Research: Cannabis smoked three times per day reduced the intensity of neuropathic pain, improved sleep and was well tolerated

Smoked cannabis for chronic neuropathic pain: a randomized controlled trial

Mark A. Ware [[The Department of Anesthesia, the Department of Family Medicine, McGill University, Montréal, Que.]], Tongtong Wang [[The Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Que.]], Stan Shapiro [[The Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Que.]], Ann Robinson [[Boreal Primum, Montréal, Que.]], Thierry Ducruet [[Boreal Primum, Montréal, Que.]], Thao Huynh [[The Department of Medicine, McGill University, Montréal, Que.]], Ann Gamsa [[The Alan Edwards Centre for Research on Pain, McGill University, Montréal, Que.]], Gary J. Bennett [[The Alan Edwards Centre for Research on Pain, McGill University, Montréal, Que.]], Jean-Paul Collet [[The Centre for Applied Health Research and Evaluation, University of British Columbia, Vancouver, BC]].

CMAJ – Canadian Medical Association Journal, August 30, 2010


Background: 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.

Methods: 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.

Results: 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.

Conclusion:: 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)

Online Appendix

Files in this Data Supplement:

Appendix 1: Methods and Results

Commentary: More evidence cannabis can help in neuropathic pain, Henry J. McQuay

BBC News Health 30 August 2010

Cannabis may relieve chronic nerve pain

Smoking cannabis from a pipe can significantly reduce chronic pain in patients with damaged nerves, a study suggests.


Cannabis plant Cannabis has been used to treat pain since the third millennium BC

A small study of 23 people also showed improvements with sleep and anxiety.

Writing in the Canadian Medical Association Journal, the researchers said larger studies using inhaler-type devices for cannabis were needed.

UK experts said the pain relief seen was small but potentially important, and more investigation was warranted.

Around 1 to 2% of people have chronic neuropathic pain -pain due to problems with signalling between nerves- but effective treatments are lacking.

Some patients with this type of chronic pain say smoking cannabis helps with their symptoms.

And researchers have been investigating whether taking cannabinoids -the chemicals within cannabis that effect pain- in pill form could have the same effect.

But the team from McGill University in Montreal said clinical trials on smoked cannabis were lacking.


The study used three different potencies of cannabis -containing 2.5%, 6% and 9.4% of the active ingredient tetrahydrocannabinol- as well as a placebo (dummy version).

Under nurse supervision, participants inhaled a single 25mg dose through a pipe three times a day for five days followed by nine days off, for four cycles.

Those given the highest dose had significantly reduced average pain compared with the placebo as well as less anxiety and depression, and better sleep.

Study leader Dr Mark Ware said: «To our knowledge, this is the first outpatient clinical trial of smoked cannabis ever reported«.

He said larger more long-term studies with higher potencies of cannabis were needed to further test the findings and to better assess safety.

Clinical trials using inhaler-type devices for delivering measured amounts of cannabis should be carried out, he added.


Professor Tony Dickenson, an expert in pain medicine at University College London, said a lot of patients with this type of pain say they benefit from cannabis but there were clearly health issues associated with self-medicating in this way.

He also said the pain relief seen was quite small but could make an important difference to patients who often suffer sleeplessness and depression because of their condition.

It was also worth investigating whether inhaling the drug was a more effective way of getting it into the body than taking it orally, he added.

«It may be important in the future to find patients who respond particularly well because it may be that it is not suitable for some groups, such as older patients«, he said.

«They didn’t get as many patients in the trial as they wanted and it shows that this sort of research is very difficult to do«.

Dr Peter Shortland, a senior lecturer in neuroscience at Barts and The London School of Medicine and Dentistry, said: «Importantly, smoking the drug did not produce the psychoactive effects commonly associated with full strength cannabis«.

He added the trial was «an encouraging step forward» but further large-scale clinical trials were warranted.

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* Too much cannabis ‘worsens pain’ 24 October 2007, Health

* Body’s own pain relief ‘is best’ 27 July 2006, Health

* Cannabis ‘reduces surgery pain’ 02 June 2006, Health

(2 de setiembre de 2010)