A multiple-dose, randomized, double-blind, placebo-controlled, parallel-group QT/QTc study to evaluate the electrophysiologic effects of THC/CBD spray

Clinical Pharmacology in Drug Development

Volumn 2, Issue 3, 2013, Pages 285-294

  Sellers, Edward M ^a   Schoedel, Kerri ^b   Bartlett, Cindy ^b   Romach, Myroslava ^a   Russo, Ethan B ^c   Stott, Colin G ^c   Wright, Stephen ^c   White, Linda ^c   Duncombe, Paul ^c   Chen, Chien Feng ^d  

^a DL Global Partners Inc   (Canada)

^b SYNEOS HEALTH   (United States)

^c Porton Down Science Park   (United Kingdom)

^d OTSUKA PHARMACEUTICAL DEVELOPMENT AND COMMERCIALIZATION INC   (United States)

Author keywords

Cannabidiol; Cannabinoids; Cardiotoxicity; Tetrahydrocannabinol; Toxic psychosis

Indexed keywords

NABIXIMOLS; PLACEBO;

ADULT; AREA UNDER THE CURVE; ARTICLE; ATRIOVENTRICULAR CONDUCTION; CARDIOTOXICITY; CONSTIPATION; CONTROLLED STUDY; DECREASED APPETITE; DISORIENTATION; DIZZINESS; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG DOSE COMPARISON; DRUG DOSE REDUCTION; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG SCREENING; DRUG TOLERABILITY; DRUG WITHDRAWAL; ELECTROCARDIOGRAM; EUPHORIA; FATIGUE; FEMALE; HEART ELECTROPHYSIOLOGY; HEART RATE VARIABILITY; HEART REPOLARIZATION; HOT FLUSH; HUMAN; HUMAN EXPERIMENT; MALE; MAXIMUM PLASMA CONCENTRATION; MENTAL DISEASE; NORMAL HUMAN; ORAL SPRAY; OUTCOME ASSESSMENT; PALLOR; PRIORITY JOURNAL; QT INTERVAL; QT PROLONGATION; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SOMNOLENCE; TACHYCARDIA; TIME TO MAXIMUM PLASMA CONCENTRATION; VOMITING; XEROSTOMIA;

EID: 84892489013     PISSN: 2160763X     EISSN: 21607648     Source Type: Journal    
DOI: 10.1002/cpdd.36     Document Type: Article

References (25)

1. International Conference on Harmonisation. E14: The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs. ICH Harmonised Tripartite Guideline, http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E14/E14_Guideline.pdf:2005 (Accessed August 23, 2012).
2. Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011; 163(7):1344-1364.
3. Berman JS, Symonds C, Birch R. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain. 2004; 112:299-306.
4. Nurmikko TJ, Serpell MG, Hoggart B, Toomey PJ, Morlion BJ, Haines D. Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain. 2007; 133(1-3):210-220.
5. Blake DR, Robson P, Ho M, Jubb RW, McCabe CS. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology. 2006; 45(1):50-52.
6. Kavia RBC, De Ridder D, Constantinescu CS, Stott CG, Fowler CJ. Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis. Mult Scler. 2010; 16(11):1349-1359.
7. Beaconsfield P, Grisburg J, Rainsbury R. Marihuana smoking. Cardiovascular effects in man and possible mechanisms. N Engl J Med. 1972; 287(5):209-212.
8. Johnson S, Domino EF. Some cardiovascular effects of marihuana smoking in normal volunteers. Clin Pharmacol Ther. 1971; 2(5):762-768.
9. Weiss JL, Watanabe AM, Lemberger L, Tamarkin NR, Cardon PV. Cardiovascular effects of delta-9-tetrahydrocannabinol in man. Clin Pharmacol Ther. 1972; 13(5):671-684.
10. Paton WDM, Pertwee RG. Mechoulam R, ed. Marihuana. New York and London: Academic Press; 1973; 287-333
11. Paton WD. Pharmacology of marijuana. Annu Rev Pharmacol. 1975; 15:191-220.
12. Gregg JM, Campbell RL, Levin KJ, Ghia J, Elliott RA. Cardiovascular effects of cannabinol during oral surgery. Anesth Analg. 1976; 55:203-213.
13. Fisher BA, Ghuran A, Vadamalai V, Antonios TF. Cardiovascular complications induced by cannabis smoking: a case report and review of the literature. Emerg Med J. 2005; 22:679-680.
14. Sidney S. Cardiovascular consequences of marijuana use. J Clin Pharmacol. 2002; 42:64S-70S.
15. Agin MA. Assessing QT variability in healthy volunteers. J Clin Pharmacol. 2003; 43:1028.
16. Mangoni AA, Kinirons MT, Swift CG, Jackson SH. Impact of age on QT interval and QT dispersion in healthy subjects: a regression analysis. Age Ageing. 2003; 32:326-331.
17. Montecucco F, Di Marzo V. At the heart of the matter: the endocannabinoid system in cardiovascular function and dysfunction. Trends Pharmacol Sci. 2012; 33(6):331-340.
18. Grotenhermen F. The toxicology of cannabis and cannabis prohibition. Chem Biodivers. 2007; 4:1744-1769.
19. Guy GW, Robson PJ. A Phase I, double blind, three-way crossover study to assess the pharmacokinetic profile of Cannabis Based Medicine Extract (CBME) administered sublingually in variant cannabinoid ratios in normal healthy male volunteers. J Cannabis Ther. 2003; (3/4): 121-152.
20. Guy GW, Robson PJ. A Phase I, open label, four-way crossover study to compare the pharmacokinetic profiles of a single dose of 20 mg of a Cannabis Based Medicine Extract (CBME) administered on 3 different areas of the buccal mucosa and to investigate the pharmacokinetics of CBME per oral in healthy male and female volunteers. J Cannabis Ther. 2003; (3/4): 79-120.
21. Favrat B, Menetrey A, Augsburger M, et al. Two cases of "cannabis acute psychosis" following the administration of oral cannabis. BMC Psychiatry. 2005; 5:17.
22. D'Souza DC, Perry E, MacDougall L, et al. The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology. 2004; 29(8):1558-1572.
23. Morgan CJ, Curran HV. Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis. Br J Psychiatry. 2008; 192(4):306-307.
24. Morgan CJ, Freeman TP, Schafer GL, Curran HV. Cannabidiol attenuates the appetitive effects of Delta 9-tetrahydrocannabinol in humans smoking their chosen cannabis. Neuropsychopharmacology. 2010; 35(9):1879-1885.
25. Morgan CJ, Schafer G, Freeman TP, Curran HV. Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study. Br J Psychiatry. 2010; 197(4):285-290.