Neural complexity is increased after low doses of LSD, but not moderate to high doses of oral THC or methamphetamine.
Conor H. Murray, Joel Frohlich, Connor J Haggarty, Ilaria Tare, Royce Lee, Harriet de Wit
Neuropsychopharmacology June 1, 2024 DOI: 10.1038/s41386-024-01809-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Within-subjects placebo-controlled study Peer reviewed |
|---|---|
| Sample size | 73 |
| Population | Healthy volunteers |
| Interventions | LSD delta-9-tetrahydrocannabinol methamphetamine |
| Dose | 13 and 26 µg (LSD), 7.5 and 15 mg (THC), 10 and 20 mg (MA) |
| Duration | Three laboratory visits; EEG recorded during anticipated peak drug effects |
| Topics | Philosophy of mind Cannabis LSD |
| Keywords | Pharmacology Psychedelics Brain research |
| Citations | 30 |
| Key points | Low doses of LSD, but not THC or methamphetamine, dose-dependently increased neural complexity in the absence of altered states of consciousness. |
Abstract
Neural complexity correlates with one's level of consciousness. During coma, anesthesia, and sleep, complexity is reduced. During altered states, including after lysergic acid diethylamide (LSD), complexity is increased. In the present analysis, we examined whether low doses of LSD (13 and 26 µg) were sufficient to increase neural complexity in the absence of altered states of consciousness. In addition, neural complexity was assessed after doses of two other drugs that significantly altered consciousness and mood: delta-9-tetrahydrocannabinol (THC; 7.5 and 15 mg) and methamphetamine (MA; 10 and 20 mg). In three separate studies (N = 73; 21, LSD; 23, THC; 29, MA), healthy volunteers received placebo or drug in a within-subjects design over three laboratory visits. During anticipated peak drug effects, resting state electroencephalography (EEG) recorded Limpel-Ziv complexity and spectral power. LSD, but not THC or MA, dose-dependently increased neural complexity. LSD also reduced delta and theta power. THC reduced, and MA increased, alpha power, primarily in frontal regions. Neural complexity was not associated with any subjective drug effect; however, LSD-induced reductions in delta and theta were associated with elation, and THC-induced reductions in alpha were associated with altered states. These data inform relationships between neural complexity, spectral power, and subjective states, demonstrating that increased neural complexity is not necessary or sufficient for altered states of consciousness. Future studies should address whether greater complexity after low doses of LSD is related to cognitive, behavioral, or therapeutic outcomes, and further examine the role of alpha desynchronization in mediating altered states of consciousness.
Comparable studies
Other randomized controlled trials on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Healthy participants | 2012 | Randomized controlled trial | n = 48 |
| Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Healthy, English-native, right-handed men who had used cannabis 15 times or less in... | 2009 | Double-blind, randomized, placebo-controlled crossover trial | n = 15 |
| Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Healthy male subjects | 2012 | Randomized controlled trial | n = 16 |
| Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Healthy, native English-speaking, right-handed men of white race/ethnicity who had used... | 2009 | Randomized controlled trial | n = 15 |
| Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition Healthy volunteers with a history of light cannabis use | 2019 | Randomized, double-blind, within-subjects crossover | n = 14 |
Citations in the library
Cited by 24
- Addressing blinding in classic psychedelic studies with innovative active placebos. The International Journal of Neuropsychopharmacology April 1, 2025
- Human brain changes after first psilocybin use. Nature Communications May 5, 2026
- Is microdosing a placebo? A rapid review of low-dose LSD and psilocybin research Journal of Psychopharmacology June 14, 2024
- LSD flattens the hierarchy of directed information flow in fast whole-brain dynamics. Imaging Neuroscience January 3, 2025
- An investigation of acute physiological and psychological moderators of psychedelic-induced personality change among healthy volunteers Neuroscience Applied December 2, 2024
and 19 more in the library
Cites 59
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans Pharmacopsychiatry July 1, 1998
and 54 more in the library