The original prediction set a December 2026 deadline, which is implausibly fast. FDA formal guidance documents typically require 12–24 months from internal drafting to public release, including stakeholder consultation and Office of Management and Budget review. The mechanistic basis is solid: fluoxetine's 5-HT2A downregulation is well-characterized and directly relevant to psilocybin and MDMA trial design. However, FDA has other tools (individual IND correspondence, advisory committee recommendations) it typically deploys before issuing cross-cutting guidance. Resolve date extended to end of 2027; confidence reduced to 0.38 to reflect that formal guidance specifically on this topic is likely but not certain within this window, and FDA may address it through less formal channels.