In an attempt to identify the factors responsible for adverse reactions to LSD and to elucidate the rising incidence of hospital admissions associated with use of the drug, the authors compared 25 psychiatric inpatients hospitalized following LSD ingestion with 25 members of a group who took LSD together regularly without reported difficulty. Although some differences were found between the groups, there were no outstanding historical or current clinical features which could be used to predict an individuals response to LSD with accuracy. These findings support the hypothesis that LSD interacts with schizoid trends, unsteady reality testing, and related factors in a complex way that makes accurate prediction of response virtually impossible.

Since approzimately the fall of 1965 the incidence of adverse LSD reactions throughout the country has mushroomed. At the UCLA Neuropsychiatric Institute prior to September 1965 one problem case associated with LSD ingestion was seen approximately every two months. Beginning at that time the incidence increased gradually from five to 20 cases a month, with three to five telephone calls being received, for every person seen, from other persons in trouble from LSD who were not subsequently seen. Other hospitals throughout the country have reported a similar increase. The demographic characteristics of the first 70 such patients seen at UCLA have previously been reported(9). These patients came most often with hallucinations, followed by anxiety to the point of panic, by depression, often with suicidal thoughts or attempts, and by confusion.

The question has thus been raised why these persons should have experienced difficulty from LSD when others claim to take the drug regularly and apparently have no adverse effects. A number of pertinent additional questions are then raised. First of all, how do we know the persons who get in trouble from alleged use of LSD are really taking LSD? Since Sandoz Pharmaceuticals, the one legitimate manufacturer, discontinued production, all LSD that is available is black market, with all the impurities and dosage confusion that is attendant upon such illegal supply. Secondly, how do we know that those persons who have difficulty from LSD were not already emotionally disturbed? (In our original study 37 percent had had psychiatric care previously and 33 percent were unemployed, which were per- haps gross indices of mental illness.)

There is no applicable chemical test for LSD once it is inside the body and no pathognomonic signs or symptoms on which to make the diagnosis. Although most typically passive, the LSD user may present with almost any kind of behavior. However, beyond the history of LSD ingestion, there are no unique features although dilated pupils along with the peculiar "I feet sorry for you nonusers" smile are characteristic.

LSD users describe the perceptual changes following drug ingestion in intense and often characteristic ways. When one hears about visual and auditory "unfolding" of nature it is typical of LSD and other psychedelics alone. In addition, the most common side effects reported by these subjects were consistent with those described elsewhere following experimental administration of LSD(3, 4). We had several drug samples spot-checked for LSD content. Although the user always overestimated the amount of LSD in his samples all did contain LSD(8).

The entire issue of predictability for the adverse LSD reaction is unsettled. This is particularly cogent in view of the fact that some researchers have advocated the use of LSD not only experimentally but in clinics where "creative and normal" persons could receive the drug in order to create a psychedelic experience for them. This study is a preliminary attempt to try to assess some of the factors in the etiology of the "bad trip," the adverse LSD reaction.

Methodology

Of the previous 70 patients reported upon, 25 were hospitalized and the rest were treated as outpatients. This group of 25 inpatients, hospitalized following adverse LSD reactions, are compared in this study with 25 other frequent LSD users who reported no difficulties from the drug. This latter comparison group claimed to have ingested the drug in doses of from 250 to 1200 m g. from once to three times a week for up to 18 months. It should be emphasized that these 25 subjects were part of an existing "religious" group who took their LSD together.

We initially made contact with this group when one of their members sought us out following a lecture which two of the authors (J.T.U. and D.D.F.) were giving on the LSD situation to a community service organization in a suburb of Los Angeles. The member had initially tried to read a statement advocating unlimited use of LSD during a question and answer session following the lecture. Afterwards, he approached us and insisted that there were many persons who were taking the drug without difficulty. They had formed a group, to be referred to as the "Disciples," which consisted of 100 regulars with as many as 500 members who met regularly and took LSD. This was before possession of LSD was made illegal in California. After we agreed to observe the group, we were "screened" by five members at the Los Angeles Airport. They were satisfied that we were not law enforcement officials and we were invited to observe some of their LSD "happenings."

