Brain Mapping-Based Model of Δ9-Tetrahydrocannabinol Effects on Connectivity in the Pain Matrix

Abstract

Cannabinoids receive increasing interest as analgesic treatments. However, the clinical use of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) has progressed with justified caution, which also owes to the incomplete mechanistic understanding of its analgesic effects, in particular its interference with the processing of sensory or affective components of pain. The present placebo-controlled crossover study therefore focused on the effects of 20 mg oral THC on the connectivity between brain areas of the pain matrix following experimental stimulation of trigeminal nocisensors in 15 non-addicted healthy volunteers. A general linear model (GLM) analysis identified reduced activations in the hippocampus and the anterior insula following THC administration. However, assessment of psychophysiological interaction (PPI) revealed that the effects of THC first consisted in a weakening of the interaction between the thalamus and the secondary somatosensory cortex (S2). From there, dynamic causal modeling (DCM) was employed to infer that THC attenuated the connections to the hippocampus and to the anterior insula, suggesting that the reduced activations in these regions are secondary to a reduction of the connectivity from somatosensory regions by THC. These findings may have consequences for the way THC effects are currently interpreted: as cannabinoids are increasingly considered in pain treatment, present results provide relevant information about how THC interferes with the affective component of pain. Specifically, the present experiment suggests that THC does not selectively affect limbic regions, but rather interferes with sensory processing which in turn reduces sensory-limbic connectivity, leading to deactivation of affective regions.

The Reorganization of Insular Subregions in Individuals with Below-Level Neuropathic Pain following Incomplete Spinal Cord Injury

“…The convergence of multimodal afferent to AI contributes to emotional awareness and the building of multifaceted but unified subjective perception [69]. Further, some researchers found the reduced activations in the hippocampus and the AI following analgesic administration [70], which have an effect on affective component of pain. Our current findings showed the increased FC in left hippocampus gyrus and left d-AI, which may have a positive effect on pain perception.…”

Association of Cannabinoid Administration With Experimental Pain in Healthy Adults

“…46,61,62,64 Four studies (22%) administered synthetic Δ 9 -THC capsules that were not specified by name. 23,56,59,67 One study (6%) administered a cannabis extract that was standardized at 20 mg of Δ 9 -THC but contained cannabidiol (CBD) in the ratio of 2:1. 58 Two studies (11%) administered nabilone, a potent synthetic analogue of THC.…”

A data science approach to the selection of most informative readouts of the human intradermal capsaicin pain model to assess pregabalin effects

“…47 Such side effects are routinely met with opioids or cannabinoids. 48,49 Several additions to the study design have been proposed to control for placebo effects, including the use of surrogate markers of pain such as nociceptive event-related cortical potentials 50 or the inclusion of non-nociceptive stimuli such as acoustic eventrelated cortical potentials. 51 Due to the complex design of the present study with pregabalin treatment and placebo sessions plus training and a dense data acquisition, additional recording of non-nociceptive bioresponses had been dismissed.…”