36.15 - Dantrolene

Authors: Sadock, Benjamin James; Sadock, Virginia Alcott

Title: Kaplan & Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 10th Edition

Copyright ©2007 Lippincott Williams & Wilkins

> Table of Contents > 12 - Substance-Related Disorders > 12.7 - Hallucinogen-Related Disorders

12.7

Hallucinogen-Related Disorders

Hallucinogenic drugs have been used for thousands of years. Historically, drug-induced hallucinogenic states were usually part of social and religious rituals. Recognition of profound effects of lysergic acid diethylamide (LSD) on mental functioning in 1943 markedly changed things. Unlike plant-based hallucinogens, such as psilocybin mushrooms and peyote cacti, more potent chemically synthesized hallucinogenic compounds, such as LSD, could be more readily researched, distributed, and used, leading to continued fascination with this heterogeneous group of drugs and to many thousands of scientific reports of hallucinogenic drug effects, speculations about mechanisms of action, and discussions of medical and societal problems resulting from hallucinogen distribution, use, and consequences.

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Preparations

Hallucinogens are natural and synthetic substances that are variously called psychedelics or psychotomimetics because, besides inducing hallucinations, they produce a loss of contact with reality and an experience of expanded and heightened consciousness. The hallucinogens are classified as Schedule I drugs; the US Food and Drug Administration (FDA) has decreed that they have no medical use and a high abuse potential.

The classic, naturally occurring hallucinogens are psilocybin (from some mushrooms) and mescaline (from peyote cactus); others are harmine, harmaline, ibogaine, and dimethyltryptamine (DMT). The classic synthetic hallucinogen is LSD, synthesized in 1938 by Albert Hoffman, who later accidentally ingested some of the drug and experienced the first LSD-induced hallucinogenic episode. Some researchers classify the substituted or so-called designer amphetamines, such as 3,4-methylenedioxyamphetamine (MDMA), as hallucinogens. Because these drugs are structurally related to amphetamines, this textbook classifies them as amphetamine-like substances, and they are covered in Section 12.3. Table 12.7-1 lists some representative hallucinogens.

Epidemiology

The incidence of hallucinogen use has exhibited two notable periods of increase. Between 1965 and 1969, there was a tenfold increase in the estimated annual number of initiates. This increase was driven primarily by the use of LSD. The second period of increase in first-time hallucinogen use occurred from around 1992 until 2000, fueled mainly by increases in use of ecstasy (i.e., MDMA). Decreases in initiation of both LSD and ecstasy were evident between 2001 and 2002, coinciding with an overall drop in hallucinogen incidence from 1.6 million to 1.1 million.

According to the text revision of the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), 10 percent of persons in the United States had used a hallucinogen at least once. Hallucinogen use is most common among young (15 to 35 years of age) white men. The ratio of whites to blacks who have used a hallucinogen is 2 to 1, the white to Hispanic ratio is about 1.5 to 1. Men represent 62 percent of those who have used a hallucinogen at some time and 75 percent of those who have used a hallucinogen in the preceding month. Persons 26 to 34 years of age show the highest use of hallucinogens, with 15.5 percent having used a hallucinogen at least once. Persons 18 to 25 years of age have the highest recent use of a hallucinogen.

Cultural factors influence the use of hallucinogens; their use in the western United States is significantly higher than in the southern United States. Hallucinogen use is associated with less morbidity and less mortality than that of some other substances. For example, one study found that only 1 percent of substance-related emergency room visits were related to hallucinogens, compared with 40 percent for cocaine-related problems. Of persons visiting the emergency room for hallucinogen-related reasons, however, more than 50 percent were younger than 20 years of age. A resurgence in the popularity of hallucinogens has been reported. According to DSM-IV-TR, the lifetime rate of hallucinogen abuse is about 0.6 percent, with a 12-month prevalence of about 0.1 percent.

