Cancer pain results from inflammation, invasion of bone or other pain-sensitive structures, or nerve injury. When cancer pain is severe and persistent, it is often resistant to treatment with opioids.
Two studies examined the effects of oral delta-9-THC on cancer pain. The first, a double-blind placebo-controlled study involving ten patients, measured both pain intensity and pain relief. It was reported that 15 mg and 20 mg doses of the cannabinoid delta-9-THC were associated with substantial analgesic effects, with antiemetic effects and appetite stimulation.
In a follow-up single-dose study involving 36 patients, it was reported that 10 mg doses of delta-9-THC produced analgesic effects during a 7-hour observation period that were comparable to 60 mg doses of codeine, and 20 mg doses of delta-9-THC induced effects equivalent to 120 mg doses of codeine. Higher doses of THC were found to be more sedative than codeine.
Another study examined the effects of a whole-plant extract with controlled cannabinoid content in an oromucosal spray. In a multicenter, double-blind, placebo-controlled study, the THC:cannabidiol nabiximols (THC:CBD) extract and THC extract alone were compared in the analgesic management of patients with advanced cancer and with moderate-to-severe cancer-related pain. Patients were assigned to one of three treatment groups: THC:CBD extract, THC extract, or placebo. The researchers concluded that the THC:CBD extract was efficacious for pain relief in advanced cancer patients whose pain was not fully relieved by strong opioids. In a randomized, placebo-controlled, graded-dose trial, opioid-treated cancer patients with poorly controlled chronic pain demonstrated significantly better control of pain and sleep disruption with THC:CBD oromucosal spray at lower doses (1–4 and 6–10 sprays/day), compared with placebo. Adverse events were dose related, with only the high-dose group (11–16 sprays/day) comparing unfavorably with the placebo arm. These studies provide promising evidence of an "adjuvant analgesic" effect of THC:CBD in this opioid-refractory patient population and may provide an opportunity to address this significant clinical challenge. An open-label extension study of 43 patients who had participated in the randomized trial found that some patients continued to obtain relief of their cancer-related pain with long-term use of the THC:CBD oromucosal spray without increasing their dose of the spray or the dose of their other analgesics.
An observational study assessed the effectiveness of nabilone in advanced cancer patients who were experiencing pain and other symptoms (anorexia, depression, and anxiety). The researchers reported that patients who used nabilone experienced improved management of pain, nausea, anxiety, and distress when compared with untreated patients. Nabilone was also associated with a decreased use of opioids, nonsteroidal anti-inflammatory drugs, tricyclic antidepressants, gabapentin, dexamethasone, metoclopramide, and ondansetron.
Animal studies have suggested a synergistic analgesic effect when cannabinoids are combined with opioids. The results from one pharmacokinetic interaction study have been reported. In this study, 21 patients with chronic pain were administered vaporized Cannabis along with sustained-release morphine or oxycodone for 5 days. The patients who received vaporized Cannabis and sustained-release morphine had a statistically significant decrease in their mean pain score over the 5-day period; those who received vaporized Cannabis and oxycodone did not. These findings should be verified by further studies before recommendations favoring such an approach are warranted in general clinical practice.