Reprinted from American Journal of Psychiatry 124 (November 1967): 674-77, copyright 1967, the American Psychiatric Association with the permission of the publisher and author.
Eleven individuals who reported adverse reactions associated with the use of marihuana were interviewed. Their difficulties included one report of panic and fear, one report of depersonalization, one report of gross confusion and disorientation, two reports of depression, and four reports of paranoid phenomena during the drug reaction. The individual who reported confusion during the reaction also experienced recurrence of confusion and hallucinations intermittently afterwards. One of the individuals who experienced depression during the reaction had similar experiences thereafter.
Two other individuals reported major changes in behavior and style of life after the use of marihuana. Four others were interviewed who had become schizophrenic subsequent to the combined use of marihuana, lysergic acid diethylamide, and amphetamine. All 17 of these individuals were of superior intelligence and all were or had been university students. None was a delinquent in the usual sense; none had ever been arrested. All but two came from middle-class backgrounds; two came from upper lower-class families.
More detailed presentation of the clinical data will be preceded by description of the marihuana reaction and followed by presentation of other reports of adverse reaction and consideration of the problems involved in the evaluation of such data.
DESCRIPTION OF THE MARIHUANA REACTION
Knowledge of usual reaction is required to interpret reports of unusual drug reaction. Bouquet summarized the effects of marihuana in terms that are consistent with the statements made by marihuana users interviewed in the clinic from which this study derives. Euphoria, a feeling of well-being, increase of self-confidence, and decreased self-criticism occur.
The user feels that he is unusually aware of the function of his limbs and that he could perform feats of physical agility or grace but that he is too tranquil to do so. The power to focus concentration is lost or relinquished. Associations are rapid and disorganized. Concepts of time and space are altered. Illusions, visual and auditory hallucinations, and sensitivity to sound occur.
Allentuck described the effects of the administration of marih-uana to 78 subjects. He stated that euphoria and difficulties in concentration and sustaining attention were frequent. Excitement, anxiety, and/or dysphonic reactions occurred in some subjects.
Physiologic responses to marihuana include tachycardia, mydriasis, and suffusion of the conjunctiva. Subjective sensations often include feelings of rightness, heaviness or pressure in the head, dryness of the mouth, and a "floating sensation."
Case I. A 21-year-old man stated that after smoking more than his usual amount he became disoriented to time and place, could not think, and had difficulty in controlling his limbs. For some weeks thereafter he intermittently experienced hallucinations resembling those he had had during the reaction. These sensations were accompanied by a degree of anxiety approaching panic.
Case 2. A 19-year-old woman stated that during a marihuana reaction she had become intensely anxious and apprehensive without any idea of what she was afraid of. She said that she had been agitated and in a state of panic.
Case 3. A 20-year-old woman stated that while smoking marihuana she would become convinced that she did not exist in a spatial sense. She would think that she was merged with the universe, or, alternatively, a point in space without dimensions. Such ideation, accompanied by anxiety, would persist for some hours after the use of the drug.
Case 4. A 19-year-old man reported that during a marihuana reaction he became convinced that his internal organs were rotting and that he would die. This was related to a conviction that he had done evil things.
Case 5. A 23-year-old woman stated that during the marihuana reaction and for some hours afterwards she would have the "horrors." She described this as a feeling that indescribably evil things would happen to her because of the kind of person she was.
Case 6. A 20-year-old woman reported that during a marihuana reaction she became convinced that her friends had informed the police that there would be a marihuana party so that they might raid the house and catch her using the drug.
Case 7. A 22-year--old man stated that during the drug reaction he would become convinced that his taking the drug was part of some gigantic plot but that he did not know what the plot was.
Case 8. A 20-year-old man stated that during the marihuana reaction he would become preoccupied with whether his friends thought he was a homosexual. There was no reality testing of this conviction during the drug reaction.
Case 9. A 23-year-old man stated that during the marihuana reaction he would become preoccupied with the possibility of a police raid and would interpret every noise he heard as caused by approaching police.
Case 10. A 20-year-old man stated that after taking marihuana he recognized that his previous goals, including what he called conventional ambition, conformity, and fear, were not as important as the need to express himself and achieve independent identity. His interest and achievement in academic areas deteriorated and his dress became nonconventional.
Case 11. A 22-year-old woman stated that after taking marihuana she recognized that her graduate school work did not permit adequate self-expression. She did not drop out of school and her intelligence was such that she continued to do passable work. She stated that her academic work had once been a source of pleasure but that she now recognized that she had been "brainwashed" by the system.
Four individuals who demonstrated sufficient thinking disorders and inappropriate affect to justify the diagnosis of schizophrenia were interviewed, and they admitted to the almost daily use of amphetamine and marihuana and the regular use of LSD.
