title: Naltrexone does not attenuate the effects of intravenous Δ9-tetrahydrocannabinol in healthy humans.
abstract: Although a wealth of preclinical evidence indicates an interplay between the μ-opioid (MOR) and cannabinoid 1 receptor (CB1R) systems, the precise nature of the cross modulation in humans is unclear. The objective of this study was to evaluate the effects of pretreatment with the MOR antagonist, naltrexone, on the subjective, behavioural and cognitive effects of the CB1R agonist, Δ9-tetrahydrocannabinol (THC), in healthy human subjects. Healthy human subjects, screened carefully for any medical or psychiatric illness, were administered either placebo or active naltrexone (25 mg) orally on each test day, followed 45 min later by placebo and 165 min later by active i.v. THC (0.025 mg/kg) in a randomized, fixed-order, double-blind manner. Subjective, behavioural and cognitive effects were assessed before and at several points after each drug administration. THC produced expected effects, including euphoria, anxiety, transient perceptual alterations, transient psychotomimetic effects and cognitive impairments. However, naltrexone did not produce any effects alone, nor did it attenuate any of THC's effects. Thus, in healthy human subjects who use cannabis intermittently, MOR antagonism does not modulate the common acute subjective, behavioural and cognitive effects of THC.
authors.affiliation: Yale University, School of Medicine, Department of Psychiatry, New Haven, CT, USA. mohini.ranganathan@yale.edu
authors.forename: Mohini
authors.initials: M
authors.lastname: Ranganathan
authors.forename: Michelle
authors.initials: M
authors.lastname: Carbuto
authors.forename: Gabriel
authors.initials: G
authors.lastname: Braley
authors.forename: Jaqueline
authors.initials: J
authors.lastname: Elander
authors.forename: Edward
authors.initials: E
authors.lastname: Perry
authors.forename: Brian
authors.initials: B
authors.lastname: Pittman
authors.forename: Rajiv
authors.initials: R
authors.lastname: Radhakrishnan
authors.forename: Richard A
authors.initials: RA
authors.lastname: Sewell
authors.forename: Deepak C
authors.initials: DC
authors.lastname: D'Souza
mesh_terms: D000293:Adolescent; D000328:Adult; D001288:Attention / Q000187:drug effects; D001519:Behavior / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000523:psychology; D004311:Double-Blind Method; D013759:Dronabinol / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D005059:Euphoria / Q000187:drug effects; D005260:Female; D006213:Hallucinogens / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007266:Inhibition, Psychological; D007275:Injections, Intravenous; D008297:Male; D002189:Marijuana Abuse / Q000523:psychology; D008568:Memory / Q000187:drug effects; D011939:Mental Recall / Q000187:drug effects; D008875:Middle Aged; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009949:Orientation / Q000187:drug effects; D010465:Perception / Q000187:drug effects; D011605:Psychoses, Substance-Induced / Q000523:psychology; D021641:Recognition, Psychology / Q000187:drug effects; D012201:Reward; D055815:Young Adult
chemical_list: D006213:Hallucinogens; D009292:Narcotic Antagonists; D009271:Naltrexone; D013759:Dronabinol