VAPORIZATION AS A SMOKELESS CANNABIS DELIVERY SYSTEM: A PILOT STUDY
Donald I. Abrams, Hector P. Vizoso, Starley B. Shade, Cheryl Jay, Mary Ellen Kelly and Neal Benowitz
The University of California San Francisco, San Francisco, California 94110, USA
Presented at the September 9-10, 2005, International Association for Cannabis as Medicine 3rd Conference in Leiden, Holland.
INTRODUCTION: The Institute of Medicine report published in 1999 suggested that although marijuana may have potential therapeutic value, smoking was not a desirable delivery system for cannabis. A 6-day proof of concept pilot study was proposed to investigate vaporization using the Volcano device as an alternative means of delivery of inhaled Cannabis sativa, to characterize preliminary pharmacokinetic and pharmacodynamic effects and to determine whether it may be an appropriate system for use in clinical effectiveness studies.
METHODS: Eighteen healthy subjects were recruited and admitted to the inpatient ward of the General Clinical Research Center (GCRC) at San Francisco General Hospital to investigate the delivery of cannabinoids by vaporization of marijuana compared to marijuana smoked in a standard cigarette. One dose ( 1.7, 3.4 or 6.8% tetrahydrocannabinol) and delivery system (smoked marijuana cigarette or vaporization system) was randomly assigned for each of the six study days. The primary endpoint was the comparison of plasma concentrations of delta-9tetrahydrocannabinol (THC), cannabidiol, cannabinol, and metabolites, including 11-OH-THC resulting from inhalation of cannabis after vaporization vs smoking. Expired carbon monoxide was measured to evaluate whether the vaporizer reduces exposure to gaseous toxins as a secondary endpoint. We also evaluated physiologic and neuropsychologic effects and queried patients for their preference of blinded dose day and delivery method. Adverse events were collected.
RESULTS: 21 participants were enrolled to obtain the 18 who completed the 6-day inpatient study. 15 men and 3 women, mean age 30 years, were included in the final analysis. The plasma THC concentrations are still being determined at this time. Results will be available in September. 14 participants preferred vaporization, 2 smoking and 2 reported no preference. While still blinded with regard to dose, 8 participants selected the day they received 3.4% THC (7 vaporized, 1 smoked) as their most preferred treatment day; 4 selected the day they received 6.8% THC via vaporization and 6 had no treatment day preference. No adverse events were observed.
CONCLUSION: Vaporization of cannabis is a safe mode of delivery. The determination of plasma THC levels and comparison of clinical effects to smoked cannabis will provide information on the effectiveness of this delivery system. Participants had a clear preference for vaporization over smoking as a delivery system for the cannabis used in this trial.
Acknowledgements: The University of California Center for Medicinal Cannabis Research and NIH Grant 5-MO1-RR00083
OPTIMIZED ADMINISTRATION OF THC FOR CLINICAL USE BY VAPORIZING
Arno Hazekamp, Renee Ruhaak, Lineke Zuurman, Joop van Gerven, Rob Verpoorte
Division of Pharmacognosy, Institute of Biology, Leiden University, The Netherlands
Center for Human Drug Research, Leiden, The Netherlands
What is currently needed for optimal use of medicinal cannabinoids is a feasible, non-smoked, rapid-onset delivery system. Smoking of cannabis plant material results in the highest bioavailability and consequently pulmonal administration of cannabinoids is considered to be very effective. The goal of this study was to evaluate the performance of the Volcano vaporizer in terms of reproducible administration of pure THC, without the formation of degradation products. Results were used for designing a clinical trial for administration of THC by vaporizing.
Methods: Using the Volcano cannabis vaporizer, THC and its acidic analogue THCA were tested for delivery of THC into the balloon of the Volcano device. The efficiency of vaporizing of these samples was compared with cannabis plant material. Analyses were performed using HPLC and quantitative 1H-NMR. After determination of the dynamics of heating up, and accuracy and stability of vaporizing temperatures of the Volcano, the temperature setting and balloon volume were systematically optimized for maximum evaporation of THC. Factors contributing to loss of THC were evaluated. Several Volcano set-ups were tested to determine variability. After validation, the Volcano was used in a methodology study to determine the effects of pulmonary administration of a rising dose of THC in twelve healthy volunteers, who were subjected to an array of physiological and psychological tests after each administration.
Results: Under optimized conditions the Volcano was found to deliver about 54% of the loaded sample in a reproducible way into the vapor phase without formation of degradation products like delta-8-THC or CBN. In the range of 2 to 8 mg of THC the delivery was found to be linear with the amount of THC loaded onto the vaporizer. Prolonged storage of the balloon before inhalation resulted in an increasing loss of THC by condensation. No significant differences in THC delivery were found between four devices tested. Full results of this phase I clinical trial are not presented here, but a clear dose-dependent effect was found in several of the used tests. During these inhalation studies the fraction of exhaled THC was found to be around 34%. Improvements in the original design of the Volcano were made based on these results for further optimization of the Volcano for administration of pure cannabinoids in a clinical setting.
Conclusions: Using the Volcano for pulmonal administration of THC, a delivery is reached that is comparable to smoking, without the presence of degradation products or harmful byproducts in significant amounts. This study confirms that the pulmonary administration of cannabinoids by evaporation certainly has a clinical potential. With the Volcano a safe and effective cannabinoid delivery system seems to be available to patients. Although our current study has concentrated on the delivery of THC it should be noted that other cannabinoids might also have a role to play for some indications.
At the International Association for Cannabis as Medicine 3rd Conference, held in Leiden, Holland, Mr. Hector Vizoso, study coordinator for Dr. Donald Abrams’ study of smoking v. vaporizing, discussed the results of their clinical trial in humans comparing cannabinoid blood levels, carbon monoxide levels, and subjective effects in subjects who smoke and at other times vaporize marijuana (with the Volcano vaporizer). When subjects used vaporizers, the study found reductions in blood carbon monoxide levels as compared to smoking. In addition, the study showed that the vaporizer produced reliable levels of cannabinoids. The study also found that more subjects preferred vaporizing over smoking. This study was funded by a grant of about $136,000 from the Center for Medicinal Cannabis Research (CMCR). MAPS and CaNORML contributed an additional $100,000 on preliminary laboratory data analyzing the content of the vapors produced by the Volcano vaporizer.
Results of a second paper on vaporization [included in the full text article] (with the Volcano vaporizer) were presented by Arno Hazekamp, Ph.D, of Leiden University. This study “confirms that the pulmonary administration of cannabinoids by evaporation certainly has a clinical potential. With the Volcano a safe and effective cannabinoid delivery system seems to be available to patients.”