Safety, pharmacodynamics, and pharmacokinetics of multiple oral doses of delta-9-tetrahydrocannabinol in older persons with dementia.
Safety, pharmacodynamics, and pharmacokinetics of multiple oral doses of delta-9-tetrahydrocannabinol in older persons with dementia.
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痴呆症的老年人的多种口服剂量的delta-9-四氢大麻酚的安全性，药效学和药代动力学。
DOI：
10.1007/s00213-015-3889-y
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发表时间：
2015-07
影响因子：
3.4
通讯作者：
Rikkert, Marcel G. M. Olde
中科院分区：
文献类型：
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作者：
Ahmed, Amir I. A.;van den Elsen, Geke A. H.;Colbers, Angela;Kramers, Cornelis;Burger, David M.;van der Marck, Marjolein A.;Rikkert, Marcel G. M. Olde
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.
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DOI：
10.1016/j.jalz.2011.03.005
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
McKhann GM;Knopman DS;Chertkow H;Hyman BT;Jack CR Jr;Kawas CH;Klunk WE;Koroshetz WJ;Manly JJ;Mayeux R;Mohs RC;Morris JC;Rossor MN;Scheltens P;Carrillo MC;Thies B;Weintraub S;Phelps CH
通讯作者：
Phelps CH
影响因子：
2.9
作者：
Stott, C. G.;White, L.;Guy, G. W.
通讯作者：
Guy, G. W.
影响因子：
64.8
作者：
MUNRO, S;THOMAS, KL;ABUSHAAR, M
通讯作者：
ABUSHAAR, M
影响因子：
4
作者：
Aso, Ester;Palomer, Ernest;Ferrer, Isidro
通讯作者：
Ferrer, Isidro
影响因子：
5.6
作者：
Aso E;Ferrer I
通讯作者：
Ferrer I