Effect of intrapulmonary tetrahydrocannabinol administration in humans.
L Zuurman, C Roy, R C Schoemaker, A Hazekamp, J Den Hartigh, J C M E Bender, R Verpoorte, J L Pinquier, A F Cohen, J M A van Gerven
Journal of psychopharmacology (Oxford, England) September 2008 DOI: 10.1177/0269881108089581 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial (crossover) Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Healthy males |
| Intervention | Delta-9-Tetrahydrocannabinol (THC) |
| Dose | 2, 4, 6 and 8 mg |
| Duration | Single session with 90-minute intervals between doses |
| Measures | Visual Analogue Scales (alertness, feeling high, external perception), EEG, pupil size, saccadic eye movements, smooth pursuit, adaptive tracking |
| Topics | Cannabis |
| Key findings | The Volcano vaporizer delivered THC with low variability and produced dose-dependent increases in heart rate, body sway, and subjective effects. Heart rate equilibrated quickly (half-life 7.68 min), while CNS effects equilibrated more slowly (39.4–84.2 min). No effects were seen on saccadic eye movements, smooth pursuit, or adaptive tracking. |
Abstract
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.