Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Alicante, Spain.
Red Temática de Investigación Cooperativa en Salud (RETICS), Red de Trastornos Adictivos, Instituto de Salud Carlos III, MICINN and FEDER, Madrid, Spain.
Br J Pharmacol. 2018 Jul;175(13):2676-2688. doi: 10.1111/bph.14226. Epub 2018 May 3.
Cannabidiol (CBD) represents a promising therapeutic tool for treating cannabis use disorder (CUD). This study aimed to evaluate the effects of CBD on the behavioural and gene expression alterations induced by spontaneous cannabinoid withdrawal.
Spontaneous cannabinoid withdrawal was evaluated 12 h after cessation of CP-55,940 treatment (0.5 mg·kg every 12 h, i.p.; 7 days) in C57BL/6J mice. The effects of CBD (5, 10 and 20 mg·kg , i.p.) on withdrawal-related behavioural signs were evaluated by measuring motor activity, somatic signs and anxiety-like behaviour. Furthermore, gene expression changes in TH in the ventral tegmental area, and in the opioid μ receptor (Oprm1), cannabinoid CB receptor (Cnr1) and CB receptor (Cnr2) in the nucleus accumbens, were also evaluated using the real-time PCR technique.
The administration of CBD significantly blocked the increase in motor activity and the increased number of rearings, rubbings and jumpings associated with cannabinoid withdrawal, and it normalized the decrease in the number of groomings. However, CBD did not change somatic signs in vehicle-treated animals. In addition, the anxiogenic-like effect observed in abstinent mice disappeared with CBD administration, whereas CBD induced an anxiolytic-like effect in non-abstinent animals. Moreover, CBD normalized gene expression changes induced by CP-55,940-mediated spontaneous withdrawal.
The results suggest that CBD alleviates spontaneous cannabinoid withdrawal and normalizes associated gene expression changes. Future studies are needed to determine the relevance of CBD as a potential therapeutic tool for treating CUD.
大麻素受体 1（CB1）拮抗剂 CP-55,940 可引起动物模型出现类似于人类吸食大麻后出现的戒断症状，如运动活动增加、焦虑样行为等。大麻二酚（CBD）是大麻素系统的内源性配体，在治疗精神分裂症、神经退行性疾病、癫痫、焦虑症、慢性疼痛等方面具有潜在的应用价值。本研究旨在观察 CBD 对 CP-55,940 诱导的自发戒断症状及相关基因表达改变的影响。
C57BL/6J 小鼠腹腔注射 CP-55,940（0.5mg·kg ，每 12 小时一次，共 7 天）建立自发戒断模型，12 小时后观察 CBD（5、10 和 20mg·kg ，腹腔注射）对戒断相关行为学指标（运动活动、躯体症状和焦虑样行为）的影响。Real-time PCR 检测 CP-55,940 诱导的中脑腹侧被盖区酪氨酸羟化酶（TH）和伏隔核阿片μ受体（Oprm1）、大麻素 CB1 受体（Cnr1）和 CB2 受体（Cnr2）基因表达改变。
CP-55,940 引起运动活动增加、刻板行为增多、梳理行为减少，而 CBD 可剂量依赖性地抑制 CP-55,940 诱导的戒断症状，包括运动活动增加、刻板行为增多、梳理行为减少。此外，CP-55,940 引起的焦虑样行为消失，而 CBD 诱导非戒断动物出现焦虑样行为。Real-time PCR 结果显示，CP-55,940 引起的基因表达改变也被 CBD 所逆转。
CBD 可缓解 CP-55,940 诱导的自发戒断症状，对戒断相关基因表达改变具有调节作用。
