LSD (lysergic acid diethylamide) is a semi-synthetic derivative of lysergic acid, an ALKALOID found in ERGOT, a parasitic fungus (Claviceps purpurea) that grows on rye and wheat. In the Middle Ages, consumption of infected grains resulted in vast outbreaks of ERGOTISM, the illness that arises from ingestion of the compounds in ergot, including ERGOTAMINE and lysergic acid. One symptom of ergotism was HALLUCINATION, which may have led people to believe that such affected people were possessed by demons. In the 1940s, the chemist Albert Hofmann at Sandoz Drug Company in Basel, Switzerland, was experimenting with various derivatives of ergot compounds in hopes of finding new medicines. He synthesized a series of compounds, one of which was LSD. At the time, he had no idea he was dealing with a potent hallucinogenic drug. In 1943, after conducting several experiments, he was forced to stop work because of peculiar sensations. He recorded these impressions in his laboratory notebook and suspected they were due to accidental ingestion of LSD. Several days later he deliberately tested his theory by ingesting 0.25 mg of the substance (we know now that this is a massive dose, since LSD is an extremely potent drug). This famous description underscored the remarkable visual hallucinations and perceptual distortions induced by the drug (see Hofmann, 1968). Reports on LSD eventually found their way into the scientific literature. Although pharmacologists and psychologists were very interested in its effects, research indicated that there was little therapeutic value to the compound. In the early 1960s, the drug became illegal, although soon after, in the late 1960s and early 1970s, its use in the ‘hippy’ sub-culture reached its peak. The psychological effects of the hallucinogenic drugs such as LSD are difficult to describe because they are so subjective, varying with the individual and the person’s expectations and experience with the drug. One of the most common reports is that of profound changes in sensory perception, including visual, tactile or auditory distortions. Images and sounds may be remarkably vivid or bizarre.
The sense of time is also extremely altered. The neuropharmacologist Solomon Snyder, upon having ingested LSD, noted that ‘two hours after having taken the drug, I felt as if I had been under its influence for thousands of years. The remainder of my life on the planet Earth seemed to stretch ahead into infinity, and at the same time I felt infinitely old’ (Snyder, 1986). Sensations may be transposed from one mode to another, a phenomenon known as SYNAESTHESIA. Snyder wrote: ‘I clapped my hands and saw sound waves passing before my eyes.’ EMOTION and the sense of self are often affected, with a feeling of depersonalization. In many cases users report they develop special insights into themselves or the world. In some instances this feeling is experienced as positive; for others it can be quite disturbing and result in profound DYSPHORIA.
LSD is an indole compound (see INDOLEAMINE), chemically related to the neurotransmitter SEROTONIN. Although it is not known precisely how LSD causes hallucinations and sensory distortions, it is suspected that marked alterations in the serotonin system and particularly in the CEREBRAL CORTEX may underlie the phenomena. There are a number of important differences between LSD and other drugs of abuse. Unlike drugs such as COCAINE, AMPHETAMINE or HEROIN, LSD does not cause a ‘rush’ or strong feeling of PLEASURE, nor is it addictive. It is possible that the hallucinogens do not effect the brain REWARD system the way most other drugs of abuse do. Animals cannot be taught SELF-ADMINISTRATION of these compounds; they seem to lack true reinforcing effects in both animals and humans.
References
Hofmann A. (1968) Psychotomimetic agents. In Drugs Affecting the Central Nervous System, vol. 2, ed. A.Burger, pp. 169–235, Marcel Dekker: New York.
Snyder S.H. (1986) Drugs and the Brain, Scientific American Library: New York.
ANN E.KELLEY
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