Second-Hand Exposure of Staff Administering Vaporised Cannabinoid Products to Patients in a Hospital Setting
0000 0004 0486 528Xgrid.1007.6School of Psychology, University of Wollongong, Wollongong, NSW 2522, Australia
The Australian Centre for Cannabinoid Clinical and Research Excellence, New Lambton Heights, NSW Australia
0000 0000 8831 109Xgrid.266842.cDiscipline of Clinical Pharmacology, School of Medicine and Public Health, University of Newcastle, Callaghan, NSW Australia
Abstract
Background
In many health settings, administration of medicinal cannabis poses significant implementation barriers including drug storage and safety for administering staff and surrounding patients. Different modes of administration also provide different yet potentially significant issues. One route that has become of clinical interest owing to the rapid onset of action and patient control of the inhaled amount (via breath timing and depth) is that of vaporisation of cannabinoid products. Although requiring a registered therapeutic device for administration, this is a relatively safe method of intrapulmonary administration that may be particularly useful for patients with difficulty swallowing, and for those in whom higher concentrations of cannabinoids are needed quickly. A particular concern expressed to researchers undertaking clinical trials in the hospital is that other patients, nurses, and clinical or research staff may be exposed to second-hand vapours in the course of administering vaporised products to patients.
Objective
The objective of this study was to take samples from two research staff involved in administering vaporised Δ9-tetrahydrocannabinol to participants in a clinical trial, to examine and quantitate cannabinoid presence.
Methods
Blood samples from two research staff were taken during the exposure period for three participants (cannabis users) over the course of approximately 2.5 h and analysed using tandem mass spectrometry.
Results
Blood samples taken over a vaporised period revealed exposure below the limit of detection for Δ9-tetrahydrocannabinol and two metabolites, using tandem mass spectrometry analytical methods.
Conclusions
These results are reassuring for hospital and clinical trial practices with staff administering vaporised cannabinoid products, and helpful to ethics committees wishing to quantify risk.
Key Point
| Staff administering vaporised cannabinoid products in a clinical setting do not appear to be at risk from second-hand exposure. |
Introduction
Medicinal cannabis use, whilst now legal in many jurisdictions, remains a topic of great controversy. For its consideration for use in mainstream medical treatment pathways as a ‘therapeutic good’, or in clinical trials in hospital settings, it is crucial to understand the acceptability and side effects of the route of administration for different products and dosing regimens. One route that has become of clinical interest is that of vaporisation of cannabinoid products. Although requiring a registered therapeutic device for administration, this is a relatively safe method of intrapulmonary administration that avoids risks associated with smoking and the formation of pyrolytic toxic compounds as it does not involve combustion [1]. It is also less likely to be associated with the cultural and societal assumptions linked with recreational cannabis use. The vaporisation route of administration may be particularly useful for patients with difficulty swallowing and for those in whom higher concentrations of cannabinoids are needed quickly. Peak plasma Δ9-tetrahydrocannabinol (THC) concentrations are reached within minutes of inhalation and have a rapid distribution phase [2–4].
The concern that other patients, nurses, and clinical or research staff may be exposed to second-hand vapours in the course of administering vaporised products to patients may limit the uptake of this form of treatment. Similar concerns have been raised for other medications, such as potential antimicrobial resistance development from exposure to nebulised antibiotics [5]. Previous well-controlled studies have determined that second-hand exposure to cannabis smoke may produce positive blood and urine test results and minor drug effects in non-smokers only under extreme conditions: non-smokers being in very close proximity to smokers using medium-high potency cannabis ad libitum in a small unventilated area for 1 h and using sensitive urinary assays with low cut-off criteria [6, 7]. Under extreme exposure conditions to inhaled cannabis smoke within a motor vehicle, no THC was detected in the oral fluid of those passively exposed [8], noting limitations with the interpretation of salivary cannabinoid assays in detecting the time of use and overall exposure, reviewed in [9]. No studies have investigated systemic exposure from second-hand vaporised cannabinoid product use. We used opportunistic sampling from staff administering vaporised pure THC within a clinical trial in a hospital setting to examine the likely risk.
Methods
In a clinical trial involving a vaporised ethanolic solution of 6 mg of THC [ISRCTN24109245] [10] using the Volcano® ‘Digit’ model vaporiser (Storz & Bickel GmbH & Co., Tuttlingen, Germany) set at 230 °C, two female clinical research staff gave informed consent to contribute blood samples to ascertain their exposure. Vaporisation of THC into the balloon and administration of the balloon filled with vapours for inhalation by trial participants (cannabis users and nonusers) was conducted in a small standard clinical assessment room on a hospital ward, away from other patients and near to imaging facilities. The approximate size of the room was 3 m × 2 m. One of the staff (A; whose BMI was 20.1) administered the balloon to the participant and remained approximately 1 m away from the participant during inhalation and exhalation. The other staff member (B; BMI 20.2) was positioned inside the room but closer to the partially opened door, approximately 2 m away from the participant. There was no specific ventilation in the room aside from a standard small air conditioning vent. Participants inhaled and exhaled on average six to ten times to empty a balloon, and two balloons were administered. The first contained vaporised THC, the second contained the placebo (ethanol flavoured air; see [10] for methodology) and participants took on average 9 min to complete inhalation of both balloons (~ 5–6 min for the THC balloon and 3–4 min for the placebo balloon). Four blood samples were collected from staff over the course of approximately 2.5 h. The first was taken prior to any drug administration. The subsequent three were taken 5 min after each of the three participants completed inhalation of the balloons, with participants spaced approximately 1 h apart. Administration to the three participants occurred in the same room following the same procedures. As such, there was the possibility of cumulative exposure over the course of this approximate 2.5 h period.
