Vaughn Dana, Kulpa Justyna, Paulionis Lina
Canopy Animal Health, Canopy Growth Corporation, Toronto, ON, Canada.
Front Vet Sci. 2020 Feb 11;7:51. doi: 10.3389/fvets.2020.00051. eCollection 2020.
To determine the safety and tolerability of escalating doses of three cannabis oil formulations, containing predominantly CBD, THC, or CBD and THC (1.5:1) vs. placebo in dogs. Randomized, placebo-controlled, blinded, parallel study. Twenty healthy Beagle dogs (10 males, 10 females). Dogs were randomly assigned to one of five treatment groups ( = 4 dogs per group balanced by sex): CBD-predominant oil, THC-predominant oil, CBD/THC-predominant oil (1.5:1), sunflower oil placebo, medium-chain triglyceride oil placebo. Up to 10 escalating doses of the oils were planned for administration via oral gavage, with at least 3 days separating doses. Clinical observations, physical examinations, complete blood counts, clinical chemistry, and plasma cannabinoids were used to assess safety, tolerability, and the occurrence of adverse events (AEs). AEs were rated as mild, moderate, or severe/medically significant. Dose escalation of the CBD-predominant oil formulation was shown to be as safe as placebo and safer than dose escalation of oils containing THC (CBD/THC oil or THC oil). The placebo oils were delivered up to 10 escalating volumes, the CBD oil up to the tenth dose (640.5 mg; 62 mg/kg), the THC oil up to the tenth dose (597.6 mg; ~49 mg/kg), and the CBD/THC oil up to the fifth dose (140.8/96.6 mg CBD/THC; ~12 mg/kg CBD + 8 mg/kg THC). AEs were reported in all dogs across the five groups and the majority (94.9%) were mild. Moderate AEs (4.4% of all AEs) and severe/medically significant AEs (0.8% of all AEs) manifested as constitutional (lethargy, hypothermia) or neurological (ataxia) symptoms and mainly occurred across the two groups receiving oils containing THC (CBD/THC oil or THC oil). Overall, dogs tolerated dose escalation of the CBD oil well, experiencing only mild AEs. The favorable safety profile of 10 escalating doses of a CBD oil containing 18.3-640.5 mg CBD per dose (2-62 mg/kg) provides comparative evidence that, at our investigated doses, a CBD-predominant oil formulation was safer and more tolerated in dogs than oil formulations containing higher concentrations of THC.
为了确定三种主要含CBD、THC或CBD与THC（1.5:1）的大麻油制剂与安慰剂相比，在犬类中递增剂量给药时的安全性和耐受性。随机、安慰剂对照、双盲、平行研究。20只健康比格犬（10只雄性，10只雌性）。犬只被随机分配到五个治疗组之一（每组4只犬，按性别均衡）：以CBD为主的油、以THC为主的油、以CBD/THC为主的油（1.5:1）、向日葵油安慰剂、中链甘油三酯油安慰剂。计划通过灌胃法给予多达10个递增剂量的油，各剂量之间至少间隔3天。通过临床观察、体格检查、全血细胞计数、临床化学和血浆大麻素评估安全性、耐受性和不良事件（AE）的发生情况。AE被评为轻度、中度或重度/具有医学意义。结果显示，以CBD为主的油制剂递增剂量给药与安慰剂一样安全，且比含THC的油制剂（CBD/THC油或THC油）递增剂量给药更安全。安慰剂油给予了多达10个递增体积，CBD油给予到第十剂量（640.5毫克；约62毫克/千克），THC油给予到第十剂量（597.6毫克；约49毫克/千克），CBD/THC油给予到第五剂量（140.8/96.6毫克CBD/THC；约12毫克/千克CBD + 8毫克/千克THC）。所有五组的犬只均报告了AE，且大多数（94.9%）为轻度。中度AE（占所有AE的4.4%）和重度/具有医学意义的AE（占所有AE的0.8%）表现为全身症状（嗜睡、体温过低）或神经症状（共济失调），主要发生在接受含THC油制剂（CBD/THC油或THC油）的两组中。总体而言，犬只对CBD油递增剂量给药耐受性良好，仅出现轻度AE。每剂含18.3 - 640.5毫克CBD（约2 - 62毫克/千克）的CBD油10个递增剂量的良好安全性概况提供了比较证据，即在我们研究的剂量下，以CBD为主的油制剂在犬类中比含较高浓度THC的油制剂更安全且耐受性更好。
