SLEEP, DREAMING, AND DRUGS

The use of "mind-altering" drugs and intoxicating drinks to hasten the onset of sleep and to enhance the experience of dreaming is a worldwide phenomenon and goes back to prehistory. The ancient Greeks used hallucinatory substances for religious purposes. The priestesses at Delphi, for example, chewed certain leaves while sitting in a smoke-filled chamber and going into a trance. On returning to consciousness, they would bring forth a divine prophecy. The various Dionysian cults encouraged their celebrants into ecstatic dream-like states through the use of wine and perhaps other drugs (Cohen, 1977).

The ancient Hindus imbibed a sacred drink called "soma," and Marijuana was used in practices of meditation. For the Arabs, Hashish (a form of marijuana) was the substance of choice, while the Incas chewed the leaves of the Coca plant (from which Cocaine may be made). The Opium poppy was used in Asia, and the ancient Mexicans used a variety of powerful Psychoactive substances, including Peyote, sacred mushrooms, and seeds from the Mexican Morning Glory plant, to enter the realm of dreams. The Australian aboriginals used the pituri, a psychoactive substance, to take them into "dream time," as they referred to it.

Belladonna and Opiates have historically been used for the specific purpose of producing vivid dreams. The most famous illustration is the story of the English poet Samuel Taylor Coleridge (1772-1834), who allegedly wrote his most celebrated work, "Kubla Khan," during a drug-induced dream (Cohen, 1977). Lysergic Acid Diethylamide (LSD) became popular in the United States and Europe during the 1960s for ostensibly facilitating higher states of consciousness and creativity. The writer John Lilley used a sensory-deprivation tank to emulate the state of sleep while taking LSD to induce creative dreaming (Cohen, 1977).

Reference to the effects of drugs and Alcohol on sleep and dreaming are also found in popular literature. It was a mixture made from poppies that caused Dorothy and her companions to fall into deep sleep in the Wizard of Oz (Baum, 1956). After ingesting a series of pills and liquids, in Through the Looking Glass, Alice finds herself in "Wonderland," where she has a conversation with an opium-smoking caterpillar who is sitting on a magic mushroom that alters the state of one who eats of it. After returning to the reality of her home in England, Alice realizes that she had, of course, fallen asleep and been dreaming (Carroll, 1951).

Modern study of the effects of drugs and alcohol on sleep and dreams dates to the mid-1950s. With the use of electrophysiological machines, including electroencephalograms (EEGs), electrooculograms, and electromyograms, the state of sleep most closely associated with dreaming was discovered, studied, and named REM, for the r apid e ye movements unique to that sleep state. In humans, REM sleep recurs in approximately 90-minute cycles throughout the sleep period, resulting in 4 or 5 REM episodes per night, each lasting from 10 to 30 minutes. Adults spend about 20 to 25 percent of their sleep period in REM sleep. Abrupt, but not gradual, awakening from REM sleep is consistently associated with the recall of vivid dreaming. While the function of REM sleep is unknown, it appears to serve a necessary function. Deprivation of REM sleep by awakenings or by the administration of REM-suppressing drugs leads to a compensatory or rebound effect-specifically, a more rapid onset and a greater amount and intensity of REM sleep.

Most psychoactive substances have profound effects on sleep and particularly on REM sleep. While the effects of drugs on REM sleep are known, their effects on dreaming are being studied. Given the association of REM sleep and dreaming, one might think that REM-enhancing drugs would increase dreaming, while REM-suppressing drugs would decrease dreaming. But no data suggest such a simple relationship. After the discontinuation of REM-suppressing drugs, a REM rebound occurs, which is reported to be associated with increased and unpleasant dreams. Some have hypothesized that the visual Hallucinations experienced during discontinuation of some drugs (e.g., alcohol) is a REM rebound intruding into wakefulness. It is too simplistic to think of dreaming and REM in a one-to-one correspondence, but it is reasonable to assume that drugs affecting REM will also affect the frequency and nature of dreams.