Numerous subsequent visits were made to the headquarters of the "Disciples." This was located in a suburb of Los Angeles where about a dozen of the group were living in a large house on spacious grounds. They were literally tilling the soil and had decorated the house in psychedelic fashion. There were pictures of Buddha and Jesus on the walls. Every Wednesday night the group gathered to have a non-LSD religious experience consisting of prayer and meditation. The drug-taking sessions were scheduled for the weekends.

The group did not go along with "drop out" part of the "turn on, tune in and drop out" that Dr. Timothy Leary advocates. They claimed to be working, making money, and to have rehabilitated themselves. Most of the members of the group, said that they were "ex-criminals and drug addicts" who were now finding a new and useful life through LSD.

After we observed a number of their "love sessions" and all-day LSD experiences, the group agreed to psychiatric interviews, including mental status examinations and the Minnesota Multiphasic Personality Inventory (MMPI). We examined the first 25 who were available on one weekend. We then compared these data to corresponding data from the 25 hospitalized patients.

Results

Background. There were no significant differences in race, sex, or age between the two groups. Both groups had comparable amounts of early parental deprivation.(Separation from one or both parents for over six months before the age of 16(2)) Both groups resided predominantly in the Los Angeles area.

Martial status. There was a highly significant difference (p less than .001) in marital status between the two groups. No inpatients were married at the time of admission to the hospital (84 percent of the inpatients had never been married) versus 60 percent married (with 19 children) in the comparison group at the time they were examined (see table 1).

Table 1
Marital Status
Status	Inpatients		Comparison Subjects
	Number	Percent	Number	Percent
Single	21	84	10	40
Married	0		15	60
Divorced	2	8
Other (widow)	1	4
No data	1	4
Total	25	100	15	100

Employment. Only 20 percent of the inpatients were earning a living at the time of admission, while over 70 percent of the controls were working; this was a highly significant difference (p less than .01 ). The comparison subjects were mainly blue-collar workers and their jobs included those of plumber, longshoreman, gas station attendant, grocery and drug store clerk, janitor, construction worker, truck loader, tractor mechanic, aircraft plant worker, stockboy, gardener, and surfboard renter. The average length of time working was three years for this comparison group (see table 2).

Table 2
Occupation
Status	Inpatients		Comparison Subjects
	Number	Percentage	Number	Percentage
Unemployed	13	52	5	20
Housewives	2	8	2	8
Students	5	20	0
White Collar Jobs	2	8	0
Artists	3	12	0
Blue Collar Jobs	0	0	18	72
Total	25	100	25	100

Religion. We could not obtain religious information for the comparison group. They had formed a new religion, and they all denied having any previous religion or that their families even had any religion. In fact they had repudiated orthodox religions totally until they "found God under LSD." Thirty-two percent of the inpatient group said they had no religion.

Police records. Table 3 shows the histories of criminal behavior - 64 percent of the comparison group had police histories. The major crimes that the comparison group had been involved in were forgery, stealing, carrying concealed weapons, manslaughter, grand theft auto, and aiding a fugitive. Disturbances of the peace, delinquency, minor fights, and petty thefts were classified as minor crimes. Only eight percent of the inpatient group gave histories of police records, which was a significantly smaller proportion (p less than.001).

Table 3
Police Record
	Inpatients		Comparison Subjects
Conviction For	Number	Percent	Number	Percent
Major crime only			3	12
Alcohol only			2	8
Drugs only	1	4	2	8
Minor crime only
(including
delinquency)	1	4	0
Major crime plus
drugs, alcohol
or minor crime			5	20
Minor crime plus
drugs or alcohol			4	16
None	23	92	9	36
Total	25	100	25	100

Education. Fifty-six percent of the comparison group finished high school and an additional 16 percent bad had some college education, for a total of 72 percent who were at least high school graduates. The remaining twenty-eight percent were high school dropouts. For the inpatient group 64 percent had finished high school, 32 percent were dropouts, and one patient was a high school student. This difference was not significant.

