Tetrahydrocannabivarin (THCv) reduces Default Mode Network and increases Executive Control Network Resting State Functional Connectivity in Healthy Volunteers.

BACKGROUND:

The cannabinoid CB1 Neutral Antagonist Tetrahydrocannabivarin (THCv) has been suggested as a possible treatment for obesity but without the depressogenic side-effects of inverse antagonists such as Rimonabant. However, how THCv might affect the resting-state functional connectivity of the human brain is as yet unknown.

METHOD:

We examined in 20 healthy volunteers the effects of a single 10mg oral dose of THCv and placebo in a randomized, within-subject, double-blind design. Using resting-state functional magnetic resonance imaging and seed based connectivity analysis we selected amygdala, insula, OFC and dmPFC regions of interest. Mood and subjective experience were also measured before and after drug administration using self-report scales.

RESULTS:

Our results revealed, as expected, no significant differences in subjective experience with a single dose of THCv. However we found reduced resting-state functional connectivity between the amygdala seed region and the DMN and increased resting-state functional connectivity between the amygdala seed region and the dACC and between the dmPFC seed region and the IFG/MFG. We also found a positive correlation under placebo for amygdala-precuneus connectivity with BMI this correlation was not apparent under THCv.

CONCLUSION:

Our findings are the first to show that treatment with the CB1 neutral antagonist THCv decreases resting state functional connectivity in the Default Mode network and increases connectivity in the Cognitive Control network and Dorsal Visual Stream network. This effect profile suggests possible therapeutic activity of THCv for obesity where functional connectivity has been found to be altered in these regions.
© The Author 2015. Published by Oxford University Press on behalf of CINP.