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Distinct acute effects of LSD, MDMA, and D-amphetamine in healthy subjects.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
February 1, 2020
Friederike Holze et al. (9 authors)
Journal ArticleResearch Support, Non-U.S. Gov'tHuman Study
Study Details

Study Goal

The researchers aimed to characterize and compare the acute autonomic, subjective, and endocrine effects of LSD, MDMA, and D-amphetamine in healthy subjects.

Results Summary

LSD induced stronger subjective effects, including altered consciousness, emotional excitation, and cognitive impairments, compared to MDMA and D-amphetamine. It also produced greater autonomic responses like increased heart rate but had distinct psychological and mystical effects.

Population

28 healthy subjects

Effective Dosage

0.1 mg (single dose)

Duration

Single-dose administration (acute effects measured)

Interactions

None mentioned

Extracted Claims (24)
InterventionDirectionEndpointPopulationDosageImpactClaim #
LSD (0.1 mg)
increase
heart rate
28 healthy subjects
-
increased
#1
MDMA (125 mg)
increase
heart rate
28 healthy subjects
-
increased
#2
D-amphetamine (40 mg)
increase
blood pressure
28 healthy subjects
-
increased
#3
LSD (0.1 mg)
increase
5 Dimensions of Altered States of Consciousness scale
28 healthy subjects
-
induced significantly higher ratings on
#4
LSD (0.1 mg)
increase
Mystical Experience Questionnaire
28 healthy subjects
-
induced significantly higher ratings on
#5
LSD (0.1 mg)
increase
subjective drug effects
28 healthy subjects
-
produced greater
#6
LSD (0.1 mg)
increase
ego dissolution
28 healthy subjects
-
produced greater
#7
LSD (0.1 mg)
increase
introversion
28 healthy subjects
-
produced greater
#8
LSD (0.1 mg)
increase
emotional excitation
28 healthy subjects
-
produced greater
#9
LSD (0.1 mg)
increase
anxiety
28 healthy subjects
-
produced greater
#10
LSD (0.1 mg)
increase
inactivity
28 healthy subjects
-
produced greater
#11
LSD (0.1 mg)
decrease
concentration
28 healthy subjects
-
induced greater impairments in subjective ratings of
#12
LSD (0.1 mg)
decrease
sense of time
28 healthy subjects
-
induced greater impairments in subjective ratings of
#13
LSD (0.1 mg)
decrease
speed of thinking
28 healthy subjects
-
induced greater impairments in subjective ratings of
#14
MDMA (125 mg)
increase
good drug effects
28 healthy subjects
-
produced greater ratings of
#15
MDMA (125 mg)
increase
liking
28 healthy subjects
-
produced greater ratings of
#16
MDMA (125 mg)
increase
high
28 healthy subjects
-
produced greater ratings of
#17
MDMA (125 mg)
increase
ego dissolution
28 healthy subjects
-
produced greater ratings of
#18
D-amphetamine (40 mg)
increase
activity
28 healthy subjects
-
increased ratings of
#19
D-amphetamine (40 mg)
increase
concentration
28 healthy subjects
-
increased ratings of
#20
MDMA (125 mg)
increase
plasma concentrations of oxytocin
28 healthy subjects
-
increased
#21
LSD (0.1 mg)
no change
plasma concentrations of brain-derived neurotrophic factor
28 healthy subjects
None
altered
#22
MDMA (125 mg)
no change
plasma concentrations of brain-derived neurotrophic factor
28 healthy subjects
None
altered
#23
D-amphetamine (40 mg)
no change
plasma concentrations of brain-derived neurotrophic factor
28 healthy subjects
None
altered
#24
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.

Medical Subject Headings (MeSH)
AdultAffectCentral Nervous System StimulantsConsciousnessCross-Over StudiesDextroamphetamineDouble-Blind MethodFemaleHallucinogensHealthy VolunteersHumansLysergic Acid DiethylamideMaleMiddle AgedN-Methyl-3,4-methylenedioxyamphetamineRetrospective StudiesTime Factors
Study Links
Quality Scores
Safety70
Efficacy85/10
Quality90/10
Citation Metrics
Total Citations146
Citations/Year29.2
Relative Citation Ratio12.86
NIH Percentile98.6%
Research Impact Scores
APT Score0.95
Weight Score3.01
Normalized Score0.80
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