Subconscious threat processing and cannabidiol: A randomized controlled trial

Poster No:

669 

Submission Type:

Abstract Submission 

Authors:

Jennifer Robinson1, Ryan Bird1, Ava White1

Institutions:

1Auburn University, Auburn, AL

First Author:

Jennifer Robinson, Ph.D.  
Auburn University
Auburn, AL

Co-Author(s):

Ryan Bird, Ph.D.  
Auburn University
Auburn, AL
Ava White  
Auburn University
Auburn, AL

Introduction:

There is strong evidence in support of a network of brain regions responsive to socially salient threat signals in the form of fearful facial expressions, even when such signals are presented subconsciously. Independent of the exploration of the neural substrate of nonconscious threat processing, research into the psychopharmacology of cannabis has revealed that the major, non-psychoactive cannabinoid found in cannabis – cannabidiol (CBD) – attenuates the normal neural response to consciously presented fearful faces. However, no study to date has examined the effect of CBD on the neural processing of fearful faces presented below the level of conscious awareness.

Methods:

We examined the effect of a single, orally administered dose of CBD on the neural response to fearful faces presented below the normal threshold for conscious awareness in the context of a double-blind, placebo controlled, randomized crossover trial in a sample of healthy participants (14 participants (M = 26.14 years, SD = 6.15).
Participants experienced CBD at one timepoint and placebo at the other timepoint. Participants were brought back for the second scanning period after a washout period of at least 72 hours. Each scan session had a pre- and post-administration scan. After the pre- scan, participants were administered the material in a tincture via dropper underneath the tongue which they were asked to hold for 60 seconds before swallowing. After consumption, they were asked to relax in the waiting room for an hour to allow the drug to take effect, after which they were scanned again.
The experimental protocol utilized a backwards masking procedure which has been shown to prevent the masked stimulus from being consciously perceived while still provoking a threat response in the amygdala (Liddell et al., 2005) programmed in Millisecond software.
Data were acquired on a 7T Siemens MAGNETOM scanner with a 32-channel head coil. Anatomical scans were acquired for registration purposes, and functional data used an optimized EPI sequence. Preprocessing of data was carried out using fMRIprep following standard procedures. First-level analyses were conducted using FSL FMRI Expert Analysis Tool (Jenkinson et al., 2012). Contrasts of interest were specified for each subject (e.g., fear, neutral, fear>neutral). ROI analyses were then conducted using FSL utilities with predefined, binarized ROI masks (left amygdala, right superior temporal sulcus (rSTS), left anterior cingulate cortex (lACC)). Extracted data were analyzed using a repeated measures ANOVA.

Results:

For the left amygdala, there was a significant difference main effect between treatments, F(1,12) = 6.252, p = .028, but no main effect of condition, and no interaction. Pairwise comparisons revealed that the mean activation was significantly higher in the placebo group than the CBD group. CBD appeared to attenuate the activation in the amygdala during the fear condition relative to placebo. For the lACC, there were no significant effects of treatment, condition, or an interaction. The rSTS demonstrated a significant simple main effect of condition, F(1,12) = 4.889, p = .047, but no significant main effect of treatment, nor a significant interaction.

Conclusions:

We found support for the elicitation of a fear/threat response in emotional and face processing regions of the brain which can be produced even in the absence of conscious awareness of the fear stimuli. Additionally, our data support the notion that CBD can attenuate the activation of the amygdala, in alignment with previous studies (Bhattacharyya et al., 2010; Fusar-Poli et al., 2009). Our research also adds to the growing body of literature suggesting potentially significant therapeutic value of CBD in the treatment of the disorders of anxiety and fear, such as generalized anxiety disorder and PTSD.

Emotion, Motivation and Social Neuroscience:

Emotional Perception
Social Neuroscience Other 1

Perception, Attention and Motor Behavior:

Perception: Visual
Perception and Attention Other 2

Keywords:

Emotions
FUNCTIONAL MRI
HIGH FIELD MR
Limbic Systems
Perception
Sub-Cortical
Vision
Other - attention

1|2Indicates the priority used for review

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Please indicate below if your study was a "resting state" or "task-activation” study.

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Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Healthy subjects

Was this research conducted in the United States?

Yes

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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

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Functional MRI

For human MRI, what field strength scanner do you use?

7T

Which processing packages did you use for your study?

FSL

Provide references using APA citation style.

Bhattacharyya, S., Morrison, P. D., Fusar-Poli, P., Martin-Santos, R., Borgwardt, S., Winton-Brown, T., Nosarti, C., O' Carroll, C. M., Seal, M., Allen, P., Mehta, M. A., Stone, J. M., Tunstall, N., Giampietro, V., Kapur, S., Murray, R. M., Zuardi, A. W., Crippa, J. A., Atakan, Z., & McGuire, P. K. (2010). Opposite Effects of Δ-9-Tetrahydrocannabinol and Cannabidiol on Human Brain Function and Psychopathology. Neuropsychopharmacology, 35(3), 764-774. https://doi.org/10.1038/npp.2009.184
Fusar-Poli, P., Crippa, J. A., Bhattacharyya, S., Borgwardt, S. J., Allen, P., Martin-Santos, R., Seal, M., Surguladze, S. A., O’Carrol, C., Atakan, Z., Zuardi, A. W., & McGuire, P. K. (2009). Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing. Archives of General Psychiatry, 66(1), 95-105. https://doi.org/10.1001/archgenpsychiatry.2008.519
Jenkinson, M., Beckmann, C. F., Behrens, T. E. J., Woolrich, M. W., & Smith, S. M. (2012). FSL. NeuroImage, 62(2), 782-790. https://doi.org/http://dx.doi.org/10.1016/j.neuroimage.2011.09.015
Liddell, B. J., Brown, K. J., Kemp, A. H., Barton, M. J., Das, P., Peduto, A., Gordon, E., & Williams, L. M. (2005). A direct brainstem–amygdala–cortical ‘alarm’ system for subliminal signals of fear. NeuroImage, 24(1), 235-243. https://doi.org/https://doi.org/10.1016/j.neuroimage.2004.08.016

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