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Hallucinogen

Background:

Hallucinogens comprise a unique collection of substances that are ingested to induce alterations of consciousness. A variety of substances with differing chemical structures are known to induce hallucinations when ingested in nontoxic doses. Hallucinations are usually visual, auditory, and tactile, in varying combinations, depending on the substance ingested, the setting, and the experiences of the person using them.

Hallucinogenic substances have been used worldwide for centuries to induce altered states for religious and spiritual purposes. Throughout history, abuseh3 of such substances probably was limited because of the moral and religious significance of their uses.

Hallucinogens can be classified and grouped by chemical structure and the compound from which they are derived. Chemically related substances tend to exhibit similar effects. Many other agents can be classified as pseudohallucinogens because they produce psychotic and delirious effects without the classic visual disturbances of true hallucinogens.

One system groups hallucinogens into 4 major classes that include indole alkaloids, piperidines, phenylethylamines, and cannabinoids. The following is a partial list of the hallucinogens by chemical derivation:

Indole Alkaloids

• Lysergic acid diethylamide (LSD)
• Psilocin
• Psilocybin

Piperidines

• Atropine
• Cocaine
• Phencyclidine (PCP)
• Ketamine

Phenylethylamines

• Mescaline
• 3,4-methylene dioxymethamphetamine (MDMA)
• Methylene dioxyamphetamine (MDA)
• 3-methoxy-4,5-methylene dioxyamphetamine(MMDA)
• 3,5-dimethoxy-4-methylamphetamine (STP)
• 2,5-dimethoxy-4-methylamphetamine (DOM)

Cannabinoids

Delta-9-tetrahydrocannabinol (THC, the active substance in marijuana)

Lysergic Acid Diethylamide

LSD first appeared in the US in 1949. Because of its potent psychotomimetic effects, it was believed to be useful in producing model psychosis for evaluation. As an experimental drug in the 1950s, LSD was used by psychiatrists and psychologists for the treatment of alcoholism and many neuroses.

LSD use also was believed to enhance creativity and promote well-being. By the late 1950s, use of LSD had been proposed as a way to achieve intellectual and spiritual awakening and enlightenment. Initial studies in the early 1960s concluded that the drug was safe. By the mid 1960s, reports of increasing illicit abuse and adverse effects in patients treated with LSD led the federal government to begin regulation and restriction of its use.

Although overall hallucinogen use remains fairly constant, LSD use and street sales of many substances marketed as LSD have increased. Since LSD first appeared on the street, its use and popularity have risen and fallen cyclically.

Phencyclidine and Ketamine

PCP and ketamine are piperidine derivatives with potent anesthetic properties and illusionogenic properties. PCP was initially marketed as an anesthetic but was withdrawn from use because of widespread reports of postanesthetic dysphoria, delirium, and psychotic behavior.

PCP was introduced as a veterinary anesthetic in the late 1960s and, beginning in California, soon became a major drug of abuse. The "peace pill", as it was dubbed in San Francisco, began to be distributed as everything from THC to LSD and often was added to marijuana cigarettes. It commonly is referred to as "angel dust."

Ketamine, a widely used anesthetic, increasingly has been found on the streets and often is ingested by large numbers of people at so-called raves.

Psilocin and Psilocybin

These indole alkaloids are found worldwide in a variety of mushrooms and have been used by indigenous peoples of Central America for centuries in religious rites. Ingesting only a few mushrooms may produce hallucinogenic affect, but, generally, large numbers of mushrooms are required. Analysis of street samples of "psilocybin" found that less than one third of the samples actually contained the alkaloid.

Mescaline

Mescaline is a phenylethylamine-derived alkaloid that is found worldwide in a variety of cacti, the best known being the North American peyote cactus. Similar to the mushroom-derived hallucinogens, mescaline in the form of peyote cactus buttons has been used in rituals by many Native Americans for centuries. To achieve the desired effect, 5-10 buttons are chewed and ingested.

Designer Drugs

Designer drugs are derived from chemically altered legitimate parent compounds. These drugs were initially derived to circumvent prosecution by the Drug Enforcement Agency. However, changes to federal drug laws in 1986 made all such chemically altered compounds illegal. Most of these substances are chemically derived from methamphetamine, but increasing numbers of opioid-derived substances are appearing in this category. The best known of the hallucinogenic amphetamine derivatives is MDMA, commonly known as ecstasy. MDA, MDEA, STP, and DOM are all varieties of these agents.

Pathophysiology: The major effects are centered in the CNS, although many of these substances produce additional systemic effects similar to those of the compounds from which they originate.

Indole amine derivatives appear to create hallucinogenic effects by acting at the 5-HT2 serotonin receptors. Most indole derivatives also produce sympathomimetic effects. Piperidine derivatives appear to block the reuptake of serotonin, dopamine, and norepinephrine and may block postsynaptic acetylcholine binding. Phenylethylamine derivatives enhance presynaptic release and block reuptake of serotonin and norepinephrine. The cannabinoids' mechanisms of action may involve alteration of the balance of catecholamine and serotonin actions.

