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Chapter: Modern Pharmacology with Clinical Applications: Contemporary Drug Abuse

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Contemporary Drug Abuse: Hallucinogens

The term hallucinogen is often used to describe a drug that produces a change in sensory perception, usually ei-ther visual or auditory.

HALLUCINOGENS

The term hallucinogen is often used to describe a drug that produces a change in sensory perception, usually ei-ther visual or auditory. Drugs commonly assigned to this class include lysergic acid diethylamide (LSD), mesca-line (derived from the peyote cactus), and psilocybin (derived from a mushroom). However, this rather lim-ited definition fails to include the other prominent prop-erty of this class of drugs, which is a change in thought and mood. For this reason the term is sometimes used in-terchangeably with psychedelic or psychotomimetic, the latter term representing the CNS effects beyond the hal-lucination itself. Most literal definitions of the term hal-lucinogen are inadequate, but it should be used to signify substances that consistently produce changes in sensory perception, thought, and mood. An hallucinogen is a drug that reliably produces alterations in perceptions as a primary effect. Drugs that should not be included are those that produce alterations in sensory perception only at toxic doses (e.g., antimuscarinic agents, anti-malarials, and opioids) and fail to produce these effects in all individuals. This does not preclude a drug’s being classified as an hallucinogen if it has other properties as well. Several drugs that reliably alter mood at low doses and produce altered sensory perceptions at slightly higher doses are close chemical analogues to the CNS stimulant class of drugs. These drugs that also reliably produce differing degrees of CNS stimulation in a dose-responsive fashion include phencyclidine (PCP), methyl-enedioxymethamphetamine (MDMA), and methylene-dioxyamphetamine (MDA).

The hallucinogens generally fall into two chemical classes. The indole alkylamines include LSD, psilocybin, psilocin, dimethyltryptamine (DMT), and diethyltrypta-mine (DET), all of which are structurally similar to serotonin. The other chemical subclass of hallucinogens contains phenylethylamine derivatives such as mesca-line, MDMA, MDA, and DOM (dimethoxymethyl am-phetamine). A related stimulatory hallucinogen, PCP, is a piperidine analogue that produces unique effects.

Extent and Pattern of Abuse

LSD is very potent and produces both CNS and periph-eral effects. Because of the rapid tolerance produced with these drugs, the typical abuser does not use the drug on a daily basis. Generally, an hallucinogen is abused approximately once per month.

Illicit PCP abuse began in the 1960s, primarily by oral ingestion. However, its use was limited because PCP frequently produced dysphoria, which was unpre-dictable.

Pharmacological Aspects

The effects of LSD may be observed for 8 hours. The specific acute effects of a drug like LSD include eupho-ria, depersonalization, enhanced awareness of sensory input, alterations in the perception of time or space or body image, and to some extent, minor stimulant ef-fects. Sometimes the dreamlike quality of the experi-ence produces relaxation, good humor, and a sense of wonder or euphoria.

Often the effect is a function of expectation and en-vironmental conditions. Someone who is anxious about the use of the hallucinogen may have drug-induced anx-iety, panic, or even paranoid ideation. The loss of indi-viduality can be perceived as a disintegration of the per-son and can lead to a panic attack. Even if the drug experience initially is euphoric, tremendous mood swings can occur and suddenly plunge the abuser into emotions of great anxiety or terror. These negative phe-nomena are not always precipitated by an unexpected or sudden frightful event but can be a function of the la-bile mood induced by the drug.

The visual hallucinations are often composed of ex-tremely vivid colors of geometric patterns, such as cones, spirals, or cobweb-like structures. Other types of hallucinations are possible. A true hallucination in-volves the belief by the individual that the (altered) sen-sations and perceptions actually represent reality. However, generally the person abusing LSD and re-lated drugs retains the ability to test reality versus illu-sion and knows that the experience is not real. Thus, the typical drug-induced hallucinatory state would be more appropriately termed a pseudohallucination, though real hallucinations are possible. The subjective or psy-chotomimetic changes are those considered to be changes in mood. These effects are somewhat more variable than the hallucinatory effects or changes in sensory perception. Though these effects can occur with LSD, they seem to be more common with other specific hallucinogens, such as MDMA and MDA.

