Where it comes from

LSD is semi-synthetic. Its starting point is lysergic acid, the core of the ergot alkaloids that fungi build on the four-ring ergoline skeleton.^[2] Hofmann was working through amides of lysergic acid at Sandoz, hoping for a useful circulatory stimulant, when he made it in 1938.^[1] The natural lysergamides are its close relatives: ergine (LSA) in morning glory seeds, and ergometrine in ergot and in some morning glories. This page does not describe how it is made.

A short history

1. 1918Arthur Stoll at Sandoz isolates ergotamine from ergot, opening the company's ergot research programme.
2. 1938Albert Hofmann makes the 25th compound in a series of lysergic acid amides, LSD-25, while looking for a circulatory and respiratory stimulant. It is shelved.
3. 1943Re-synthesising it, Hofmann absorbs a trace and notices unusual effects (16 April). Three days later he takes a measured amount and cycles home: 'Bicycle Day'.
4. 1947Sandoz begins supplying LSD to researchers under the name Delysid, for experimental psychiatry.
5. 1953The CIA's MKUltra programme begins, including covert LSD experiments on unwitting people.
6. 1965-1970US controls tighten: the 1965 Drug Abuse Control Amendments, criminal possession in 1968, and Schedule I under the Controlled Substances Act in 1970. Most research stops.
7. 2008-2014The first controlled LSD therapy trial in decades runs in Switzerland and is published in 2014.^[5]
8. 2024FDA grants Breakthrough Therapy designation to MM120, an LSD tartrate formulation, for generalized anxiety disorder; Phase 3 trials follow.

How it acts

LSD's psychedelic effects are attributed mainly to agonism at the serotonin 5-HT2A receptor, though it also binds other serotonin and dopamine receptors. A 2017 crystal structure of LSD bound to the closely related 5-HT2B receptor showed a loop of the receptor folding over the molecule like a lid, which slows its release and helps explain why its effects last so long from such small amounts.^[3]

What the clinical research shows

• Alcohol use disorder. A meta-analysis of six randomised trials from the 1960s (536 participants) found that a single LSD session within alcoholism treatment roughly doubled the odds of improvement (odds ratio 1.96).^[4]
• Anxiety with life-threatening illness. A Swiss pilot trial in 12 patients was the first controlled LSD therapy study in decades.^[5] A larger Swiss crossover trial in 42 patients found reductions in anxiety and depression that held at the 16-week end point, with one serious adverse event (transient acute anxiety).^[6]
• Generalized anxiety disorder. In a US Phase 2b trial, 198 adults received a single treatment of MM120 at one of four dose levels or placebo. The two highest levels reduced anxiety scores at four weeks by 5 to 6 points more than placebo on a 56-point scale; the two lowest did not separate from placebo. Visual perceptual changes, nausea and headache were the most common adverse events.^[7]

These trials screen out people at higher risk, prepare participants, and monitor them throughout. Their results do not describe what happens outside those conditions.

Risks

• It can trigger or worsen psychosis and mania, especially with a personal or family history of psychotic or bipolar disorder.
• In an analysis of 62 online reports of classic psychedelics combined with lithium, 47% described seizures.^[8]
• Illicit products are often not what they claim to be; some sold as LSD have contained NBOMe compounds, which have caused deaths.
• A minority of people report lasting visual disturbances afterwards (hallucinogen persisting perception disorder).

More on interactions and emergencies is on the harm reduction page.

Legal status in the United States

LSD is a Schedule I controlled substance under federal law.^[9] Lysergic acid and lysergic acid amide are Schedule III.^[10] Ergotamine and ergonovine, the ergot alkaloids used in medicine, are List I chemicals, regulated because they can be diverted as precursors.^[11] State law can add further restrictions. For other countries, see legal status.