play a role therein: and I would wonder about longterm effects upon mood (since depression is correlated with decreased neurogenesis, SSRIs upregulate neurogenesis). There are conflicting preclinical findings regarding rimonabant's impact upon depression-related processes, though rimonabant does promote FAAH breakdown, which in turn reduces the levels of the endogenous cannabinoid anandamide. Depression has been reported to be a 'mild' side effect of rimonabant in clinical trials.
Does this mean that longterm use of rimonabant, as would be expected in the treatment of obesity and (likely) addiction, would cause impairment in learning/memory, and risk depression? I don't pretend to know, but it will be worth watching as the drug moves forward with all sorts of hoopla. Since the role of adult neurogenesis is not really understood--IF this is suppressed longterm, no one can be certain what the implications would be. One of those phenomena that will be assessed retrospectively after the first million or two patients are treated.
Harry
NeuroInvestment |
