Daniel X Freedman R N Pechnick

HALLUCINOGENS The term hallucinogen literally means producer of HALLUCINATIONS. A variety of drugs and medicines as well as various disease states can lead to the development of hallucinations. They can occur during a high fever, after acute brain injuries, or as part of a DELIRIUM, accompanied by confusion in judgment, intellect, memory, emotion, and level of consciousness. The patient is said to be ''out of it''—not in touch with reality. In fact, many infections affecting the brain, conditions that disrupt the availability of nutrients essential for brain function, or direct brain injury can cause transient or prolonged delirium. Disease states not directly involving the brain also can alter brain function. For example, the overproduction of thyroid or adrenal hormones in endocrine disease can cause psychotic mental symptoms. In addition, poisoning or other toxic reactions can produce hallucinations.

Some drugs used to treat certain illnesses, although not prescribed for their behavioral effects, may be PSYCHOACTIVE and cause auditory and/or visual hallucinations in some but not all patients. High doses of the adrenal hormone, cortisone, which is prescribed to reduce inflammation in arthritis or allergies, can produce elation or depression and mood-related hallucinations. Similarly, the administration of thyroid hormones for the treatment of thyroid grand deficiencies can cause restlessness, nervousness, excitability and irritability, and psychotic mental symptoms. Drugs derived from the belladonna plant, such as atropine and SCOPOLAMINE, have many uses in clinical medicine but in high doses can cause memory lapses and illusions. Delirium also may result from the sudden withdrawal after the chronic administration of certain drugs, especially ethanol (ALCOHOL) and SEDATIVE drugs of the BARBITURATE class. The vivid hallucinations of DELIRIUM TREMENS (DTs) during the WITHDRAWAL from alcohol have been vividly portrayed in the cinema and television.

Many drugs that affect behavior can alter the level of consciousness or the perception of the environment. PHENCYCLIDINE (known as PCP or ''angel dust'') can produce a state of altered consciousness in which sensations from the body and relationship to the environment are misinterpreted. The subject may experience numbness in the limbs and feel as though they are removed from their bodies. These distorted perceptions of the real world can lead to confusion, delusions, and hallucinations—and violent behavior can occur with the slightest provocation. There is controversy as to whether these varied reactions are psychotomimetic (imitating mental illness with psychoses), but not about the extent to which, depending on the dose, subjects are out of it. High and/or frequent doses of stimulants such as Amphetamine, Methamphetamine (''speed'' or ''ice''), or COCAINE can cause paranoid thought or delusions. Moreover, high doses of MARIJUANA or Hashish can lead to dreamy illusions or hallucinations. Thus, many drugs under certain conditions can cause hallucinations as part of the production of a complex behavioral syndrome, which may include a general alteration of the level of consciousness and the disruption of the ability of the brain to process information and appreciate the real world.

The term hallucinogens has come to mean a group of compounds that reliably, temporarily, and universally alter consciousness without delirium, sedation, excessive stimulation, or any intellectual or memory impairment as prominent effects. Indeed these altered mental effects are the main effects of such drugs. There are a number of synonyms for drugs that produce hallucinations that occur with clear consciousness, but the term psychedelic has come into wide use. In the 1960s the term was coined by Humphrey Osmond, a British psychiatrist who came to North America to continue studies of the psychiatric effects of MESCALINE and LSD, and was enthusiastic about their use in enhancing insight in psychotherapy. The term psychedelic was invented from greek roots to mean ''mind manifesting,'' from psyche (mind, soul) + deloun (to show). This refers to the convincing clarity with which a subjective experience is compellingly revealed to the subject who has taken a hallucinogen. What is seen, thought, and felt is vivid—contrasting sharply with the normally ordered perceptions of the world in which we move about and perform our practical tasks. Key to the hallucinogenic experience is that drab everyday reality, while clearly perceived in this drug state, has simply lost its importance in favor of vivid subjec tive sensations and perceptions and interpretations of them that absorb attention. A door is recognized but not simply for its utility; rather the grain of the wood and its fine detail becomes fascinating, and the grain of the wood seems to move and flow. Thus, during the hallucinogenic experience, it is not the utility of what is seen but rather some aspect of shapes and colors and passing thoughts or memories that take on a life of their own, commanding attentive interest. The color of an object is more important than the object. The subjective impact is that thoughts and sights have some uncanny, undeniable, but inexplicit meaning. The sense of great truth is present, but not an urge to test the truth of these images. Rather, one is a spectator of a ''TV show in the head.'' These events are not only clearly ''seen'' but remembered without confusion. This has been called ''consciousness expanding,'' implying control over a vast span of experiencing. That is wrong, since judgment is not enhanced. Rather, the effect is of enhancing the sense of importance of normally unimportant subjective experiences of sensations and perceptions.

