Treatment-resistant depression (TRD) describes major depression that has not responded well enough to standard treatments. Definitions vary, but a common one is a poor response to at least two different antidepressants. Health Canada used that wording when it approved esketamine nasal spray in 2020 for adults who had not responded adequately to at least two antidepressants in the current episode (Health Canada decision summary).
Psilocybin has been tested in TRD in several trials. The largest phase 2 trial, with 233 adults, found a larger week-3 drop at the highest dose than at a very low control dose, though sustained response at 12 weeks did not clearly support the result (Goodwin et al., 2022). The 2026 EPISODE trial in 144 people missed its primary endpoint (Mertens et al., 2026). Ketamine’s modern story began with an 18-person TRD crossover trial in 2006 (Zarate et al., 2006).
In Canada, psilocybin is not approved for TRD or anything else, and Health Canada lists clinical trials, the Special Access Program and section 56 exemptions as the legal routes (Health Canada). This is a description of research, not medical advice.
Sources
- Health Canada Regulatory Decision Summary, Spravato
- Goodwin et al., NEJM, 2022
- Mertens et al., JAMA Psychiatry, 2026
- Health Canada: Psilocybin and psilocin
Last checked .