Johnson, J.R., Burnell-Nugent, M., Lossignol, D., Ganae-Motan, E.D., Potts, R., & Fallon, M.T. (2010). 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. Journal of Pain and Symptom Management, 39(2), 167–179.

To compare the efficacy of a tetrahydrocannabinol:cannabidiol (THC:CBD) extract, a nonopioid analgesic endocannabinoid system modulator, and a THC extract to the efficacy of placebo in relieving the pain of patients with advanced cancer; to compare the safety and tolerability of the treatments with those of placebo

Patients with cancer pain, who experienced inadequate analgesia despite chronic opioid dosing, were randomized to THC:CBD extract (n = 60 patients), THC extract (n = 58), or placebo (n = 59) for a two-week, multicenter randomized double-blind, placebo-controlled trial.

• The sample was composed of 177 patients.
• Mean patient age was 60.2 years.
• Of all patients, 82 were female and 95 were male.
• In the sample, the primary cancer sites were breast (29), prostate (24), and lung (20). In the sample, pain classifications included mixed pain (89), bone pain (65), neuropathic (39), visceral (37), and somatic/incident (18). Baseline morphine equivalents median was 120 mg.

• Multisite
• Hospice, hospital, and university settings
• The United Kingdom, Belgium, and Romania

Randomized, double-blind, placebo-controlled, parallel-group study

• Numeric Rating Scale (NRS), 0–10
• Brief Pain Inventory (Short Form) (BPI-SF)
• European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C30) Version 3.0
• Patient-generated diary
• Analysis of covariance (ANCOVA)

• Compared to the placebo and THC groups, approximately twice as many patients in the THC:CBD group had an NRS reduction from baseline of at least 30% (THC:CBD = 23 patients [43%], THC = 12 patients [23%], placebo = 12 patients [21%]).
• The THC groups showed a nonsignificant change, similar to the change in the placebo group.
• In median dose of opioid background medication and in mean number of doses of breakthrough medication across treatment groups, authors observed no change from baseline.
• Authors noted no significant group differences in sleep quality or nausea scores or in pain control assessment. However, the EORTC QLQ-C30 showed, compared to placebo, worsening of nausea and vomiting in the THC:CBD group. The EORTC QLQ-C30 showed no worsening of nausea and vomiting in the THC group.

THC:CBD may be of benefit as an adjunct to opioid when pain is not fully controlled despite chronic opioid therapy. However, this conclusion warrants further investigation; the EORTC questionnaire showed a worsening of nausea and vomiting in the THC:CBD group, compared to the placebo group. In addition, patients in this study reported a consistent impairment of cognitive function. In addition, though authors reported at least a 30% reduction in NRS from baseline in the THC:CBD group, from baseline no change occurred, across treatment groups, in median dose of opioid background medication or mean number of doses of breakthrough medication.

• Treatment models may have varied, country to country.
• The study was very short, with a duration of only two weeks.

THC:CBD extract—a nonopioid analgesic, endocannabinoid system modulator—may be a useful adjunct in managing the pain of patients who have inadequate analgesia from chronic opioids. However, one must consider the potential side effects (i.e. nausea, vomiting, impaired cognitive functions) that may occur as a result of adding this medication.