Lysergic acid diethylamide

Lysergic acid diethylamide (LSD) is synthesized from d-lysergic acid, a naturally occurring ergot alkaloid found in the fungus Claviceps purpurea, which grows on wheat and other grains. LSD shares structural features with serotonin (5-hydroxytryptamine; a major CNS neurotransmitter and neuromodulator) [81]. LSD binds to serotonin receptors in the CNS and acts as a serotonin agonist. The principal psychological effects of LSD are perceptual distortions of color, sound, distance, and shape (synesthesia); depersonalization and loss of body image; and rapidly changing emotions from ecstasy to depression or paranoia. The physiologic effects of LSD are related to its sympathomimetic actions and include mydriasis (most frequent and consistent), tachycardia, increased body temperature, diaphoresis, and hypertension; at higher doses, parasympathomimetic actions may be observed [e.g., salivation, lacrimation, nausea, and vomiting (muscarinic actions)]. Neuromuscular effects may include paresthesia, muscle twitches, and incoordination (nicotinic actions) [81].

LSD is used illicitly because of its hallucinogenic effects. The most common adverse effects of LSD are panic attacks. In addition, unpredictable recurrence of hallucinations (flashbacks) may occur weeks or months after last drug use, and LSD may elicit psychotic reactions. No evidence suggests that repeated LSD use results in dependence or withdrawal symptoms [81].

Popular dosage forms include powder, gelatin capsule, tablet, and LSD-impregnated sugar cubes, filter paper, or postage stamps. The drug is rapidly absorbed from the GI tract; the effects begin within 40–60 minutes, peaking at ~2–4 hours, and subside by 6–8 hours. The elimination t_1/2 is ~3 hours. The metabolism of LSD in humans is incompletely understood, but 2-oxo-3-hydroxy-LSD is present in urine at concentrations of 10- to 43-fold greater than LSD [82]. N-demethyl-LSD is also present in urine specimens, but at concentrations approximately equivalent to those of LSD [83].

The typical dose is low (20–80 μg) and is rapidly metabolized, and only ~1%–2% of the drug is excreted unchanged in urine. Thus detection of LSD presents an especially difficult analytical challenge. Even with sensitive assays, the detection window for LSD is generally only 12–24 hours [84]. Immunoassays are targeted to detect LSD, and confirmation assays may be performed by GC–MS, GC–MS/MS, LC–MS/MS, or LC–MS [16].