Abstract
INTRODUCTION: This phase I open-label study examined pharmacokinetics, safety, and tolerability of escalating doses of a novel combination cannabinoid medication (1:1 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).