Since with hallucinogens everything—even the most familiar scenes—seems novel and is seen in a new way, the experience is in startling contrast with our normal view of the world. Such effects invite many uses. The intrinsic effects of hallucinogenic drugs not only shift perceptions, making the old new, but evoke a loosening of emotions and thoughts. Hence there were efforts to use hallucinogenic drugs therapeutically—to stimulate and enhance new ways of examining problems. But in spite of the alluring promise, no lasting improvement in learning or problem solving has been found after numerous studies. Similarly, the effects produced by hallucinogens seem so significant and strikingly different from everyday life that they can readily be used to enhance mystical thought and belief. Some Native American groups thus use the hallucinogen PEYOTE in religious ceremonies. The intent is to dispose the celebrants to higher thoughts (to be ''in the mind of God''); they are told not to attend to the odd perceptions and rather to relax and contemplate higher thoughts. Because with hallucinogens one is not interested in tracking detail, there is greater suggestibility and dependence on structure, on a leader, on a prior belief, or on the flow of music to guide, interpret, or ''carry'' one through the experiences.

Whether these drugs produce actual hallucinations or, more commonly, illusions (which the subject usually feels are very real but knows are not) has sometimes been debated, but not the fact that these perceptions occur. Seeing geometric abstract designs is not unusual. A characteristic effect is the experience of sound triggering color and of the mixing rather than the clear separation of different sensory modalities—called synesthesia. For example, sounds may be "seen," or colors "heard." What has just been seen—say, a wall clock— sometimes persists as one focuses on a face. Rather than suppressing a previous perception as we normally do, it may linger. Perceptual boundaries are thus loosened.

The commonly abused hallucinogenic substances can be classified according to their chemical structure. All these hallucinogens are organic compounds, and some are found in nature. Hallucinogenic drugs can be placed in two major groups. The first is known as the indole-type hallucinogens. This family of hallucinogens has in common some h serotonin

(neurotransmitter)

structural similarities to the NEUROTRANSMITTER SEROTONIN, suggesting that their mechanism of action could involve the disruption of or some alteration in neurotransmission in NEURONS (nerve cells) that use serotonin as the chemical messenger. The indole-type hallucinogens include lysergic acid derivatives such as LYSERGIC ACID DIETHYLAMIDE (LSD) and other compounds that have structural similarities, such as DIMETHYLTRYPTAMINE (DMT), PSILOCYBIN, and psilocin (see Figure 1).

The second major group of hallucinogens is the substituted phenethylamines (see Figure 2). These are MESCALINE, 2,5-dimethoxy-4-methylampheta-mine (DOM or STP), 3,4-methylenedioxy-amphetamine, (MDA), and 3,4-methylenedioxy-methamphetamine (MDMA or ecstasy). These hallucinogens are structurally related to the phenethyl-amine-type neurotransmitters, NOREPINEPHRINE, epinephrine, and DOPAMINE. As with the indole-type hallucinogens, the structural similarities of the phenethylamine-type hallucinogens to these natural neurotransmitters may indicate that at least

Figure 1

Indole-type Hallucinogens xr oh c-ch2nh2

norepinephrine

(neurotransmitter)

H3CO^srCH2-CH2NH2

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