We licked the frogs so you don’t have to: A comprehensive history and analysis of the chemical syntheses of the classical psychedelics Bufotenin(e) and 5-methoxy-N,N-dimethyltryptamine
Bibliographic record
Abstract
Bufotenin (also spelt as bufotenine) and its methylated derivative, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) are potent psychedelics (although the activity of the former is attenuated due to its low propensity to cross the blood-brain-barrier) that are found in many plants but also excreted by specific species of toads. The compounds are regulated differently around the world, and although they have been used in traditional medicine, 20th century prohibition culture has slowed research into their utility for ameliorating psychological disorders and inflammatory & neurodegenerative diseases. However, the global trend towards legalization and a renewed interest in the therapeutic potential of psychedelics has increased the number of clinical and preclinical studies of these and related materials. This necessitates access to large amounts of these compounds, but they are not commercially available on scale. This leaves researchers with a need to either contract for, or make their own, bufotenin. The first synthesis was reported in 1935 by Hoshino and coworkers, and novel syntheses are still being disclosed in the 2020s. This is the first effort to collate and compare all extant academic and patent syntheses (as of fall 2024) into a single review so that researchers can identify the most appropriate route for their own purposes. We conclude by highlighting outstanding challenges that are ripe for solutions to reduce the cost of any future commercial-scale production.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.003 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 0.005 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".