An overview of the Cannabis-based compounded preparations in Italian pharmacies

Over the last few months, an increasing number of Italian pharmacists had to supply medicinal products based on Cannabis sativa L. (Cannabaceae), prescribed by physicians to individual patients. Compounded preparations are mainly intended for oral administration, in the form of a liquid extract. Extraction in aqueous or organic solvents is a way to obtain a highly concentrated content of cannabinoids and other beneficial components. Cannabis tea can be prepared directly by patient or the caregiver, using medicinal Cannabis flos exactly dosed by the pharmacist in filters or in sprinkle capsules. Due to limited cannabinoid solubility in water, even in the case of low content of cannabis in the dosage form, a saturated solution of THC is obtained; it can be supposed therefore that cannabis tea has only a limited potency. The addition of milk in water can improve cannabinoid solubility. Ethanol extracts have also been used, considering the higher solubility of the active principles in this solvent than in water. An example of this use is the industrial medicinal product, Sativex based on a hydroalcoholic mixture containing THC and CBD in 1:1 ratio. Nevertheless, the solvent of choice for cannabis extraction is oil; in Italian pharmacies, concentrated extracts of cannabinoids in olive oil are prepared, even though standardized operative conditions for compounding are not yet available. To compound these preparations, different Cannabis varieties, with standardized THC and CBD concentrations, are available on the market. Given the experience of the Laboratory of Chemical and Toxicological Analysis, University of Milan, more than 2000 oily preparations were analysed over 2017 and 2018. In order to prepare the oil, the most used/prescribed Cannabis varieties were Bedrocan followed by Bediol and than FM2. Physicians also prescribed the other cannabis varieties (Bedica; Bedrobinol; Bedrolite), alone or in combinations. Recently the Canadian variety Pedanios was introduced. As expected, the preparation method is strongly relevant for cannabinoid extraction and therefore for the oil cannabinoid content; composition of the oily extracts is strongly influenced by operative conditions of the different compounding methods