LAUSR

Cannabinoids mainly contained in the female cannabis flowering tops has proved useful in neuropathic pain modulation inhibiting neuronal transmission in pain pathways though pronounced anti-nociceptive effects1. Although most studies up to date have been performed involving a limited number of participants, a series of methodological limitations (e.g. lack of standardized administered preparations or dosages), and an unclear description of the long-term effects, a recent metanalysis study has however shown conclusive and substantial evidence of medical cannabis efficacy for the treatment of patients with chronic neuropathic pain and multiple sclerosis spasticity symptoms2. Conversely, the evidence of efficacy on other types of pain is still limited or insufficient2-4. The combination of the psychoactive cannabis alkaloid 9-tetrahydrocannabinol (THC) with the non-psychotropic alkaloid cannabidiol (CBD), together with their non-psychoactive carboxylated forms – tetrahydrocannabinolic acid and cannabidiolic acid – has demonstrated a greater activity than THC alone in treating both neuropathic pain and spasticity in multiple sclerosis5-8. As heat, oxygen and light progressively decarboxylate the two acidic compounds into THC and CBD, the storage of the flowering tops in closed packets kept in the dark, possibly in a nitrogen atmosphere, is advised. The heating of the flowering tops at a high temperature should also be avoided when preparing cannabis tea or oil products for oral administration9,10. From November 2015, the Military Pharmaceutical Chemical Works of Florence, Italy, started autonomous cultivation and production of medical cannabis, authorized by a Decree of the Italian Ministry of Health11. From January 2017, the batches of the so-called Cannabis FM2, with standardized amount of 6.5% THC and 8% CBD, came into the market. The Italian National Institute of Health, committed to evaluate cannabinoid concentration and their stability in cannabis flowering tops, cannabis tea and oil, have recently demonstrated the poor extraction efficiency of water for cannabinoids required for cannabis medical action together with the extremely short stability (e.g. two days) of the same cannabinoids in aqueous preparations. This has pushed towards the preparation of cannabis oil with a maximum extraction yield and a minimum active compound degradation up to one year9,10. Indeed, the amount of cannabinoids in Italian FM2 cannabis flowering tops grown at a fixed temperature with light-dark cycles, in oil prepared with a standardized procedure, shows within a year only slight changes, which do not affect therapeutic continuity in treated individuals, therefore assuring a homogeneous product of defined stability9. Thus, the cannabis oil prepared by FM2 cannabis flowering tops seems to suit perfectly the multicentre, double blind, placebo controlled clinical trials aimed to definitively assess whether cannabis or cannabinoids used for therapeutic purposes are an effective or ineffective treatment. The prime unmet need is to establish a therapeutic range of THC/CBD concentrations effective in the treatment of neuropathic pain and associated with an acceptable safety profile. In fact, both in a national and international context, there is an enormous discrepancy between daily-administered dosages and administration times even when only using cannabis oil (Tables I-III). European Review for Medical and Pharmacological Sciences 2018; 22: 863-865