Tolerance to effects of high-dose oral δ9-tetrahydrocannabinol and plasma cannabinoid concentrations in male daily cannabis smokers.
Oral cannabinoids are taken for medicinal or recreational purposes, yet little is known about tolerance to their effects after high-dose extended exposure. The development of tolerance to effects of around-the-clock oral synthetic Δ9-tetrahydrocannabinol (THC) (20 mg every 3.5-6 h) was evaluated in 13 healthy male daily cannabis smokers residing on a secure research unit: 40 mg on Day 1; 100 mg on Days 2-4; 120 mg on Days 5-6. Systolic and diastolic blood pressure (BP), heart rate, and symptoms of subjective intoxication (100 mm visual-analogue scales, VAS) were assessed the morning of Day 1 (before any oral THC), and on Days 2, 4 and 6, every 30 min for 3 h after the first morning THC dose. Morning subjective intoxication ratings increased from Days 1 to 2, and then declined on Days 4 and 6. The morning THC dose increased intoxication ratings on Day 2, but had less effect on Days 4 and 6, a pattern consistent with tolerance. THC lowered BP and increased heart rate over the six days. Plasma THC and 11-OH-THC concentrations increased significantly over the first five days of dosing. Six days of around-the-clock, oral THC produced tolerance to subjective intoxication, but not to cardiovascular effects.
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
David A
DA
Gorelick
Robert S
RS
Goodwin
Eugene
E
Schwilke
David M
DM
Schwope
William D
WD
Darwin
Deanna L
DL
Kelly
Robert P
RP
McMahon
Fang
F
Liu
Catherine
C
Ortemann-Renon
Denis
D
Bonnet
Marilyn A
MA
Huestis
D000293:Adolescent; D000328:Adult; D002186:Cannabinoids / Q000097:blood*; D002188:Cannabis / Q000737:chemistry*; D002849:Chromatography, Gas; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000008:administration & dosage* / Q000097:blood; D004361:Drug Tolerance; D006801:Humans; D008297:Male; D008385:Marijuana Smoking / Q000009:adverse effects / Q000378:metabolism*; D013058:Mass Spectrometry; D008875:Middle Aged; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D055815:Young Adult
D002186:Cannabinoids; D043884:Receptor, Cannabinoid, CB1; D013759:Dronabinol