Development and pharmacokinetic characterization of pulmonal and intravenous delta-9-tetrahydrocannabinol (THC) in humans.
The aim of the present study was to develop a physiologically compatible inhalation solution of delta-9-tetrahydrocannabinol (THC), and to compare the pharmacokinetic and analgesic properties of pulmonal THC versus pulmonal placebo and intravenous (iv) THC, respectively. Eight healthy volunteers were included in this randomized, double-blind, crossover study. The aqueous THC formulations were prepared by using a solubilization technique. iv THC (0.053 mg/kg body weight), pulmonal THC (0.053 mg/kg), or a placebo inhalation solution was administered as single dose. At defined time points, blood samples were collected, and somatic and psychotropic side effects as well as vital functions monitored. An ice water immersion test was performed to measure analgesia. Using a pressure-driven nebulizer, the pulmonal administration of the THC liquid aerosol resulted in high THC peak plasma levels within minutes. The bioavailability of the pulmonal THC was 28.7 +/- 8.2% (mean +/- SEM). The side effects observed after pulmonal THC were coughing and slight irritation of the upper respiratory tract, very mild psychotropic symptoms, and headache. The side effects after iv THC were much more prominent. Neither pulmonal nor iv THC significantly reduced experimentally induced pain.
Naef
Myrtha
M
Department of Clinical Research, University of Bern, Murtenstrasse 35, CH-3010 Bern, Switzerland.
Russmann
Stefan
S
Petersen-Felix
Steen
S
Brenneisen
Rudolf
R
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D001682:Biological Availability; D018592:Cross-Over Studies; D004311:Double-Blind Method; D013759:Dronabinol / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods / Q000523:psychology; D018709:Statistics, Nonparametric
D000336:Aerosols; D013759:Dronabinol