Short answer: Evidence suggests serotonergic psychedelics can produce antidepressant-like effects even without formal psychotherapy. For example, a randomized trial of inhaled 5‑MeO‑DMT (GH001) prohibited protocolized psychotherapy yet reported larger early improvements than placebo, as described in JAMA Psychiatry.
Smaller studies with ayahuasca and DMT that used only minimal structured therapy have also reported rapid mood improvements, and human biomarker findings like higher serum BDNF after ayahuasca point to a pharmacologic contribution. This does not prove psychotherapy is unnecessary, but it indicates the drug effects may matter on their own.
Caveats: many trials still include some psychological support, blinding is difficult, and allegiance bias is possible. The size and durability of effects without therapy remain uncertain, and direct comparative studies are limited.
Bottom line: psychedelics may act as pharmacologic antidepressants without structured psychotherapy, but more rigorous, independent replication is needed. Hope that helps.