This Article Full Text (PDF) All Versions of this Article: 0269881108089581v1 22/7/707    most recent References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Zuurman, L. Articles by van Gerven, J. Search for Related Content PubMed PubMed Citation Articles by Zuurman, L. Articles by van Gerven, J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB TETRAHYDROCANNABINOL Social Bookmarking                         What's this?

Effect of intrapulmonary tetrahydrocannabinol administration in humans

Centre for Human Drug Research, Pharmacology CNS, Leiden, The Netherlands, linekezuurman{at}gmail.com

C. Roy

Sanofi-aventis, Recherche-Développement, Paris, France

RC Schoemaker

Centre for Human Drug Research, Statistics, Leiden, The Netherlands

A. Hazekamp

Department of Pharmacognosy, Leiden University, Leiden, The Netherlands

J. den Hartigh

Hospital Pharmacy, Leiden University Medical Center, Leiden, The Netherlands

JCME Bender

Farmalyse BV, Zaandam, The Netherlands

R. Verpoorte

Department of Pharmacognosy, Leiden University, Leiden, The Netherlands

JL Pinquier

Sanofi-aventis, Recherche-Développement, Paris, France

AF Cohen

Centre for Human Drug Research, Pharmacology CNS, Leiden, The Netherlands

JMA van Gerven

Centre for Human Drug Research, Leiden, The Netherlands

This randomised, double-blind, placebo-controlled, cross-over study was designed to identify which pharmacodynamic parameters most accurately quantify the effects of delta-9-Tetrahydrocannabinol (THC), the predominantly psychoactive component of cannabis. In addition, we investigated the acceptability and usefulness of a novel mode of intrapulmonary THC administration using a Volcano® vaporizer and pure THC instead of cannabis. Rising doses of THC (2, 4, 6 and 8 mg) or vehicle were administered with 90 minutes intervals to twelve healthy males using a Volcano® vaporizer. Very low between-subject variability was observed in THC plasma concentrations, characterising the Volcano® vaporizer as a suitable method for the administration of THC. Heart rate showed a sharp increase and rapid decline after each THC administration (8 mg: 19.4 bpm: 95% CI 13.2, 25.5). By contrast, dose dependent effects of body sway (8 mg: 108.5%: 95% CI 72.2%, 152.4%) and different subjective parameters did not return to baseline between doses (Visual Analogue Scales of 'alertness' (8 mg: -33.6 mm: 95% CI -41.6, -25.7), 'feeling high' (8 mg: 1.09 U: 95% CI 0.85, 1.33), 'external perception' (8 mg: 0.62 U: 95% CI 0.37, 0.86)). PK/PD-modeling of heart rate displayed a relatively short equilibration half-life of 7.68 min. CNS parameters showed equilibration half-lives ranging between 39.4 - 84.2 min. Some EEG-frequency bands, and pupil size showed small changes following the highest dose of THC. No changes were seen in saccadic eye movements, smooth pursuit and adaptive tracking performance. These results may be applicable in the development of novel cannabinoid agonists and antagonists, and in studies of the pharmacology and physiology of cannabinoid systems in humans.

Key Words: THC • cannabis • cannabinoid • CB1 receptor • Volcano® vaporizer • healthy volunteers • human • pharmacodynamics • pharmacokinetics

This version was published on September 1, 2008

Journal of Psychopharmacology, Vol. 22, No. 7, 707-716 (2008)
DOI: 10.1177/0269881108089581


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