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Review
. 2018 Mar 7;3(3):CD012182.
doi: 10.1002/14651858.CD012182.pub2.

Cannabis-based Medicines for Chronic Neuropathic Pain in Adults

Affiliations
Free PMC article
Review

Cannabis-based Medicines for Chronic Neuropathic Pain in Adults

Martin Mücke et al. Cochrane Database Syst Rev. .
Free PMC article

Abstract

Background: This review is one of a series on drugs used to treat chronic neuropathic pain. Estimates of the population prevalence of chronic pain with neuropathic components range between 6% and 10%. Current pharmacological treatment options for neuropathic pain afford substantial benefit for only a few people, often with adverse effects that outweigh the benefits. There is a need to explore other treatment options, with different mechanisms of action for treatment of conditions with chronic neuropathic pain. Cannabis has been used for millennia to reduce pain. Herbal cannabis is currently strongly promoted by some patients and their advocates to treat any type of chronic pain.

Objectives: To assess the efficacy, tolerability, and safety of cannabis-based medicines (herbal, plant-derived, synthetic) compared to placebo or conventional drugs for conditions with chronic neuropathic pain in adults.

Search methods: In November 2017 we searched CENTRAL, MEDLINE, Embase, and two trials registries for published and ongoing trials, and examined the reference lists of reviewed articles.

Selection criteria: We selected randomised, double-blind controlled trials of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment of conditions with chronic neuropathic pain in adults, with a treatment duration of at least two weeks and at least 10 participants per treatment arm.

Data collection and analysis: Three review authors independently extracted data of study characteristics and outcomes of efficacy, tolerability and safety, examined issues of study quality, and assessed risk of bias. We resolved discrepancies by discussion. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 30% and 50% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardised mean differences for pain intensity, sleep problems, health-related quality of life (HRQoL), and psychological distress. For tolerability, we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawal due to adverse events and specific adverse events, nervous system disorders and psychiatric disorders. For safety, we calculated NNTH for serious adverse events. Meta-analysis was undertaken using a random-effects model. We assessed the quality of evidence using GRADE and created a 'Summary of findings' table.

Main results: We included 16 studies with 1750 participants. The studies were 2 to 26 weeks long and compared an oromucosal spray with a plant-derived combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) (10 studies), a synthetic cannabinoid mimicking THC (nabilone) (two studies), inhaled herbal cannabis (two studies) and plant-derived THC (dronabinol) (two studies) against placebo (15 studies) and an analgesic (dihydrocodeine) (one study). We used the Cochrane 'Risk of bias' tool to assess study quality. We defined studies with zero to two unclear or high risks of bias judgements to be high-quality studies, with three to five unclear or high risks of bias to be moderate-quality studies, and with six to eight unclear or high risks of bias to be low-quality studies. Study quality was low in two studies, moderate in 12 studies and high in two studies. Nine studies were at high risk of bias for study size. We rated the quality of the evidence according to GRADE as very low to moderate.Primary outcomesCannabis-based medicines may increase the number of people achieving 50% or greater pain relief compared with placebo (21% versus 17%; risk difference (RD) 0.05 (95% confidence interval (CI) 0.00 to 0.09); NNTB 20 (95% CI 11 to 100); 1001 participants, eight studies, low-quality evidence). We rated the evidence for improvement in Patient Global Impression of Change (PGIC) with cannabis to be of very low quality (26% versus 21%;RD 0.09 (95% CI 0.01 to 0.17); NNTB 11 (95% CI 6 to 100); 1092 participants, six studies). More participants withdrew from the studies due to adverse events with cannabis-based medicines (10% of participants) than with placebo (5% of participants) (RD 0.04 (95% CI 0.02 to 0.07); NNTH 25 (95% CI 16 to 50); 1848 participants, 13 studies, moderate-quality evidence). We did not have enough evidence to determine if cannabis-based medicines increase the frequency of serious adverse events compared with placebo (RD 0.01 (95% CI -0.01 to 0.03); 1876 participants, 13 studies, low-quality evidence).Secondary outcomesCannabis-based medicines probably increase the number of people achieving pain relief of 30% or greater compared with placebo (39% versus 33%; RD 0.09 (95% CI 0.03 to 0.15); NNTB 11 (95% CI 7 to 33); 1586 participants, 10 studies, moderate quality evidence). Cannabis-based medicines may increase nervous system adverse events compared with placebo (61% versus 29%; RD 0.38 (95% CI 0.18 to 0.58); NNTH 3 (95% CI 2 to 6); 1304 participants, nine studies, low-quality evidence). Psychiatric disorders occurred in 17% of participants using cannabis-based medicines and in 5% using placebo (RD 0.10 (95% CI 0.06 to 0.15); NNTH 10 (95% CI 7 to 16); 1314 participants, nine studies, low-quality evidence).We found no information about long-term risks in the studies analysed.Subgroup analysesWe are uncertain whether herbal cannabis reduces mean pain intensity (very low-quality evidence). Herbal cannabis and placebo did not differ in tolerability (very low-quality evidence).

