Effects of Cannabidiol and a Novel Cannabidiol Analog against Tactile Allodynia in a Murine Model of Cisplatin-Induced Neuropathy: Enhanced Effects of Sub-Analgesic Doses of Morphine

大麻二酚及其新型类似物对顺铂诱导神经病变小鼠模型触觉异常性疼痛的影响:亚镇痛剂量吗啡的增强作用

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Abstract

OBJECTIVE: This research examined whether a cannabidiol (CBD)-opioid pharmacotherapy could attenuate cisplatin-induced tactile allodynia. METHODS: Mice (C57BL/6) were given 6 doses of 2.3 mg/kg cisplatin intraperitoneally (IP) on alternating days to induce tactile allodynia as quantified using an electric von Frey (eVF). Test groups in Experiment 1 received either vehicle, 0.1 or 2.5 mg/kg morphine, 1.0 or 2.0 CBD, or the 2 drugs in combination. Test groups in Experiment 2 received either vehicle, 0.1 or 2.5 mg/kg morphine, 1.0, 2.0, 3.0, or 4.0 mg/kg NB2111 (a long-acting CBD analogue), or the 2 drugs in combination. Drugs were administered IP 45 min before eVF assessment. RESULTS: Cisplatin produced tactile allodynia that was attenuated by 2.5 mg/kg morphine. Both CBD and NB2111 produced dose-dependent attenuation of tactile allodynia. CBD and NB2111, given in combination with sub-analgesic doses of morphine, produced attenuation of tactile allodynia equivalent to 2.5 mg/kg morphine. CONCLUSIONS: While both CBD and NB2111, either alone or in combination with sub-analgesic doses of opioids, exhibited analgesic effects, NB2111 could be capable of superior analgesia over time by virtue of enhanced pharmacokinetics.

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