Rationale Data on safety, pharmacodynamics, and pharmacokinetics\nof tetrahydrocannabinol (THC) are lacking in dementia\npatients.\nMethods In this randomized, double-blind, placebo-controlled,\ncrossover trial, we evaluated the safety, pharmacodynamics,\nand pharmacokinetics of THC in ten patients with\ndementia (mean age 77.3Ã?±5.6). For 12 weeks, participants\nrandomly received oral THC (weeks 1ââ?¬â??6, 0.75 mg; weeks\n7ââ?¬â??12, 1.5 mg) or placebo twice daily for 3 days, separated\nby a 4-day washout period.\nResults Only 6 of the 98 reported adverse events were related\nto THC. Visual analog scale (VAS) feeling high, VAS external\nperception, body sway-eyes-open, and diastolic blood pressure\nwere not significantly different with THC. After the\n0.75-mg dose, VAS internal perception (0.025 units; 95 %\nCI 0.010ââ?¬â??0.040) and heart rate (2 beats/min; 95 % CI 0.4ââ?¬â??\n3.8) increased significantly. Body sway-eyes-closed increased\nonly after 1.5 mg (0.59Ã?°/s; 95%CI 0.13ââ?¬â??1.06). Systolic blood\npressure changed significantly after both doses of THC\n(0.75 mg, ?7 mmHg, 95 % CI ?11.4, ?3.0; 1.5 mg,\n5 mmHg, 95%CI 1.0ââ?¬â??9.2). The median Tmax was 1ââ?¬â??2 h, with\nTHC pharmacokinetics increasing linearly with increasing\ndose, with wide interindividual variability (CV% up to\n140 %). The mean Cmax (ng/mL) after the first dose (0ââ?¬â??6 h)\nwas 0.41 (0.18ââ?¬â??0.90) for the 0.75-mg dose and 1.01 (0.53ââ?¬â??\n1.92) for the 1.5-mg dose. After the second dose (6ââ?¬â??24 h), the\nCmax was 0.50 (0.27ââ?¬â??0.92) and 0.98 (0.46ââ?¬â??2.06), respectively.\nConclusions THC was rapidly absorbed and had dose-linear\npharmacokinetics with considerable interindividual variation.\nPharmacodynamic effects, including adverse events, were minor.\nFurther studies are warranted to evaluate the pharmacodynamics\nand efficacy of higher THC doses in older persons\nwith dementia.
Loading....