LSD: chemistry

LSD is a semisynthetic psychedelic derived from ergot [1], first synthesized by Albert Hofmann in 1938, with its psychoactive effects discovered in 1943 [2][3]. Stoll and Hofmann synthesized it from the ergot alkaloid ergotamine [4], and LSD can be derived from ergot alkaloids such as ergotamine and ergonovine [5]. It is one of the most potent drugs known [6]: only microgram amounts are needed to produce overt hallucinations [7].

Its full psychedelic effects come primarily from activating the serotonin 5-HT2A receptor [8], and its binding to serotonin receptors is what causes the psychedelic effects [4]. Subjective effects appear dose-dependently starting at 25 µg [8], and pharmacokinetics are dose-proportional with first-order elimination [8], meaning the body clears it at a rate proportional to how much is present rather than at a fixed amount per hour. A ceiling for good drug effects appears around 100 µg [8]. The 200 µg dose produced greater ego dissolution than the 100 µg dose [8], and also induced significant anxiety [8]. Average duration of effects lengthens with dose, from 6.7 to 11 hours across the 25-200 µg range [8]. Onset generally falls between 30 and 60 minutes, with effects lasting 10 to 12 hours [7].

Chronic use of serotonergic antidepressants can blunt LSD's subjective effects [9], while tricyclic antidepressants or lithium can increase them [9] — a pharmacological interaction, not a safety comparison in either direction.

References

1. LSD - Wikipedia — Wikipedia
2. The pharmacology of lysergic acid diethylamide: a review — PubMed (National Library of Medicine)
3. Lysergic Acid Diethylamide (LSD) (Archived) — National Center for Biotechnology Information (NCBI)
4. LSD - American Chemical Society — American Chemical Society
5. LSD | Definition, Psychological Effects, & Ergot Fungus | Britannica — Encyclopædia Britannica
6. Lysergide (LSD) drug profile | The European Union Drugs Agency (EUDA) — European Union Drugs Agency
7. D-Lysergic Acid Diethylamide (drug fact sheet) — DEA Diversion Control Division
8. Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects — Neuropsychopharmacology (Nature)
9. Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans — Neuropsychopharmacology (Nature)