PMID- 25035121
OWN - NLM
STAT- MEDLINE
DCOM- 20151102
LR  - 20140827
IS  - 1873-7862 (Electronic)
IS  - 0924-977X (Linking)
VI  - 24
IP  - 9
DP  - 2014 Sep
TI  - Safety and pharmacokinetics of oral delta-9-tetrahydrocannabinol in healthy older 
      subjects: a randomized controlled trial.
PG  - 1475-82
LID - S0924-977X(14)00175-8 [pii]
LID - 10.1016/j.euroneuro.2014.06.007 [doi]
AB  - 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((R)), 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.
CI  - Copyright (c) 2014 Elsevier B.V. and ECNP. All rights reserved.
FAU - Ahmed, Amir I A
AU  - Ahmed AI
AD  - 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.
FAU - van den Elsen, Geke A H
AU  - van den Elsen GA
AD  - Department of Geriatric Medicine and Radboud Alzheimer Centre, Radboud University 
      Medical Center, Nijmegen, The Netherlands.
FAU - Colbers, Angela
AU  - Colbers A
AD  - Department of Pharmacy, Radboud University Medical Center, Nijmegen, The 
      Netherlands.
FAU - van der Marck, Marjolein A
AU  - van der Marck MA
AD  - Department of Geriatric Medicine and Radboud Alzheimer Centre, Radboud University 
      Medical Center, Nijmegen, The Netherlands.
FAU - Burger, David M
AU  - Burger DM
AD  - Department of Pharmacy, Radboud University Medical Center, Nijmegen, The 
      Netherlands.
FAU - Feuth, Ton B
AU  - Feuth TB
AD  - Department for Health Evidence, Radboud University Medical Center, Nijmegen, The 
      Netherlands.
FAU - Rikkert, Marcel G M Olde
AU  - Rikkert MG
AD  - Department of Geriatric Medicine and Radboud Alzheimer Centre, Radboud University 
      Medical Center, Nijmegen, The Netherlands.
FAU - Kramers, Cornelis
AU  - Kramers C
AD  - Department of Pharmacology and Toxicology, Radboud University Medical Center, 
      Nijmegen, The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140628
PL  - Netherlands
TA  - Eur Neuropsychopharmacol
JT  - European neuropsychopharmacology : the journal of the European College of 
      Neuropsychopharmacology
JID - 9111390
RN  - 0 (Analgesics, Non-Narcotic)
RN  - 7J8897W37S (Dronabinol)
SB  - IM
MH  - Administration, Oral
MH  - Aged
MH  - Aged, 80 and over
MH  - Aging/*drug effects
MH  - Analgesics, Non-Narcotic/*administration & dosage/*pharmacokinetics
MH  - Attention/drug effects
MH  - Cross-Over Studies
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Dronabinol/*administration & dosage/analogs & derivatives/*pharmacokinetics
MH  - Electrocardiography
MH  - Female
MH  - Humans
MH  - Male
MH  - Pain Measurement
MH  - Reaction Time/drug effects
MH  - Retrospective Studies
OTO - NOTNLM
OT  - Cannabinoids
OT  - Delta-9-tetrahydrocannabinol
OT  - Elderly
OT  - Pharmacokinetics
OT  - Safety
EDAT- 2014/07/19 06:00
MHDA- 2015/11/03 06:00
CRDT- 2014/07/19 06:00
PHST- 2014/03/03 00:00 [received]
PHST- 2014/06/06 00:00 [revised]
PHST- 2014/06/20 00:00 [accepted]
PHST- 2014/07/19 06:00 [entrez]
PHST- 2014/07/19 06:00 [pubmed]
PHST- 2015/11/03 06:00 [medline]
AID - S0924-977X(14)00175-8 [pii]
AID - 10.1016/j.euroneuro.2014.06.007 [doi]
PST - ppublish
SO  - Eur Neuropsychopharmacol. 2014 Sep;24(9):1475-82. doi: 
      10.1016/j.euroneuro.2014.06.007. Epub 2014 Jun 28.