PMID- 31733631 OWN - NLM STAT- MEDLINE DCOM- 20201228 LR - 20210731 IS - 1740-634X (Electronic) IS - 0893-133X (Print) IS - 0893-133X (Linking) VI - 45 IP - 3 DP - 2020 Feb TI - Distinct acute effects of LSD, MDMA, and D-amphetamine in healthy subjects. PG - 462-471 LID - 10.1038/s41386-019-0569-3 [doi] AB - 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. FAU - Holze, Friederike AU - Holze F AUID- ORCID: 0000-0002-4582-6610 AD - Department of Biomedicine and Department of Clinical Research, Division of Clinical Pharmacology and Toxicology, University Hospital Basel, University of Basel, Basel, 4056, Switzerland. FAU - Vizeli, Patrick AU - Vizeli P AUID- ORCID: 0000-0002-5954-4446 AD - Department of Biomedicine and Department of Clinical Research, Division of Clinical Pharmacology and Toxicology, University Hospital Basel, University of Basel, Basel, 4056, Switzerland. FAU - Muller, Felix AU - Muller F AD - Psychiatric University Hospital (UPK), University of Basel, Basel, 4012, Switzerland. FAU - Ley, Laura AU - Ley L AD - Department of Biomedicine and Department of Clinical Research, Division of Clinical Pharmacology and Toxicology, University Hospital Basel, University of Basel, Basel, 4056, Switzerland. FAU - Duerig, Raoul AU - Duerig R AD - Department of Biomedicine and Department of Clinical Research, Division of Clinical Pharmacology and Toxicology, University Hospital Basel, University of Basel, Basel, 4056, Switzerland. FAU - Varghese, Nimmy AU - Varghese N AD - Psychiatric University Hospital (UPK), University of Basel, Basel, 4012, Switzerland. AD - Transfaculty Research Platform Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland. FAU - Eckert, Anne AU - Eckert A AUID- ORCID: 0000-0002-9341-3669 AD - Psychiatric University Hospital (UPK), University of Basel, Basel, 4012, Switzerland. AD - Transfaculty Research Platform Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland. FAU - Borgwardt, Stefan AU - Borgwardt S AUID- ORCID: 0000-0002-5792-3987 AD - Psychiatric University Hospital (UPK), University of Basel, Basel, 4012, Switzerland. FAU - Liechti, Matthias E AU - Liechti ME AUID- ORCID: 0000-0002-1765-9659 AD - Department of Biomedicine and Department of Clinical Research, Division of Clinical Pharmacology and Toxicology, University Hospital Basel, University of Basel, Basel, 4056, Switzerland. matthias.liechti@usb.ch. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191116 PL - England TA - Neuropsychopharmacology JT - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JID - 8904907 RN - 0 (Central Nervous System Stimulants) RN - 0 (Hallucinogens) RN - 8NA5SWF92O (Lysergic Acid Diethylamide) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - TZ47U051FI (Dextroamphetamine) SB - IM MH - Adult MH - Affect/drug effects/physiology MH - Central Nervous System Stimulants/*administration & dosage MH - Consciousness/*drug effects/physiology MH - Cross-Over Studies MH - Dextroamphetamine/*administration & dosage MH - Double-Blind Method MH - Female MH - Hallucinogens/*administration & dosage MH - Healthy Volunteers MH - Humans MH - Lysergic Acid Diethylamide/*administration & dosage MH - Male MH - Middle Aged MH - N-Methyl-3,4-methylenedioxyamphetamine/*administration & dosage MH - Retrospective Studies MH - Time Factors PMC - PMC6969135 EDAT- 2019/11/17 06:00 MHDA- 2020/12/29 06:00 PMCR- 2019/11/16 CRDT- 2019/11/17 06:00 PHST- 2019/08/15 00:00 [received] PHST- 2019/11/08 00:00 [accepted] PHST- 2019/11/04 00:00 [revised] PHST- 2019/11/17 06:00 [pubmed] PHST- 2020/12/29 06:00 [medline] PHST- 2019/11/17 06:00 [entrez] PHST- 2019/11/16 00:00 [pmc-release] AID - 10.1038/s41386-019-0569-3 [pii] AID - 569 [pii] AID - 10.1038/s41386-019-0569-3 [doi] PST - ppublish SO - Neuropsychopharmacology. 2020 Feb;45(3):462-471. doi: 10.1038/s41386-019-0569-3. Epub 2019 Nov 16.