The effects of ethanol (alcohol) on sleep are complex and somewhat paradoxical. The acute bedtime administration of ethanol to healthy, non-alcoholic volunteers shortens the latency to sleep onset and, depending on dose, may initially increase the amount of relaxed, deep slow-wave (delta-wave) sleep (Williams & Salamy, 1972). Additionally, ethanol reduces the amount of REM sleep, usually affecting the flint or second REM period. An ethanol concentration in the blood of 50-milligram percent (mg%) or greater (100-mg% is legal intoxication in most states) is necessary for observing these sleep effects. The sleep effects of ethanol are observed only during the first half of an 8-hour sleep period. Ethanol is metabolized at a constant rate, and consequently the usual dose of ethanol (50-90 mg%) given in these studies is almost completely eliminated from the body after 4 or 5 hours.

Following elimination of ethanol, an apparent compensatory effect on sleep occurs. During the latter half of sleep, increased amounts of REM sleep and increased wakefulness or light sleep is found (Williams & Salamy, 1972). Within three to four nights of repeated administration of the same dose, the initial effects on sleep are lost (e.g., tolerance occurs), while the secondary disruption of sleep during the latter half of the night remains. REM sleep time and sleep latency return to their basal levels, and the effects on slow-wave sleep, when initially present, do not persist. When nightly administration of ethanol is discontinued, a REM rebound is seen. But the REM rebound after repeated nightly ethanol administration in healthy, nonalcoholic subjects is not a particularly consistent result (Vogel et al., 1990). In alcoholics, however, the REM rebound is intense and persistent (Williams & Salamy, 1972). Some believe the presence of a REM rebound is a characteristic of drugs with a high addictive potential.

Morphine, the opiate Analgesic (derived from the opium poppy), decreases the number and the duration of REM sleep episodes and delays the onset of the first REM period (Kay et al., 1969). It also increases awakenings and light sleep and suppresses slow-wave sheep. Heroin, a semisynthetic opiate, also suppresses REM sleep and slow-wave sleep and increases wakefulness and light sleep, producing a disruption of the usual continuity of sleep. Heroin appears to be more potent than morphine in its sleep effects. The synthetic opiate, Methadone, has similar effects on sleep and wakefulness, with a potency more comparable to that of morphine. When an opiate is administered just before the onset of sleep, the EEG pattern shows isolated bursts of delta waves on the background of a waking pattern. Animal studies have correlated these delta bursts with the behavior of head nodding (a possible physiological correlate to the street term "being on the nod"). Repeated administration of the opiates at the same dose leads to tolerance of the sleep effects of these drugs, particularly the REM sleep effects (Kay et al., 1969). The cessation of opiate use leads to a protracted REM rebound, increased REM sleep, and a shortened latency to the first REM episode.

Among the stimulants, Amphetamine, when administered before sleep, delays sleep onset, increases wakefulness during the sleep period, and specifically suppresses REM sleep (Rechtschaffen & Maron, 1964). Cessation of chronic amphetamine use is associated with an increase in slow-wave sleep on the first recovery night and, on subsequent nights, with increased amounts of REM sleep and a reduced latency to the first episode of REM sleep, a REM rebound.

Caffeine interferes with sleep in most nontolerant individuals (Greden, 1997). Once tolerance has developed, people are much less likely to report sleep disturbances, or they may sense that their inability to sleep because of caffeine intake has completely disappeared. To illustrate, 53 percent of those consuming less than 250mg per day (about 2 to 3 cups of coffee) agreed that caffeine before bedtime would prevent sleep, compared to 43 percent of those consuming 250 to 749 mg per day, and only 22 percent of those taking 750 mg per day or more. Even though the higher level caffeine consumers denied that caffeine interferes with their sleep, studies done in sleep laboratories confirm that caffeine consumers do have greater sleep latency, more frequent awakenings, and altered sleep architecture, and that these effects are dose-related (Greden, 1997). One study that investigated the effects of day-long consumption of coffee and tea on sleep onset and sleep quality demonstrated that caffeinated beverages had a dose dependent negative effect on sleep onset (P<.001), sleep time (P[.001) and sleep quality (P<.001) (Hindmarch, 2000).

