In a crossover trial, every participant receives both conditions, for example psilocybin and a comparison, in a randomized order. Each person serves as their own control, so smaller groups can still show a difference.
Two well-known 2016 psilocybin studies in people with life-threatening cancer used this design. In one, 51 adults received a very low dose and a high dose five weeks apart, in counterbalanced order (Griffiths et al., 2016). In the other, 29 adults received psilocybin or niacin, then crossed over at 7 weeks (Ross et al., 2016). A Yale cluster headache trial was also registered as a crossover study (Schindler et al., 2022).
The weak point with psychedelics is lasting effects. Once someone has had psilocybin, the drug may still be shaping their mood when they get the comparison, and they may now know which session was which. That is why the end-of-life trials’ authors treat the comparison before the switch as the main result, and why the crossover ended the double-blind comparison early in the Baltimore study (Griffiths et al., 2016).
Sources
- Griffiths et al., Journal of Psychopharmacology, 2016
- Ross et al., Journal of Psychopharmacology, 2016
- Schindler et al., Headache, 2022
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