Electronic Vaporization of Nicotine Salt or Freebase produces differential effects on metabolism, neuronal activity and behavior in male and female C57BL/6J mice.

Intermittent theta burst stimulation (iTBS) applied to the midline cerebellum has effects on mood and cognition in patients with neuropsychiatric disease. In bipolar disorder, depressive and cognitive symptoms are often inadequately treated with current therapeutic options. This randomized, double-blind, sham-controlled clinical trial evaluated the safety, tolerability, and efficacy of applying 10 sessions of iTBS, delivered twice daily, targeting cerebellar vermis (CBM-iTBS) in subjects with bipolar disorder. Primary outcome measures were change in depression using the Montgomery-Åsberg Depression Rating Scale and change in cognition using the NIH Toolbox Cognitive Battery from baseline to post-treatment (primary endpoint), and 1-, 3-, and 8-week follow-ups. Significant improvements in depression in sham (n = 18, mean age 37.8, 83 % female) and active (n = 12, mean age 41.9, 83 % female) treatment arms were observed post-treatment (active and sham, p = 0.02 and 0.001, respectively). Additionally, 1-week (sham), 3-week (sham), and 8-week (active) follow-ups all showed significant depression improvement (all p < 0.05), with no statistical separation between groups in the depressed cohort. Importantly, CBM-iTBS was well-tolerated, with the only affective switching to mania or mixed state occurring during follow-up in one active and one sham participant. The active group outperformed sham on measures of life satisfaction, meaning, self-efficacy, and reduced anger at varied time-points, with broad mood improvements in both groups. Cognitive performance improved in both treatment arms, with greater cognitive improvements in picture sequence memory testing and reaction time for the active group. In conclusion, CBM-iTBS is safe, feasible, and tolerable in individuals with bipolar disorder. Significant improvements with both active and sham iTBS on mood and cognitive measures suggest prominent placebo and learning effects. Future CBM-iTBS trials should consider modifications to treatment dose, coil design, and cerebellar target region.