Friederike Holze | M.Sc University Hospital Basel Direct within-subject comparison of the acute subjective and autonomic effects of LSD, MDMA, and amphetamine in healthy subjects
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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. d-Amphetamine showed a significantly larger increase in blood pressure compared with LSD and MDMA. All substances produced a significant increase in VAS good drug effect, drug liking, drug high, happiness, and trust ratings. On the AMRS, MDMA and d-amphetamine both increased concentration, respectively), self-confidence, heightened mood, and well-being. Only LSD increased bad drug effect, fear, speed of thinking, and change in the sense of time in the VASs. Additionally, only LSD significantly increased ratings of anxiety in the AMRS. 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. LSD significantly increased effects on all 5D-ASC dimensions and subscales, whereas MDMA only increased “blissful state” ratings. MDMA and LSD increased ego dissolution (“the boundaries between myself and my surroundings seemed to blur”) on the 5D-ASC. Furthermore, LSD significantly increased all MEQ30 scores compared with placebo. MDMA increased ineffability, positive mood, and transcendence 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.
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Friederike Holze is a PhD Student at the Division of Clinical Pharmacology and Toxicology, University Hospital Basel. She is the first to compare acute effects of a prototypic hallucinogen, entactogen, and stimulant directly within healthy subjects. In her double-blind, placebo-controlled, cross-over study she investigates the differences in the acute subjective and autoomic responses to LSD, MDMA and d.amphetamine and Placebo. 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.
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