How much evidence is there for microdosing having an effect significantly larger than placebo? From this conversation with James Fadiman I got the impression that it is more underwhelming than I thought.
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.
We haven’t seen rigorous well-controlled trials of microdosing of psychedelic vs a placebo. One recent study, in which citizen scientists blinded themselves, strongly suggest a placebo effect. There is so much “magic” associated with psychedelics that that taking a tiny dose is likely to have an unusually strong placebo effect. But more research needs to be done.
It’s important to understand that ALL the research done on psychedelics—research that has already produced potentially revolutionary treatments for PTSD, depression, existential distress and addiction—has been privately funded by philanthropists. This area is still too controversial for government funding. I can’t think of another case where philanthropy has achieved so much in twenty years.
How much evidence is there for microdosing having an effect significantly larger than placebo? From this conversation with James Fadiman I got the impression that it is more underwhelming than I thought.
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.
We haven’t seen rigorous well-controlled trials of microdosing of psychedelic vs a placebo. One recent study, in which citizen scientists blinded themselves, strongly suggest a placebo effect. There is so much “magic” associated with psychedelics that that taking a tiny dose is likely to have an unusually strong placebo effect. But more research needs to be done.
It’s important to understand that ALL the research done on psychedelics—research that has already produced potentially revolutionary treatments for PTSD, depression, existential distress and addiction—has been privately funded by philanthropists. This area is still too controversial for government funding. I can’t think of another case where philanthropy has achieved so much in twenty years.