Previous psychiatric history. Seventy-six percent of the comparison group had no previous psychiatric history (see table 4). Sixteen percent had been in outpatient treatment and eight percent had been inpatients. This is not significantly different from the 44 percent of the inpatient group who had had previous psychiatric care.

[table 4- missing]

Drug history. Half of the inpatient group were taking only LSD at the time of admission and the other half were taking both LSD and marihuana or LSD and other drugs, in approximately equal numbers (see table 5). The comparison group was taking either LSD alone (44 percent) or LSD and marihuana (56 percent). It was part of the "Disciples"' religion not to take other drugs.

[table 5 - missing]

As for past drug history prior to six weeks before being seen in the emergency room, 40 percent of the inpatient group had taken only psychedelics. Twenty percent of the inpatient group had taken multiple drugs excluding heroin, while 20 percent had used multiple drugs including heroin. Thus 40 percent were chronic multiple drug users. Twenty percent had never used any drugs in the remote past. In the comparison group in the remote past (before joining the "Disciples") 32 percent had taken only psychedelics, 44 percent were multiple drug users excluding heroin, and 24 percent were multiple drug users including heroin. Thus 68 percent were chronic multiple drug users. It should be noted that none of these differences was statistically significant.

Diagnosis. As recorded in the hospital charts, the resident psychiatrists diagnosed 40 percent of the inpatients as psychotics and 28 percent as neurotic; diagnoses character disorder, borderline psychotic, multiple diagnoses accounted for eight percent each (see table 6). Four percent each were diagnosed as addict and adolescent adjustment reactions. We compared diagnostic frequencies with a random sample of 95 other inpatients in the same hospital. The differences in frequency were small and appeared to be random; greater differences would occur by chance seven times in ten.

[table 6 - missing]

No attempt was made to classify the comparison group diagnostically since so many were functioning without symptoms, were not in psychiatric treatment, and were working at the time they were seen. Their indices of psychosocial disturbance were: previous school trouble (28 percent dropped out of high school), police trouble (64 percent), past psychiatric history (24 percent had had previous outpatient or inpatient care), and past history of symptoms (one person admitted to hallucinations while on LSD and another person had had anxiety symptoms prior to but not after taking LSD). Eighty percent of the group claimed to have extra-sensory perception when under LSD, but this was considered to be a part of their religious beliefs and not truly delusional.

We did, however, assess psychopathology on the mental status examination (for the comparison group) and by the MMPI (for both groups). On mental status examination two comparison subjects showed a clinical concreteness in their interpretations of proverbs and, one subject could not subtract sevens or threes serially. The latter subject subsequently volunteered that he bad been "out of my head with pot" at the time of the examination and then did the subtractions correctly.

One of the subjects who was unable to abstract stated that he often could not think straight since, he had begun to take LSD, but he had held his job as mechanic for 18 months without difficulty. He had never seen a psychiatrist, but had been addicted to barbiturates and dextroamphetamine sulfate in the remote past and had been arrested several years previously for drunk driving. His MMPI revealed a definite personality disorder associated with passive-aggressive, antisocial, paranoid, and sexually deviant trends.

The other comparison subject who was unable to abstract proverbs was a 24-year-old married father of two who had no previous psychiatric history. He had been on marihuana, barbiturates, and dextroamphetamine sulfate before joining the religious group two months prior to the initial interviewing. He had a drug and theft police record and claimed to have had trouble talking (stammering) which was cured by LSD. He had used LSD approximately 40 times in reported doses of up to 900 m g. Before he joined the group, LSD had caused "the past to come rushing forth," and occasionally "suspicious thoughts," but this was never true after joining the group.

About ten months after the initial interview one of us (J.T.U.) received a call from this man's wife. She stated that he had been using LSD almost every day for several months, and that she had just signed papers to have him committed to the hospital. However, he was refusing to talk to anyone but the senior author, and the judge had acquiesced. His wife stated that he had quit his job and often stayed away from home, wandering about in the woods for days at a time. He refused to eat anything colored red and threw out everything red in their house, and he frequently told her to shut up while he conversed with Jesus and the saints. The final "straw" for her was when he refused to pick up the unemployment checks.