Authors' conclusions: The potential benefits of cannabis-based medicine (herbal cannabis, plant-derived or synthetic THC, THC/CBD oromucosal spray) in chronic neuropathic pain might be outweighed by their potential harms. The quality of evidence for pain relief outcomes reflects the exclusion of participants with a history of substance abuse and other significant comorbidities from the studies, together with their small sample sizes.

Conflict of interest statement

MM: none known; MM is a specialist in palliative care who treats patients with chronic neuropathic pain.

TP: none known; TP is a specialist pain physician and manages patients with neuropathic pain.

LR: none known; PR is a specialist in palliative care who treats patients with chronic neuropathic pain.

FP is a specialist in pain medicine who treats patients with chronic neuropathic pain. He has received speaking fees for one educational lecture for Janssen‐Cilaq (2015) on fibromyalgia and participated in an advisory board for the same company focusing on an unrelated product (2015).

WH is a specialist in general internal medicine, psychosomatic medicine and pain medicine, who treats patients with fibromyalgia and chronic neuropathic pain. He is a member of the medical board of the German Fibromyalgia Association. He is the head of the steering committee of the German guideline on fibromyalgia and a member of the steering committee of the European League Against Rheumatism (EULAR) update recommendations on the management of fibromyalgia. He received speaking fees for one educational lecture from Grünenthal (2015) on pain management.

Figures

Figure 1
Figure 1
Study flow diagram
Figure 2
Figure 2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
Figure 3
Figure 3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study
Analysis 1.1
Analysis 1.1
Comparison 1 Cannabis‐based medicines versus placebo at final treatment, Outcome 1 Pain relief of 50% or greater.
Analysis 1.2
Analysis 1.2
Comparison 1 Cannabis‐based medicines versus placebo at final treatment, Outcome 2 Patient Global Impression much or very much improved.
Analysis 1.3
Analysis 1.3
Comparison 1 Cannabis‐based medicines versus placebo at final treatment, Outcome 3 Withdrawals due to adverse events.
Analysis 1.4
Analysis 1.4
Comparison 1 Cannabis‐based medicines versus placebo at final treatment, Outcome 4 Serious adverse events.
Analysis 1.5
Analysis 1.5
Comparison 1 Cannabis‐based medicines versus placebo at final treatment, Outcome 5 Pain relief of 30% or greater.
Analysis 1.6
Analysis 1.6
Comparison 1 Cannabis‐based medicines versus placebo at final treatment, Outcome 6 Mean pain intensity.
Analysis 1.7
Analysis 1.7
Comparison 1 Cannabis‐based medicines versus placebo at final treatment, Outcome 7 Health‐related quality of life.
Analysis 1.8
Analysis 1.8
Comparison 1 Cannabis‐based medicines versus placebo at final treatment, Outcome 8 Sleep problems.
Analysis 1.9
Analysis 1.9
Comparison 1 Cannabis‐based medicines versus placebo at final treatment, Outcome 9 Psychological distress.
Analysis 1.10
Analysis 1.10
Comparison 1 Cannabis‐based medicines versus placebo at final treatment, Outcome 10 Withdrawals due to lack of efficacy.
Analysis 1.11
Analysis 1.11
Comparison 1 Cannabis‐based medicines versus placebo at final treatment, Outcome 11 Any adverse event.
Analysis 1.12
Analysis 1.12
Comparison 1 Cannabis‐based medicines versus placebo at final treatment, Outcome 12 Specific adverse event: nervous system disorders.
Analysis 1.13
Analysis 1.13
Comparison 1 Cannabis‐based medicines versus placebo at final treatment, Outcome 13 Specific adverse event: psychiatric disorders.

Update of

  • Cochrane Database Syst Rev. doi: 10.1002/14651858.CD012182

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