Patients who seek medical care after self-administering mind-altering substances may have used any of a large variety of compounds. Several of these agents are discussed elsewhere in this manual (eg, amphetamines, cocaine, marijuana, phencyclidine and ketamine, and toluene). Many of the drugs discussed in this chapter are entactogens (“to touch within”), enhancing sensations and promoting illusions (eg, LSD, MDMA). Others have primarily sympathomimetic characteristics, with hallucinations a smaller part of the overall experience (eg, cathinones). Several have been used widely for personal experimentation as well as clinically to facilitate psychotherapy. The use of classic hallucinogens such as LSD has declined over the past decades. There is a current resurgence of novel hallucinogen use with compounds such as the 2C-NBOMe series and synthetic cathinones, and with traditional hallucinogens such as ayahuasca. Table II-33 lists some common and uncommon hallucinogens.

Despite many intriguing theories and much current research, the biochemical mechanism of hallucinations is not known. The hallucinogenic effects of LSD are thought to be mediated by 5-HT2 receptor activation, and many other agents are thought to alter the activity of serotonin and dopamine in the brain. Central and peripheral sympathetic stimulation may account for some of the side effects, such as anxiety, agitation, psychosis, dilated pupils, tachycardia, and hyperthermia. Some agents (eg, MDMA) are directly neurotoxic.

The toxic dose is highly variable, depending on the agent and the circumstances (see Table II-33). LSD is a highly potent hallucinogen. In general, entactogenic effects do not appear to be dose related; therefore, increasing the dose does not intensify the desired effects. Likewise, paranoia or panic attacks may occur with any dose and depend on the surroundings and the patient's current emotional state. In contrast, hallucinations, visual illusions, and sympathomimetic side effects are dose related. The toxic dose may be only slightly greater than the recreational dose. In human volunteers receiving recreational doses of MDMA, elimination was nonlinear, implying that small increases in dosing may increase the risk for toxicity.

1. Mild-to-moderate intoxication
   1. A person experiencing a panic reaction or “bad trip” is conscious, coherent, and oriented but is anxious and fearful and may display paranoid or bizarre reasoning. The patient may also be tearful, combative, or self-destructive. Delayed intermittent “flashbacks” may occur after the acute effects have worn off and are usually precipitated by use of another mind-altering drug.
   2. A person with dose-related sympathomimetic side effects may also exhibit hyperthermia, tachycardia, hypertension, mydriasis (dilated pupils), diaphoresis, bruxism, short attention span, tremor, and hyperreflexia.
2. Life-threatening toxicity
   1. Intense sympathomimetic stimulation can cause seizures, severe hyperthermia, hypertension, intracranial hemorrhage, and cardiac arrhythmias. Hyperthermic patients are usually obtunded, agitated or thrashing about, diaphoretic, and hyperreflexic. Untreated, hyperthermia may result in hypotension, coagulopathy, rhabdomyolysis, and hepatic and other organ failure. Hyperthermia has been associated with LSD, methylene dioxyamphetamine (MDA), MDMA, paramethoxyamphetamine (PMA), and synthetic cathinones.
   2. Severe hyponatremia resulting in cerebral edema and death has been reported after use of MDMA and may result from excess water intake, excessive sweating (eg, dancing) and inappropriate secretion of antidiuretic hormone.
   3. The use of 2,5-dimethoxy-4-bromoamphetamine (DOB) has resulted in ergot-like vascular spasm, circulatory insufficiency, and gangrene (Ergot Derivatives).

Is based on a history of use and the presence of signs of sympathetic stimulation or the appearance of responding to internal stimuli. Diagnosis of hyperthermia requires a high level of suspicion and use of a thermometer that accurately measures core temperature (eg, rectal probe).

1. Specific levels. Serum drug levels are neither widely available nor clinically useful in emergency management. The amphetamine derivatives (eg, DOB, STP, MDA, MDMA) cross-react with some of the available screening tests for amphetamine-class drugs. Monoclonal amphetamine assays used for workplace drug testing will produce negative results for amphetamine derivatives. LSD and the other nonamphetamine hallucinogens listed in Table II-33 are not usually identified on routine toxicology screening. Recently, several LSD screening immunoassays have become available, although they are of limited use because of false-positive and false-negative results and a short window of detection (4-12 hours), and they are not widely used in clinical laboratories.
2. Other useful laboratory studies include electrolytes, glucose, BUN, and creatinine. In hyperthermic patients, obtain prothrombin time, hepatic aminotransferases, creatine kinase (CK), and urinalysis for occult blood (myoglobinuria will be present).

1. For a patient with a “bad trip” or panic reaction, provide gentle reassurance and relaxation techniques in a quiet environment.
   1. Treat agitation or severe anxiety states with benzodiazepines such as midazolam, lorazepam, or diazepam. Butyrophenones such as haloperidol may be useful.
   2. Treat seizures, hyperthermia, rhabdomyolysis, hypertension, and cardiac arrhythmias if they occur.
2. Specific drugs and antidotes. There is no specific antidote. Sedating doses of benzodiazepines such as diazepam (2-10 mg) may alleviate anxiety, and hypnotic doses (10-20 mg) can induce sleep for the duration of the “trip.”
3. Decontamination. Most of these drugs are taken orally in small doses, and decontamination procedures are relatively ineffective and likely to aggravate psychological distress. Consider the use of activated charcoal only after recent (within 30-60 minutes) large ingestions.
4. Enhanced elimination. These procedures are not useful. Although urinary acidification may increase the urine concentration of some agents, it does not significantly enhance total-body elimination and may aggravate myoglobinuric renal failure.