Frequency:

In the US: The National Institute on Drug Abuse data from 1994 indicate a slight decline in hallucinogen abuse from 1976-1992 but then increased use in 1993 and 1994. In 1994, 2.7% of adolescents aged 12-17 years and 5.1% of adults aged 18-25 years reported using hallucinogens. The Monitoring the Future Study reports an annual rate of LSD use in 8.4% of high school seniors in 1995. Drug Abuse Warning Network (DAWN) reports an increase in LSD-related ED visits in the latest 1994 data. Lifetime hallucinogen use was reported in 8.7% of total respondents to the 1994 National Household Survey on Drug Abuse.

Clinical History:

• Although most patients who present to the ED with hallucinogen intoxication have a history of recent ingestion, not all are diagnosed easily.
   
• Consider possible hallucinogen ingestion in patients with acute psychotic behavior and attempt to trace the onset and causes of the behavior.
   
• A history of previous hallucinogen abuse may indicate acute ingestion, flashback behavior, or psychotic break caused by the abuse.
   
• Make an effort to screen patients for other potential exposures or ingestions as well as infectious, traumatic, or other underlying etiologies of the behavior.
   
• Question family, friends, and prehospital care personnel closely for clues to possible etiology of the behavior.
   
• Lysergic acid diethylamide
   
  • Patients presenting for ED care are generally those for whom the hallucinogenic experiences have become uncomfortable (ie, “bad trips”) or those who have become injured or appear at risk for self-injury because of their behavior. Initial evaluation may reveal a patient who is agitated and psychotic.
  • The patient may be confused or disoriented, display distorted perceptions and impaired judgment, and have impaired concentration and intellectual functions. Physical examination may reveal mydriasis, tachycardia, and tachypnea without any other significant physical findings. Examine the patient thoroughly for traumatic injuries and the possibility of other etiologies, such as CNS infections or other acute intoxication. Laboratory evaluation may include urine drug assays, urinalysis, and blood glucose. Perform additional testing if etiology of the behavior is in doubt.
     
• Phencyclidine and ketamin
   
  • Individuals who ingest these substances often have been found in bizarre situations or have placed themselves in danger. The dissociative properties of these drugs allow the abusers to believe they are outside of their body, and the anesthetic properties prevent normal pain feedback mechanisms that usually limit physical activity.
  • Individuals with significant intoxication can sustain tremendous and even life-threatening injuries without perceived pain. They often fluctuate from combative and anxious to sedated and somnolent. Patients generally have mixed nystagmus, comprising horizontal, vertical, and rotatory. Rotatory nystagmus strongly suggests PCP intoxication.
  • Most patients have mild-to-moderate hypertension and approximately one third have tachycardia. Confusion, altered perceptions, visual hallucinations, and significant violent or self-destructive behavior may occur. The period of psychotic behavior may be prolonged, with episodes of severe depression and schizophrenia.
     
• Psilocin and psilocybin
   
  • The most common effects are perceptual distortions or hallucinations. Hallucinations are generally visual but other types may occur. Some patients experience euphoria and tachycardia, and most patients have some mydriasis. Hyperreflexia, anxiety, and drowsiness may occur.
  • Some species of toxic mushrooms may cause adverse GI reactions, including cramping, nausea and vomiting, and diarrhea. Always consider the possibility of toxic mushroom ingestion in patients presenting with a history of mushroom use.
     
• Mescaline
   
  • Initial responses include agitation, diaphoresis, and abdominal cramping with nausea and vomiting. Initially, mildly elevated blood pressure with reflex bradycardia and mildly elevated body temperature may occur. Larger ingestions can produce hypotension and respiratory depression. Often the individual ritualistically collects and re-ingests the vomited material to maximize the hallucinogenic effect. These adverse effects generally persist for only 1-2 hours.
  • Feelings of euphoria and associated hallucinations generally begin 2-4 hours postingestion. The sympathomimetic effects may persist throughout the intoxication. Hallucinations are mostly visual, but all forms may occur. A sense of expansion of self and tremendous power has been described, with associated intense visual images in bright colors and geometric patterns. Adverse perceptions of self, anxiety, and depression can occur. The intoxication generally lasts 6-8 hours and usually is followed by somnolence.
  • Patients presenting after mescaline ingestion often complain of the sympathomimetic effects and GI distress associated with the ingestion. Although physical injury can occur because of the dysphoria and sense of power, this is less common than with PCP.
     
• Designer drugs
   
  • As amphetamine derivatives, the designer drugs all have sympathomimetic effects that account for the adverse effects (eg, hypertension, tachycardia, hyperthermia).
  • Seizures may occur.

Physical:

• Patient presentations may vary from appearing anxious and agitated to somnolent or sedated.
   
• Mydriasis is often present, particularly with LSD use.
   
• Tachycardia, tachypnea, and mild-to-moderate elevation of blood pressure often are noted.
   
• Temperature generally is normal, but a patient experiencing episodes of extreme exertion, combative behavior, or infection may present with hyperthermia.
   
• The neurologic examination should be nonfocal, with varying degrees of cognitive distortions or deficits.
   
• Traumatic injuries may be present and may be caused by the altered perceptions of reality or combative or destructive behavior.

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