Modulation of long-term potentiation following microdoses of LSD captured by thalamo-cortical modelling in a randomised, controlled trial.
Robin J Murphy, Kate Godfrey, Alexander D Shaw, Suresh Muthukumaraswamy, Rachael Sumner
BMC Neuroscience February 5, 2024 DOI: 10.1186/s12868-024-00844-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 80 |
| Population | Healthy adult males |
| Intervention | Lysergic acid diethylamide (LSD) |
| Dose | 10 µg |
| Duration | 6 weeks of microdosing every third day, with assessments at baseline, 2.5 hours after first dose, and after 6 weeks |
| Topics | LSD Neuroplasticity |
| Keywords | Dynamic causal modelling Long-term potentiation Psychedelics LSD Hallucinogens Neuroscience brain science Neural science Brain research Neuroplasticity brain plasticity |
| Citations | 16 |
| Key findings | Standard ERP analyses showed no evidence of changes in visually induced LTP from microdosed LSD, but dynamic causal modeling revealed differences in laminar connectivity in primary visual cortex between LSD and placebo groups. |
Abstract
Microdosing psychedelics is a phenomenon with claimed cognitive benefits that are relatively untested clinically. Pre-clinically, psychedelics have demonstrated enhancing effects on neuroplasticity, which cannot be measured directly in humans, but may be indexed by non-invasive electroencephalography (EEG) paradigms. This study used a visual long-term potentiation (LTP) EEG paradigm to test the effects of microdosed lysergic acid diethylamide (LSD) on neural plasticity, both acutely while on the drug and cumulatively after microdosing every third day for six weeks. Healthy adult males (n = 80) completed the visual LTP paradigm at baseline, 2.5 h following a dose of 10 µg of LSD or inactive placebo, and 6 weeks later after taking 14 repeated microdoses. Visually induced LTP was used as indirect index of neural plasticity. Surface level event-related potential (ERPs) based analyses are presented alongside dynamic causal modelling of the source localised data using a generative thalamocortical model (TCM) of visual cortex to elucidate underlying synaptic circuitry. Event-related potential (ERP) analyses of N1b and P2 components did not show evidence of changes in visually induced LTP by LSD either acutely or after 6 weeks of regular dosing. However modelling the complete timecourse of the ERP with the TCM demonstrated changes in laminar connectivity in primary visual cortex. This primarily included changes to self-gain and inhibitory input parameters acutely. Layer 2/3 to layer 5 excitatory connectivity was also different between LSD and placebo groups. After regular dosing only excitatory input from layer 2/3 into layer 5 and inhibitory input into layer 4 were different between groups. Without modulation of the ERPs it is difficult to relate the findings to other studies visually inducing LTP. It also indicates the classic peak analysis may not be sensitive enough to demonstrate evidence for changes in LTP plasticity in humans at such low doses. The TCM provides a more sensitive approach to assessing changes to plasticity as differences in plasticity mediated laminar connectivity were found between the LSD and placebo groups. ANZCTR registration number ACTRN12621000436875; Registered 16/04/2021 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381476 .
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 14
- Psychedelic-Induced Neural Plasticity: A Comprehensive Review and a Discussion of Clinical Implications. Brain Sciences January 25, 2025
- Psychedelics for the Treatment of Obsessive–Compulsive Disorder: Efficacy and Proposed Mechanisms The International Journal of Neuropsychopharmacology November 29, 2024
- Concurrent stress modulates the acute and post-acute effects of psilocybin in a sex-dependent manner Neuropharmacology December 24, 2024
- Is microdosing a placebo? A rapid review of low-dose LSD and psilocybin research Journal of Psychopharmacology June 14, 2024
- Effects of psychoplastogens on blood levels of brain-derived neurotrophic factor (BDNF) in humans: a systematic review and meta-analysis Molecular Psychiatry November 29, 2024
and 9 more in the library
Cites 26
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology 2023
- The neural basis of psychedelic action. Nature Neuroscience October 24, 2022
- Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics Frontiers in Psychiatry September 10, 2021
and 21 more in the library