# Research timeline and gaps: Psychedelic Microdosing and Mental Health

Selected publication milestones, not an exhaustive history or discovery priority claim.

**2018 — Intermittent rodent psilocin/ketamine anxiety-proxy study gives modest possible anxiogenic boundary rather than clinicalLSD evidence.** [Original PMID29537989](https://pubmed.ncbi.nlm.nih.gov/29537989/).

**2018 — Open-label microdose-event creativity tasks supply early quantitative exploratory support without placebo isolation.** [Original PMID30357434](https://pubmed.ncbi.nlm.nih.gov/30357434/).

**2019 — Controlled low-dose LSD alters interval timing without robust subjective effects; acute pharmacology becomes experimentally testable.** [Original PMID30478716](https://pubmed.ncbi.nlm.nih.gov/30478716/).

**2019 — Healthy acute dose-response study shows measurable subjective action while most cognition and mood outcomes remain unchanged.** [Original PMID31331617](https://pubmed.ncbi.nlm.nih.gov/31331617/).

**2019 — Six-week naturalistic tracking reports symptom declines and mainly dose-day changes, motivating controlled repeat-dose studies.** [Original PMID30726251](https://pubmed.ncbi.nlm.nih.gov/30726251/).

**2020 — Microdosing demographic/diagnosis survey identifies self-selection and concurrent-drug differences.** [Original PMID32108529](https://pubmed.ncbi.nlm.nih.gov/32108529/).

**2021 — Verified base-dose pharmacokinetics show5microgram subjective-null versus10/20microgram perception, defining a dose-dependent boundary.** [Original PMID32975835](https://pubmed.ncbi.nlm.nih.gov/32975835/).

**2021 — Citizen self-blinding separates randomized capsule exposure from guessed allocation and reports no accumulated between-group benefit.** [Original PMID33648632](https://pubmed.ncbi.nlm.nih.gov/33648632/).

**2021 — Prospective baseline expectations predict later wellbeing improvement, strengthening a competing explanation.** [Original PMID33479342](https://pubmed.ncbi.nlm.nih.gov/33479342/).

**2021 — Acute plasmaBDNF positive is reported; it remains a peripheral biomarker rather than validated treatment mediation.** [Original PMID33860175](https://pubmed.ncbi.nlm.nih.gov/33860175/).

**2022 — Repeated controlled10/20base-equivalent LSD produces subjective effects but no residual mood or cognitive advantage.** [Original PMID35106880](https://pubmed.ncbi.nlm.nih.gov/35106880/).

**2022 — Preregistered psilocybin microdose crossover is symptom-null with later blind breaking.** [Original PMID34915762](https://pubmed.ncbi.nlm.nih.gov/34915762/).

**2022 — Psilocybin mushroom microdose subjective recognition andEEG effects coexist with wellbeing/cognition nulls.** [Original PMID35918311](https://pubmed.ncbi.nlm.nih.gov/35918311/).

**2022 — Full-doseCOMP360TRDprimaryweek-three positive has dose and sustained-response limits distinct from microdosing.** [Original PMID36322843](https://pubmed.ncbi.nlm.nih.gov/36322843/).

**2023 — Six-week home LSD trial separates transient dose-day mood elevation from no persistent pre/post change.** [Original PMID36997080](https://pubmed.ncbi.nlm.nih.gov/36997080/).

**2024 — Restricted high-BDI acute low-dose crossover positive raises a symptomatic-population question without testing sustained treatment.** [Original PMID38042914](https://pubmed.ncbi.nlm.nih.gov/38042914/).

**2024 — Same home-trial wearable sleep analysis identifies a delayed measurable effect rather than clinical symptom efficacy.** [Original PMID38622150](https://pubmed.ncbi.nlm.nih.gov/38622150/).

**2025 — Two-center six-week ADHD clinical primary fails despite drug perception and measured allocation guesses.** [Original PMID40105807](https://pubmed.ncbi.nlm.nih.gov/40105807/).

**2025 — Same home-trial PK analysis finds no peripheralBDNF alteration, limiting uniform plasticity-marker claims.** [Original PMID40251818](https://pubmed.ncbi.nlm.nih.gov/40251818/).

**2025 — Positive-controlled chronic mouse cardiac study finds no observedLSD remodeling, with human rare/longterm risk unresolved.** [Original PMID41789300](https://pubmed.ncbi.nlm.nih.gov/41789300/).

**2026 — Direct eight-week open-label MDD improvement is published, furnishing exploratory clinical support requiring causal isolation.** [Original PMID41202873](https://pubmed.ncbi.nlm.nih.gov/41202873/).

**2026 — Same depressed-mood crossover reward analysis relates neural changes to48hour symptoms without mediator manipulation.** [Original PMID41529826](https://pubmed.ncbi.nlm.nih.gov/41529826/).

**2026 — Later effectively blinded psilocybin longitudinal trials report no corrected emotional/cognitive benefit.** [Original PMID41110634](https://pubmed.ncbi.nlm.nih.gov/41110634/).

**2026 — Pooled original truffle creativity trials retain a restricted guess-adjusted originality positive.** [Original PMID41187880](https://pubmed.ncbi.nlm.nih.gov/41187880/).

**2026 — Full-doseEPISODEprimaryresponse null preserves endpoint hierarchy despite favorable exploratory scales and safety signals.** [Original PMID41848690](https://pubmed.ncbi.nlm.nih.gov/41848690/).

## Research gaps

Complete outcome-paper methods, analyzed sample, missing-data handling, dose distribution and comparator/rater masking for the completed LSDDEP2 trial; additional independent symptomatic trials and anxiety-specific estimates.

Dose/base-tartrate normalization and individual perceptibility measured before declaring a regimen subperceptual.

Independent expectancy manipulation and safe interpretation of postdose allocation-guess adjustment.

Clinical relevance of reward/connectivity/EEG/BDNF signals rather than assumed plasticity-mediated therapy.

Longerterm, uncommon and cardiovascular harms; small trial echo/mouse nulls do not quantify rarehuman risk.

Regimen-specific comparative efficacy, support intensity and function without transferring full-dose/ketamine positives ornulls.

## Boundary experiment

Registered symptomatic-MDD trial of titrated 5–20 microgram base-equivalentLSD twiceweekly for 8 weeks versus credible sensory-matched active comparator, with equalcontact/co-care and an expectancy-factor manipulation or prespecified sensitivity analyses; follow throughwithdrawal and relapse.