Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects
Friederike Holze, Patrick Vizeli, Felix Müller, Laura Ley, Raoul Duerig, Nimmy Varghese, Anne Eckert, Stefan Borgwardt, Matthias E. Liechti
Neuropsychopharmacology November 16, 2019 DOI: 10.1038/s41386-019-0569-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, cross-over study Peer reviewed |
|---|---|
| Sample size | 28 |
| Population | Healthy subjects |
| Interventions | LSD MDMA d-amphetamine placebo |
| Dose | 0.1 mg LSD, 125 mg MDMA, 40 mg d-amphetamine |
| Topics | LSD MDMA |
| Keywords | Hallucinogen Stimulant Placebo Dextroamphetamine Pharmacology |
| Citations | 250 |
| Key points | LSD, MDMA, and d-amphetamine produce comparable autonomic responses but clearly distinct subjective and endocrine effects. |
Abstract
Abstract Lysergic acid diethylamide (LSD) is a classic psychedelic, 3,4-methylenedioxymethamphetamine (MDMA) is an empathogen, and d -amphetamine is a classic stimulant. All three substances are used recreationally. LSD and MDMA are being investigated as medications to assist psychotherapy, and d -amphetamine is used for the treatment of attention-deficit/hyperactivity disorder. All three substances induce distinct acute subjective effects. However, differences in acute responses to these prototypical psychoactive substances have not been characterized in a controlled study. We investigated the acute autonomic, subjective, and endocrine effects of single doses of LSD (0.1 mg), MDMA (125 mg), d -amphetamine (40 mg), and placebo in a randomized, double-blind, cross-over study in 28 healthy subjects. All of the substances produced comparable increases in hemodynamic effects, body temperature, and pupil size, indicating equivalent autonomic responses at the doses used. LSD and MDMA increased heart rate more than d -amphetamine, and d -amphetamine increased blood pressure more than LSD and MDMA. LSD induced significantly higher ratings on the 5 Dimensions of Altered States of Consciousness scale and Mystical Experience Questionnaire than MDMA and d -amphetamine. LSD also produced greater subjective drug effects, ego dissolution, introversion, emotional excitation, anxiety, and inactivity than MDMA and d -amphetamine. LSD also induced greater impairments in subjective ratings of concentration, sense of time, and speed of thinking compared with MDMA and d -amphetamine. MDMA produced greater ratings of good drug effects, liking, high, and ego dissolution compared with d -amphetamine. d -Amphetamine increased ratings of activity and concentration compared with LSD. MDMA but not LSD or d -amphetamine increased plasma concentrations of oxytocin. None of the substances altered plasma concentrations of brain-derived neurotrophic factor. These results indicate clearly distinct acute effects of LSD, MDMA, and d -amphetamine and may assist the dose-finding in substance-assisted psychotherapy research.
Comparable studies
Other randomized controlled trials on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases Patients with anxiety associated with life-threatening diseases | 2014 | Randomized controlled trial | n = 12 |
| Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users | 1994 | Double-blind, saline placebo-controlled, randomized study | n = 12 |
| Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Healthy subjects (8 women, 8 men) | 2014 | Double-blind, randomized, placebo-controlled, crossover study | n = 16 |
| Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Healthy human participants | 2018 | Double-blind, randomized, counterbalanced, cross-over study | n = 24 |
| LSD-induced entropic brain activity predicts subsequent personality change. Healthy adults | 2016 | Balanced-order, placebo-controlled study | n = 19 |
Citations in the library
Cited by 202
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- The Subjective Effects of Psychedelics May Not Be Necessary for Their Enduring Therapeutic Effects ACS Pharmacology & Translational Science December 10, 2020
- Adverse effects of psychedelics: From anecdotes and misinformation to systematic science. Journal of Psychopharmacology February 2, 2022
- Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology 2023
- Psychedelics, Mystical Experience, and Therapeutic Efficacy: A Systematic Review Frontiers in Psychiatry July 12, 2022
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Cites 49
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- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later Journal of Psychopharmacology May 30, 2008
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