Effects

LSD is one of the most potent hallucinogens known; one-billionth of a gram of LSD per gram of brain produces profound mental changes. Although subjective effects occur in some individuals after doses as low as 50 micrograms, typical street doses range from 10 to 300 micrograms—street dosages vary widely. Misrepresentation also frequently occurs; someone will try to purchase synthetic Tetrahydrocannabinol (THC), the active ingredient of marijuana, and receive LSD. Thus, the intake of LSD can be accidental as well as intentional, and the lack of quality control in illicit supplies is a hazard. Because of its high potency, LSD can be applied to paper blotters or the backs of postage stamps from which it is dissolved for consumption. Unsubstantiated reports of LSD added to stick-on tattoos for young children have caused alarm, even though absorption through skin would be far too slow to deliver enough drug to the brain to produce and sustain a trip.

The absorption of LSD from the gastrointestinal tract and other mucous membranes occurs rapidly, with drug diffusion to all tissues, including brain.

The onset of psychological and behavioral effects occurs approximately 30 minutes after oral administration, peaks in the next 2 to 4 hours, depending on the dose, with gradual return to normal by 10 to 12 hours. The first 4 hours after a 200-microgram dose are called a trip. In the next 4 to 8 hours, when over half the drug has left the brain, the ''TV show in the head'' has stopped. At this point subjects think the drug is no longer active, but later they recognize that they, in fact, had paranoid thoughts and ''ideas of reference'' in the last 4 to 8 hours of the trip. This simply means that there is the feeling of being at the center of things, being hyperalert, and having a conviction that everything going on refers to oneself. This is a regular but little publicized aftereffect, which finally dissipates 10 to 12 hours after the dose.

From 12 to 24 hours after the trip, there may be some slight letdown or feeling of fatigue—as if one had been on a long, steep roller coaster ride. After these intense and even frightening moments, the ordinary world might for a time seem drab. There is no craving to take more LSD to relieve this boredom; one trip usually produces satiation for a time, although some may want to repeat the experience. Memory for the events during the trip is quite clear. Those who revisit the experience sooner or later decide they have learned what they can and go on with the practical, daily affairs of living. In one experiment on CREATIVITY, subjects received either LSD or the stimulant amphetamine during a period of pleasant surroundings and music. The only difference between the two groups six months later was a slight tendency for those who had received LSD to buy more recordings! So the promise of lasting insight or creativity was not kept.

Drugs that make one feel different—alcohol being typical—can signal a ''holiday from daily reality.'' The way the effects of such drugs are interpreted is critical. BEER at the Super Bowl means ''loudly letting go'' and champagne at the White House means a time for graceful speech and feelings. Thus personal and social expectations (called set—or how one is set to go) and the surroundings (called setting) have much to do with the ultimate effects of drugs. This is distinctively and especially the case with psychedelics. Thus when the chemist Albert Hofmann first ingested the active ingredient of the Mexican mushroom, psilocybin, the perceptions capturing his attention were related to Aztec symbols and art! For some, therefore, the trip may simply be funny and odd—for others it will have special meanings. Set and setting partially determine the character of such trips.

Fundamentally, LSD produces a heightened clarity and awareness of sensory signals—of sights, sounds, touch, lights, and colors. Similarly there is special significance given to thoughts, memories, or verbal interchanges. For example, gestures or inflections of speech or many cues that are normally in the background are felt to be more important than what is being said or usually meant—and in looking at a picture, the central figures may take on a life of their own, the small background details that are normally ignored emerging, capturing attention.

While awareness is strikingly increased, control over what is being attended to is weakened. For all these reasons, unstable surroundings or confused motives at the time of drug ingestion may lead to a less-controlled trip or even a panic-generating trip. Many are aware that the trip is not quite real and fundamentally feel as if they are ''spectators'' of what they are so intensely experiencing. Many rely on guides, a group, or the rhythm of music to carry them through this period of altered perceptions in which control is diminished. Thus, personal intent and reliable surroundings are major factors affecting the different kinds of experiences that people will have.