OTHER REPORTS OF ADVERSE REACTION
Allentuck administered the equivalent of between 30 and 330 mg. of tetrahydrocannabinol orally to 72 subjects. Six subjects had acute brain syndromes during the reaction. Three others became psychotic within the next few weeks. It was Allentuck's opinion that these latter psychoses would have occurred even if the drug had not been administered.
Ames administered between .24 and .46 gm. of a cannabis extract orally to each of ten subjects. One subject experienced intense anxiety and five subjects exhibited some degree of delusional thinking.
De Farias observed nine subjects smoking 2.82 gm. and seven of the same subjects smoking 1.56 gm. of cannabis. Delirium and confusion with apprehension of impending death occurred in one subject.
Chopra and associates implicated marihuana in the difficulties of 600 patients admitted to mental hospitals in India. They classified these reactions as acute mania, chronic mania, and dementia. Hallucinations, a dare-devil attitude with unresistable impulses to do willful damage, and amnesia for the attack upon remission characterized acute mania. The patients with chronic mania were cheerful, boastful, and had a sense of well-being. Data such as these have been questioned by many on several accounts. Such a large proportion of the population in the area involved uses cannabis that a high proportion of hospitalized patients would give such a history even if the drug were harmless. The criteria whereby psychoses caused by marihuana differ from other psychoses is not explicit.
Benabud reported evidences of acute or subacute cannabis effect in 49 percent of the 1,252 patients admitted to a Moroccan mental hospital in 1956. He considered certain types of excitation, impulsivity, oneiric, and visual hallucinatory states to be cannabis-induced. One or more of these phenomena were present in such disorders or were superimposed on other psychopathological conditions.
Benabud defined six percent of the admissions in the year studied as "cannabis-mobilized psychoses." This is defined as a psychosis of a functional type precipitated by cannabis intoxication. He defined 11 percent of the admissions in the year studied as "cannabis-aggravated psychoses." This is defined as a preexistent psychotic condition made worse by the use of cannabis.
Benabud's report, like that of Chopra and associates, has been subjected to some criticism. So many people in the area use cannabis that many hospital patients would have done so by chance alone. Many difficulties ascribed to cannabis could have resulted from other causes.
The reports of Allentuck, Ames, and De Farias, previously noted, do not have the weaknesses of the Chopra and associates and the Benabud reports. Specific psychotic syndromes were observed to occur during the marihuana reaction.
There is good reason for controversy as to the prevalence of adverse reaction to marihuana. For proper evaluation of adverse drug effect, information is required as to number of untoward reactions, the size of the population using the drug, dosage, and the nature of the population using the drug. As will be discussed below, none of this information is available for marihuana.
In the case of marihuana a definition of adverse reaction is also required. The evaluation of adverse reaction is, in addition, dependent on the interpretation of such a statement as, "Marihuana in itself does not prod6ce functional psychopathology but may precipitate such in individuals who are so predisposed."
There is no accurate or reasonably accurate way of determining how many acute difficulties occur during or immediately after marihuana use. Most of these reactions do not come to medical attention. There are great differences in the potency of different preparations. The populations from which the reports of adverse reactions in this study are derived might be defined as university nonconformist. These individuals are of superior intelligence, more than average education, and not delinquent in the usual sense. It is not justified to assume that adverse reactions would be the same in this group, a delinquent group in a large city of the United States, and the urban poor of Morocco.
There is some difficulty in the evaluation of changes in style of life subsequent to marihuana use. Many individuals so change direction without drug use; many begin to use drugs only after they have so changed direction. No one has the right to define a change in style of life and goals of life as psychopathology. Nevertheless, when this occurs immediately after drug use it may be permissible to consider such a change to be an adverse drug reaction.
Perhaps all investigators would agree that marihuana cannot produce functional psychopathology but can only precipitate it in individuals so predisposed. Many would interpret this as an exoneration of the drug. Others would hold that the occurrence of psychopathology in an individual at a given time requires many factors and that more people have predisposition to mental illness than develop it. In this sense marihuana usage might precipitate trouble that would not have otherwise occurred or would have otherwise occurred at a later time.
It is the author's opinion that the literature does indicate that marihuana, depending on dose and subject, can precipitate acute brain syndromes, panic, and delusional thinking during the reaction. The use of the drug can initiate changes in style of life. It is left to others to decide whether this constitutes psychopathology.
It is the clinical impression of the author that this dissolution of ordinary adaptive and defensive psychological structure that occurs during the marihuana reaction is potentially dangerous for individuals with a predisposition to schizophrenia.
The evaluation of the harm a drug does requires some consideration of its benefits. Users of marihuana state that it is a source of positive pleasure, that it enhances creativity, that it provides insight, and that it enriches their lives. These are hardly minor claims. All but two of the 11 individuals reporting adverse reactions considered the benefits to far outweigh the unfortunate aspects and planned to continue use of the drug.