LSD, the mind-blowing chemical banned during the 1960s as a dangerous drug, may enjoy a revival of scientific interest from researchers searching for a tool to probe the mysteries of brain chemistry.
Recent advances made in understanding chemicals that relay nerve impulses in the brain, known as neurotransmitters, and the action of drugs on these chemicals have set the stage for a new look at LSD as a study tool.
"There is a place for LSD in (such studies). Nobody is doing them on humans today, but I predict that they will," said Dr. Daniel X. Freedman, a longtime LSD researcher, who is Braun professor of biological psychiatry at UCLA's Neuropsychiatric Institute.
"LSD is no less interesting to scientists today than it ever was," said Jerold Winter, a State University of New York at Buffalo researcher who has worked with LSD for many years.
Another longtime LSD researcher, James Appel of the University of South Carolina, said LSD's remarkable potency is one reason for scientists' continued interest in the drug despite the subsequent development of other similar drugs.
LSD was first synthesized in 1938 by a Swiss chemist, Albert Hofmann. From its first test in 1943, LSD's capacity to produce profound psychic changes and startling visual images in rainbow colors forecast what was to become a worldwide fascination with the chemical, first as a research aid and later as a means to "turn on, tune in and drop out."
Research aimed at exploring the drug's potential usefulness fell into two categories. The first category involved using LSD for basic research to learn more about the brain's chemistry. The second category, more clinical in nature, was to test the drug's usefulness as a treatment for mental illness or as a way to enhance psychotherapy.
Researchers in the first group were fascinated by the resemblance of LSD's effects to the hallucinations experienced by patients with severe schizophrenia. During the 1950s, many researchers in this country and in Europe conducted experiments aimed at learning whether the drug would produce a model psychosis. One purpose was to see whether it could be used to test antipsychotic drugs such as chlorpromazine, then being developed.
Researchers were struck by the fact that extremely small amounts of LSD were capable of producing profound mental changes. This finding bolstered the growing conviction that mental illness might be the result of undetectable traces of a psychoactive substance produced by the body itself. This view challenged the general belief that mental illness was caused by social and psychological factors.
On the clinical side, psychiatrists began administering LSD to artists, musicians and writers as reports began to grow that the drug could enhance creativity. Some psychiatrists saw value in use of the drug on normal people who seemed to benefit from the mystical experiences some had.
Other research interests were directed at LSD's possible use as a treatment for alcoholism and certain mental illnesses. Later, the drug was tested as a means of relieving anxiety in terminal cancer patients. In 1960, Dr. Sidney Cohen, an early LSD researcher at UCLA, did a survey of 65 LSD researchers who up to that time had tested the drug on 25,000 subjects. He reported that "no one was ever harmed" by the controlled use of LSD.
In the 1950s and '60s even the Army and the CIA showed interest by launching secret studies to see whether LSD could be dumped into water supplies to incapacitate enemy populations.
Whether much of true scientific value was learned from many of these studies is questioned by some researchers today. Part of the problem is that serious scientific work was interrupted prematurely during the late 1960s by government controls imposed as a result of the negative public reaction to the widespread recreational use of LSD and reports of its harmful effects.
Although many of the reports of harm later proved to be unfounded, the drug's only legal manufacturer stopped production and the government banned its unauthorized use. Although scientists still were able to obtain the drug for research, many now say the stigma that accompanied LSD increased paperwork and crippled their interest.
Ironically, according to Ronald Siegel, a psychiatric researcher at UCLA and an expert on hallucinogens, the illicit use of LSD is as great today as it was in the 1960s. The big difference, he said, is that the typical dosage today is only one-fourth to one-half of that taken in LSD's heyday. The consequence of the lower dose, Siegel said, is that far fewer people have "bad trips" and the drug consequently does not attract the public censure it did 25 years ago.
Statistics gathered by the National Institute for Drug Abuse indicate that LSD ranked 19th in 1989 among drugs of abuse reported to be involved in emergency visits to 700 emergency rooms around the country. During 1989, according to the institute, 1,351 visits involved LSD, compared to the top four drugs of abuse causing problems: 61,665 visits for cocaine, 46,735 for a combination of alcohol and another drug, 20,566 for heroin and 9,867 for marijuana.
Accordingly, Congress has not made LSD a high-priority research item in its funding considerations. Nevertheless, the institute funds 10 research projects involving LSD, none with human subjects, according to Dr. Chris Hartell, deputy director of preclinical research.
Thirty years ago, Freedman, the UCLA researcher, discovered that LSD achieves what he calls "the TV show in the head" partly because of the effect it has on a neurotransmitter called serotonin. Serotonin and other nerve transmitters, as well as the sites on nerve cells known as receptors where neurotransmitters act as on-and-off switches, have become a major area of interest among neuroscientists.
The intense scientific interest in neurotransmitters in the brain is due to the vital role they play in key bodily functions. Serotonin, for example, has been implicated in states of consciousness, mood, depression and anxiety. Because serotonin seems to control the different switches affecting various emotional states, scientists believe these switches can be blocked by a chemical with a similar molecular structure. Researchers are now looking for such a chemical that could become the basis for a new therapeutic drug.
Freedman and others believe that LSD, whose structure closely resembles serotonin, could be a valuable tool with which to explore the intricate chemical pathways in which serotonin acts.
Freedman has been conducting animal studies on the tendency to become tolerant to LSD under certain circumstances. If moderate doses of the drug are administered to animals four days in a row, no "trip" occurs. But if there is a two-day interval between doses, the usual effects occur.
Animals on a trip, according to Freedman, ruffle their fur profusely, are easily startled and refuse to climb a rope or press a bar for food for at least 30 minutes after the first dose of LSD. But after four days of treatment they revert to normal behavior.
"True, we don't know positively that they had a mind trip, but we do know that if we perform the same experiment on humans they have no trip after four days. When the initial drug effect disappears, that's tolerance," he said. While tolerance to LSD has been known for a long time, why it occurs is a mystery. Freedman believes that exploring tolerance may provide information on the opposite effect--what turns the trip on.
Today, he says, it would be possible to study precisely which sites in the brain are more active biochemically in the presence of LSD and which sites are less active. Using the knowledge gained from tolerance studies, the time would be ripe to test the capacity of experimental drugs to block LSD's effects in humans.
Information gained from human studies has implications for understanding the biochemistry of both normal and abnormal mental states. For example, the amount of serotonin available at certain sites in the brain affects in part illnesses such as depression and obsessive-compulsive disorders.
Would drugs that turn off the TV show in the head be useful for treating these illnesses? Freedman speculates that LSD once more will play a role in human psychopharmacology.
Scientists who are interested in using LSD as a tool in basic research are not the only investigators who believe the drug still has an important role to play.
"The drums are beginning to beat again for legitimate research with LSD in psychotherapy," said Dr. Oscar Janiger, a Los Angeles psychiatrist who in the 1950s and '60s studied LSD's effects as an aid to psychotherapy and as a way to enhance creativity. "It's only a matter of time before research with humans resumes," Janiger said.
In 1988, the 50th anniversary of the first synthesis of LSD, Janiger was instrumental in forming a foundation based in Los Angeles and named for LSD's discoverer, Albert Hofmann. A library that is to be established is intended to become a world information center dedicated to the study of human consciousness.