Neuropharmacology

Although most hallucinogenic substances vary in their pharmacological effects, LSD can serve as a hallucinogenic prototype. The pharmacodynamic effect of LSD remains controversial, although it is generally agreed that the drug acts on the serotonergic system, either as an antagonist or as an agonist. Data at this time suggest that LSD acts as a partial agonist at postsynaptic serotonin receptors.

Most hallucinogens are well absorbed after oral ingestion, although some are ingested by inhalation, smoking, or intravenous injection. Tolerance for LSD and other hallucinogens develops rapidly and is virtually complete after 3 or 4 days of continuous use. Tolerance also reverses quickly, usually in 4 to 7 days. Neither physical dependence nor withdrawal symptoms occur with hallucinogens, but a user can develop a psychological dependence on the insight-inducing experiences of episodes of hallucinogen use.

Diagnosis

The DSM-IV-TR lists a number of hallucinogen-related disorders (Table 12.7-2), but contains specific diagnostic criteria only for hallucinogen intoxication (Table 12.7-3) and hallucinogen persisting perception disorder (flashbacks) (Table 12.7-4). The diagnostic criteria for the other hallucinogen use disorders are contained in the DSM-IV-TR sections that are specific to each symptom—for example, hallucinogen-induced mood disorder (see Table 15.3-10).

Hallucinogen Dependence and Hallucinogen Abuse

Long-term hallucinogen use is not common. As stated above, no physical addiction occurs. Although psychological dependence occurs, it is rare, in part because each LSD experience is different and in part because there is no reliable euphoria. Nonetheless, hallucinogen dependence and hallucinogen abuse are genuine syndromes, defined by DSM-IV-TR criteria (see Tables 12.1-3, 12.1-4, and 12.1-5).

Hallucinogen Intoxication

Intoxication with hallucinogens is defined in DSM-IV-TR as characterized by maladaptive behavioral and perceptual changes and by certain physiological signs (Table 12.7-3). The differential diagnosis for hallucinogen intoxication includes anticholinergic and amphetamine intoxication and alcohol withdrawal. The preferred treatment for hallucinogen intoxication is talking down the patient; during this process, guides can reassure patients that the symptoms are drug induced, that they are not going crazy, and that the symptoms will resolve shortly. In the most severe cases, dopaminergic antagonists—for example, haloperidol (Haldol)—or benzodiazepines—for example, diazepam (Valium)—can be used for a limited time. Hallucinogen intoxication usually lacks a withdrawal syndrome.

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Table 12.7-1 Overview of Representative Hallucinogens

Agent Locale Chemical Classification Biological Sources Common Route Typical Dose Duration of Effects Adverse Reactions
Lysergic acid diethylamide Globally distributed, semisynthetic Indolealkylamine Fungus in rye yields lysergic acid Oral 100 µg 6–12 hr Extensive, including pandemic 1965–1975
Mescaline Southwestern U.S. Phenethylamine Peyote cactus, L. williamsii Oral 200–400 mg or 4–6 cactus buttons 10–12 hr Little or none verified
Methylene-dioxyam-phetamine (MDA) U.S., synthetic Phenethylamine Synthetic Oral 80–160 mg 8–12 hr Documented
Methylenedi-oxymetham-phetamine (MDMA) U.S., synthetic Phenethylamine Synthetic Oral 80–150 mg 4–6 hr Documented
Psilocybin Southern U.S., Mexico, South America Phosphorylated hydroxylated DMT Psilocybin mushrooms Oral 4–6 mg or 5–10 g of dried mushroom 4–6 hr Psychosis
Ibogaine West Central Africa Indolealkylamine Tabernanthe iboga Eating powdered root 200–400 mg 8–48 hr CNS excitation, death?
Ayahuasca S. American tropics Harmine, other β-carbolines Bark or leaves of Banisteriopsis caapi As a tea 300–400 mg 4–8 hr None reported
Dimethyltryptamine S. America, synthetic Substituted tryptamine Leaves of Virola calophylla As a snuff, IV 0.2 mg/kg I.V. 30 min None reported
Morning glory American tropics and warm zones D-Lysergic acid alkaloids Seeds of I. violacea, T.corymbosa Orally as infusion 7–13 seeds 3 hr Toxic delirium
Nutmeg and mace Warm zones of Europe, Africa, Asia Myristicin and aromatic ethers Fruit of M. fragrans, commerical spcies Orally or as a snuff 1 teaspoon, 5–15 g Unknown Similar to atropinism, with seizures, death
Yopo/Cohoba Northern South America, Argentina β-carbolines and tryptamines Beans of Anadenanthera peregrina Smoked or as a snuff Unknown Unknown Ataxia, hallucinations, seizures?
Bufotenin Northern South America, Argentina 5-OH-dimethyl-tryptamine Skin glands of toads; seeds of A. peregrina As a snuff or IV Unknown 15 min None reported
(Courtesy of Henry David Abraham, M.D.)

