Modulation of effective connectivity during emotional processing by Δ9-tetrahydrocannabinol and cannabidiol
Paolo Fusar‐poli, Paul Allen, Sagnik Bhattacharyya, José Alexandre S. Crippa, Andrea Mechelli, Stefan Borgwardt, Rocío Martín‐Santos, Marc L. Seal, Colin O’Carrol, Zerrin Atakan, Antônio Waldo Zuardi, Philip Mcguire
The International Journal of Neuropsychopharmacology September 24, 2009 DOI: 10.1017/s1461145709990617 via OpenAlex
Summary
Cannabidiol (CBD), but not delta-9-tetrahydrocannabinol (THC), disrupts forward connectivity between the amygdala and the anterior cingulate cortex during the neural response to fearful faces. This disruption may represent a neurophysiological correlate of CBD's anxiolytic properties. The study used dynamic causal modelling and Bayesian model selection to analyze effective connectivity in 15 healthy subjects under a double-blind, randomized, placebo-controlled fMRI paradigm while they viewed faces eliciting different levels of anxiety.
Study at a glance
| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 15 |
| Population | Healthy subjects |
| Interventions | Cannabidiol Delta 9-tetrahydrocannabinol |
| Dose | 600 mg of cannabidiol (CBD) and 10 mg Delta 9-tetrahydrocannabinol (Delta 9-THC) |
| Topics | Anxiety Cannabis |
| Keywords | Ventromedial prefrontal cortex Amygdala Psychology Neuroscience |
| Citations | 165 |
| Key finding | CBD, but not THC, disrupted forward connectivity between the amygdala and anterior cingulate cortex during the neural response to fearful faces. |
Abstract
Cannabis sativa, the most widely used illicit drug, has profound effects on levels of anxiety in animals and humans. Although recent studies have helped provide a better understanding of the neurofunctional correlates of these effects, indicating the involvement of the amygdala and cingulate cortex, their reciprocal influence is still mostly unknown. In this study dynamic causal modelling (DCM) and Bayesian model selection (BMS) were used to explore the effects of pure compounds of C. sativa [600 mg of cannabidiol (CBD) and 10 mg Delta 9-tetrahydrocannabinol (Delta 9-THC)] on prefrontal-subcortical effective connectivity in 15 healthy subjects who underwent a double-blind randomized, placebo-controlled fMRI paradigm while viewing faces which elicited different levels of anxiety. In the placebo condition, BMS identified a model with driving inputs entering via the anterior cingulate and forward intrinsic connectivity between the amygdala and the anterior cingulate as the best fit. CBD but not Delta 9-THC disrupted forward connectivity between these regions during the neural response to fearful faces. This is the first study to show that the disruption of prefrontal-subocritical connectivity by CBD may represent neurophysiological correlates of its anxiolytic properties.