Staff gave 5 mL of blood, collected into EDTA tubes, which were covered with aluminium foil to prevent light exposure and kept on ice until the end of the day when they were centrifuged at 2000×g for 10 min at 4 °C and the plasma extracted. Plasma samples were stored frozen at − 80 °C and subsequently defrosted for assay by tandem mass spectrometry [11]. Plasma (50 µL) samples were combined with 100 µL of acetonitrile containing deuterated internal standards. Samples were then vortexed before being centrifuged at 15,000×g for 5 min. The supernatant was transferred into vials for measurement using liquid chromatography tandem mass spectrometry. The instrument was composed of a Shimadzu Nexera X2 ultra-high performance liquid chromatograph (Shimadzu Corporation, Kyoto, Japan) with a SCIEX 6500QTrap, a Kinetex Biphenyl column using a gradient of acetonitrile and 0.1% formic acid. The limit of quantitation was 0.5 ng/mL for each THC, and the metabolites 11-hydroxy-Δ9-tetrahydrocannabinol (OH-THC) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (COOH-THC). The limit of detection was 0.2 ng/mL for THC, 0.15 ng/mL for OH-THC and 0.25 ng/mL for COOH-THC.
One of the research staff (B) also performed a urinary drug test several hours after these procedures (ProScreen™ Dip Test (US Diagnostics Inc, Huntsville, AL, USA); cut-off 50 ng/mL). Both staff also performed salivary tests for THC (Oratect® IIIB (AlereTM Toxicology Services, Portsmouth, VA, USA); cut-off 40 ng/mL).
Results
No cannabinoids were detected in plasma from either staff member (A or B) at baseline, nor, as shown in Table 1, at any of the three timepoints taken 5 min after completion of inhalation of THC vapours by each of three participants spaced 1 h apart. The urinary drug test was negative for cannabinoids. The salivary THC tests were both negative.
Sample THC OH-THC COOH-THC A (1) <LOD <LOD <LOD A (2) <LOD <LOD <LOD A (3) <LOD <LOD <LOD B (1) <LOD <LOD <LOD B (2) <LOD <LOD <LOD B (3) <LOD <LOD <LOD
That the experiment and assays were valid, is evidenced by the quantification of THC and metabolites in the plasma of two of the THC-exposed male research participants (X and Y) shown in Table 2 (blood was not successfully drawn from the third participant because of unviable veins). Plasma concentrations in Table 2 correspond to baseline (pre-drug administration; 1), 5 min after inhalation of the two balloons (2) and 1 h later (3). Participant Y was a heavy cannabis user, explaining cannabinoid concentrations present at baseline.
Sample THC OH-THC COOH-THC X (1) <LOD <LOD <LOD X (2) 183.4 1.6 <LOD X (3) 15.2 1.0 4.9 Y (1) 12.9 3.4 75.6 Y (2) 223.5 4.5 66.1 Y (3) 28.9 6.3 68.3
Conclusions
These results suggest that there is little risk of second-hand exposure to clinical or research staff from administering vaporised THC within a clinical setting. Previous research has suggested that 35% of THC vapours inhaled are exhaled directly after inhalation [1] and we previously showed that 80% of the THC loaded into the vaporiser is delivered into the balloon [10]. Overall, this efficiency of delivery method is comparable to that achieved through a smoking route of cannabis administration [1]. These conditions and the conditions within which this small study was performed emulate administration of medicinal cannabis on a hospital ward, without the smoke, and optimised the opportunity to detect cannabinoids in the biological fluids of staff, yet none were detected. Together with the fact that newer vaporisers, e.g. MiniVap (Hermes Medical Engineering, San Sebastián, Spain) have less ‘gas escape’ than the one used in this study, these outcomes should reassure researchers of the safety for staff in administering medicinal cannabis to patients in this setting. Nevertheless, the THC dose used in this study was relatively low (6 mg), and while higher doses are also not expected to result in detectable cannabinoids in clinical staff exposed under these conditions, replication of these findings with a larger sample size, more timepoints, alternate vaporisers, and with vaporisation of cannabis plant matter is warranted.
Acknowledgements
The authors thank Sarah Gallagher, Elke Macdonald and Gabrielle Puckett for assistance with blood sampling, and Prof. Dion Forstner, Prof. Gary Liney and Robba Rai for access to facilities for the conduct of the study at the Cancer Therapy Centre, Liverpool Hospital facilitated by the Ingham Institute, Liverpool, NSW, Australia.
Compliance with Ethical Standards
Funding
The original study that enabled the analyses reported here was funded by the National Health and Medical Research Council of Australia (APP1007593). Nadia Solowij was supported by an Australian Research Council Future Fellowship (FT1101007752).
Conflict of interest
Nadia Solowij, Peter Galettis, Samantha J. Broyd, Peter de Krey and Jennifer H. Martin have no conflicts of interest directly relevant to the content of this article.
Ethics approval
All procedures performed involving human participants were in accordance with the ethical standards of the institutional research committees and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Consent to participate
Informed consent was obtained from all individual participants included in the study.