Supposed Benefits Of Psychedelic Microdosing To Mental Health May Actually Reflect Strong Placebo Response

By Matthew Warren

An increasingly large body of work suggests that many illicit psychoactive drugs could be useful as treatments for certain mental health problems. Studies have found, for instance, that the psychedelics psilocybin (from magic mushrooms) and LSD can reduce symptoms of anxiety and depression, while MDMA may be useful in treating PTSD.  

It’s a different story for a practice known as “microdosing”, however. This involves taking a small quantity of a psychedelic substance — normally too little to produce any perceptible effects — repeatedly over a period of time (every few days for several weeks, say). And as we reported in 2019, although results from some surveys or poorly-controlled trials suggest that microdosing can improve people’s mood or certain aspects of cognition, more rigorous placebo-controlled trials have failed to find any such effects.

A new study in Scientific Reports could explain why. The team, led by Laura Kartner from Imperial College London, finds that people who plan on microdosing do go on to experience a boost to wellbeing and a reduction in anxiety and depression. But the level of improvement depends on how much they expect to improve in the first place, suggesting that any effects on wellbeing may be the result of a strong placebo response.

The researchers recruited 253 people who were planning on microdosing a psychedelic drug such as psilocybin, LSD, or ayahuasca. In the week before the participants began microdosing, they completed a survey about their expectations, indicating how confident they were that the experience would have a positive effect, for instance, and how successful they thought it would be in improving their wellbeing. They also completed a number of other scales, including measures of wellbeing, depressive symptoms, anxiety, and personality traits. Then, once they began microdosing, participants completed weekly measures of wellbeing, depression, and anxiety, and recorded how much of the drug they had taken and whether they had experienced any psychoactive effects.

The team found that after participants started microdosing, their wellbeing increased and symptoms of depression and anxiety decreased. Most of these effects emerged in the first week of taking the drugs, then remained at a similar level for the rest of the four week period. But, importantly, their expectations in the week before beginning to take the drug predict the extent of these changes: those who had a greater expectation that microdosing would produce positive effects tended to show more positive changes in all three measures.

At first glance, it might seem like the study supports the use of microdosing. But the fact that people’s expectations were tied to their response suggests that what seems like a useful therapeutic effect might actually be a placebo effect, driven by what participants want or expect to occur. That could explain why previous placebo-controlled studies have found that microdosing doesn’t produce any beneficial response beyond that of a placebo. Of course, in this case there was no placebo arm of the study, so it’s impossible to tell for sure.

The authors also posit one other intriguing possibility: that the drugs do produce a pharmacological effect in the brain at this low dose, but this doesn’t boost wellbeing — instead, it actually accentuates the placebo response. For instance, microdosing might promote “plasticity” in the brain — the ability to reorganise networks and form new pathways — and this could potentially make any expectation effects even more pronounced. Again, only well-controlled trials will be able to determine whether that’s the case.

Whatever’s going on in the brain during microdosing, it’s clearly worth further examination. But as this study shows, in the absence of more rigorous research, there’s good reason to be sceptical of bold claims about the benefits of microdosing to people’s mental health.

Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing

Matthew Warren (@MattBWarren) is Editor of BPS Research Digest