Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study of the Efficacy, Safety, and Tolerability of THC:CBD Extract and THC Extract in Patients with Intractable Cancer-Related Pain
R. Johnson, M. Burnell-Nugent, D.Lossignol, E. D. Ganae-Motan, R. Potts, M. T. Fallon
- 43% of participants experienced a ≥30% reduction in cancer-related pain intensity after cannabinoid treatment
- 20% of cats and 25% of dogs will be diagnosed with cancer in their lifetime
- After 2 weeks of receiving CBD+THC in addition to all other treatments, there was a statistically significant reduction in pain severity when compared with placebo
- The addition of CBD resulted in a increase of 20% in the response rate
- A greater proportion of patients in the cannabinoid treatment group reduced other pain medication doses whereas the highest proportion of increases in dose was in the placebo group
- Administration of THC+CBD was well tolerated and no safety concerns were identified
OBJECTIVES & HYPOTHESIS → The study compared the efficacy of a THC:CBD and a THC-only extract with placebo, in relieving pain in patients with advanced cancer and with at least moderately severe cancer-related pain. 70%-90% of patients with advanced cancer experience significant pain alongside inadequate pain relief with opioids and standard adjuvant analgesics despite dose adjustments. Unacceptable side effects are common with standard pain medication. In this study, both a THC:CBD extract and a THC-only extract were compared against placebo to ascertain if the inclusion of CBD provided a different efficacy or safety profile.
METHODS → 177 patients in a chronic opioid treatment with cancer pain entered a 2 week, double-blind, randomized, placebo-controlled, parallel-group trial. Patients went through a baseline period during which they completed a study diary, recording pain score, background medication and additional pain medication on each day. Patients were then randomized to be treated with THC+CBD, THC only or placebo. The endpoints were the change from baseline in Numerical Rating Scale (NRS) pain score and use of concomitant analgesia. Secondary endpoints included: use of opioid background medication, patient assessments of sleep quality, nausea, memory, concentration, and appetite over the previous 24 hours. A reduction in pain NRS of approximately 30% is considered to represent a clinically important difference and proportions of responders (patients with a reduction in pain NRS of approximately 30%, which is considered clinically important) were compared between treatments.
RESULTS → Change from baseline in mean pain NRS score was statistically significantly in favor of THC+CBD compared with placebo (improvement of -1.37 vs. -0.69), whereas the THC group showed a nonsignificant change (-1.01 vs. -0.69). 43% of patients taking THC+CBD achieved a 30% or greater improvement in their pain score, twice as many as the patients in the THC and placebo groups (THC 23%, placebo 21%). The median difference from placebo was statistically significant for a reduction in pain, which was in favor of THC:CBD extract (0.55 points) but not for the THC extract (0.24 points). Patients maintained stable dosing throughout the treatment period, that is, there was no observed tendency to increase the treatment dose with time. The change in number of daily doses of concomitant medication between baseline and end of study showed a trend toward a decrease in the number of doses taken in the THC+CBD group and an increase in the placebo group. Most drug-related adverse events were mild/moderate in severity. No statistically significant differences in patient-assessed sleep quality or nausea were noted between the study medications and placebo. None of the reported side effects raised concerns regarding treatment safety.