When interviewed, he detailed his plans for beginning a new church. He spoke about green vapors interchanging from his body into the atmosphere through the umbilicus and leaned forward to whisper, "You wouldn't eat anything red, would you?" He denied having any problems, however, and claimed total happiness.

Another MMPI was obtained and compared with that from the previous year's comparison group testing. His initial MMPI (presymptomatic) showed a paranoid personality pattern. The second testing yielded a very similar profile with even more guardedness, denial, and evasiveness.

A comparison of the MMPIs on both groups revealed:

1. Most of the comparison subjects were quite defensive toward the MMPI (two-thirds at least moderately so), and they did not exaggerate or "fake sick." The inpatients did overstate; three profiles were clearly invalid, and several others were borderline. Only one inpatient was notably defensive.
   
   
2. PD (psychopathic deviate) was the predominant peak in the comparison group and Sc (schizophrenia) was the most frequent peak of the hospitalized group (see figure 1 ). All 25 inpatients had one or more deviant scores (elevations at or over a T score of 70). In contrast, only 11 of the 25 comparison subjects had one or more pathological scores. Eight men among the comparison cases and none of the inpatients had the specific sexual deviation pattern (Code 45 or Code 54).
   
   
3. A majority of the inpatients obtained mixed, borderline, and overtly psychotic patterns; only five of the 25 comparison subjects appeared borderline psychotic on the testing, although a few others were ambiguously defensive. However, none of these five were openly schizoid patterns; rather, all were of a controlled and potentially paranoid type.
   
   
4. The comparison subjects obtained character disorder types of patterns quite consistently, but many of these were well within the normal range. Although character disorder elements occurred consistently in the profiles of the inpatients, they were complex, mixed, and predominantly psychotic patterns.
   
   
5. To summarize our results, the inpatient and comparison groups did not show significant differences in race, sex, age, education, or early parental deprivation. Significant differences were found in marital status, occupational history, and police records. Severe psychopathology was seen clinically in the inpatient group while hospitalized. No comparable clinical psychopathology was evident in the comparison sample. The MMPT profiles clearly corresponded to these results, although the comparison group was much more defensive toward the testing. (MMPI profiles are shown in figure 1.)
   
   

Discussion

It can be asked whether all those who had chronic adverse LSD reactions were emotionally predisposed or were to some degree emotionally ill prior to LSD ingestion. This is very difficult to answer. Well known at many hospitals are the anecdotal reports of local interns and residents who were carefully screened before taking LSD (or had even been psychoanalyzed) but who subsequently had severe adverse reactions from LSD. In addition there are now a number of reports of nonprofessional persons screened by psychiatric history and/or psychological testing who have had adverse LSD reactions. Although 44 percent of our inpatients with a history of previous psychiatric care is a high figure, it is certainly less than 100 percent. None of the 24 percent of the comparison group who had previous psychiatric treatment had difficulty from their ingestion of LSD.

Among psychiatric patients with LSD histories, we are now seeing at the hospital fewer chronic, multiple drug users who are obviously emotionally disturbed. Instead we are seeing more teenagers who tried LSD once, for example at a party, got over its effects in 12 to 16 hours, but then presented at a hospital some months later with recurrent symptomatology without ever having taken the drug again. A decreasing proportion of our patients are chronic drug users. However, it is not clearly demonstrable whether this is due to a change in incidence or to a shift in selective referrals to our hospital.

This brings us to a consideration of set or, specifically, the attitude with which one approaches the LSD experience and the setting or environment in which one takes the LSD. Everyone recognizes the importance of these factors in the LSD experience. In fact people now have "psychedelic experiences" in groups in the proper setting where they hallucinate, etc., but never take drugs at all ( 5 ).

