title: Safety and pharmacokinetics of oral delta-9-tetrahydrocannabinol in healthy older subjects: a randomized controlled trial.
abstract: 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.
authors.affiliation: 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. Electronic address: amirahmed1@hotmail.com.
authors.forename: Amir I A
authors.initials: AI
authors.lastname: Ahmed
authors.affiliation: Department of Geriatric Medicine and Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Geke A H
authors.initials: GA
authors.lastname: van den Elsen
authors.affiliation: Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Angela
authors.initials: A
authors.lastname: Colbers
authors.affiliation: Department of Geriatric Medicine and Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Marjolein A
authors.initials: MA
authors.lastname: van der Marck
authors.affiliation: Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
authors.affiliation: Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Ton B
authors.initials: TB
authors.lastname: Feuth
authors.affiliation: Department of Geriatric Medicine and Radboud Alzheimer Centre, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Marcel G M Olde
authors.initials: MG
authors.lastname: Rikkert
authors.affiliation: Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Cornelis
authors.initials: C
authors.lastname: Kramers
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000187:drug effects*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001288:Attention / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D010147:Pain Measurement; D011930:Reaction Time / Q000187:drug effects; D012189:Retrospective Studies
chemical_list: D018712:Analgesics, Non-Narcotic; D013759:Dronabinol
keywords: Cannabinoids; Delta-9-tetrahydrocannabinol; Elderly; Pharmacokinetics; Safety