THC strongly disrupts connectivity between the striatum and cortex, but co-administering CBD mitigates this effect in the limbic striatum network. In one study, inhaled cannabis with 8 mg THC or 8 mg THC plus 10 mg CBD disrupted associative and sensorimotor networks, while THC alone also disrupted the limbic striatum network. In a second study, oral 600 mg CBD increased connectivity in the associative network and caused minor disruptions in limbic and sensorimotor networks. The insula emerges as a key region affected by cannabinoid-induced changes in functional connectivity, with implications for understanding cannabis-related disorders and developing cannabinoid therapeutics.
Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are two major cannabis constituents with contrasting actions: THC is psychoactive and addiction-promoting, while CBD may have opposite effects. In two placebo-controlled, double-blind studies, inhaled THC (8 mg) strongly disrupted functional connectivity in associative and sensorimotor striatal networks, and this disruption was selectively alleviated in the limbic striatum when co-administered with CBD (10 mg). Oral CBD (600 mg) alone increased connectivity in the associative network but caused minor decreases in limbic and sensorimotor networks. The insula emerged as a key region affected by cannabinoid-induced connectivity changes, with implications for cannabis-related disorders and cannabinoid therapeutics.
In a six-week phase 3 trial, the combination drug dextromethorphan-bupropion (AXS-05) reduced depressive symptoms more than placebo in adults with major depressive disorder. Those taking the drug showed an average 15.9-point drop on the Montgomery-Asberg Depression Rating Scale versus a 12.0-point drop with placebo, a statistically significant difference. Benefits appeared as early as one week. At six weeks, 39.5% of the drug group achieved remission compared to 17.3% of the placebo group, and 54.0% had a clinical response versus 34.0%. Common side effects included dizziness, nausea, and headache. The drug was not linked to weight gain or sexual dysfunction.
In a randomized trial, the combination drug dextromethorphan-bupropion (AXS-05) improved depressive symptoms more than bupropion alone in adults with moderate-to-severe major depressive disorder. Over six weeks, the average reduction in depression scores was 13.7 points with the combination versus 8.8 points with bupropion. By week six, 46.5% of those taking the combination achieved remission, compared to 16.2% taking bupropion. The combination was generally well tolerated, with common side effects including dizziness, nausea, and dry mouth, and was not linked to weight gain or sexual dysfunction.