Department of Neuroscience, The Scripps Research Institute, SP30-2400, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
La Jolla Alcohol Research, Inc., La Jolla, CA, USA.
Psychopharmacology (Berl). 2018 Sep;235(9):2541-2557. doi: 10.1007/s00213-018-4946-0. Epub 2018 Jun 16.
Previous studies report sex differences in some, but not all, responses to cannabinoids in rats. The majority of studies use parenteral injection; however, most human use is via smoke inhalation and, increasingly, vapor inhalation.
To compare thermoregulatory and locomotor responses to inhaled ∆-tetrahydrocannabinol (THC), cannabidiol (CBD), and their combination using an e-cigarette-based model in male and female rats METHODS: Male and female Wistar rats were implanted with radiotelemetry devices for the assessment of body temperature and locomotor activity. Animals were then exposed to THC or CBD vapor using a propylene glycol (PG) vehicle. THC dose was adjusted via the concentration in the vehicle (12.5-200 mg/mL) and the CBD (100, 400 mg/mL) dose was also adjusted by varying the inhalation duration (10-40 min). Anti-nociception was evaluated using a tail-withdrawal assay following vapor inhalation. Plasma samples obtained following inhalation in different groups of rats were compared for THC content.
THC inhalation reduced body temperature and increased tail-withdrawal latency in both sexes equivalently and in a concentration-dependent manner. Female temperature, activity, and tail-withdrawal responses to THC did not differ between estrus and diestrus. CBD inhalation alone induced modest hypothermia and suppressed locomotor activity in both males and females. Co-administration of THC with CBD, in a 1:4 ratio, significantly decreased temperature and activity in an approximately additive manner and to similar extent in each sex. Plasma THC varied with the concentration in the PG vehicle but did not differ across rat sex.
In summary, the inhalation of THC or CBD, alone and in combination, produces approximately equivalent effects in male and female rats. This confirms the efficacy of the e-cigarette-based method of THC delivery in female rats.
先前的研究报告显示，在大鼠对大麻素的某些但不是所有反应中存在性别差异。大多数研究使用的是注射给药；然而，大多数人类使用的是通过吸入烟雾，并且越来越多地通过蒸气吸入。
使用电子烟模型比较吸入 Δ-四氢大麻酚（THC）、大麻二酚（CBD）及其组合对雄性和雌性大鼠体温调节和运动的影响。
雄性和雌性 Wistar 大鼠被植入无线电遥测设备，以评估体温和运动活动。然后，动物通过丙二醇（PG）载体暴露于 THC 或 CBD 蒸气中。通过改变载体中的浓度（12.5-200mg/mL）来调整 THC 剂量，并且通过改变吸入时间（10-40 分钟）来调整 CBD（100、400mg/mL）剂量。吸入蒸气后通过尾部回缩试验评估镇痛作用。比较吸入不同组大鼠的血浆样本中的 THC 含量。
THC 吸入以浓度依赖的方式降低了雌雄大鼠的体温并增加了尾部回缩潜伏期。在发情期和间情期，雌性对 THC 的体温、活动和尾部回缩反应没有差异。CBD 单独吸入会引起雄性和雌性大鼠体温轻微下降并抑制运动活动。以 1:4 的比例共同给予 THC 和 CBD 会以近似相加的方式显著降低温度和活动，并且在每个性别中程度相似。血浆 THC 随 PG 载体中的浓度而变化，但在不同性别大鼠之间没有差异。
总之，单独吸入 THC 或 CBD 或联合吸入，在雄性和雌性大鼠中产生大致相同的效果。这证实了电子烟输送 THC 方法在雌性大鼠中的有效性。
