Pilot clinical and pharmacokinetic study of [DELTA].sup.9-Tetrahydrocannabinol nanoparticle oro-buccal spray in patients with advanced cancer experiencing uncontrolled pain

• Published in: PloS one Vol. 17; no. 10; p. e0270543
• Main Authors: Clarke, Stephen, Butcher, Belinda E, McLachlan, Andrew J, Henson, Jeremy D, Rutolo, David, Hall, Sean, Vitetta, Luis
• Format: Journal Article
• Language: English
• Published: Public Library of Science 14.10.2022
• Subjects: Cancer; Care and treatment; Chronic pain; Complications and side effects; Medical marijuana; Patient outcomes; Australia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0270543

This pilot study aimed to assess the safety, tolerability, pharmacokinetics and exploratory analgesic effect of a novel water-soluble oro-buccal nanoparticle spray of a cannabis-based medicine (MDCNS-01) in patients with advanced incurable malignancy with unrelieved pain from opioid analgesic. The study was a non-blinded single arm 2 stage study. Stage I was a single escalating dose (n = 5) [2.5 mg [DELTA]9-THC and 2.5 mg CBD) versus a 3-fold escalated dose. Stage II was an up-titrated dose in patients with advanced cancers and intractable pain (n = 25). During Stage I with an increased cannabis-based medicine dose, maximum observed plasma concentrations of cannabinoids were dose dependant. The water-soluble formulation in the current study resulted in a higher median (min, max) systemic exposure of [DELTA]9-THC than CBD (AUC from 2.5 mg each of [DELTA]9-THC and CBD, was 1.71 ng mL.h.sup.-1 (1.1, 6.6) and 0.65 ng mL.h.sup.-1 (0.49, 4.1), respectively). During stage II a subgroup of patients diagnosed with breast and prostate cancers with bone metastases, had the highest mean pain score improvement from baseline of 40% (unadjusted) and 33% (adjusted for rescue medication use). For all patients the most reported adverse events were mild or moderate drowsiness affecting 11 (44%) and 4 (6%) patients, respectively, and nausea and vomiting that affected 18 (72%) patients. The water-soluble cannabis-based medicine provided acceptable bioavailability for [DELTA]9-THC/CBD, appeared safe and tolerable in advanced incurable cancers with uncontrolled pain with preliminary evidence of analgesic efficacy.