Due to a lack of published pharmacokinetic (PK) and/or pharmacodynamic (PD) data, informed physician and patient decision-making surrounding appropriate dosing of cannabis for medical purposes is limited. This Phase 1, multiple-dose study evaluated the safety, tolerability, PK and PD of Spectrum Red softgels (2.5 mg Δ9-tetrahydrocannabinol (THC) and <0.25 mg cannabidiol (CBD)). Participants (n = 41) were randomized to one of five groups: 5 mg THC and 0.06 mg CBD daily (Treatment A), 10 mg THC and 0.12 mg CBD daily (Treatment B), 15 mg THC and 0.18 mg CBD daily (Treatment C), 20 mg THC and 0.24 mg CBD daily (Treatment D) or placebo. Study medication was administered in divided doses, every 12 h, ∼60 min after a standardized meal, for 7 consecutive days. All treatment-emergent adverse events (TEAEs) (65/65) were of mild-to-moderate severity; none was serious. The highest number of TEAEs (30/65) occurred on the first day of treatment. The most common TEAEs included somnolence, lethargy and headache (reported by eight, seven and five participants, respectively). On Day 7, maximum observed plasma concentration of 11-carboxy-THC increased by 2.0- and 2.5-fold as the dose doubled between Treatments A and B and between Treatments B and D, respectively. Mean peak post-treatment ratings of self-reported subjective effects of ‘feel any effect’ and ‘dazed’ differed between Treatment D and placebo on Days 1, 3 and 7. Over a week of twice-daily dosing of Spectrum Red softgels, daily doses of THC up to 20 mg and of CBD up to 0.24 mg were generally safe and became better tolerated after the first day of treatment. A prudent approach to improve tolerability with Spectrum Red softgels might involve initial daily doses no higher than 10 mg THC and 0.12 mg CBD in divided doses, with titration upward over time as needed based on tolerability.

中文翻译：

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光谱红软胶囊在健康参与者中的安全性、药代动力学和药效学

由于缺乏已发表的药代动力学 (PK) 和/或药效学 (PD) 数据，医生和患者围绕医疗目的大麻适当剂量的知情决策受到限制。这项 1 期多剂量研究评估了 Spectrum Red 软胶囊（2.5 mg Δ9-四氢大麻酚 (THC) 和 <0.25 mg 大麻二酚 (CBD)）的安全性、耐受性、PK 和 PD。参与者 (n = 41) 被随机分为五组之一：每天 5 毫克 THC 和 0.06 毫克 CBD（治疗 A）、每天 10 毫克 THC 和 0.12 毫克 CBD（治疗 B）、每天 15 毫克 THC 和 0.18 毫克 CBD（治疗C)，每天 20 毫克 THC 和 0.24 毫克 CBD（治疗 D）或安慰剂。研究药物分次给药，每 12 小时一次，标准膳食后约 60 分钟给药一次，连续 7 天。所有治疗引起的不良事件 (TEAE) (65/65) 均为轻度至中度严重程度；没有一个是严重的。治疗第一天发生的 TEAE 数量最多（30/65）。最常见的 TEAE 包括嗜睡、嗜睡和头痛（分别有 8 名、7 名和 5 名参与者报告）。第 7 天，随着治疗 A 和 B 之间以及治疗 B 和 D 之间剂量加倍，观察到的 11-羧基-THC 最大血浆浓度分别增加了 2.0 倍和 2.5 倍。在第 1 天、第 3 天和第 7 天，治疗 D 和安慰剂之间自我报告的主观效果“感觉有任何影响”和“茫然”的平均峰值治疗后评级有所不同。每天两次服用 Spectrum Red 软胶囊超过一周THC 剂量高达 20 mg 和 CBD 剂量高达 0.24 mg 通常是安全的，并且在治疗第一天后耐受性更好。提高 Spectrum Red 软胶囊耐受性的谨慎方法可能包括每日初始剂量不高于 10 mg THC 和 0.12 mg CBD 分次剂量，并根据耐受性根据需要随时间向上滴定。