PMID- 27121791
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160429
LR  - 20160428
IS  - 2160-763X (Print)
IS  - 2160-763X (Linking)
VI  - 2
IP  - 3
DP  - 2013 Jul
TI  - A Multiple-Dose, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group 
      QT/QTc Study to Evaluate the Electrophysiologic Effects of THC/CBD Spray.
PG  - 285-94
LID - 10.1002/cpdd.36 [doi]
AB  - Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray has proved 
      efficacious in the treatment of spasticity in multiple sclerosis and chronic 
      pain. A thorough QT/QTc study was performed to investigate the effects of THC/CBD 
      spray on electrocardiogram (ECG) parameters in compliance with regulatory 
      requirements, evaluating the effect of a recommended daily dose (8 sprays/day) 
      and supratherapeutic doses (24 or 36 sprays/day) of THC/CBD spray on the QT/QTc 
      interval in 258 healthy volunteers. The safety, tolerability, and pharmacokinetic 
      profile of THC/CBD spray were also evaluated. Therapeutic and supratherapeutic 
      doses of THC/CBD spray had no effect on cardiac repolarization with primary and 
      secondary endpoints of QTcI and QTcF/QTcB, respectively, showing similar results. 
      There was no indication of any effect on heart rate, atrioventricular conduction, 
      or cardiac depolarization and no new clinically relevant morphological changes 
      were observed. Overall, 19 subjects (25.0%) in the supratherapeutic (24/36 daily 
      sprays of THC/CBD spray) dose group and one (1.6%) in the moxifloxacin group 
      withdrew early due to intolerable AEs. Four psychiatric serious adverse events 
      (AEs) in the highest dose group resulted in a reduction in the surpatherapeutic 
      dose to 24 sprays/day. In conclusion, THC/CBD spray does not significantly affect 
      ECG parameters. Additionally, THC/CBD spray is well tolerated at therapeutic 
      doses with an AE profile similar to previous clinical studies.
CI  - (c) The Author(s) 2013.
FAU - Sellers, Edward M
AU  - Sellers EM
AD  - DL Global Partners, Inc., Toronto, ON, Canada.
FAU - Schoedel, Kerri
AU  - Schoedel K
AD  - INC Research, Toronto, Toronto, ON, Canada.
FAU - Bartlett, Cindy
AU  - Bartlett C
AD  - INC Research, Toronto, Toronto, ON, Canada.
FAU - Romach, Myroslava
AU  - Romach M
AD  - DL Global Partners, Inc., Toronto, ON, Canada.
FAU - Russo, Ethan B
AU  - Russo EB
AD  - GW Pharma Ltd, Salisbury, Wiltshire, UK.
FAU - Stott, Colin G
AU  - Stott CG
AD  - GW Pharma Ltd, Salisbury, Wiltshire, UK.
FAU - Wright, Stephen
AU  - Wright S
AD  - GW Pharma Ltd, Salisbury, Wiltshire, UK.
FAU - White, Linda
AU  - White L
AD  - GW Pharma Ltd, Salisbury, Wiltshire, UK.
FAU - Duncombe, Paul
AU  - Duncombe P
AD  - GW Pharma Ltd, Salisbury, Wiltshire, UK.
FAU - Chen, Chien-Feng
AU  - Chen CF
AD  - Otsuka Pharmaceutical Development and Commercialization, Inc., Princeton, NJ, 
      USA.
LA  - eng
PT  - Journal Article
DEP - 20130514
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
OTO - NOTNLM
OT  - cannabidiol
OT  - cannabinoids
OT  - cardiotoxicity
OT  - tetrahydrocannabinol
OT  - toxic psychosis
EDAT- 2013/07/01 00:00
MHDA- 2013/07/01 00:01
CRDT- 2016/04/29 06:00
PHST- 2012/09/25 00:00 [received]
PHST- 2013/03/08 00:00 [accepted]
PHST- 2016/04/29 06:00 [entrez]
PHST- 2013/07/01 00:00 [pubmed]
PHST- 2013/07/01 00:01 [medline]
AID - 10.1002/cpdd.36 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2013 Jul;2(3):285-94. doi: 10.1002/cpdd.36. Epub 2013 
      May 14.