Pharmacokinetics, Safety, and Tolerability of a Medicinal Cannabis Formulation in Patients with Chronic Non-cancer Pain on Long-Term High Dose Opioid Analgesia: A Pilot Study.

ABSTRACT

INTRODUCTION: This phase I open-label study examined pharmacokinetics, safety, and tolerability of escalating doses of a novel combination cannabinoid medication (11 tetrahydrocannabinol [THC]/cannabidiol [CBD]) in patients with chronic non-cancer pain (CNCP) on high dose opioid analgesia. METHODS: Nine people with CNCP and oral morphine equivalent daily dose of 60 mg or higher were recruited. Blood concentrations of THC, 11-hydroxytetrahydrocannabinol (OH-THC), 11-nor-9-carboxy-tetrahydrocannabinol (COOH-THC), and CBD were assayed weekly. Concentrations were measured after a single dose of 2.5 mg THC/2.5 mg CBD on day 1, and daily escalating doses up to a single dose of 12.5 mg THC/12.5 mg CBD on day 29. Follow-up was on day 36 after a 7-day washout. Secondary outcome data encompassed pain, mood, and sleep parameters. RESULTS: The parent compounds THC, and CBD, and metabolites OH-THC and COOH-THC were detected at most time points. In general, the concentration of all analytes increased until 2 h post-administration, decreasing to approximately pre-dose concentrations by 8 h. There was considerable inter- and intra-individual variability. The study medication was well tolerated. Eight participants reported at least one adverse event (AE), with a total of 62 AEs; most common were euphoric mood, headache, and agitation, none classified as severe. There was no significant change to pain severity self-ratings, nor use of pain medications. Improvements in pain interference scores, mood, and some sleep parameters were observed. CONCLUSION: The THC/CBD formulation was tolerated well in a group of patients with CNCP. Between-participant variability supports personalized dosing and "start low-go slow" titration. To validate and quantify improvements in secondary efficacy outcomes a randomized placebo-controlled study is needed. TRIAL REGISTRATION Australian New Zealand Clinical Trials Register (CT-2019-CTN-01224-1).

Many studies use healthy volunteers when they look at the way medicines are absorbed in the body and their clinical effects. The aim of this project was to examine a new formulation of medicinal cannabis in people who have chronic pain and other health conditions to help us to plan a larger study. We wanted information on how quickly it was absorbed and whether there were any negative effects of the medicine. We wondered whether the fact that participants were on a number of other medications might mean that we see different results to those seen with healthy volunteers. We found that the results of our group were very similar to those seen in other studies. Although we only tested a small number of participants we did not observe serious negative effects of the medication, and saw some positive effects on mood and sleep. We now have the data to assist us in planning a larger study which should provide important guidance to prescribers of medicinal cannabis in the future.