title: Subjective and physiological effects after controlled Sativex and oral THC administration.
abstract: Sativex is a cannabis-plant extract delivering nearly 1:1 Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) by oromucosal spray. It has been suggested that CBD attenuates THC-induced tachycardia, anxiety, and euphoria. In this study, pharmacodynamic effects were compared over 10.5 h in nine cannabis smokers randomly assigned to receive placebo, 5 and 15 mg oral synthetic THC, and low (5.4 mg THC, 5.0 mg CBD) and high (16.2 mg THC, 15.0 mg CBD) doses of Sativex. At therapeutic doses, no substantial CBD-induced modulation of THC's effects was evident. Oral THC and Sativex produced similar, clinically insignificant increases in heart rate, anxiety, and "good drug effects" with no serious adverse events. Oral and oromucosal THC have slower absorption, lower rate of THC delivery to the brain, and fewer associated adverse events as compared with smoked cannabis. These results indicate that Sativex has a pharmacodynamic safety profile comparable to that of oral THC at low, therapeutic doses.
authors.affiliation: Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: E L
authors.initials: EL
authors.lastname: Karschner
authors.forename: W D
authors.initials: WD
authors.lastname: Darwin
authors.forename: R P
authors.initials: RP
authors.lastname: McMahon
authors.forename: F
authors.initials: F
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Wright
authors.forename: R S
authors.initials: RS
authors.lastname: Goodwin
authors.forename: M A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001007:Anxiety / Q000139:chemically induced; D001921:Brain / Q000378:metabolism; D002185:Cannabidiol; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004338:Drug Combinations; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009061:Mouth Mucosa / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D010936:Plant Extracts; D011619:Psychotropic Drugs; D002185:Cannabidiol; D013759:Dronabinol; C587251:nabiximols