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The term "hallucinogen" describes a diverse group of xenobiotics that alter and distort perception, thought, and mood without clouding the sensorium. Hallucinogens can be categorized by their chemical structures, and further divided into natural and synthetic members of each family. The major structural classes of hallucinogens include the lysergamides, tryptamines (indolealkylamines), amphetamines (phenylethylamines), arylhexamines, cannabinoids, harmine alkaloids, belladonna alkaloids, and the tropane alkaloids. In addition, there are several unique hallucinogens, such as Salvia divinorum, nutmeg, kratom, and kava kava. This chapter focuses on lysergamides, tryptamines, phenylethlyamines, and these unique hallucinogens. More on the other classes can be found in Chap. 71 (Monoamine oxidase inhibitors), Chap. 75 (Amphetamines), Chap. 83 (Cannabinoids), and Chap. 85 (Phencyclidine and Ketamine).


The term "hallucination" may be defined as false perception that has no basis in the external environment. The term is derived from the Latin alucinari, "to wander in mind." While the term "psychedelic" has been used for years to refer to the recreational and nonmedical effects of hallucinogens, other terms, like entheogen and entactogen, frequently appear in Internet discussions. Entheogens are "substances which generate the god or spirit within," while entactogens create an awareness of "the touch within."41 These terms all refer to the same xenobiotics, used with differing intent or in varying settings. Hallucinations differ from illusions, which are distorted perceptions of objects based in reality.


Hallucinogens have been used for thousands of years by many different cultures, largely during religious ceremonies. The ancient Indian holy book, Rig-Veda, written over 3500 years ago, describes a sacramental xenobiotic called Soma both as a god and as an intoxicating xenobiotic. Although debated for many years, the source of Soma is now believed to be the juice of the mushroom Amanita muscaria.98,105 The Aztecs used the psilocybin-containing teonanacatl (flesh of the gods), and Ololiuqui (morning glory species) in their religious ceremonies. To this day, the Native American Church in the United States uses peyote in religious ceremonies.


Synthetic hallucinogen use is often said to have begun with the discovery of lysergic acid diethylamide, or LSD. The synthesis of LSD resulted from extensive research on the medicinal uses of ergot alkaloids derived from the fungus, Claviceps purpurea. From medieval times through recent years, several large-scale epidemics of vasospastic ischemia, gangrene, and hallucinations (collectively called ergotism) have resulted from C. purpurea contamination of cereal crops.136 The hallucinations from Claviceps ingestion have been attributed to the ergot alkaloid lysergic acid amide from which LSD was chemically synthesized. Claviceps purpurea has been suggested, but subsequently disproved, as the cause of the mass hysteria leading up to the Salem witch trials. Many of these adverse effects after ingestion of C. purpurea have been attributed to the serotonergic agonist effects of the ergot alkaloids (see Chap. 51).38


In 1938, Albert Hofmann, a Swiss chemist, synthesized LSD-25, the twenty-fifth substance in a series of lysergic acid derivatives being ...

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