“Lysergic Acid Diethylamide (LSD-25): Xv. the Effects Produced By Substitution of a Tap Water Placebo”, 1955 (; backlinks; similar):
The purpose of this paper is to study the responses given to a questionnaire by subjects who received a tap water ‘placebo’ instead of lysergic acid diethylamide (LSD-25), and to relate the number of responses to other variables. These variables are: body weight, number of responses on a health questionnaire, arithmetic test scores, scores on the Wechsler-Bellevue Intelligence Scale, and Rorschach test responses.
…Figure 4 shows for each question the percentage and number of subjects out of 28 who gave a positive response at least once during the 0.5, 2.5, and 4.5-hour intervals. The questions appear in the figure in the order of decreasing percentages of response to them. The time of the response and the magnitude are disregarded in this tabulation. The question receiving the greatest percentage response was (Subject 24), “Are your palms moist?” As many as 60.7% reported this symptom. Half of the subjects reported headache (Subject 13), fatigue (Subject 44), and drowsiness (Subject 45). About 36% reported anxiety (Subject 47). Illness (Subject 1), and dizziness (Subject 15) were reported by 28.6 per cent of the group and 25% indicated a dream-like feeling (Subject 46), increased appetite (Subject 6), unsteadiness (Subject 16), a hot feeling (Subject 22), heaviness of hands and feet (Subject 30), and weakness (Subject 43). There were 19 questions which received positive responses from 10–22 per cent of the subjects. Less than 10% of the group (or no more than two subjects) responded positively to the remaining questions, but each question received a positive response from at least one subject.
…The findings point out that a substance such as tap water, which is generally considered chemically and pharmacologically inactive, is capable of eliciting certain responses from certain subjects who believe they have received lysergic acid diethylamide. These observations emphasize once more the need for placebo controls in studies investigating the effects of drugs; without them changes which are produced merely by the situation and not by the drug are frequently falsely attributed to the action of the drug…Most subjects who respond to a placebo tend to do so most markedly during the first 0.5 hour after receiving the substance. At this time their anticipation of, and anxiety about, the effects of LSD-25 are probably greatest. Gradually the effects wear off, as the anticipation wears off. Individual differences exist in the time of peak effect, but this is the most common finding. The questions which elicited the greatest percentage response from the group were those related to anxiety (moist palms and feeling anxious) or to phenomena which commonly occur without the presence of any foreign agent (drowsiness, fatigue, and headache). The remaining questions received random responses. The fact that there is a wide range in the number of positive responses made to the questionnaire is of major interest.