Chronic neuropathic pain affects 1%–2% of the adult population and is often refractory to standard pharmacologic treatment. Patients with chronic pain have reported using smoked cannabis to relieve pain, improve sleep and improve mood.
Adults with post-traumatic or postsurgical neuropathic pain were randomly assigned to receive cannabis at four potencies (0%, 2.5%, 6% and 9.4% tetrahydrocannabinol) over four 14-day periods in a crossover trial. Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle, followed by a nine-day washout period. Daily average pain intensity was measured using an 11-point numeric rating scale. We recorded effects on mood, sleep and quality of life, as well as adverse events.
We recruited 23 participants (mean age 45.4 [standard deviation 12.3] years, 12 women [52%]), of whom 21 completed the trial. The average daily pain intensity, measured on the 11-point numeric rating scale, was lower on the prespecified primary contrast of 9.4% v. 0% tetrahydrocannabinol (5.4 v. 6.1, respectively; difference = 0.7, 95% confidence interval [CI] 0.02–1.4). Preparations with intermediate potency yielded intermediate but nonsignificant degrees of relief. Participants receiving 9.4% tetrahydrocannabinol reported improved ability to fall asleep (easier, p = 0.001; faster, p < 0.001; more drowsy, p = 0.003) and improved quality of sleep (less wakefulness, p = 0.01) relative to 0% tetrahydrocannabinol. We found no differences in mood or quality of life. The most common drug-related adverse events during the period when participants received 9.4% tetrahydrocannabinol were headache, dry eyes, burning sensation in areas of neuropathic pain, dizziness, numbness and cough.
A single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated. Further long-term safety and efficacy studies are indicated. (International Standard Randomised Controlled Trial Register no. ISRCTN68314063)
Chronic neuropathic pain has a prevalence of 1%–2%,1 and treatment options are limited.2 Pharmacotherapy includes anticonvulsants, antidepressants, opioids and local anesthetics,3,4 but responses vary and side effects limit compliance.
Cannabis sativa has been used to treat pain since the third millennium BC.5 An endogenous pain-processing system has been identified, mediated by endogenous cannabinoid ligands acting on specific cannabinoid receptors.6 These findings, coupled with anecdotal evidence of the analgesic effects of smoked cannabis,7 support a reconsideration of cannabinoid agents as analgesics.
Oral cannabinoids such as tetrahydrocannabinol, cannabidiol and nabilone have, alone and in combination, shown efficacy in central8,9 and peripheral10 neuropathic pain, rheumatoid arthritis11 and fibromyalgia.12
The analgesic effects of smoked cannabis remain controversial, although it is used by 10%–15% of patients with chronic noncancer pain13 and multiple sclerosis.14 Clinical trials are needed to evaluate these effects, given that the risks and benefits of inhaled cannabinoids may differ from oral agents. To date, three small clinical trials of the analgesic efficacy of smoked cannabis have been reported.15–17 All studies were conducted in residential laboratories, and participants smoked multiple doses of the drug at each time point. No study adequately reported data related to adverse events.
We conducted a clinical trial using a standardized single-dose delivery system to explore further the safety and efficacy of smoked cannabis in outpatients with chronic neuropathic pain.