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In the case of nicotine, preclinical studies showed evidence that the rewarding effects of nicotine are reduced by stimulation of GLP-1 receptors in the medial habenula, which is a brain region that mediates nicotines aversive effects [48]
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This review has deliberately distinguished failed biology from failed pharmacology, emphasizing that genuine on-target toxicity, repeated lack of efficacy in well-designed human studies, or insurmountable technical barriers justify abandonment
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