Hallucinogenic Drugs – LSD

LSD is a synthetic compound based on ergot alkaloids

Unlike mescaline, psilocybin, and DMT, LSD is a synthetic compound, although its structure is based on a family of fungal alkaloids. The famous story about the synthesis of LSD and the discovery of its astonishing psychoactive potency is presented in another post. Once LSD was made available to psychiatrists and medical researchers in the late 1940s and early 1950s, the drug began to be intensively studied. Indeed, there were only six published papers on LSD before 1951, but from 1951 to 1962 more than 1000 LSD-related articles appeared in the scientific literature (U.S. Department of Health, Education, and Welfare, 1968).

During this period, researchers were first beginning to appreciate that nerve cells in the brain communicate with each other chemically by means of neurotransmitters like serotonin. When LSD was reported to alter serotonergic activity (see the section below on the pharmacology of hallucinogenic drugs), the finding generated tremendous excitement about the possibility of understanding human mental activity and behavior at a chemical and physiological level.

Some researchers approached LSD as a psychotomimetic drug that would help reveal the biochemical underpinnings of schizophrenia. However, the LSD model proved to be inadequate in a number of ways, and it subsequently gave way to a PCP/ketamine model that is discussed later in the post. Others believed that LSD could be a valuable tool in psychotherapy or psychoanalysis. One way of using LSD was in psycholytic therapy, which was mainly practiced in continental Europe. This therapeutic method was based on the concept of drug-induced “psycholysis,” meaning psychic loosening or opening. It involved giving LSD in low but gradually increasing doses to promote the release of repressed memories and enhance communication with the analyst.

British, Canadian, and American psychiatrists, on the other hand, tended to prefer psychedelic therapy, in which the patient was typically given a single high dose of LSD with the hope of gaining insight into his or her problems through a drug-induced spiritual experience. During the 1950s and 1960s, a number of studies were performed using this technique to treat alcoholic patients (Mangini, 1998). Unfortunately, these studies were marred by poor experimental control and inconsistent findings, leading to a cessation of this work by the early 1970s.

Interestingly, at the same time that LSD was being investigated as a possible aid to psychotherapy, it was also being considered by the United States government as a potential psychological weapon. In the early 1950s, the Central Intelligence Agency (CIA) began a top secret program called MK- ULTRA that was designed to investigate the possible use of LSD as a mind control agent (Lee and Shlain, 1992). In one particularly disgraceful part of this program, CIA operatives administered LSD to unsuspecting members of the public in order to observe their behavioral reactions. According to Lee and Shlain (1992), Fidel Castro and then Egyptian president Gamal Abdel Nasser were among the foreign leaders targeted for LSD “attacks,” although it appears that no such attacks were actually carried out before the program was eventually disbanded.

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LSD’s popularity exploded with the hippie culture of the 1960s. As part of their nonconformist, anti-Establishment attitudes, hippies openly sought mind expansion through the use of psychedelic drugs, especially LSD. However, the inevitable backlash soon occurred amid growing anecdotal accounts as well as scientific reports of LSD-related problems. A 1965 federal law greatly restricted new research on LSD, and soon thereafter Sandoz stopped distributing LSD for research purposes and recalled all of the existing drug that had previously been supplied to investigators. After a long period of inactivity, however, clinical research on LSD has begun to make a slow comeback.

An organization called MAPS (Multidisciplinary Association for Psychedelic Studies) has been promoting new research on the potential psychotherapeutic applications of hallucinogens (see the MAPS Web site at www.maps.org). Nevertheless, given the general cultural and governmental attitudes toward LSD and other hallucinogenic drugs, it seems unlikely that these compounds will enter mainstream psychiatric practice any time soon.

Recreational use of LSD was banned nationwide in 1967. Of course, LSD didn’t disappear, it merely went underground.

Indeed, in recent years hallucinogenic drug use has increased as a new generation of young people has rediscovered these sub-stances. LSD is active orally, and that is the standard mode of administration. The drug is so potent that a single dose in crystalline form is barely visible to the naked eye. Consequently, larger amounts of LSD representing many doses are usually dissolved in water and then droplets containing single-dose units are applied to a sheet of paper (a “blotter”) and dried. The paper is subsequently divided into individual squares, often decorated with fanciful designs, and sold as single-dose “tabs” to be swallowed by the user.

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