The state induced by anesthetics and sedative-hypnotics involves a generalized disconnect from the functional waking state awareness of time and space. In the brain, the general depression of activity is mediated by the inhibitory neurotransmitter GABA (gamma-aminobutyric acid), and most of the sedative-hypnotics are believed to exert their effects by interacting with GABA receptors.
A recent discovery is GHB (gamma-hydroxybutyric acid), which produces a profound stage three and four sleep state, and has therefore found a use in the treatment of narcolepsy—where insufficient night-sleep can cause sudden collapse in the daytime. Recreational users have discovered that at lower dosages, GHB produces a profound relaxation of smooth muscles, thereby heightening sexual-sensual experience. Predictably, this has led to its exploitation and abuse in combination with alcohol as a so-called “date-rape” drug, and its classification as a Schedule I prohibited substance (Dean and Morgenthaler, 1997; Pendell, 2002).
The opiate analgesic drugs, such as morphine, codeine, and heroin, specifically disconnect the person from awareness of pain sensations, also slowing the breath, producing relaxation, and dissociating perception from the environment.
Nitrous oxide is a gas used in dentistry and medicine for its anesthetic and analgesic properties. In the nineteenth-century the discovery of its unusual psychoactive properties attracted the attention of the philosopher William James among others. Users characterize the experience as interesting and significant, as well as pleasurable—though they are often unable to bring back any insights that hold up in the light of reason. In the nineteenth-century, carnival-like public demonstrations of what was called “laughing gas” were held, and it continues to attract the interest of some recreational users. In terms of brain chemistry, nitrous oxide acts as an antagonist at the NMDA type of glutamate receptor (Pendell, 1995).
Glutamate is the major excitatory neurotransmitter of the brain, important in learning and memory. Besides nitrous oxide the dissociative anesthetics ketamine and PCP also function as NMDA-glutamate antagonists. Ketamine (as well as PCP), at subclinical doses, can cause visual hallucinations, somewhat reminiscent of LSD-like patterns, but with accompanying marked disconnect from sensory awareness of the physical body. Some researchers are now investigating whether neurotransmitter interactions with glutamate receptors may be responsible for the hallucinations of schizophrenia (Pendell, 2005; Jansen, 2001).
Plant extracts from the solanaceous nightshade family (henbane, scopolamine, datura) were notoriously used by shamanic practitioners of witchcraft in the European Middle Ages (Heiser, 1987). They also act by inducing a strong dissociation from ordinary awareness of the body and environment, which may then lead to out-of-body visionary states such as flying through the air. In South American indigenous tribes, the healers (curanderos) will sometimes use datura plant extracts for diagnosing, especially in cases of sorcery, but will typically take a lower dose, and also have an assistant watching over them, in case they get disoriented. Among the Chumash Indians of Southern California, preparations from the local datura plant were used in adolescent initiation ceremonies, marking the transition from childhood to adulthood (Schultes and Hofmann, 1992).