While every trip has an individual characteristic, there are regularities in the trips. This has been called a ''march of effects'' following drug ingestion. Thus, observers note, the first sign of feeling different is like ''butterflies in the stomach'' or a slight nausea and feeling of ''whoops, here we go'' as if on a roller coaster. Parts of the body simultaneously feel strange or different. At about the same time (30-40 minutes after drug ingestion), the cheeks are slightly flushed and pupil size begins to increase, maximizing within an hour or two. These changes are due to the effects of LSD on the sympathetic and parasympathetic nervous systems. The pupils react normally but are enlarged. After 4 hours they slowly begin to return to normal size, which finally is achieved at 10 to 12 hours after taking LSD. At the beginning of the trip, all soon note that what is at the periphery of their vision suddenly seems as clear as what is normally at the center of vision. Over the next 90 minutes, there is a feeling that tension is welling up. Laughing or crying will relieve the tension. Often subjects say they

Dr. Timothy Leary (center) in the custody of U.S. customs officials in New York City, October 11, 1966. Leary had been arrested under a section of federal law prohibiting users of narcotics or convicted narcotics violators from leaving or re-entering the U.S. without permission. (© Bettmann/CORBIS)

are laughing because of what they see or crying because of their feelings. But this is simply based on a need to relieve the fluctuating rise of tension. The trip moves on into the second and third hours when perceptual fluctuations and intensities are mainly noted. People also report perceiving several feelings simultaneously. A common observation is, ''I don't know if I'm anxious, thrilled, or terrified.'' Just as perceptions are in flux, so are feelings, and these feelings and emotions may capture center stage in the second and third hours. Throughout the trip, people feel as if they are on the brink of an exhilarating but also dangerous experience. This intensity dies down about 4 hours after the usual dosage. If very large doses of LSD (500-1,000 micrograms) are taken, there is less capacity to be a spectator and far more intense self-absorption and fear. Some call this ''dying of the ego'' and relate the experience to mystical versions of death and rebirth.

Since the familiar seems novel and is seen in a different way, specialists in perception have been interested in what is called the ''breakdown of constancies'' that occurs with the drug. Normally we correct for what the retina sees by putting the world into order. We usually suppress the nonessential and focus on what we need to do to get about during the day. Just as with a camera, the retina sees the hand placed 6 to 8 inches in front of the eye as large. But the brain corrects for it and keeps size constant. Under LSD, corrections for constancy do not seem to happen. Many sensations that are normally dampened can thus have free play under the drug and the world will seem far less regular than it does in daily life.

One of the aftereffects in some—clearly not all—people is called ''flashbacks.'' Days, months, or years after tripping, with no particular trigger or with an intense sensation, there may be a sudden few minutes in which subjects feel like they are back under the drug. They also may see flashing lights and other optical illusions. These flashbacks may be very disturbing. Flashbacks can occur after only a single drug experience and unpredictably. There has been no explanation as to why or how flashbacks occur. Scientists cannot predict (by observing a trip) if flashbacks will later occur or who is vulnerable. While these aftereffects are upsetting to some, most people do not experience them or those that do are not bothered. Others simply observe that their dreams may be more intense for a time after the drug experiences. One scientist noted that riding on a train to work, he was distracted from focusing on his newspaper for several months by the telephone poles whizzing by. These were normally at the periphery of his attention as he was reading, but after LSD, he could no longer suppress this irrelevant detail. There were more reports of such phenomena after publicity about them; given the millions of trips with LSD, these aftereffects are certainly infrequent but not rare.

Perhaps the most alarming bad effects of the drug have been the panic states occurring during a trip. Native Americans note that if one is in conflict, the effects of mescaline during religious ceremonies are unpleasant and can evoke terror. They then pray with the panicked person and ''talk him down. ' One cannot predict whether a panic experience will occur. ''One good trip does not predict a second one'' is the general wisdom concerning this risk. Higher doses lead to less control and more intense effects, but panic states can occur at doses as low as 75 to 100 micrograms. For those who might be at risk for other mental disorders, hallucinogenic experiences may often destabilize them and precipitate some form of mental illness. For others, the experience may lead to a subsequent absorption with the unreal (''dropping out''), rather than coping with the challenges that the tasks of the ordinary world present. Occasional suicides or rare impulsive acting out of odd ideas arising during a trip have led some to loss of control and tragedy.

For most, the experiences have few negative or positive aftereffects. Although it has often been suspected, no permanent change to the cells of the brain (brain damage) has ever been scientifically established. There is no generally accepted evidence that the drug produces chromosomal abnormalities or damage to a developing fetus (although no nonprescription drugs during pregnancy is the only safe rule to follow). The bad effects of a period of diminished control are unpredictable, and in that fact lies the real risk. Thus, it is the intensity of the experience and how well or poorly it can be managed, the unpredictable flashbacks, and how this ''TV show in the head'' or this ''waking dream'' gets woven into one's subsequent life that are at issue when hazards are considered.

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