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Table 12.7-2 DSM-IV-TR Hallucinogen-Related Disorders

Hallucinogen use disorders
Hallucinogen dependence
Hallucinogen abuse
Hallucinogen-induced disorders
Hallucinogen intoxication
Hallucinogen persisting perception disorder (flashbacks)
Hallucinogen intoxication delirium
Hallucinogen-induced psychotic disorder, with delusions
   Specify if:
      With onset during intoxication
Hallucinogen-induced psychotic disorder, with hallucinations
   Specify if:
      With onset during intoxication
Hallucinogen-induced mood disorder
   Specify if:
      With onset during intoxication
Hallucinogen-induced anxiety disorder
   Specify if:
      With onset during intoxication
Hallucinogen-related disorder not otherwise specified
(From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text rev. Washington, DC: American Psychiatric Association; copyright 2000, with permission.)

Hallucinogen Persisting Perception Disorder

Long after ingesting a hallucinogen, a person can experience a flashback of hallucinogenic symptoms. This syndrome is diagnosed as hallucinogen persisting perception disorder (Table 12.7-4) in DSM-IV-TR. According to studies, from 15 to 80 percent of users of hallucinogens report having experienced flashbacks. The differential diagnosis for flashbacks includes migraine, seizures, visual system abnormalities, and posttraumatic stress disorder. The following can trigger a flashback: emotional stress; sensory deprivation, such as monotonous driving; or use of another psychoactive substance, such as alcohol or marijuana.

Table 12.7-3 DSM-IV-TR Diagnostic Criteria for Hallucinogen Intoxication

  1. Recent use of a hallucinogen.
  2. Clinically significant maladaptive behavioral or psychological changes (e.g., marked anxiety or depression, ideas of reference, fear of losing one's mind, paranoid ideation, impaired judgment, or impaired social or occupational functioning) that developed during, or shortly after, hallucinogen use.
  3. Perceptual changes occurring in a state of full wakefulness and alertness (e.g., subjective intensification of perceptions, depersonalization, derealization, illusions, hallucinations, synesthesias) that developed during, or shortly after, hallucinogen use.
  4. Two (or more) of the following signs, developing during, or shortly after, hallucinogen use:
    1. pupillary dilation
    2. tachycardia
    3. sweating
    4. palpitations
    5. blurring of vision
    6. tremors
    7. incoordination
  5. The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder.
(From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text rev. Washington, DC: American Psychiatric Association; copyright 2000, with permission.)

Table 12.7-4 DSM-IV-TR Diagnostic Criteria for Hallucinogen Persisting Perception Disorder (Flashbacks)

  1. The reexperiencing, following cessation of use of a hallucinogen, of one or more of the perceptual symptoms that were experienced while intoxicated with the hallucinogen (e.g., geometric hallucinations, false perceptions of movement in the peripheral visual fields, flashes of color, intensified colors, trails of images of moving objects, positive afterimages, halos around objects, macropsia, and micropsia).
  2. The symptoms in Criterion A cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
  3. The symptoms are not due to a general medical condition (e.g., anatomical lesions and infections of the brain, visual epilepsies) and are not better accounted for by another mental disorder (e.g., delirium, dementia, schizophrenia) or hypnopompic hallucinations.
(From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text rev. Washington, DC: American Psychiatric Association; copyright 2000, with permission.)

