Adverse Reactions to Psychedelic Drugs. A Review of the Literature, Rick J. STRASSMAN, 1984.

Adverse Reactions to Psychedelic Drugs. A Review of the Literature



DOI : 10.1097/00005053-198410000-00001


The use of naturally occurring and synthetically derived compounds for their “psychedelic” effects has been a part of human culture for thousands of years. The basic pharmacology of the major synthetic psychedelic compounds primarily lysergic acid diethylamide [LSD]-25 is described and reference is made to their potentially beneficial psychological effects.

Adverse reactions, defined as dysphoric and/or maladaptive/dysfunctional responses to the use of these drugs, sometimes require careful clinical judgment in order to diagnose. These reactions can be effectively classified along a temporal continuum, Acute, short-lived reactions are often fairly benign, whereas chronic, unremitting courses carry a poor prognosis. Delayed, intermittent phenomena “flashbacks” and LSD-precipitated functional disorders that usually respndtc treatment appropriate for the n-3n-psychedeilic-precipiated illnesses they resemble, round out this temporal means of classification, The question of organic brain damage as well as permanent changes in personality, attitudes, and creativity in patients and normals who have repeatedly ingested psychedelic drugs is controversial, but tends to point to subtle or nonsignificant changes.

Future areas for study of the psychedelics’ tic effects are suggested.



The use of naturally occurring, exogenously administered substances for inducing altered states of con
sciousness extends back to ancient times. Cannabis products and certain species of mushrooms were used as long ago as the time of the Vedas, in India, nearly 5000 B.C. In the New World, mushrooms and certain cacti, barks, and vines were employed for similar pur poses by indigenous cultures 147. Abuse apparently was fairly rare, perhaps because careful cultural, religious, and social proscriptions determined a uniform manner in which these substances were used and the experiences one was expected to have as a result of their use 167.

The “modern era of speciflcallv mind-altering drugs is often said to have begim with Albert Hofmann’s accidental ingestion of LSD-25 in 1943 77. However, interest in mescaline/neyote was briefly pursued at the turn of the century 48 and in the 19305 94, 98.

A great flurry of scientific activity with LSD and Similarly acting drugs occurred in the 1950s and 1960s, ‘Department of Psychiatry, University of California, Davis, Medical Center, 2315 Stockton Boulevard, Sacramento, California 958j7, but was just as quickly aborted in the late 1960s as fears of adverse acute and chronic effects of wide spread use and abuse began to come to the attention of media and legislators.

Therapeutic and “growth-enhancing” aspects of these substances were widely pursued early on, spurred by such “auto-experimenters’? 9 as Aldous Huxley 82, Timothy Leary 97, and Carlos Castsneda 32, A discussion of these aspects of “psychedelic” drug use is beyond the scope of this paper, but interested readers are referred to Grof 65-67, Caldwell 31, Tart 151, Hoffer and Osmond 76, and others 64, 145, 146, as representative selections.


The confusion regarding the tenninology of this class of drugs, of which LSD-25 is considered the
prototype. is reflective of the various orientations respective investigators have taken in approaching them.

For those who have been struck by the primarily perceptual effects of these drugs, the terms hallucinogenic or illusogenic are used. The similarity between the effects of LSD-like substances and certain psychotic phenomena a feature that caused them to be employed as potentially producing a “model’ of schizophrenia has induced others to label them as psychotoinimetics or psychotogens 39.

Psychedelic, a term attributed to Osmond 64, p. 8 and defined as “mindmanifesting,” although somewhat vague, also carries a less restrictive connotation, and for that reason is the preferred term in this paper. Other words that have been used to describe this class of drugs include psychodysleptics 29, p. 4 mind distortive or mind disruptive, deliriants, and mind-exnandinR drugs,


Psychedelic drugs can be distinguished from other centrally active drugs that can also under certain conditions induce perceptual distortions e.g., anticholinergics, paranoid and other delusions e.g., amphetamineS, and other alterations of cognition, behavior, and affect e.g., opiates, bromides. They are capable of, when pathological effects are absent or minimal, “reliably inducing or compelling states of altered perception, thought, and feeling that are not or cannot be experienced otherwise except in dreams or at times of religious exaltation” 84, pp. 563-564.

Lysergic acid diethylamide-25 is the prototypical psychedelic compound, and was often the active ingredient in most street “psychedelics,” during the period in which most of the reference studies were performed. even those labeled “mescaline” or “psiiocybin” Unless otherwise mentioned, LSD-25 will be used inter changeably with “psychedelic” in this paper. It is, as are psilocybin, psilocin, diethyl-tryptamine, and dimethyltryptamine, a member of the indolealkylamine class ‘fdr:;s. Mescaline one of the most active ingredients in peyote cactus is a phenylisopropylamme 84. Phencychcline PeP, “hog,” “angel’s dust,” etc., an arylcyclohexylainine, has attained great currency in the last 10 years, as a common street “psychedelic” in its own right, as well as a substitute/adulterant for other psychedelics. Many current satpies of thugs sold as psychedelic, are often found tocontain variable amounts of PCP. However, PCP did not become a popularly abused street psychedelic until the mid-1970s, a time by which almost all of the major reports of adverse reactions to LSD had been published. The effects of PCP can be differentiated both pharmacologically and clinically from true psychedelics 84. The interested reader is referred to Lisansky et al. 101 for a fuller discussion of these important distinctions.

On the basis of a subjective effects and neurophysiological actions, b cross-tolerance between compounds, and c response to selective antagonists, Martin and Sloan 105 have classified LSD, mescaline, psilocybin, and psilocin as “LSD-like” Differences among the various LSD-like drugs referred to here as the psychedelics are primarily a matter of rate or onset, peripheral side effects, duration of action, and intensity of experience. For example, LSD is longer acting 8 to 12 hours and more potent average dose of 100 to 500 pg than mescaline average dose of 209 to 500 nig arid average duration of 6 to 8 hours and psilocybin or psilocin average duration of 4 to .12 hours and a dose range of it to 50 mg.