Study register · detailRCT · Anxiety Disorders · 2009
Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing
Fusar-Poli et al.·Archives of General Psychiatry
MixedGRADEModerate459 citations
Samplen = 15 Pat.
Duration3 separate scanning sessions
ControlPlacebo
EndpointBOLD signal
Blindingdoppelblind
DesignRCT
Max. dose600.0 mg
Routeoral
”Key finding
Delta9-THC increased anxiety and intoxication, while CBD showed a trend toward anxiety reduction with differing effects on brain activation and autonomic responses.
Summary
n=15 healthy subjects, fMRI during emotional face recognition; THC increases amygdala activation in response to fear stimuli, CBD reduces it — differential neural effects on fear networks.
P
PopulationHealthy English-speaking men with minimal cannabis use (≤15× lifetime), n=15
I
InterventionOral 10 mg Δ⁹-THC vs. 600 mg CBD, each before fMRI paradigm with emotionally fear-inducing faces
C
ControlPlacebo (double-blind, randomised, crossover design over 3 sessions)
O
OutcomeΔ⁹-THC increased anxiety and psychotic symptoms; CBD reduced BOLD signal in amygdala/ACC in response to fear faces and correlated with reduced autonomic arousal (SCR fluctuations)
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
Context: Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown.
Objective: To investigate the effects of 2 main psychoactive constituents of Cannabis sativa (Delta9-tetrahydrocannabinol [Delta9-THC] and cannabidiol [CBD]) on regional brain function during emotional processing.
Design: Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10 mg of Delta9-THC, 600 mg of CBD, or a placebo in a double-blind, randomized, placebo-controlled design.
Participants: Fifteen healthy, English-native, right-handed men who had used cannabis 15 times or less in their life.
Main Outcome Measures: Regional brain activation (blood oxygenation level-dependent response), electrodermal activity (skin conductance response [SCR]), and objective and subjective ratings of anxiety.
Results: Delta9-Tetrahydrocannabinol increased anxiety, as well as levels of intoxication, sedation, and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD. The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of Delta9-THC but decreased following administration of CBD. Cannabidiol attenuated the blood oxygenation level-dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations. Delta9-Tetrahydrocannabinol mainly modulated activation in frontal and parietal areas.
Conclusions: Delta9-Tetrahydrocannabinol and CBD had clearly distinct effects on the neural, electrodermal, and symptomatic response to fearful faces. The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of Delta9-THC may be related to effects in other brain regions.