Ahmed Amir I A, van den Elsen Geke A H, Colbers Angela, Kramers Cornelis, Burger David M, van der Marck Marjolein A, Olde Rikkert Marcel G M
Department of Psychogeriatric Medicine, Vincent van Gogh Institute, Overloonseweg 4, 5804 AV, Venray, The Netherlands,
Psychopharmacology (Berl). 2015 Jul;232(14):2587-95. doi: 10.1007/s00213-015-3889-y. Epub 2015 Mar 11.
Data on safety, pharmacodynamics, and pharmacokinetics of tetrahydrocannabinol (THC) are lacking in dementia patients.
In this randomized, double-blind, placebo-controlled, crossover trial, we evaluated the safety, pharmacodynamics, and pharmacokinetics of THC in ten patients with dementia (mean age 77.3 ± 5.6). For 12 weeks, participants randomly received oral THC (weeks 1-6, 0.75 mg; weeks 7-12, 1.5 mg) or placebo twice daily for 3 days, separated by a 4-day washout period.
Only 6 of the 98 reported adverse events were related to THC. Visual analog scale (VAS) feeling high, VAS external perception, body sway-eyes-open, and diastolic blood pressure were not significantly different with THC. After the 0.75-mg dose, VAS internal perception (0.025 units; 95% CI 0.010-0.040) and heart rate (2 beats/min; 95% CI 0.4-3.8) increased significantly. Body sway-eyes-closed increased only after 1.5 mg (0.59°/s; 95% CI 0.13-1.06). Systolic blood pressure changed significantly after both doses of THC (0.75 mg, -7 mmHg, 95% CI -11.4, -3.0; 1.5 mg, 5 mmHg, 95% CI 1.0-9.2). The median T max was 1-2 h, with THC pharmacokinetics increasing linearly with increasing dose, with wide interindividual variability (CV% up to 140%). The mean C max (ng/mL) after the first dose (0-6 h) was 0.41 (0.18-0.90) for the 0.75-mg dose and 1.01 (0.53-1.92) for the 1.5-mg dose. After the second dose (6-24 h), the C max was 0.50 (0.27-0.92) and 0.98 (0.46-2.06), respectively.
THC was rapidly absorbed and had dose-linear pharmacokinetics with considerable interindividual variation. Pharmacodynamic effects, including adverse events, were minor. Further studies are warranted to evaluate the pharmacodynamics and efficacy of higher THC doses in older persons with dementia.
痴呆患者缺乏四氢大麻酚（THC）的安全性、药效学和药代动力学数据。
在这项随机、双盲、安慰剂对照的交叉试验中，我们评估了THC在10名痴呆患者（平均年龄77.3±5.6岁）中的安全性、药效学和药代动力学。在12周内，参与者随机接受口服THC（第1 - 6周，0.75毫克；第7 - 12周，1.5毫克）或安慰剂，每日两次，共3天，中间有4天的洗脱期。
98例报告的不良事件中只有6例与THC有关。视觉模拟量表（VAS）的兴奋感、VAS外部感知、睁眼身体摇摆和舒张压在使用THC时无显著差异。在0.75毫克剂量后，VAS内部感知（0.025单位；95%可信区间0.010 - 0.040）和心率（2次/分钟；95%可信区间0.4 - 3.8）显著增加。仅在1.5毫克后睁眼身体摇摆增加（0.59°/秒；95%可信区间）。两种剂量的THC后收缩压均有显著变化（0.75毫克，-7毫米汞柱，95%可信区间-11.4，-3.0；1.5毫克，5毫米汞柱，95%可信区间1.0 - 9.2）。中位达峰时间为1 - 2小时，THC药代动力学随剂量增加呈线性增加，个体间差异较大（变异系数高达140%）。0.75毫克剂量首次给药后（0 - 6小时）的平均血药浓度峰值（纳克/毫升）为0.41（0.18 - 0.90），1.5毫克剂量为1.01（0.53 - 1.92）。第二次给药后（6 - 24小时），血药浓度峰值分别为0.50（0.27 - 0.92）和0.98（0.46 - 2.06）。
THC吸收迅速，具有剂量线性药代动力学，个体间差异较大。包括不良事件在内的药效学效应较小。有必要进一步研究评估更高THC剂量在老年痴呆患者中的药效学和疗效。
