by Keith A. Trujillo, Ph.D. and Andrea B. Chinn
Last Revised 10/2/96
At high enough doses, many drugs will produce hallucinations, usually as a side-effect of toxicity. What distinguishes this class of drugs is that they cause hallucinations at very low doses and the hallucinations are a direct result of the drug and not a toxic drug effect. While most psychedelics produce alterations in perceptions, many also effect mood, thinking, and physiological processes.
Because there are so many psychedelics (over 90 different species of plants and many more synthetic agents), it is necessary to subdivide this category of drugs. One popular way of categorizing these drugs is on the basis of their effects and mechanisms of action. This discussion will primarily focus on the serotonergic hallucinogen, LSD. Other subgroups within this drug class include the methylated amphetamines which produce alterations in mood and consciousness but little sensory change, the anticholinergic hallucinogens which produce a dreamlike trance in the user, and the dissociative anesthetics which produce surgical anesthesia while leaving the individual semiconscious. Each of these subcategories produces unique effects and it is thought that they each act on different mechanisms to produce their effects.
Psychedelics have been documented in many customs and religious practices for centuries. The Aztecs used peyote cactus, psilocybe mushrooms, and morning glory seeds to produce visual hallucinations. They believed these visions could reveal the future, help them solve problems, and aid in healing the sick.
The modern history of psychedelic use began in 1938 when Albert Hoffman, a Swiss chemist, began synthesizing various derivatives of lysergic acid. Lysergic acid derivatives were known to cause contractions of the uterus and Hoffman was interested in exploring these compounds in hopes of finding clinically useful drugs. After synthesizing a series of compounds, preliminary testing resulted in uninteresting findings and so the compounds were shelved. Five years later, Hoffman decided to reexamine the compounds. While mixing up a new batch of the 25th lysergic acid compound (LSD-25), he accidentally spilled a small amount on his hand and began to feel peculiar. He concluded that the reason for his strange experience was due to contact with LSD and decided to test his theory. A few days later he consumed what he thought to be a small dose, 0.25 mg. Because of the extreme potency of LSD, however, 0.25 mg is a rather large dose, at least twice as much as is required to cause hallucinatory effects.
LSD was quickly distributed to psychologists and psychiatrists to examine its potential in the understanding or treatment of mental disorders. Because of its ability to produce hallucinations, it was thought that the study of LSD might lead to a better understanding of schizophrenia. However, it was soon found that the hallucinations produced by LSD were very different than those experienced by schizophrenics. Another research area that received attention was the potential of LSD as an adjunct to psychotherapy. Because of its reported abilities to "dissolve the ego" and allow access to the unconscious, it was thought that LSD might speed up the psychotherapeutic process. Although there were some noted successes reported in this area, fears about the drug led to government restrictions on its availability.
By the mid 1960's LSD became a popular street drug, being promoted by some individuals, such as Harvard Professor Timothy Leary, as a vehicle for achieving personal or cosmic insights. LSD was also receiving negative publicity. There were allegations, now known to be false, that LSD caused chromosome damage and users were likely to have mutant children. LSD has also been blamed for insanity, suicide, acts of violence, and homicidal behavior. With these controversies, the use of LSD declined through the 1970's and 1980's and reached a low in 1990. However, it appears that LSD use may be on the rise, as indicated by an increased LSD availability, increased frequency of self-reported use, and an increased frequency of emergency room admissions involving LSD.
The measureable physiological effects of psychedelics are similar to amphetamine and cocaine. These include such effects as pupil dilation, increased heart rate and blood pressure, increased body temperature, and increased sweating. The psychological effects are more profound, and include changes in visual perception, feelings of deep insight into oneself and the world, deep religious feelings, and an increase in the ability to enjoy and appreciate art. Performance in a variety of tasks is usually impaired by these drugs as the user has difficulty remaining motivated and attending to the task.
The neurobiology of psychedelics is still not well understood. Because psychedelics are not a homogeneous group of drugs, it is difficult to isolate what mechanisms are responsible for producing hallucinations. However, many of the drugs in this class produce alterations in the brain serotonin systems, and it is likely that these changes play a primary role in hallucinogenic effects.
The first evidence of the role of serotonin came from studying the chemical structures of some of the psychedelic drugs. Many of these drugs share a chemical structure similar to serotonin. Further studies demonstrated that LSD and other psychedelics bind to serotonin receptors, and the potency of the binding correlates with the potency of the drug as a psychedelic. Blocking serotonin receptors may be a common effect of psychedelics but it cannot be the only explanation for the hallucinogenic effects, as other drugs block serotonin receptors without causing hallucinations.
Another problem with the serotonin analysis comes from what we know about another psychedelic drug, mescaline. Mescaline produces vivid visual hallucinations nearly identical to LSD yet its chemical structure is different from other drugs in this class. Instead of having a chemical structure similar to serotonin, mescaline is structurally more similar to amphetamine, which have quite distinct effects. It is likely that mescaline and LSD do share some mechanism of action as studies demonstrate cross-tolerance between LSD, mescaline, and other psychedelics.
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Keith A. Trujillo, Ph.D.
Andrea B. Chinn
Comments to author: keith@mailhost1.csusm.edu
All contents copyright (C) 1996, Keith A. Trujillo, Ph.D. All rights reserved.
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