Pilot clinical and pharmacokinetic study of Δ9-Tetrahydrocannabinol (THC)/Cannabidiol (CBD) nanoparticle oro-buccal spray in patients with advanced cancer experiencing uncontrolled pain

PLoS One. 2022 Oct 14;17(10):e0270543. doi: 10.1371/journal.pone.0270543. eCollection 2022.

Abstract

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 Δ9-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 Δ9-THC than CBD (AUC from 2.5 mg each of Δ9-THC and CBD, was 1.71 ng mL.h-1 (1.1, 6.6) and 0.65 ng mL.h-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 Δ9-THC/CBD, appeared safe and tolerable in advanced incurable cancers with uncontrolled pain with preliminary evidence of analgesic efficacy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / therapeutic use
  • Analgesics, Opioid / therapeutic use
  • Cannabidiol* / adverse effects
  • Cannabinoids*
  • Cannabis*
  • Dronabinol / adverse effects
  • Humans
  • Male
  • Nanoparticles*
  • Neoplasms* / chemically induced
  • Neoplasms* / complications
  • Neoplasms* / drug therapy
  • Pain, Intractable*
  • Pilot Projects
  • Water

Substances

  • Analgesics
  • Analgesics, Opioid
  • Cannabinoids
  • Water
  • Cannabidiol
  • Dronabinol

Grants and funding

The sole source of funding was from the funder organization (Medlab Clinical), no other institution had a funding role of the study. The funder organization provided support in the form of salaries for authors JDH, DR, SH, and LV. The funder organization funded the independent statistician BB. The funder organization did not have any role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. JDH and LV in their current adjunct academic roles with the University of Sydney and University of New South Wales respectively provided input into the study protocol design and manuscript preparation. The specific roles of all authors are articulated in the ‘Author Contributions’ section. The URL of the funder is https://www.medlab.co/.