# Registration Submission Draft — Independent Psilocybin Safety Review

This is a copy-ready draft for a real review team to submit to PROSPERO and/or the OSF Generalized Systematic Review registration. It is **not registered yet**.

## Administrative fields

- **Review title:** Serious medical and severe psychiatric harms after one monitored 25 mg psilocybin administration in adults with major depressive disorder: a systematic review and independent replication of a pilot evidence synthesis
- **Review stage at registration:** Independent database searching, screening, and extraction not started. A prior single-author pilot exists and is disclosed.
- **Named contact:** To be supplied by the accountable human review lead.
- **Review team:** Unassigned; see `review-team-roles.csv`.
- **Funding:** No external funding declared for the website-author pilot. Independent-team funding must be entered before submission.
- **Conflicts:** Every reviewer must complete `reviewer-conflict-disclosure.csv`; psychedelic-industry, advocacy, clinical, publication, and intellectual conflicts are all relevant.
- **Anticipated start/end:** To be set after the information specialist and two reviewers are confirmed.

## Rationale

Existing psilocybin trials often report adverse events using inconsistent windows, attribution rules, severity thresholds, and denominators. The review therefore fixes one narrow clinical scenario and separates direct evidence from TRD, dose, regimen, and comparator indirectness.

## Objective

Estimate outcome-specific absolute risks and uncertainty after one monitored 25 mg oral synthetic-psilocybin administration in screened adults with MDD, and determine which outcomes remain unestimable.

## Participants, intervention, comparator, outcomes, design

Use the exact definitions in `PSILOCYBIN_INDEPENDENT_REPLICATION_PROTOCOL_V0.2.md` and `estimand-registry.csv`.

## Searches

Database inception to final search date, no language restriction. MEDLINE, Embase, PsycINFO, CENTRAL, ClinicalTrials.gov, WHO ICTRP, Scopus/Web of Science, citation searching, regulatory/sponsor sources, and author contact. Strategies are frozen in `search-strategies-v0.6.csv` pending information-specialist peer review.

## Study selection and data extraction

Two independent reviewers with concealed first-pass decisions; adjudication by a third person. All exclusions and conflicts are retained. Independent extraction uses structured arm-level fields.

## Risk of bias and certainty

Result-level RoB 2 and outcome-level GRADE, both independently judged before adjudication.

## Synthesis

Absolute risks per 1,000 administrations, exact intervals, compatible risk differences, and prespecified rare-event sensitivity analyses. No automatic pooling, continuity correction, or cross-context score.

## Dissemination

Publish the protocol, search histories, deduplicated record set where licensing permits, screening decisions, excluded full-text reasons, extraction data, RoB judgments, GRADE profile, code, and amendments. Preserve a machine-readable release manifest.

## Required disclosure text

> A single-author pilot search and synthesis preceded this registration. The registered project prospectively governs a new independent replication. Independent reviewers will be blinded to pilot decisions during first-pass screening, extraction, and risk-of-bias assessment. The pilot is not represented as preregistered or independently replicated.