Background

Scientific interest in understanding the effects of cannabinoids in humans has grown in recent years with the recognition that different compounds within cannabis plant matter can have vastly different but also synergistic effects. The primary psychoactive constituent of cannabis, ∆⁹-tetrahydrocannabinol (THC), has therapeutic effects in humans, but has also largely been associated with a range of adverse effects, including the induction of psychotic-like symptoms and memory impairment [1]. Another major constituent of cannabis plant matter, cannabidiol (CBD), has been shown to have anxiolytic and antipsychotic properties [2,3] and to ameliorate some of the adverse effects of THC [4,5]. THC and CBD have been shown to have opposing effects on regional brain activation in a range of cognitive tasks [6]. Studies of administration of these compounds to humans have relied on the oral administration of CBD and either smoked, vaporised, oral or intravenous administration of THC. Oromucosal sprays containing THC and CBD in a 1:1 ratio (nabiximols (Sativex^R)) are increasingly being studied for therapeutic efficacy, but these deliver low doses, and higher doses of CBD in particular are thought to be required for meaningful modification of clinical outcomes [7]. Orally administered cannabinoids result in slow and erratic absorption with limited and highly variable bioavailability [8,9]. Smoking and intravenous administration produce reliable and similar pharmacokinetic profiles [9,10], but respectively carry toxic risks and loss of active drug by combustion, or are invasive.

Intrapulmonary administration of cannabinoids is regarded as an effective mode of delivery since it results in fast onset of action and high systemic bioavailability [9]. The vaporisation of cannabinoids (heating plant matter or pure compounds to a temperature where active cannabinoid vapours form but below the point of combustion) is a safe method of intrapulmonary administration because it avoids risks associated with smoking and the formation of pyrolytic toxic compounds as a result of combustion [11]. While some studies have reported on the effects of vaporised THC e.g. [12–14], no study has yet reported on CBD administered via vaporiser. Oral dosing with CBD impedes the potential to examine its interactive effects with THC when the two compounds are administered simultaneously, a scenario with ecological validity for understanding effects in recreational and medicinal cannabis users. Alternative routes of administration of CBD with rapid action, such as vaporisation, would also benefit further investigations of its therapeutic potential as an anxiolytic or antipsychotic, among other applications.

The purpose of this article is to describe methodology developed for the administration of THC alone, CBD alone and their co-administration by means of a vaporiser for studies of acute cannabinoid effects in humans. Since the therapeutic (anxiolytic and antipsychotic) doses of orally administered CBD have generally been quite high (e.g. around 600 mg), we attempted to determine whether it may be possible to vaporise similarly high doses of CBD both alone, and in combination with THC. We report optimised protocols for the delivery of 160 mg or more of CBD by vaporisation.