There have been 3 laboratory based double blind, placebo controlled studies of microdosing. None of them have shown evidence for any of the positive effects reported anecdotally, other than feeling just a tiny bit high (which could be considered potentially positive regarding potential antidepressant effects, but could also be considered through the lens of abuse liability). Results range from no effect to slight impairment. It could have been that these studies did not measure the outcomes that would show an effect, or that some of them only looked at acute effects rather than a chronic dosing regiment such as those many endorse (e.g., taking it once every 3 or 4 days). Nonetheless, so far there is no evidence of benefit. I also think that the benefits anecdotally reported for microdosing are especially prone to placebo effects. Surely part of reported success is due to placebo effect, but that is true for most medical interventions. What you get in the real world is a combo of direct underlying efficacy (or whatever you wan to call it) and the placebo effect. The challenge is to see if any of the benefit is not due to the placebo effect. My best guess at this point is that there is some direct non-placebo effect, and I am more compelled by the anecdotes on mood and depression treatment. After all, we have known for 70+ years that chronically augmenting serotonin transmission in various ways can be effective to treat depression (although there is certainly lots of room for improvement), so an effect of chronic 5-HT2a agonism on depression wouldn’t be that surprising. It could be that some of the other reported effects (e.g., cognitive enhancement, creativity) are indirectly mediated by this improvement in mood.
There have been 3 laboratory based double blind, placebo controlled studies of microdosing. None of them have shown evidence for any of the positive effects reported anecdotally, other than feeling just a tiny bit high (which could be considered potentially positive regarding potential antidepressant effects, but could also be considered through the lens of abuse liability). Results range from no effect to slight impairment. It could have been that these studies did not measure the outcomes that would show an effect, or that some of them only looked at acute effects rather than a chronic dosing regiment such as those many endorse (e.g., taking it once every 3 or 4 days). Nonetheless, so far there is no evidence of benefit. I also think that the benefits anecdotally reported for microdosing are especially prone to placebo effects. Surely part of reported success is due to placebo effect, but that is true for most medical interventions. What you get in the real world is a combo of direct underlying efficacy (or whatever you wan to call it) and the placebo effect. The challenge is to see if any of the benefit is not due to the placebo effect. My best guess at this point is that there is some direct non-placebo effect, and I am more compelled by the anecdotes on mood and depression treatment. After all, we have known for 70+ years that chronically augmenting serotonin transmission in various ways can be effective to treat depression (although there is certainly lots of room for improvement), so an effect of chronic 5-HT2a agonism on depression wouldn’t be that surprising. It could be that some of the other reported effects (e.g., cognitive enhancement, creativity) are indirectly mediated by this improvement in mood.