Flashbacks are spontaneous, transitory recurrences of the substance-induced experience. Most flashbacks are episodes of visual distortion, geometric hallucinations, hallucinations of sounds or voices, false perceptions of movement in peripheral fields, flashes of color, trails of images from moving objects, positive afterimages and halos, macropsia, micropsia, time expansion, physical symptoms, or relived intense emotion. The episodes usually last a few seconds to a few minutes, but sometimes last longer. Most often, even in the presence of distinct perceptual disturbances, the person has insight into the pathological nature of the disturbance. Suicidal behavior, major depressive disorder, and panic disorders are potential complications.

A 20-year-old undergraduate presented with a chief complaint of seeing the air. The visual disturbance consisted of perception of white pinpoint specks in both the central and peripheral visual fields too numerous to count. They were constantly present and were accompanied by the perception of trails of moving objects left behind as they passed through the patient's visual field. Attending a hockey game was difficult, as the brightly dressed players left streaks of their own images against the white of the ice for seconds at a time. The patient also described the false perception of movement in stable objects, usually in his peripheral visual fields; halos around objects; and positive and negative afterimages. Other symptoms included mild depression, daily bitemporal headache, and a loss of concentration in the last year.

The visual syndrome had gradually emerged over the past 3 months following experimentation with the hallucinogenic drug LCD-25 on three separate occasions in the preceding 3 months. He feared he had sustained some kind of “brain damage” from the drug experience. He denied use of any other agents, including amphetamines, phencyclidine, narcotics, or alcohol, to excess. He had smoked marijuana twice a week for a period of 7 months at age 17.

The patient had consulted two ophthalmologists, both of whom confirmed that the white pinpoint specks were not vitreous floaters (diagnostically insignificant particulate matter floating in the vitreous humor of the eye that can cause the perception of “specks”). A neurologist's examination also proved negative. A therapeutic trial of an anticonvulsant medication resulted in a 50 percent improvement in the patient's visual symptoms and remission of his depression. (Courtesy of DSM-IV-TR Casebook.)

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Hallucinogen Intoxication Delirium

The DSM-IV-TR allows for the diagnosis of hallucinogen intoxication delirium (see Table 10.2-6), a relatively rare disorder beginning during intoxication in those who have ingested pure hallucinogens. Hallucinogens are often mixed with other substances, however, and the other components or their interactions with the hallucinogens can produce clinical delirium.

Hallucinogen-Induced Psychotic Disorders

If psychotic symptoms are present in the absence of retained reality testing, a diagnosis of hallucinogen-induced psychotic disorder may be warranted (see Table 14.4-7). DSM-IV-TR also allows clinicians to specify whether hallucinations or delusions are the prominent symptoms. The most common adverse effect of LSD and related substances is a “bad trip,” an experience resembling the acute panic reaction to cannabis but sometimes more severe; a bad trip can occasionally produce true psychotic symptoms. The bad trip generally ends when the immediate effects of the hallucinogen wear off, but its course is variable. Occasionally, a protracted psychotic episode is difficult to distinguish from a nonorganic psychotic disorder. Whether a chronic psychosis after drug ingestion is the result of the drug ingestion, is unrelated to the drug ingestion, or is a combination of both the drug ingestion and predisposing factors is currently unanswerable.

Occasionally, the psychotic disorder is prolonged, a reaction thought to be most common in persons with preexisting schizoid personality disorder and prepsychotic personalities, an unstable ego balance, or much anxiety. Such persons cannot cope with the perceptual changes, body-image distortions, and symbolic unconscious material stimulated by the hallucinogen. The rate of previous mental instability in persons hospitalized for LSD reactions is high. Adverse reactions occurred in the late 1960s when LSD was being promoted as a self-prescribed psychotherapy for emotional crises in the lives of seriously disturbed persons. Now that this practice is less frequent, prolonged adverse reactions are less common.