The parallels between the LSD subject and the good hypnotic subject are striking, particularly in the realm of passivity and suggestibility. Our comparison group dressed alike and even used identical phrases in answering questions. One of their favorites was "for sure," chanted over and over. They obviously received a tremendous amount of support, both during and between trips, from the group itself. The average length of stay with the group was eight months, and 24 of the 25 controls claimed that LSD (taken with the group) had led them to "God, love, or peace of mind." They may thus have been successful LSD users because the group support out-weighed or overcome the adverse potentials of the drug.

We should not conclude, however, that set and settings are the only determinants of the type of trip one has. There is one study reported where all subjects expected psychosis, but all felt only relaxed and friendly after LSD(l). There is an ever-growing LSD mythology, too, much of it having to do with set and setting(6, 7). For example, one commonly hears that a bad LSD experience will not result if:

- One is in a calm frame of mind (no fights that day with spouse or employer);

- One takes the LSD with one or two good friends or with an experienced sitter or guide present;

- The room has soft lighting and a thick carpet or mattress to sit on;

- One is listening to the Indian music of Ravi Shankar and reading reassuring phrases from the Tibetan Book of the Dead; and perhaps if one has a "downer" or chlorpromazine pill at hand.

But we have hospitalized many persons who had taken these precautions and who also had had up to 100 previous good LSD experiences. Our inpatient group took their LSD in many varied settings, from kick- type, acid-test parties (56 percent) to isolated ingestions in their rooms (16 percent). However, some (8 percent) were most careful and serious about the preparations for taking LSD. (There were no data for setting in 20 percent of the inpatient group.) Despite their hospitalizations a large proportion of the inpatients persisted in claiming benefit from the drug and many returned to it after discharge.

How reliable were the data from our comparison group? Obviously they were proselytizers of LSD. This could explain why they all claimed no previous religion and even no religion for their parents. It also could explain why they claimed to have developed "ESP" as well as to have found love from LSD and also why they identified themselves as a "bunch of ex-criminals and drug addicts" before using the drug.

Summary

Twenty-five hospitalized psychiatric patients with adverse LSD reactions were compared to a sample of 25 subjects who had not had adverse reactions from the repeated use of LSD.

In all of our comparisons there were no historical elements or current clinical aspects that were unique to either group. Clearly there is no single factor that guarantees immunity from an adverse LSD reaction. The prediction of successful versus unsuccessful users is further complicated by the occurrence of cases in which subjects used LSD 100 times or more with no adverse reactions and then subsequently developed psychiatric symptomatology. Set and setting appear to help but not to guarantee against adverse complications.

One hypothesis, strongly supported by our test data, is that the LSD interacts with schizoid trends, unsteady reality testing, and related psychological factors. Such a complex interaction - which is difficult to anticipate even with the best of clinical and test data - would predict that adverse LSD reactions will be with us for some time to come.

REFERENCES

1. Blum, R., ed.: Utopiates: The Use and Users of LSD-25. New York: Atherton Press, 1964.
2. Brill, N. Q., and Liston, E. H., Jr.: Parental Loss in Adults with Emotional Disorders, Arch. Gen. Psychiat. 14:307-314,1966.
3. Cohen, S.: LSD: Side Effects and Complications, J. Nerv. Ment. Dis. 130:30-40,1960.
4. Cole, J. O., and Katz, M. K.: "The Psychotomimetic Drugs: An Overview," in Solomon, D., ed.: LSD: The Consciousness Expanding Drug. New York: G. P. Putnams' Sons, 1964
5. Hoffman, R.: The Psychedelic Game, Mademoiselle, March 1966, p. 179.
6. Ungerleider, J. T., and Fisher, D. D.: Research and Joyride, The Nation 202:574-576, May 16, 1966.
7. Ungerleider, J. T., and Fisher, D. D.: LSD : Fact and Fantasy, Arts and Architecture 18-20, December 1966.
8. Ungerleider, J. T., and Fisher, D. D.: Problems of LSD and Emotional Disorders, Calif. Med. 106:49-55, 1967.
9. Ungerleider, J. T., Fisher, D. D., and Fuller, M.: The Dangers of LSD, J.A.M.A. 197:389-392. 1966.