The impact of a focused behavioral intervention on brain cannabinoid signaling and interoceptive function: Implications for mood and anxiety

The Wim Hof method (WHM) is a behavioral intervention technique that consists of deep breathing exercises, cold exposure and meditation. In light of the crucial role of the cannabinoid system in modulating neurotransmitter release through a negative feedback mechanism that aims at the maintenance of network homeostasis, our study investigated changes in cannabinoid type 1 (CB1) receptor binding following a longitudinal (6 weeks) WHM intervention in 4 male controls using the F18]FMPEP-d2 PET tracer, an inverse CB1 receptor agonist. Results revealed a global increase in CB1 receptor binding of ∼20%, with largest increases found in brain regions associated with the interoceptive network such as the anterior cingulate, the orbitofrontal cortex OFC), the anterior insular cortex (AIC) and the brainstem. Furthermore, in the same participants a whole-body cold-stress paradigm was used to systematically evoke sympathetic and parasympathetic responses. Post-intervention, participants showed increased engagement of regions like the anterior insula and the orbitofrontal cortex that have been respectively classified as belonging to the brain’s interoceptive (AIC) and executive (OFC) sub-networks. Our results suggest that a relatively short 6-week WHM intervention positively impacts brain markers that have been associated with stress resistance, mood, anxiety and interoceptive function.