This self-blinding experiment (n=191) finds that the placebo and microdosing groups both experienced similar improvements in self-rated psychological well-being and cognitive function (e.g. mood, energy, creativity) after four weeks. This study provides more evidence that microdosing benefits can be attributed to expectancy (placebo) effects.
“Microdosing is the practice of regularly using low doses of psychedelic drugs. Anecdotal reports suggest that microdosing enhances well-being and cognition; however, such accounts are potentially biased by the placebo effect. This study used a ‘self-blinding’ citizen science initiative, where participants were given online instructions on how to incorporate placebo control into their microdosing routine without clinical supervision. The study was completed by 191 participants, making it the largest placebo-controlled trial on psychedelics to-date. All psychological outcomes improved significantly from baseline to after the 4 weeks long dose period for the microdose group; however, the placebo group also improved and no significant between-groups differences were observed. Acute (emotional state, drug intensity, mood, energy, and creativity) and post-acute (anxiety) scales showed small, but significant microdose vs. placebo differences; however, these results can be explained by participants breaking blind. The findings suggest that anecdotal benefits of microdosing can be explained by the placebo effect.“
This paper was accompanied with a commentary/insight by Cameron (2021).
A related study on the effects of microdosing (without blinding) that showed that the expected effects were different from the actual effects was recently done by Polito and Stevenson (2019).
This study was unique in that it combined microdosing in a naturalistic (at home/normal life) environment with the blinding that usually happens in a clinical trial. This bridges the gap between large naturalistic studies (without blinding) and clinical trails that usually have a very small number of participants.
The participants (n=191) acquired their own microdoses (e.g. psilocybin-containing mushrooms 24% or LSD 61%) and with a clever QR system, they were randomized to three different conditions (placebo, half-half, microdosing). The microdosing part of the study lasted for four weeks. Each week the participants took four pills (placebo or up to two microdoses).
The participants were mostly male (70%), middle-aged (33.5), and healthy (33% indicated prior psychiatric diagnosis such as depression, 7% current (lower that the average population))
The following outcomes were measured at baseline, week five (after microdosing or placebo), and a follow-up at week nine:
- Psychological well-being (RPWB)
- Mindfulness (CAMS)
- Life satisfaction (SWL)
- Paranoid thoughts (GPTS)
- Personality + intellect trait (B5)
- Cognitive performance (CPS)
Every Sunday the following measures were taken:
- Well-being (WEMWB)
- Depressive symptomatology (QIDS)
- Anxiety (STAIT)
- Social connectedness (SCS)
And during the dosing period:
- Positive and negative affect (PANAS)
- Visual Analogue Scale (VAS, drug intensity, mood, energy, creativity, focus, and temper)
- Cognitive performance (CPS)
The self-blinding was done in the following fashion:
“In summary, the two key elements of self-blinding are to hide the active components inside opaque capsules while preparing identical looking placebos (1) and to position non human-readable QR codes along the capsules prior to randomization (2). With the QR codes in place, it is possible for the experimenter to recover knowledge of capsule types after randomization without revealing that information to participants.”
The blinding was broken (breaking blind) at a higher rate than chance. This means that participants were often (72% vs 63% if random guesses) able to guess if they had taken a microdose. The higher the microdose, the more change the blind was broken (usually at 12 µg of LSD or higher). This information was also used in the analysis of the data.
The authors discuss what this study means in the discussion:
“owever, when looking at the between-group comparisons of the same outcomes, no significant differences were found between the placebo and microdose groups. On the cognitive tests, which are less subjective than the self-reported psychological outcomes, the microdose group did not even improve from baseline to week 5 and the between-groups comparisons were not significant either. Thus, our study validates the positive anecdotal reports about the psychological benefits of microdosing (significant improvements from baseline in a broad range of psychological measures); however, our results also suggest that these improvements are not due to the pharmacological action of microdosing, but are rather explained by the placebo effect (lack of significant between-groups differences).“
The study was limited in that it couldn’t verify the drugs being used (and how the microdosages were prepared). The authors also couldn’t follow the participants (see if they took the pills).
The current study was in a healthy population, and the authors note that a clinical population may possibly benefit from microdosing. But, when doing a further analysis of the current data, they didn’t find significant differences between those scoring highest and lowest on well-being scores.
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March 2, 2021