Page 2 - Cannabis for the Management of Pain: Assessment of Safety Study

1234 The Journal of Pain Cannabis for the Management of Pain
Perspective: This study evaluated the safety of cannabis use by patients with chronic pain over 1
year. The study found that there was a higher rate of adverse events among cannabis users compared
with controls but not for serious adverse events at an average dose of 2.5 g herbal cannabis per day.
ª 2015 The Authors. Published by Elsevier Inc. on behalf of the American Pain Society. This is an open
access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Key words: Cannabis, safety, chronic pain, adverse events, cohort study.

he medical use of cannabis is an issue of major disease or arrhythmia, or who suffered from significant
public health importance. Several countries have and unstable bronchopulmonary disease. Patients were
Tpolicies to allow patients to possess and use instructed not to drive a car or operate a motor vehicle
cannabis for medical purposes. Recently, Health Canada while under the effects of cannabis. Written informed
released the Marihuana for Medical Purposes Regula- consent was obtained from all participants.
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tions, which require a signed document from a health
professional for a patient to access cannabis for medical
purposes. A lack of data on the safety and efficacy of Study Drug
cannabis is a major barrier to physicians’ involvement. Herbal cannabis was provided by Prairie Plant Systems
Several randomized controlled trials of smoked Inc and contained 12.5 6 1.5% tetrahydrocannabinol
cannabis have shown efficacy in chronic pain and (THC) (see Supplementary Material S-1). Patients in the
spasticity. 1,4,17,18 These trials have been short cannabis group were able to use the delivery system
(1–3 weeks of exposure) with small sample sizes with which they were most comfortable. They were
(n = 20–60 participants). Several oral cannabinoid advised to take the first dose in the evening, begin
prescription medications are available, and adverse with low doses, and titrate upward to the maximum
events from clinical trials of these compounds have tolerated dose. An upper limit recommendation of
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been reviewed ; some have been studied for periods 5 g/d was made to reduce the risk of diversion; higher
of up to 1 year. 14,19 Given the potential health concerns doses were allowed when deemed appropriate by the
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of recreational cannabis use, more safety data on the prescribing physician. Cannabis was dispensed by the
long-term medical use of herbal cannabis are needed. site pharmacy at weekly intervals for the first month
We conducted a multicenter cohort study to evaluate and then monthly for the remainder of the study. Before
safety issues in patients with chronic pain using cannabis dispensing, patients returned unused cannabis for
as part of their pain management regimen. weighing and destruction.

Methods
Outcome Measures
Objectives
Primary Outcome
The primary objective was to assess the risk of adverse
events associated with cannabis when used in the treat- The primary outcome of this study was the incidence of
adverse events (AEs) as defined by the International Con-
ment of chronic pain. Secondary objectives were to 9
examine the effects of cannabis on pulmonary and neu- ference on Harmonization. AEs were reported as serious
(SAEs) or non-serious using the International Conference
rocognitive function, and to explore the effectiveness of
cannabis on chronic pain, including pain intensity and on Harmonization guidelines, and coded using the Med-
ical Dictionary for Regulatory Activities (MedDRA version
quality of life.
11.0). Causality and severity were assessed by the study
physician using the World Health Organization-Uppsala
Study Design 13
Monitoring Centre causality assessment system and
A prospective cohort study with a 1-year follow-up was Common Terminology Criteria for Adverse Events v3.0. 3
conducted in 7 clinical centers across Canada between Serious and unexpected AEs were reported to Health
January 2004 and April 2008. Canada and the institutional research ethics boards.

Study Population Secondary Outcomes
Patients 18 years of age or older were eligible if they Neurocognitive function. Neurocognitive testing
experienced chronic non-cancer pain for at least 6 comprised 2 subtests of the Wechsler Memory Scale—Third
months, with moderate to severe pain for which conven- Edition (Verbal Paired Associates I—Recall and Verbal
tional treatments had been considered medically inap- Paired Associates II, including recall and recognition) and
propriate or inadequate. Patients using cannabis as part 2 subtests of the Wechsler Adult Intelligence Scale—Third
of their treatment formed the cannabis group; those Edition (Digit Symbol-Coding, Picture Arrangement).
who were not using cannabis formed the control group, Pulmonary function. Pulmonary function testing con-
matched by site. We excluded patients who were preg- sisted of slow vital capacity, functional residual capacity,
nant or breast-feeding, who had a history of psychosis, residual volume, total lung capacity, forced expiratory
who exhibited significant and unstable ischemic heart volume in 1 second (FEV 1 ), forced vital capacity (FVC),