An active placebo is a control that makes people feel something, such as flushing or drowsiness, so that the comparison group is harder to tell apart from the treatment group. A plain inactive pill is easy to spot when the test drug is a psychedelic, because the effects are strong and obvious.
The idea is old. In the 1962 Good Friday Experiment, Walter Pahnke gave the control group nicotinic acid, a B vitamin that causes a warm flush, so they would feel something too (Doblin, 1991). Modern trials still use the trick: a 2022 alcohol use disorder trial compared psilocybin with diphenhydramine, an antihistamine (Bogenschutz et al., 2022), and a 2023 depression trial used niacin in identical capsules (Raison et al., 2023).
It often doesn’t work well. In the 2022 alcohol trial, about 94% of participants guessed their group correctly (Bogenschutz et al., 2022). Reviewers say this kind of functional unblinding is one reason effect sizes in psychedelic trials are likely overestimated (Muthukumaraswamy et al., 2021). Some trials use a very low dose of the same drug instead, which raises its own questions about what counts as “no treatment”.
Sources
- Bogenschutz et al., JAMA Psychiatry, 2022
- Raison et al., JAMA, 2023
- Doblin, 1991, Good Friday follow-up (MAPS archive)
- Muthukumaraswamy et al., 2021
Last checked .