A 22-year-old female photography student presented to the hospital with inappropriate mood and bizarre thinking. She had no prior psychiatric history. Nine days before admission, she ingested one or two psilocybin mushrooms. Following the immediate ingestion, the patient began to giggle. She then described euphoria, which progressed to auditory hallucinations and belief in the ability to broadcast her thoughts on the media. Two days later she repeated the ingestion, and continued to exhibit psychotic symptoms to the day of admission. When examined she heard voices telling her she could be president, and reported the sounds of “lambs crying.” She continued to giggle inappropriately, bizarrely turning her head from side to side ritualistically. She continued to describe euphoria, but with an intermittent sense of hopelessness in a context of thought blocking. Her self-description was “feeling lucky.” She was given haloperidol, 10 mg twice a day, along with benztropine (Cogentin) 1 mg three times a day and lithium carbonate (Eskalith) 300 mg twice a day. On this regimen her psychosis abated after 5 days.

Hallucinogen-Induced Mood Disorder

The DSM-IV-TR provides a diagnostic category for hallucinogen-induced mood disorder (see Table 15.3-10). Unlike cocaine-induced mood disorder and amphetamine-induced mood disorder, in which the symptoms are somewhat predictable, mood disorder symptoms accompanying hallucinogen abuse can vary. Abusers may experience manic-like symptoms with grandiose delusions or depression-like feelings and ideas or mixed symptoms. As with the hallucinogen-induced psychotic disorder symptoms, the symptoms of hallucinogen-induced mood disorder usually resolve once the drug has been eliminated from the person's body.

Hallucinogen-Induced Anxiety Disorder

Hallucinogen-induced anxiety disorder (see Table 16.7-3) also varies in its symptom pattern, but few data about symptom patterns are available. Anecdotally, emergency room physicians who treat patients with hallucinogen-related disorders frequently report panic disorder with agoraphobia.

A 20-year-old man had a 7-year history of polysubstance abuse, including having used LSD an estimated 400 times. While driving with his girlfriend, he ingested an unknown quantity of LSD and became intoxicated; he reported using no other drugs at this time. Within minutes after ingestion, he began to experience visual hallucinations that intensified as he drove. When he attempted to speak to his girlfriend, he saw that she had become a giant lizard. He became terrified and attempted to kill her by crashing the car, injuring himself and his passenger. By the time of discharge from the hospital 3 days later, his panic had resolved.

Hallucinogen-Related Disorder Not Otherwise Specified

When a patient with a hallucinogen-related disorder does not meet the diagnostic criteria for any of the standard hallucinogen-related disorders, the patient may be classified as having hallucinogen-related disorder not otherwise specified (Table 12.7-5). DSM-IV-TR does not have a diagnostic category of hallucinogen withdrawal, but some clinicians anecdotally report a syndrome with depression and anxiety after cessation of frequent hallucinogen use. Such a syndrome may best fit the diagnosis of hallucinogen-related disorder not otherwise specified.

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Table 12.7-5 DSM-IV-TR Diagnostic Criteria for Hallucinogen- Related Disorder Not Otherwise Specified

The hallucinogen-related disorder not otherwise specified category is for disorders associated with the use of hallucinogens that are not classifiable as hallucinogen dependence, hallucinogen abuse, hallucinogen intoxication, hallucinogen persisting perception disorder, hallucinogen intoxication delirium, hallucinogen-induced psychotic disorder, hallucinogen-induced mood disorder, or hallucinogen-induced anxiety disorder.
(From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text rev. Washington, DC: American Psychiatric Association; copyright 2000, with permission.)

