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We combined live\u2010cell F\u00f6rster resonance energy transfer sensors for D\u2010glucose and L\u2010lactate, intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    imaging, glycogen assays, and whole\u2010cell patch\u2010clamp capacitance measurements to define how cannabinoid ligands shape astrocyte physiology in primary rat cultures. The CB1\u2010selective agonist ACEA triggered rapid, transient elevations in [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\u1d62 and metabolic readouts, whereas the CB2\u2010biased ligands AM1241 and Gp1a produced sustained metabolic effects, including prolonged increases in intracellular D\u2010glucose and L\u2010lactate. AM1241 additionally evoked glycogen depletion. Ligand applications also increased membrane capacitance, consistent with enhanced exocytotic activity and altered membrane dynamics. CB1 immunoreactivity predominated over a weak CB2\u2010like signal, and RT\u2010qPCR detected Cnr1 but not Cnr2 transcripts under our conditions. Accordingly, we interpret AM1241\/Gp1a actions as ligand\u2010evoked effects that are predominantly CB1\u2010linked (and\/or off\u2010target at the concentrations used). Together, these results show that cannabinoid ligands robustly remodel astrocytic energy metabolism and membrane behavior chiefly through CB1\u2010associated pathways, highlighting a functional axis between cannabinoid signaling, Ca\n                    <jats:sup>2+<\/jats:sup>\n                    mobilization, glycogen remodeling, and exocytosis in astrocytes.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70332-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  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