Neurocognitive moderation of repetitive transcranial magnetic stimulation (rTMS) effects on cannabis use in schizophrenia: a preliminary analysis

Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for cannabis use disorder in schizophrenia; however, gaps in the literature remain as to the potential role of neurocognitive functioning in treatment response. We evaluated the moderating role of select cognitive functions including baseline executive functioning, verbal memory, and sustained attention, and we explore the mediating role of changes in task performance on changes in cannabis use in both active and sham rTMS groups. Participants underwent high-frequency (20 Hz) rTMS applied to the bilateral dorsolateral prefrontal cortex 5x/week for 4 weeks. Weekly self-report of cannabis use and semi-quantitative urinary carboxy-tetrahydrocannabinol levels were recorded. A neurocognitive battery assessing verbal memory, visuospatial working memory, verbal working memory, sustained attention, delayed discounting, and complex planning was administered pre- and post-treatment. Better baseline performance on tasks assessing sustained attention, delayed discounting, and complex planning moderated the extent to which participants in the active group reduced cannabis use. There were no significant indirect pathways between treatment, changes in neuropsychological performance, and changes in cannabis use; however, active rTMS improved complex planning and sustained attention. These preliminary findings suggest that there is a moderating role of sustained attention, delayed discounting, and complex planning on the effects of rTMS on cannabis use. Further, mediation models suggest rTMS may exert direct effects on cannabis use independent of its effects on cognitive functioning in people with SCZ. Trial Registration: clinicaltrials.gov: NCT03189810.