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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| 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 CBD |
| Keywords | Ventromedial prefrontal cortex Amygdala Anterior cingulate cortex Anxiolytic Cognition Cannabinoid |
| Citations | 165 |
| Key findings | 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.
In the evidence
This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.
-
CBD, but not THC, disrupted amygdala-to-anterior-cingulate forward connectivity during fearful-face processing, proposed as a correlate of its anxiolytic properties.
Synthesized
-
State of the evidence: CBD Supports
CBD, but not THC, disrupted forward connectivity between the amygdala and anterior cingulate during processing of fearful faces, proposed as a correlate of its anxiolytic properties.
Synthesized
Comparable studies
Other randomized controlled trials on cannabis for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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 |
| 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 |
| Cannabis containing equivalent concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) induces less state anxiety than THC-dominant cannabis Healthy recreational cannabis users | 2022 | Randomized controlled trial, within-subjects | n = 26 |
| Psychedelic symptoms of cannabis and cocaine use as a function of trait impulsivity Regular drug users | 2015 | Three-way crossover study | n = 122 |
| Effects of Cannabinoids on Emotional States and Alcohol Use Among Underrepresented Groups: Moderation by Perceived Discrimination. Participants who identify with a racial, ethnic, gender, or sexual identity that is... | 2025 | Randomized controlled trial | n = 172 |
Citations in the library
Cited by 30
- Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD): Toward a New Age Frontiers in Immunology September 21, 2018
- Inverted U-Shaped Dose-Response Curve of the Anxiolytic Effect of Cannabidiol during Public Speaking in Real Life Frontiers in Pharmacology May 11, 2017
- The neuropsychopharmacology of cannabis: A review of human imaging studies Pharmacology & Therapeutics October 20, 2018
- Plastic and Neuroprotective Mechanisms Involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders Frontiers in Pharmacology May 23, 2017
- Endocannabinoid system and psychiatry: in search of a neurobiological basis for detrimental and potential therapeutic effects Frontiers in Behavioral Neuroscience 2011
and 25 more in the library
Cites 5
- Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Archives of General Psychiatry 2009
- The acute effects of synthetic intravenous Delta9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychological Medicine October 2009
- The endocannabinoid system: emotion, learning and addiction. Addiction Biology June 2008
- Disturbances of visual information processing in early states of psychosis and experimental delta-9-tetrahydrocannabinol altered states of consciousness. Schizophrenia Research December 1, 2006
- Effects of synthetic delta9-tetrahydrocannabinol on binocular depth inversion of natural and artificial objects in man. Psychopharmacology March 1999