Effects of acute Δ9-tetrahydrocannabinol on next-day extinction recall is mediated by post-extinction resting-state brain dynamics.
Christine A Rabinak, Craig A Peters, Hilary A Marusak, Samiran Ghosh, K Luan Phan
Neuropharmacology December 2018 DOI: 10.1016/j.neuropharm.2018.10.002 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, placebo-controlled, between-subjects study Peer reviewed |
|---|---|
| Sample size | 77 |
| Population | Healthy adults |
| Dose | 7.5 mg |
| Topics | Cannabis |
| Keywords | Amygdala Cannabinoid Extinction Hippocampus Resting-state functional connectivity Ventromedial prefrontal cortex |
| Key points | Compared with placebo, THC was associated with lower static amygdala-hippocampus resting-state connectivity and higher dynamic amygdala-vmPFC connectivity after extinction learning. Lower amygdala-hippocampus static connectivity was associated with greater hippocampal activation and better extinction recall, and it mediated the link between THC administration and extinction recall. |
Abstract
We have previously demonstrated that an acute dose of Δ9-tetrahydrocanninbinol (THC), administered prior to extinction learning, facilitates later recall of extinction learning and modulates the underlying neural circuitry, including the ventromedial prefrontal cortex (vmPFC), hippocampus (HPC), and amygdala (AMYG). It remains unknown whether THC-induced changes in fear-extinction neural circuitry can be detected following extinction learning, which may reflect ongoing processes involved consolidation of the extinction memory. To address this gap, we used a randomized, double-blind, placebo-controlled, between-subjects design to compare acute pharmacological effects of THC (7.5 mg) vs. placebo (PBO) on post-extinction resting-state functional connectivity (RS-FC) within fear-extinction circuitry in 77 healthy adults (THC = 40; PBO = 37). RS-FC was examined between vmPFC, HPC, and AMYG using two complementary approaches: 1) static RS-FC (average correlation in ROI-ROI pairs across the entire scan); and 2) dynamic (i.e., time-varying) RS-FC (sliding window correlation time series' variance). RS-FC was then linked to behavioral and brain measures of extinction recall. Compared to PBO, THC administration was associated with lower AMYG-HPC static RS-FC, but higher AMYG-vmPFC dynamic RS-FC. Lower AMYG-HPC static RS-FC was associated with higher HPC activation, as well as, better extinction recall. Moreover, lower AMYG-HPC static RS-FC following extinction learning mediated the link between THC administration and extinction recall. Post-extinction RS-FC patterns may reflect sustained effects of THC on fear-extinction circuitry even in the absence of an overt task, and/or effects of ongoing processes that serve to strengthen the neural connections supporting the consolidation of the memory and better extinction recall.
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 8
- Randomized trial of delta-9-tetrahydrocannabinol (THC) versus placebo to augment the effects of prolonged exposure therapy on fear extinction learning in post-traumatic stress disorder: Study rationale and protocol. Contemporary Clinical Trials 2026
- Resting State Brain Networks under Inverse Agonist versus Complete Knockout of the Cannabinoid Receptor 1. ACS Chemical Neuroscience April 17, 2024
- Is resting-state functional connectivity altered in regular cannabis users? A systematic review of the literature. Psychopharmacology May 2022
- Targeting the Endocannabinoid System in the Treatment of Posttraumatic Stress Disorder: A Promising Case of Preclinical-Clinical Translation? Biological Psychiatry July 1, 2021
- A systematic review of neuroimaging and acute cannabis exposure in age-of-risk for psychosis Translational Psychiatry April 13, 2021
and 3 more in the library
Cites 4
- Cannabinoid Modulation of Frontolimbic Activation and Connectivity During Volitional Regulation of Negative Affect. Neuropsychopharmacology June 2016
- Signature of consciousness in the dynamics of resting-state brain activity. Proceedings of the National Academy of Sciences of the United States of America January 5, 2015
- Cannabinoid modulation of prefrontal-limbic activation during fear extinction learning and recall in humans. Neurobiology of Learning and Memory September 2014
- Cannabinoid Modulation of Amygdala Reactivity to Social Signals of Threat in Humans Journal of Neuroscience March 5, 2008