Use of cannabis and cannabinoid-containing substances is increasing among geriatric patients, despite relatively sparse preclinical evidence in aged models. To better understand the effects of exogenous cannabinoids on aging male and female rodents, we compared the age- and dose-dependent physiological and behavioral effects of the synthetic cannabinoid CP55940 in young–adult and aged C57BL/6 mice. Locomotion, body temperature, thermal nociception, and fecal output were measured following CP55940 administration. Our findings indicate that CP55940 is more potent and efficacious in older mice, evidenced by exaggerated antinociception and locomotor inhibition when compared to younger adult mice. In addition, we report that low doses of CP55940 paradoxically stimulate locomotion in young–adult (4 m) mice; however, this hormesis-like response is not as evident in aged animals (21–24 m). These bidirectional effects appear to be mediated via the endocannabinoid CB1 and CB2 receptors.

尽管老年模型中的临床前证据相对较少，但老年患者对大麻和含大麻素物质的使用正在增加。为了更好地了解外源性大麻素对衰老雄性和雌性啮齿动物的影响，我们比较了合成大麻素 CP55940 对年轻成年和老年 C57BL/6 小鼠的年龄和剂量依赖性生理和行为影响。施用 CP55940 后测量运动、体温、热伤害感受和粪便排出量。我们的研究结果表明，与年轻的成年小鼠相比，CP55940 对老年小鼠的镇痛作用和运动抑制作用更强，这证明了这一点。此外，我们报告说，低剂量的 CP55940 反而会刺激年轻成年 (4 m) 小鼠的运动；然而，这种类似毒物兴奋效应的反应在老年动物（21-24 m）中并不那么明显。这些双向作用似乎是通过内源性大麻素 CB1 和 CB2 受体介导的。