Clinical Features

Lsysergic Acid Diethylamide

A large class of hallucinogenic compounds with well-studied structure–activity relationships is represented by the prototype LSD. LSD is a synthetic base derived from the lysergic acid nucleus from the ergot alkaloids. That family of compounds was discovered in rye fungus and was responsible for lethal outbreaks of St. Anthony's fire in the Middle Ages. The compounds are also present in morning glory seeds in low concentrations. Many homologs and analogs of LSD have been studied. None of them has potency exceeding that of LSD.

Physiological symptoms from LSD are typically few and relatively mild. Dilated pupils, increased deep tendon motor reflexes and muscle tension, and mild motor incoordination and ataxia are common. Increased heart rate, respiration, and blood pressure are modest in degree and variable, as are nausea, decreased appetite, and salivation.

The usual sequence of changes follows a pattern of somatic symptoms appearing first, then mood and perceptual changes, and, finally, psychological changes, although effects overlap and, depending on the particular hallucinogen, the time of onset and offset varies. The intensity of LSD effects in a nontolerant user generally is proportional to dose, with 25 µg as an approximate threshold dose.

The syndrome produced by LSD resembles that produced by mescaline, psilocybin, and some of the amphetamine analogs. The major difference among LSD, psilocybin, and mescaline is potency. A 1.5 µg/kg dose of LSD is roughly equivalent to 225 µg/kg of psilocybin, which is equivalent to 5 mg/kg of mescaline. With mescaline, onset of symptoms is slower and more nausea and vomiting occurs, but in general, the perceptual effects are more similar than different.

Tolerance, particularly to the sensory and other psychological effects, is evident as soon as the second or third day of successive LSD use. Four to 6 days free of LSD is necessary to lose significant tolerance. Tolerance is associated with frequent use of any of the hallucinogens. Cross-tolerance among mescaline, psilocybin, and LSD occurs, but not between amphetamine and LSD, despite the chemical similarity of amphetamine and mescaline.

Previously distributed as tablets, liquid, powder, and gelatin squares, in recent years, LSD has been commonly distributed as “blotter acid.” Sheets of paper are soaked with LSD, dried, and perforated into small squares. Popular designs are stamped on the paper. Each sheet contains as many as a few hundred squares; one square containing 30 to 75 µg of LSD is one chewed dose, more or less. Planned massive ingestion is uncommon but happens by accident.

The onset of action of LSD occurs within an hour, peaks in 2 to 4 hours, and lasts 8 to 12 hours. The sympathomimetic effects of LSD include tremors, tachycardia, hypertension, hyperthermia, sweating, blurring of vision, and mydriasis. Death caused by cardiac or cerebrovascular pathology related to hypertension or hyperthermia can occur with hallucinogenic use. A syndrome similar to neuroleptic malignant syndrome has reportedly been associated with LSD. Death can also be caused by a physical injury when LSD use impairs judgment about traffic or a person's ability to fly, for example. The psychological effects are usually well tolerated, but when persons cannot recall experiences or appreciate that the experiences are substance induced, they may fear the onset of insanity.

With hallucinogen use, perceptions become unusually brilliant and intense. Colors and textures seem to be richer than in the past, contours sharpened, music more emotionally profound, and smells and tastes heightened. Synesthesia is common; colors may be heard or sounds seen. Changes in body image and alterations of time and space perception also occur. Hallucinations are usually visual, often of geometric forms and figures, but auditory and tactile hallucinations are sometimes experienced. Emotions become unusually intense and may change abruptly and often; two seemingly incompatible feelings may be experienced at the same time. Suggestibility is greatly heightened, and sensitivity or detachment from other persons may arise. Other common features are a seeming awareness of internal organs, the recovery of lost early memories, the release of unconscious material in symbolic form, and regression and the apparent reliving of past events, including birth. Introspective reflection and feelings of religious and philosophical insight are common. The sense of self is greatly changed, sometimes to the point of depersonalization, merging with the external world, separation of self from body, or total dissolution of the ego in mystical ecstasy.

