LSD, MESCALINE, & PSILOCYBIN
LSD, mescaline, and psilocybin are commonly called hallucino-gens because of their ability to alter consciousness such that the individual senses things that are not present. They induce, often in an unpredictable way, perceptual symptoms, including shape and color distortion. Psychosis-like manifestations (depersonaliza-tion, hallucinations, distorted time perception) have led some to classify these drugs as psychotomimetics. They also produce somatic symptoms (dizziness, nausea, paresthesias, and blurred vision). Some users have reported intense reexperiencing of per-ceptual effects (flashbacks) up to several years after the last drug exposure.Hallucinogens differ from most other drugs described in that they induce neither dependence nor addiction. However, repetitive exposure still leads to rapid tolerance (also called tachyphylaxis). Animals do not self-administer hallucino-gens, suggesting that they are not rewarding to them. Additional studies show that these drugs also fail to stimulate dopamine release, further supporting the idea that only drugs that activate the mesolimbic dopamine system are addictive. Instead, halluci-nogens increase glutamate release in the cortex, presumably by enhancing excitatory afferent input via presynaptic serotonin receptors (eg, 5HT2A) from the thalamus.
LSD is an ergot alkaloid. After synthesis, blotter paper or sugar cubes are sprinkled with the liquid and allowed to dry. When LSD is swallowed, psychoactive effects typically appear after 30 minutes and last 6–12 hours. During this time, subjects have impaired ability to make rational judgments and understand common dan-gers, which puts them at risk for accidents and personal injury.
In an adult, a typical dose is 20–30 mcg. LSD is considered neurotoxic and like most ergot alkaloids, may lead to strong con-tractions of the uterus that can induce abortion .The main molecular target of LSD and other hallucinogens is the 5-HT2A receptor. This receptor couples to G proteins of the Gq type and generates inositol trisphosphate (IP3), leading to a release of intracellular calcium. Although hallucinogens, and LSD in particular, have been proposed for several therapeutic indica-tions, efficacy has never been demonstrated.