Department of Elderly, Vincent van Gogh Institute, Venray, The Netherlands; Department of Geriatric Medicine and Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Geriatric Medicine and Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands.
Eur Neuropsychopharmacol. 2014 Sep;24(9):1475-82. doi: 10.1016/j.euroneuro.2014.06.007. Epub 2014 Jun 28.
There is a great concern about the safety of THC-based drugs in older people (≥65 years), as most of THC-trials did not include such group. In this phase 1, randomized, double-blind, double-dummy, placebo-controlled, cross-over trial, we evaluated the safety and pharmacokinetics of three oral doses of Namisol(®), a novel THC in tablet form, in older subjects. Twelve healthy older subjects (6 male; mean age 72±5 years) randomly received a single oral dose of 3mg, 5mg, or 6.5mg of THC or matching placebo, in a crossover manner, on each intervention day. The data for 11 subjects were included in the analysis. The data of 1 subject were excluded due to non-compliance to study medication. THC was safe and well tolerated. The most frequently reported adverse events (AEs) were drowsiness (27%) and dry mouth (11%). Subjects reported more AEs with THC 6.5mg than with 3mg (p=0.048), 5mg (p=0.034) and placebo (p=0.013). There was a wide inter-individual variability in plasma concentrations of THC. Subjects for whom the Cmax fell within the sampling period (over 2h), Cmax was 1.42-4.57ng/mL and Tmax was 67-92min. The AUC0-2h (n=11) was 1.67-3.51ng/mL. Overall, the pharmacodynamic effects of THC were smaller than effects previously reported in young adults. In conclusion, THC appeared to be safe and well tolerated by healthy older individuals. Data on safety and effectiveness of THC in frail older persons are urgently required, as this population could benefit from the therapeutic applications of THC.
人们非常关注基于四氢大麻酚（THC）的药物在老年人（≥65 岁）中的安全性，因为大多数 THC 试验都没有纳入此类人群。在这项 1 期、随机、双盲、双模拟、安慰剂对照、交叉试验中，我们评估了新型 THC 片剂 Namisol(®)在老年受试者中的安全性和药代动力学。12 名健康的老年受试者（6 名男性；平均年龄 72±5 岁）以交叉方式随机接受了 3mg、5mg 或 6.5mg THC 或匹配安慰剂的单次口服剂量。11 名受试者的数据被纳入分析。由于对研究药物的不依从，1 名受试者的数据被排除。THC 是安全且耐受良好的。最常报告的不良事件（AE）是嗜睡（27%）和口干（11%）。与 3mg（p=0.048）、5mg（p=0.034）和安慰剂（p=0.013）相比，6.5mg THC 组报告的 AE 更多。THC 的个体间血药浓度差异很大。对于 Cmax 在采样期间（超过 2 小时）内的受试者，Cmax 为 1.42-4.57ng/mL，Tmax 为 67-92min。AUC0-2h（n=11）为 1.67-3.51ng/mL。总体而言，THC 的药效作用小于以前在年轻成年人中报道的作用。总之，THC 似乎对健康的老年人是安全且耐受良好的。迫切需要有关 THC 在体弱老年人中的安全性和有效性的数据，因为这一人群可能受益于 THC 的治疗应用。