No clear evidence indicates a drastic personality change or chronic psychosis produced by long-term LSD use by moderate users not otherwise predisposed to these conditions. Some heavy users of hallucinogens, however, may experience chronic anxiety or depression and may benefit from a psychological or pharmacological approach that addresses the underlying problem.

Many persons maintain that a single experience with LSD has given them increased creative capacity, new psychological insight, relief from neurotic or psychosomatic symptoms, or a desirable change in personality. In the 1950s and 1960s, psychiatrists showed great interest in LSD and related substances, both as potential models for functional psychosis and as possible pharmacotherapeutic agents. The availability of these compounds to researchers in the basic neurosciences has led to many scientific advances.

Phenethylamines

Phenethylamines are compounds with simple chemical structures and structural similarity to the neurotransmitters dopamine and norepinephrine. Mescaline (3,4,5-trimethoxyphenethylamine), a classic hallucinogen in every sense of the term, was the first hallucinogen isolated from the peyote cactus that grows in the southwestern United States and northern Mexico. Mescaline human pharmacology was characterized in 1896 and its structure verified by synthesis 23 years later. Although many psychoactive plants have been recognized dating to before recorded history, mescaline was the only structurally identified hallucinogen until LSD was described in 1943.

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Mescaline

Mescaline is usually consumed as peyote “buttons,” picked from the small blue-green cacti Lophophora williamsii and Lophophora diffusa. The buttons are the dried, round, fleshy cacti tops. Mescaline is the active hallucinogenic alkaloid in the buttons. Use of peyote is legal for the Native American Church members in some states. Adverse reactions to peyote are rare during structured religious use. Peyote usually is not consumed casually because of its bitter taste and sometimes severe nausea and vomiting preceding the hallucinogenic effects.

Many structural variations of mescaline have been investigated and structural activity relationships fairly well characterized. One analog, 2,5-dimethoxy-4-methylamphetamine (DOM), also known as STP, an unusually potent amphetamine with hallucinogen properties, had a relatively brief period of illicit popularity and notoriety in the 1960s.

Another series of phenethylamine analogs with hallucinogenic properties is the 3,4-methylenedioxyamphetamine (MDA)–related amphetamines. The currently most popular and, to society, most troublesome member of this large family of drugs is MDMA, or ecstasy, more a relatively mild stimulant than hallucinogen. MDMA produces an altered state of consciousness with sensory changes and, most important for some users, a feeling of enhanced personal interactions. MDMA is discussed in more detail in Section 12.3 on amphetamine-related disorders.

Many plants contain N,N-dimethyltryptamine (DMT), which is also found normally in human biofluids at very low concentrations. When DMT is taken parenterally or by sniffing, a brief, intense hallucinogenic episode can result. As with mescaline in the phenethylamine group, DMT is one of the oldest, best documented, but least potent of the tryptamine hallucinogens. Synthesized homologs of DMT have been evaluated in humans and structure activity relationships reasonably well described.

Psilocybin Analogs

An unusual collection of tryptamines has its origin in the world of fungi. The natural prototype is psilocybin itself. That and related homologs have been found in as many as 100 species of mushroom, largely of the Psilocybe genus.

Psilocybin is usually ingested as mushrooms. Many species of psilocybin-containing mushrooms are found worldwide. In the United States, large Psilocybe cubensis (gold caps) grow in Florida and Texas and are easily grown with cultivation kits advertised in drug-oriented magazines and on the Internet. The tiny Psilocybe semilanceata (liberty cap) grows in lawns and pastures in the Pacific Northwest. Psilocybin remains active when the mushrooms are dried or cooked into omelets or other foods.

Psilocybin mushrooms are used in religious activities by Mexican Indians. They are valued in Western society by users who prefer to ingest a mushroom instead of a synthetic chemical. Of course, one danger of eating wild mushrooms is misidentification and ingestion of a poisonous variety. At a large American university, 24 percent of students reported using psychedelic mushrooms or mescaline, compared with 17 percent who reported LSD use. Psilocybin sold as pills or capsules usually contains phencyclidine (PCP) or LSD instead.