MDMA (XTC, or ecstasy) possesses hallucinogenic activity similar to that of mescaline but also produces stimulant activity similar to that of amphetamine. Initially MDMA produces euphoria, increases the abil-ity to communicate with others, increases the degree of intimacy one feels toward others in the surroundings, in-creases self-esteem and mood, and generally appears reduce perceived intensity of psychological problems. Hallucinatory activity occurs at higher doses. One residual effect of abuse is the MDMA hangover, which is the occurrence on the second day after abuse of drowsiness and sore jaw muscles along with other pos-sible side effects due to the stimulant properties of the drug.

MDA, which is similar to MDMA, has been termed the love drug because it produces a feeling of closeness to others. Typically, a dose of 75 mg produces the pri-mary psychotomimetic effects, while a dose of 150 mg produces LSD-like effects, and a dose of 300 mg pro-duces amphetaminelike CNS stimulation. The amphet-aminelike stimulation of the CNS and periphery is prominent with both MDA and MDMA. To a lesser de-gree this stimulation also occurs with LSD. The effects that can be produced by stimulatory doses of hallucino-gens include tachycardia, hypertension, and arrhyth-mias.

PCP is unique in terms of its hallucinogenic proper-ties and its other pharmacological effects. It possesses CNS stimulatory actions, but it is also a dissociative anesthetic. It induces a wide variety of psychotomimetic and hallucinatory effects during emergence from anes-thesia. Because it possesses CNS stimulant properties comparable with those of amphetamine, it does not pro-duce depression of the cardiovascular system like other anesthetics, though it does depress the respiratory sys-tem. At a low dose, individuals believe they are thinking and acting rapidly and efficiently. The general mood is happiness, though (especially at higher doses) the indi-vidual can vacillate between euphoria and depression. It primarily produces auditory hallucinations. At higher doses the stimulatory effects are more pronounced and the likelihood of tremendous mood swings more likely. At near anesthetic doses, it produces more typical de-pressant effects, including motor incoordination, catalepsy, vacant stare, or even amnesia. Coma is pro-duced subsequent to respiratory depression.

Tolerance and Dependence

Tolerance to the effects of hallucinogens develops rap-idly. In fact, a high degree of tolerance can be produced after as few as three to four daily doses of drug. Generally, the abuser self-imposes the requirement for a 2- to 3-day drug-free period before another drug ses-sion. Additionally, there is a tremendous degree of cross-tolerance between the hallucinogens, so other LSD-like hallucinogens cannot be abused during the drug-free period either. One danger with the stimulant subclass of hallucinogens is rapid development of toler-ance to some of their effects while the stimulatory prop-erties remain and produce various side effects. Despite the apparent overlap of effects with stimulant drugs, however, there is no cross-tolerance with the CNS stim-ulants such as amphetamine.

There are no observable physical withdrawal signs during drug abstinence, nor is there a tremendous crav-ing for drug during the drug-free period. Therefore, clearly no dependence is attributed to the hallucinogens. Though there is an abuse potential with this class of drug, and individuals express drug-seeking behavior, there does not seem to be the magnitude of craving found with other drug classes, such as the CNS stimulants.

Treatment Strategies

The difference between the abused and the lethal dose of LSD is very large, so little pharmacological interven-tion is necessary. Treatment involves limiting external stimuli and placing the individual in a safe environment.

Treatment of PCP intoxication also involves limiting external stimuli, minimizing lighting, noise, and unneces-sary physical contact. The life-threatening nature of PCP overdose, however, may require symptomatic treatment of respiratory depression by artificial respiration or use of neuroleptics to control violent rage or panic anxiety.

Mechanism of Action

Hallucinogens disorganize neural function in the CNS. The structural similarities between the indole hallucino-gens and the endogenous neurotransmitter serotonin led to the hypothesis that a primary mechanism of action for the hallucinogens is the activation of the 5-HT2-receptor. LSD acts directly on this receptor as an agonist. Other drugs, such as MDMA, induce the release of endogenous serotonin, which activates the serotonin receptor.

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