The effect of cannabidiol (CBD) on low-frequency activity and functional connectivity in the brain of adults with and without autism spectrum disorder (ASD)

Abstract

Background: The potential benefits of cannabis and its major non-intoxicating component cannabidiol (CBD) are attracting attention, including as a potential treatment in neurodevelopmental disorders such as autism spectrum disorder (ASD). However, the neural action of CBD, and its relevance to ASD, remains unclear. We and others have previously shown that response to drug challenge can be measured using functional magnetic resonance imaging (fMRI), but that pharmacological responsivity is atypical in ASD.

Aims: We hypothesized that there would be a (different) fMRI response to CBD in ASD.

Methods: To test this, task-free fMRI was acquired in 34 healthy men (half with ASD) following oral administration of 600 mg CBD or matched placebo (random order; double-blind administration). The 'fractional amplitude of low-frequency fluctuations' (fALFF) was measured across the whole brain, and, where CBD significantly altered fALFF, we tested if functional connectivity (FC) of those regions was also affected by CBD.

Results: CBD significantly increased fALFF in the cerebellar vermis and the right fusiform gyrus. However, post-hoc within-group analyses revealed that this effect was primarily driven by the ASD group, with no significant change in controls. Within the ASD group only, CBD also significantly altered vermal FC with several of its subcortical (striatal) and cortical targets, but did not affect fusiform FC with other regions in either group.

Conclusion: Our results suggest that, especially in ASD, CBD alters regional fALFF and FC in/between regions consistently implicated in ASD. Future studies should examine if this affects the complex behaviours these regions modulate.

Keywords: Cannabidiol; Cannabis sativa; autism spectrum disorder; functional connectivity; low-frequency fluctuations.

Conflict of interest statement

Declaration of conflicting interest: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.

Drug effects on the fractional amplitude of low-frequency fluctuations across the grey matter (cannabidiol > placebo). Numbers above the slices indicate location in z-direction (in millimetres). Scans are oriented in neurological convention, where right (R) equals right, and left (L) equals left. P values (P), as indicated by the colour bar, are corrected for multiple comparisons (TFCE, FWE).

Figure 2.

Post-hoc test of drug effects on the fractional amplitude of low-frequency fluctuations within each region of interest (cannabidiol > placebo) in autism spectrum disorder. (A) Drug effects within the cerebellar vermis IV; (B) drug effects within the right fusiform gyrus. Numbers above the slices indicate location inz-direction (in millimetres). Scans are oriented in neurological convention, where right (R) equals right, and left (L) equals left. P values (P), as indicated by the colour bar, are corrected for multiple comparisons (TFCE, FWE).

Figure 3.

Drug effects on functional connectivity of cerebellar vermis VI in the ASD group (cannabidiol > placebo).T-values (T) of edges, as indicated by colour bar, are corrected for multiple comparisons at connection- and seed-level (p = 0.05 and pFDR = 0.05, respectively). Abbreviations – ASD: autism spectrum disorder; CBD: cannabidiol; L.Caud: left caudate; L.SFG: left superior frontal gyrus; L.SPL: left superior parietal lobe; L.toMTG: left middle temporal gyrus (temporo-occipital part); R.aSMG: right anterior supramarginal gyrus; R.Caud: right caudate; R.SPL: right superior parietal lobe; PLC: placebo; Verm6: cerebellar vermis VI.