Chemists
Who made these molecules, and what "made" actually means. Credit here is split four ways — first synthesis, discovering what a compound does, isolating a natural product, and popularising something someone else made — because collapsing those into one verb gets the history wrong. MDMA was synthesized in 1912 by a chemist who never knew what it was.
- Alexander "Sasha" Shulgin 1925–2014
Synthesized and personally tested over 200 psychoactive compounds, most of them phenethylamines and tryptamines, and published the syntheses and dose/duration reports himself in PiHKAL (1991) and TiHKAL (1997) rather than in journals. That choice is why most of this taxonomy has documented human data at all. He did not discover MDMA — Merck synthesized it in 1912 — but he resynthesized it in 1976, and passing it to the psychologist Leo Zeff is how it reached psychotherapy.
5 molecules on this site · 200+ synthesized and self-tested; 179 phenethylamine and 55 tryptamine entries across PiHKAL and TiHKAL
- David E. Nichols 1944–
Medicinal chemist whose work established much of what is known about how psychedelics bind at 5-HT2A. Created the lysergamides AL-LAD, ETH-LAD and PRO-LAD, the entactogen MDAI, and the dopamine agonist dihydrexidine. His lab developed the N-benzylphenethylamine motif as a research tool; the potent 25x-NBOMe compounds built on it were the work of others, and he has been public about regretting how that work was taken up.
2 molecules on this site · dozens of novel compounds across ~300 published papers
- Albert Hofmann 1906–2008
Working on ergot alkaloids at Sandoz, Hofmann first synthesized LSD-25 in 1938 and set it aside; he discovered its effects only in 1943, after accidental exposure. He went on to isolate and synthesize psilocybin and psilocin from Psilocybe mexicana, giving both compounds their first defined chemistry. The same programme produced methylergometrine, still used to control post-partum haemorrhage.
3 molecules on this site · numerous ergot derivatives; the LSD, psilocybin and psilocin work is the lasting part
- Leo Sternbach 1908–2005
Created the benzodiazepines. Chlordiazepoxide (Librium) came out of a compound he had shelved as unpromising and which was submitted for testing during a lab clean-up in 1957; diazepam (Valium) followed in 1963 and became the most prescribed drug in America for over a decade. Nitrazepam, flurazepam, flunitrazepam and clonazepam came from the same programme.
2 molecules on this site · 241 patents; the benzodiazepine class
- Paul Janssen 1926–2003
One of the most productive drug developers of the twentieth century. His fentanyl (1960) remade surgical anaesthesia and, decades later, the illicit opioid supply; haloperidol and risperidone did comparable work in psychiatry. The same lab produced the shorter-acting analogues sufentanil, alfentanil and carfentanil.
3 molecules on this site · 80+ medicines brought to market
- John W. Huffman 1932–2022
Made over 400 synthetic cannabinoids to probe the CB1 and CB2 receptors, publishing each structure openly. JWH-018 and its siblings were lifted from those papers and sprayed onto herbal blends sold as "Spice" and "K2". Huffman was unambiguous about it: "It bothers me that people are so stupid as to use this stuff."
1 molecule on this site · 400+ synthetic cannabinoids
- Daniel Trachsel
Swiss medicinal chemist who has continued systematic phenethylamine work after Shulgin, with a particular interest in fluorinated analogues. Co-authored Phenethylamine: von der Struktur zur Funktion (2013) with David Lehmann and Christoph Enzensperger. Unlike Shulgin he does not self-experiment and has said so publicly.
0 molecules on this site · dozens; roughly 70 documented compounds
- Raphael Mechoulam 1930–2023
Opened cannabinoid science. With Yechiel Gaoni he elucidated the structure of cannabidiol (1963) and Δ9-THC (1964) and completed their total synthesis in 1965 — before that, nobody knew which molecule in cannabis was responsible for what. He later directed the work that isolated the first endocannabinoid, anandamide, and created the HU series including the very potent HU-210.
3 molecules on this site · dozens of cannabinoids, including the HU series
- Gordon Alles 1901–1963
A pharmacologist rather than a synthetic chemist, and his contribution is discovery rather than invention. Amphetamine already existed when in 1929 he established what it does — self-experimenting while looking for an ephedrine substitute for asthma — and he prepared and patented the sulfate salt that Smith, Kline & French sold as Benzedrine. He did the same for MDA in 1930, taking 126 mg and describing the effects, though he did not publish that account until 1959.
2 molecules on this site · no reliable figure; the amphetamine and MDA findings are the significant ones
- Bryan Molloy 1939–2004
With Klaus Schmiegel, synthesized the compound series that produced fluoxetine, working from a project Molloy and Ray Fuller began in 1970. David Wong then retested the series for serotonin-selective reuptake inhibition and identified fluoxetine as the most selective of them. It was not the first SSRI to reach a market — zimelidine was, in 1982, and was withdrawn within about eighteen months — but it was the first to succeed commercially, and it changed how depression is treated.
1 molecule on this site · dozens of aryloxyphenylpropylamines screened to find one candidate
- Anton Köllisch 1888–1916
Synthesized MDMA at Merck in 1912 as an intermediate in a route to a haemostatic drug. Nobody tested it for psychoactivity and Köllisch died in the First World War without learning what he had made.
1 molecule on this site · one that mattered, and he never knew
- Lazăr Edeleanu 1861–1941
First synthesized amphetamine in 1887, as phenylisopropylamine. Its stimulant properties went unnoticed for forty years until Gordon Alles found them.
1 molecule on this site · first synthesis of amphetamine, plus the oil-refining process he is better known for
- Yechiel Gaoni 1930–2019
Co-author with Raphael Mechoulam of the papers that established the structures of cannabidiol (1963) and Δ9-THC (1964) and their total synthesis (1965). The THC work is routinely credited to Mechoulam alone; it was joint.
2 molecules on this site · the cannabinoid structural work, jointly with Mechoulam
- William Devane
With Lumír Hanuš, isolated anandamide from porcine brain in 1992 — the first endocannabinoid found, and the reason the receptor Δ9-THC binds turned out to have a native ligand.
1 molecule on this site · co-isolated anandamide
- Lumír Ondřej Hanuš 1948–
With William Devane, isolated and characterised anandamide in 1992 while working in Mechoulam's laboratory.
1 molecule on this site · co-isolated anandamide
- David T. Wong 1935–
Proposed retesting the Lilly aryloxyphenylpropylamine series for selective serotonin reuptake inhibition and showed that one of them — fluoxetine — was by far the most selective. Fluoxetine is usually credited to a team of four: Wong, Bryan Molloy, Klaus Schmiegel and Ray Fuller.
1 molecule on this site · identified fluoxetine within the Molloy/Schmiegel series
- Calvin L. Stevens 1923–2014
Synthesized ketamine in 1962 while looking for a less deliriant replacement for phencyclidine. Neither ketamine nor PCP is the work of any of the ten chemists this site started from, which is itself worth noticing.
1 molecule on this site · ketamine, plus academic synthetic work