GHB was first synthesized in 1960 and introduced as a general anesthetic. Because of its narrow safety margin and its addictive potential, it is not available in the USA for this purpose. Sodium oxybate can, however, be prescribed (under restricted access rules) to treat narcolepsy, because GHB decreases daytime sleepiness and episodes of cataplexy through a mechanism unrelated to the reward system. Before causing sedation and coma, GHB causes euphoria, enhanced sensory perceptions, a feeling of social closeness, and amnesia. These properties have made it a popular “club drug” that goes by colorful street names such as “liquid ecstasy,” “grievous bodily harm,” or “date rape drug.” As the latter name suggests, GHB has been used in date rapes because it is odorless and can be readily dissolved in beverages. It is rapidly absorbed after ingestion and reaches a maximal plasma concentration 20–30 minutes after ingestion of a 10–20 mg/kg dose. The elimination half-life is about 30 minutes.
Although GABAB receptors are expressed on all neurons of the VTA, GABA neurons are much more sensitive to GHB than are dopamine neurons (Figure 32–3). This is reflected by the EC50s, which differ by about one order of magnitude, and indicates the difference in coupling efficiency of the GABAB receptor and the potassium channels responsible for the hyperpolarization. Because GHB is a weak agonist, only GABA neurons are inhibited at the concentrations typically obtained with recreational use. This feature may underlie the reinforcing effects of GHB and the basis for addiction to the drug. At higher doses, however, GHB also hyperpolarizes dopamine neurons, eventually completely inhibiting dopamine release. Such an inhibition of the VTA may in turn preclude its activation by other addictive drugs and may explain why GHB might have some usefulness as an “anticraving” compound.
LSD, MESCALINE, & PSILOCYBIN
LSD, mescaline, and psilocybin are commonly called hallucinogens 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 (depersonalization, 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 perceptual effects (flashbacks) up to several years after the last drug exposure.
Hallucinogens differ from most other drugs described in this chapter in that they induce neither dependence nor addiction. However, repetitive exposure still leads to rapid tolerance (also called tachyphylaxis). Animals do not self-administer hallucinogens, suggesting that they are not rewarding to them. Additional