Acute effects of a prototypic hallucinogen, entactogen, and stimulant have never been compared directly within healthy subjects. Therefore, we assessed and compared responses to the hallucinogen lysergic acid diethylamide (LSD), the entactogen 3,4-methylenedioxymethamphetamine (MDMA), the stimulant d-amphetamine, and placebo in humans in a controlled laboratory setting.
We used a double-blind, placebo-controlled, cross-over study design in 28 healthy volunteers (14 females, 14 males) to investigate the acute subjective and autonomic responses to 0.1 mg LSD, 125 mg MDMA, 40 mg d-amphetamine, and placebo. Acute subjective drug effects were assessed using visual analog scales (VASs), the adjective mood rating scale (AMRS), the addiction research inventory (ARCI), and the five-dimensions of altered states of consciousness scale (5D-ASC). Mystical experiences were assessed with the 30-item Mystical Experience Questionnaire (MEQ30). Maximal responses were compared using repeated-measures ANOVAs followed by Tukey post-hoc tests.
All substances significantly increased blood pressure, heart rate, and body temperature compared with placebo (all p<0.001). d-Amphetamine showed a significantly larger increase in blood pressure compared with LSD and MDMA (both p<0.001). All substances produced a significant increase in VAS good drug effect, drug liking, drug high, happiness, and trust ratings (all p<0.001). On the AMRS, MDMA and d-amphetamine both increased concentration (p<0.01 and p<0.001, respectively), self-confidence (both p<0.01), heightened mood (both p<0.01), and well-being (both p<0.001). Only LSD increased bad drug effect (p<0.001), fear (p<0.001), speed of thinking (p<0.01), and change in the sense of time (p<0.001) in the VASs. Additionally, only LSD significantly increased ratings of anxiety in the AMRS (p<0.001). LSD produced significant effects on all subscales of the ARCI whereas d-amphetamine and MDMA only showed effects on the Amphetamine and Morphine-Benzedrine Group scales (all p<0.001). LSD significantly increased effects on all 5D-ASC dimensions and subscales, whereas MDMA only increased “blissful state” ratings (p<0.01). MDMA and LSD increased ego dissolution (“the boundaries between myself and my surroundings seemed to blur”) (p<0.01 and p<0.001, respectively) on the 5D-ASC. Furthermore, LSD significantly increased all MEQ30 scores compared with placebo. MDMA increased ineffability (p<0.001), positive mood (p<0.001), and transcendence (p<0.05) on the MEQ30. In contrast, d-amphetamine produced no alterations of mind on the 5D-ASC and no mystical-type experiences in the MEQ30.
LSD, MDMA, and d-amphetamine produce separable acute subjective responses in healthy humans. In particular, LSD induced subjective effects that were clearly very distinct from those of MDMA and d-Amphetamine.