The CB1 Neutral Antagonist Tetrahydrocannabivarin Reduces Default Mode Network and Increases Executive Control Network Resting State Functional Connectivity in Healthy Volunteers.
Ewelina Rzepa, Luke Tudge, Ciara McCabe
The International Journal of Neuropsychopharmacology September 10, 2015 DOI: 10.1093/ijnp/pyv092 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, within-subject, double-blind, placebo-controlled study Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Healthy volunteers |
| Interventions | Tetrahydrocannabivarin (THCv) placebo |
| Dose | 10 mg oral |
| Topics | Default mode network |
| Keywords | Cannabinoids Default mode FMRI Obesity Resting state Reward |
| Key points | A single 10 mg oral dose of THCv in healthy volunteers reduced resting-state functional connectivity between the amygdala and the default mode network, while increasing connectivity between the amygdala and dorsal anterior cingulate cortex and between the dorsal medial prefrontal cortex and inferior frontal/medial frontal gyri. Subjective experience did not differ from placebo. The authors propose this connectivity profile suggests possible therapeutic activity for obesity. |
Abstract
The cannabinoid cannabinoid type 1 (CB1) neutral antagonist tetrahydrocannabivarin (THCv) has been suggested as a possible treatment for obesity, but without the depressogenic side-effects of inverse antagonists such as Rimonabant. However, how THCv might affect the resting state functional connectivity of the human brain is as yet unknown. We examined the effects of a single 10mg oral dose of THCv and placebo in 20 healthy volunteers in a randomized, within-subject, double-blind design. Using resting state functional magnetic resonance imaging and seed-based connectivity analyses, we selected the amygdala, insula, orbitofrontal cortex, and dorsal medial prefrontal cortex (dmPFC) as regions of interest. Mood and subjective experience were also measured before and after drug administration using self-report scales. Our results revealed, as expected, no significant differences in the subjective experience with a single dose of THCv. However, we found reduced resting state functional connectivity between the amygdala seed region and the default mode network and increased resting state functional connectivity between the amygdala seed region and the dorsal anterior cingulate cortex and between the dmPFC seed region and the inferior frontal gyrus/medial frontal gyrus. We also found a positive correlation under placebo for the amygdala-precuneus connectivity with the body mass index, although this correlation was not apparent under THCv. Our findings are the first to show that treatment with the CB1 neutral antagonist THCv decreases resting state functional connectivity in the default mode network and increases connectivity in the cognitive control network and dorsal visual stream network. This effect profile suggests possible therapeutic activity of THCv for obesity, where functional connectivity has been found to be altered in these regions.
Comparable studies
Other randomized controlled trials on default mode network, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Healthy volunteers | 2012 | Within-subjects, placebo-controlled, task-free fMRI study | n = 30 |
| The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers | 2014 | Placebo-controlled study | |
| Ketamine Decreases Resting State Functional Network Connectivity in Healthy Subjects: Implications for Antidepressant Drug Action Healthy subjects | 2012 | Randomized, placebo-controlled, double-blind, crossover rsfMRI challenge | |
| Antidepressants Normalize the Default Mode Network in Patients With Dysthymia Subjects with dysthymic disorder and healthy control participants aged 18 to 53 years | 2013 | Randomized controlled trial | n = 41 |
| Functional Connectivity Measures After Psilocybin Inform a Novel Hypothesis of Early Psychosis Healthy volunteers | 2012 | Within-subject, placebo-controlled experimental study | n = 15 |
Citations in the library
Cited by 9
- Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity Journal of Psychopharmacology April 23, 2019
- Individual and combined effects of cannabidiol and Δ 9 -tetrahydrocannabinol on striato-cortical connectivity in the human brain Journal of Psychopharmacology May 20, 2022
- Individual and combined effects of Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) on striato-cortical connectivity in the human brain bioRxiv (Cold Spring Harbor Laboratory) November 21, 2020
- Δ9-Tetrahydrocannabinol Alters Limbic and Frontal Functional Brain Connectomes Among Young Adult Cannabis Users. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging May 1, 2026
- Daily Cannabidiol Administration for 10 Weeks Modulates Hippocampal and Amygdalar Resting-State Functional Connectivity in Cannabis Users: A Functional Magnetic Resonance Imaging Open-Label Clinical Trial Cannabis and Cannabinoid Research July 26, 2023
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