LSD. LSD is the most potent hallucinogenic drug and produces significant psychedelic effects with a total dose of as little as 25-50 μg. This drug is > 3000 times more potent than mescaline. LSD is sold on the illicit market in a variety of forms. A popular contemporary system involves postage stamp-sized papers impregnated with varying doses of LSD (50-300 μg or more). While most street samples sold as LSD actually contain LSD, samples of mushrooms and other botanicals sold as sources of psilocybin and other psychedelics have a low probability of containing the advertised hallucinogen.
The effects of hallucinogenic drugs are variable, even in the same individual on different occasions. LSD is absorbed rapidly after oral administration, with effects beginning at 40-60 minutes, peaking at 2-4 hours, and gradually returning to baseline over 6-8 hours. At a dose of 100 μg, LSD produces perceptual distortions and sometimes hallucinations; mood changes, including elation, paranoia, or depression; intense arousal; and sometimes a feeling of panic. Signs of LSD ingestion include pupillary dilation, increased blood pressure and pulse, flushing, salivation, lacrimation, and hyperreflexia. Visual effects are prominent. Colors seem more intense, and shapes may appear altered. The subject may focus attention on unusual items such as the pattern of hairs on the back of the hand.
A "bad trip" usually consists of severe anxiety, although at times it is marked by intense depression and suicidal thoughts. Visual disturbances usually are prominent. The bad trip from LSD may be difficult to distinguish from reactions to anticholinergic drugs and phencyclidine. There are no documented toxic fatalities from LSD use, but fatal accidents and suicides have occurred during or shortly after intoxication. Prolonged psychotic reactions lasting 2 days or more may occur after the ingestion of a hallucinogen. Schizophrenic episodes may be precipitated in susceptible individuals, and there is some evidence that chronic use of these drugs is associated with the development of persistent psychotic disorders (McLellan et al., 1979).
Claims about the potential of psychedelic drugs for enhancing psychotherapy and for treating addictions and other mental disorders have not been supported by controlled treatment outcome studies. Consequently, there is no current indication for these drugs as medications.
Tolerance, Physical Dependence, and Withdrawal. Frequent, repeated use of psychedelic drugs is unusual, and thus tolerance is not commonly seen. Tolerance does develop to the behavioral effects of LSD after three or four daily doses, but no withdrawal syndrome has been observed. Cross-tolerance among LSD, mescaline, and psilocybin has been demonstrated in animal models.
Pharmacological Intervention. Because of the unpredictability of psychedelic drug effects, any use carries some risk. Dependence and addiction do not occur, but users may require medical attention because of "bad trips." Severe agitation may respond to diazepam (20 mg orally). "Talking down" by reassurance also is effective and is the management of first choice. Antipsychotic medications (Chapter 16) may intensify the experience and thus are not indicated.
A particularly troubling after-effect of the use of LSD and similar drugs is the occasional occurrence of episodic visual disturbances. These originally were called "flashbacks" and resembled the experiences of prior LSD trips. Flashbacks belong to an official diagnostic category called the hallucinogen persisting perception disorder (HPPD; American Psychiatric Association, 1994). The symptoms include false fleeting perceptions in the peripheral fields, flashes of color, geometric pseudohallucinations, and positive afterimages (Abraham and Aldridge, 1993). The visual disorder appears stable in half the cases and represents an apparently permanent alteration of the visual system. Precipitants include stress, fatigue, emergence into a dark environment, marijuana, antipsychotic agents, and anxiety states.
MDMA ("Ecstasy") and MDA. MDMA and MDA are phenylethylamines that have stimulant as well as psychedelic effects. MDMA became popular during the 1980s on college campuses because of testimonials that it enhances insight and self-knowledge. It was recommended by some psychotherapists as an aid to the process of therapy, although no controlled data exist to support this contention. Acute effects are dose-dependent and include feelings of energy, altered sense of time, and pleasant sensory experiences with enhanced perception. Negative effects include tachycardia, dry mouth, jaw clenching, and muscle aches. At higher doses, visual hallucinations, agitation, hyperthermia, and panic attacks have been reported. A typical oral dose is one or two 100-mg tablets and lasts 3-6 hours, although dosage and potency of street samples are variable (~100 mg per tablet).
MDA and MDMA produce degeneration of serotonergic nerve cells and axons in rats. While nerve degeneration has not been demonstrated in humans, the cerebrospinal fluid of chronic MDMA users has low levels of serotonin metabolites (Ricaurte et al., 2000). Thus, there is possible neurotoxicity with no evidence that the claimed benefits of MDMA actually occur.
Phencyclidine (PCP). PCP deserves special mention because of its widespread availability and because its pharmacological effects are different from those of the psychedelics such as LSD. PCP was developed originally as an anesthetic in the 1950s and later was abandoned because of a high frequency of postoperative delirium with hallucinations. It was classified as a dissociative anesthetic because, in the anesthetized state, the patient remains conscious with staring gaze, flat facies, and rigid muscles. PCP became a drug of abuse in the 1970s, first in an oral form and then in a smoked version enabling a better regulation of the dose. The effects of PCP have been observed in normal volunteers under controlled conditions. As little as 50 μg/kg produces emotional withdrawal, concrete thinking, and bizarre responses to projective testing. Catatonic posturing also is produced and resembles that of schizophrenia. Abusers taking higher doses may appear to be reacting to hallucinations and may exhibit hostile or assaultive behavior. Anesthetic effects increase with dosage; stupor or coma may occur with muscular rigidity, rhabdomyolysis, and hyperthermia. Intoxicated patients in the emergency room may progress from aggressive behavior to coma, with elevated blood pressure and enlarged nonreactive pupils.
PCP binds with high affinity to sites located in the cortex and limbic structures, resulting in blocking of N-methyl-D-aspartate (NMDA)–type glutamate receptors (Chapter 14). LSD and other psychedelics do not bind to NMDA receptors. There is evidence that NMDA receptors are involved in ischemic neuronal death caused by high levels of excitatory amino acids; as a result, there is interest in PCP analogs that block NMDA receptors but with fewer psychoactive effects. Both PCP and ketamine ("Special K"), another "club drug," produce similar effects by altering the distribution of the neurotransmitter glutamate.
Tolerance, Dependence, and Withdrawal. PCP is reinforcing in monkeys, as evidenced by self-administration patterns that produce continuous intoxication. Humans tend to use PCP intermittently, but a small fraction may use it daily. Tolerance to the behavioral effects of PCP develops in animals, but this has not been studied systematically in humans. Signs of a PCP withdrawal syndrome have been observed in monkeys after interruption of daily access to the drug, and include somnolence, tremor, seizures, diarrhea, piloerection, bruxism, and vocalizations.
Pharmacological Intervention. Overdose must be treated by life support because there is no antagonist of PCP effects and no proven way to enhance excretion, although acidification of the urine has been proposed. PCP coma may last 7-10 days. The agitated or psychotic state produced by PCP can be treated with diazepam. Prolonged psychotic behavior requires antipsychotic medication. Because of the anticholinergic activity of PCP, antipsychotic agents with significant anticholinergic effects such as chlorpromazine should be avoided.