Nicotine has a paradoxical effect on sleep. In a study using rats, the higher the dose of nicotine that was administered, the lower the total sleep time (Salin-Pascual, 1999). In a study that observed the effects of nicotine transdermal patches on depressed patients, nicotine increased REM sleep time and alleviated some symptoms of depression (Salin-Pascual, 1998). Yet, another study that assessed the effects of 24-hour transdermal nicotine replacement, at four different doses, on sleep showed no changes in sleep efficiency from baseline for any of the four doses used (Wolter, 1996). Sleep disturbances are possible when a person is attempting to withdraw from nicotine addiction, along with ability to concentrate. Research has demonstrated that such withdrawal symptoms are lessened by maintaining an adequate blood level of nicotine, as can be supplied by transdermal patches. In that regard, sleep can appear to be enhanced by the administration of 24-hour nicotine patches (Tsoh, 1996).

Cocaine also has stimulant effects on the central nervous system, and its effects on electroencephalogram readings were first studied by Berger in 1931; he was the researcher who developed the EEG (Berger, 1931). Cocaine was found to increase fast-frequency EEG activity, suggesting an alerting effect. The self-reported use of cocaine during the late afternoon and early evening is associated with reduced nocturnal sleep time. Systematic electro-physiological studies show a reduction of REM sleep (Watson et al., 1989). Cessation of chronic cocaine abuse is followed by increased sleep time and a REM rebound.

The three classic Hallucinogens are LSD, Mescaline, and Psilocybin. The state experienced following use of hallucinogens is somewhat similar to dreaming. Since REM sleep is highly correlated with dreaming, scientists expected the hallucinogens to facilitate REM sleep, but LSD is the only hallucinogen that has been studied for its effects on sleep. One study done in humans showed that LSD enhanced REM sleep early in the night, although it did not alter the total amount of REM sleep for the night (Muzio et al., 1966). However, studies done in animals all indicate that LSD increases wakefulness and decreases REM sleep (Kay & Martin, 1978). The frequency changes seen in the waking EEG of animals (similar among all three hallucinogens) suggest an arousing effect. Thus the REM suppression in animals may not be a specific REM effect but rather a sleep-suppressing effect (Fair-child et al., 1979).

Another drug with hallucinogenic effects is marijuana, its active ingredient being Tetrahydrocannabinol (THC). The effects of THC on the waking EEG pattern are quite distinct from the effects of the classic hallucinogens cited above (Fairchild et al., 1979). THC has sedating effects at lower doses and hallucinatory effects at higher doses. The acute administration of marijuana or THC to humans is associated with an increase in slow-wave sleep and a reduction in REM sleep (Pivik et al., 1972). When THC is administered chronically (long-term), the effects on slow-wave and REM sleep diminish, indicating the presence of tolerance. Discontinuing the use of marijuana is associated with increased wakefulness and increased REM sleep time (Feinberg et al., 1976).

Most of these drugs, which are also drugs of abuse, seem to alter sleep and specifically the amount and timing of REM sleep. Each affects chemicals in the brain that control sleep and wake and, with chronic use, some adaptation seems to occur. A characteristic REM rebound is seen on discontinuation of dependent drug use. (It may be that the ancients' experience of enhanced dreaming was the REM rebound that is typically associated with protracted drug use.) Some studies indicate that, in the former drug dependent, the occurrence and intensity of the REM rebound has been predictive of relapse to drug use. How the sleep-wake pattern changes, and specifically the REM changes associated with these drugs, contribute to abused drugs' excessive use needs further study.

ACKNOWLEDGMENTS

Supported by National Institutes of Health (NIAAA) grant no. R01 AA07147 awarded to T. Roehrs and (NHLBI) grant no. P50 HL42215 awarded to T. Roth.

(See also: Addiction: Concepts and Definitions ; Benzodiazepines: Complications ; Sedative-Hypnotics ; Sedatives: Adverse Consequences of Chronic Use ; Tolerance and Physical Dependence )

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Timothy A. Roehrs

Thomas Roth

Revised by Ron Gasbarro