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Postmortem studies show elevated GSK3 activity in individuals with MDD and bipolar disorder, and animal models demonstrate that GSK3 inhibition in the nucleus accumbens produces antidepressant effects (150, 151)

73 In a trial comparing lofexidine with diazepam, no differences were seen in OOWS or SOWS on days 3 and 4 (peak withdrawal)

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It also functions as a stabilizer of a low acetyl CoA/CoA concentration ratio and as an acetyl store to supply energy in carbohydrate and lipid metabolic pathways [34] (Fig