Cannabinoids for Therapeutic Use

Abstract

The two main modes of cannabinoid administration, oral ingestion of tetrahydrocannabinol (THC) and smoking of dry cannabis plant material, both have specific advantages and disadvantages. Disadvantages of oral ingestion include slow and erratic absorption, delayed onset of action and low systemic bioavailability, whereas disadvantages of smoking include mucosal damage and short duration of effect. In recent years several new modes of cannabinoid delivery have been tested. Alternative routes of systemic pulmonary administration include inhalation with a vaporizer and the use of cannabinoids in aerosol form. They avoid or reduce the formation of carcinogenic combustion products found in cannabis smoke. Sublingual (buccal) administration of liquid cannabis extracts has been tested in clinical trials in the UK. This mode is easy to administer and might enable easier dose titration than oral capsules. Transdermal delivery achieves a sustained and steadier action than inhalation or oral administration of THC, and is being investigated in preclinical studies by groups in the US and Israel. Use of ethosomal carriers has been shown to enhance skin permeation by the lipophilic cannabinoids. Rectal administration of THC-hemisuccinate suppositories has been tested in some patients; systemic bioavailability is twice as high as with oral administration because of the reduced first-pass effect. Water-soluble agonists to the cannabinoid receptor that allow intravenous administration have been developed. Dexanabinol, a non-psychotropic neuroprotective cannabinoid derivative, was given intravenously in clinical studies to decrease the consequences of severe closed head injuries. Increasing water solubility, for example by the use of cyclodextrin technology, also improved the possibilities of topical cannabinoid administration to the eye for glaucoma treatment. Several of these new approaches to cannabinoid delivery now under preclinical and clinical investigation may find their way into clinical practice within a few years.