Additional Hallucinogens

Ibogaine

Ibogaine is a complex alkaloid found in the African shrub Tabernanthe iboga. Ibogaine is a hallucinogen at the 400-mg dose range. The plant originates in Africa and traditionally is used in sacramental initiation ceremonies. Although it has not been a popular hallucinogen because of its unpleasant somatic effects when taken at hallucinogenic doses, patients exposed to ibogaine may be encountered by a psychiatrist because of the therapeutic claims.

Ayahuasca

Ayahuasca, much discussed on Internet hallucinogen Web sites, originally referred to a decoction from one or more South American plants. The substance contains the alkaloids harmaline and harmine. Both of those β-carboline alkaloids have hallucinogenic properties, but the resulting visual sensory alterations are accompanied by considerable nausea.

Salvia Divinorum

American Indians in northern Oaxaca, Mexico, have used Salvia divinorum as a medicine and as a sacred sacrament, which is now widely discussed, advertised, and sold on the Internet. When the plant is chewed or dried leaves smoked, it produces hallucinogen effects. Salvinorin-A, an active component in the plant, is parenterally potent, active at 250-µg doses when smoked, and of scientific and potential medical interest because it binds to the opioid κ-receptor.

Treatment

Hallucinogen Intoxication

Persons have historically been treated for hallucinogen intoxication by psychological support for the remainder of the trip, so-called “talking down.” This is a time-consuming and potentially hazardous undertaking, given the lability of a patient with hallucinogen-related delusions. Accordingly, treatment of hallucinogen intoxication is the oral administration of 20 mg of diazepam. This medication brings the LSD experience and any associated panic to a halt within 20 minutes and should be considered superior to “talking down” the patient over a period of hours or to administering antipsychotic agents. The marketing of lower doses of LSD and a more sophisticated approach to treatment of casualties by drug users themselves have combined to reduce the appearance of this once-common disorder in psychiatric treatment facilities.

Hallucinogen Persisting Disorder

Treatment for hallucinogen persisting perception disorder is palliative. The first step in the process is correct identification of the disorder; it is not uncommon for the patient to consult a number of specialists before the diagnosis is made. Pharmacological approaches include long-lasting benzodiazepines, such as clonazepam (Klonopin) and, to a lesser extent, anticonvulsants including valproic acid (Depakene) and carbamazepine (Tegretol). Currently, no drug is completely effective in ablating symptoms. Antipsychotic agents should only be used in the treatment of hallucinogen-induced psychoses, because they may have

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a paradoxical effect and exacerbate symptoms. A second dimension of treatment is behavioral. The patient must be instructed to avoid gratuitous stimulation in the form of over-the-counter drugs, caffeine, and alcohol, and avoidable physical and emotional stressors. Marijuana smoke is a particularly strong intensifier of the disorder, even when passively inhaled. Finally, three comorbid conditions are associated with hallucinogen persisting perception disorder: panic disorder, major depression, and alcohol dependence. All these conditions require primary prevention and early intervention.

Hallucinogen-Induced Psychosis

Treatment of hallucinogen-induced psychosis does not differ from conventional treatment for other psychoses. In addition to antipsychotic medications, a number of agents are reportedly effective, including lithium carbonate, carbamazepine, and electroconvulsive therapy. Antidepressant drugs, benzodiazepines, and anticonvulsant agents may each have a role in treatment as well. One hallmark of this disorder is that, as opposed to schizophrenia, in which negative symptoms and poor interpersonal relatedness may commonly be found, patients with hallucinogen-induced psychosis exhibit the positive symptoms of hallucinations and delusions while retaining the ability to relate to the psychiatrist. Medical therapies are best applied in a context of supportive, educational, and family therapies. The goals of treatment are the control of symptoms, a minimal use of hospitals, daily work, the development and preservation of social relationships, and the management of comorbid illnesses such as alcohol dependence.

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