What is the pharmacological activity of LSD?

Answer: Lysergic acid diethylamide (LSD) is a hallucinogenic drug that produces its psychoactive effect by activating serotonin receptors.

lsd hallucinogen image

Also called “acid” for short, lysergic acid diethylamide is a hallucinogen that acts at the serotonin (5-HT) receptors. It also has some activity as a dopamine agonist as well.

LSD is a psychedelic compound. It may produce a general sense of well-being, increased or altered perception of the senses, and may also cause hallucinations. It is used recreationally and also for spiritual purposes, although it may have applications in helping patients with a variety of psychiatric disorders. LSD has very low addiction potential and very low toxicity, but is nonetheless classified as a Schedule 1 drug according to the Controlled Substances Act as put forward by the Drug Enforcement Agency and the Food and Drug Administration. Tolerance rapidly develops to the effects of LSD even after a single exposure. Stopping consumption for a few weeks should allow the body sufficient time to reverse the effects of exposure.

The most common routes of administration for LSD is either through sublingual absorption (a piece of LSD soaked paper is placed under the tongue) or orally. LSD is highly potent, as doses as low as 20 micrograms is generally regarded as the threshold for activity for producing an effect (Psychopathology and Psychophysiology of Minimal LSD-25 Dosage). The effect of the drug may persist for up to 10 hours.

LSD is primarily metabolized and degraded by liver enzymes. The superclass of enzymes cytochrome P450 degrades LSD into a metabolically inactive compound called 2-oxo-3-hydroxy LSD (Pharmacokinetics and Concentration-Effect Relationship of Oral LSD in Humans)

Once in the blood stream, LSD can travel to the brain where it acts as an agonist at serotonin receptors and dopamine receptors. In particular, the 5-HT1A, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5A, 5-HT6, and D2 receptors are activated by LSD.

A 2017 study used crystallography to determine the 3-dimensional structure of LSD attached to its binding site at the serotonin 2B receptor subclass (Structure of an LSD-Bound Human Serotonin Receptor).