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 hours, approximately 60 minutes after a standardized meal, for seven consecutive days. All treatment-emergent adverse events (TEAEs) (65/65) were of mild to moderate severety; 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 8, 7, and 5 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 upwards over time as needed based on tolerability.

中文翻译：

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频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。

由于缺乏公开的药代动力学（PK）和/或药效学（PD）数据，围绕大麻适当剂量用于医学目的的知情医师和患者决策受到限制。这项1期多剂量研究评估了Spectrum Red软胶囊（2.5 mgΔ9-四氢大麻酚（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）随机分为五组之一：每天5 mg THC和0.06 mg CBD（治疗A），每天10 mg THC和0.12 mg CBD（治疗B），每天15 mg THC和0.18 mg CBD（治疗） C），每天20毫克四氢大麻酚和0.24毫克CBD（治疗D）或安慰剂。在标准餐后约60分钟，每12小时分7次连续服用研究药物。所有治疗紧急不良事件（TEAE）（65/65）均为轻度至中度严重程度。没有一个是认真的。在治疗的第一天，发生最多的TEAE（30/65）。最常见的TEAE包括嗜睡，嗜睡和头痛（分别由8、7和5名参与者报告）。在第7天，随着剂量分别在处理A和B之间以及处理B和D之间加倍，最大观察到的11-羧基-THC血浆浓度增加了2.0倍和2.5倍。治疗D和安慰剂在第1天，第3天和第7天，自我报告的“感觉到任何效果”和“晕眩”的主观效果的平均峰值后治疗等级有所不同。在一周两次的Spectrum Red软胶囊给药中， THC的每日剂量最高为20 mg，CBD的每日剂量最高为0。24 mg通常是安全的，并且在治疗的第一天后耐受性更好。一种谨慎的方法来提高Spectrum Red软胶囊的耐受性，可能涉及分剂量不超过10 mg THC和0.12 mg CBD的初始日剂量，并根据耐受性的需要随时间逐步滴定。