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Cannabis for peripheral neuropathy: The good, the bad, and the unknown

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References

CBD MAY PROTECT AGAINST ADVERSE EFFECTS

Studies of CBD alone are limited to preclinical data.29 Evidence suggests that CBD alone or combined with THC can suppress chronic neuropathic pain, and that CBD may have a protective effect after nerve injury.30

Nabiximols, an oromucosal spray preparation with equal amounts of THC and CBD, has been approved in Canada as well as in European countries including the United Kingdom. Although its use has not been associated with many of the adverse effects of inhaled cannabis,30–32 evidence of efficacy from clinical trials has been mixed.

Lynch et al,31 in a 2014 randomized, double-blind, placebo-controlled crossover pilot study31 evaluated nabiximols in 16 patients with neuropathic pain related to chemotherapy. No statistically significant difference was found between treatment and placebo. However, the trial was underpowered.

Serpell et al,32 in a 2014 European randomized, placebo-controlled parallel-group study, evaluated 246 patients with peripheral neuropathy with allodynia, with 128 receiving active treatment (THC-CBD oromucosal spray) and 118 receiving placebo. Over the 15-week study, participants continued their current analgesic treatments.

Pain was reduced in the treatment group, but the difference from placebo was not statistically significant. However, the treatment group reported significantly better sleep quality and Patient Global Impression of Change measures (reflecting a patient’s belief of treatment efficacy).

META-ANALYSES CONFIRM EFFECT

Three meta-analyses of available studies of the effects of cannabis on neuropathic pain have been completed.

Andreae et al, 2015: 5 trials, 178 patients

Andreae et al1 evaluated 5 randomized controlled trials in 178 patients in North America. All had had neuropathy for at least 3 months, with a pain level of at least about 3 on a scale of 10. Two studies had patients with HIV-related neuropathy; the other 3 involved patients with neuropathy related to trauma, diabetes, complex regional pain syndrome, or spinal cord injury. All trials used whole cannabis plant provided by NIDA, and the main outcomes were patient-reported pain scales. No study evaluated pain beyond 2 weeks after trial termination.

They found that 1 of every 5 to 6 patients treated with cannabis had at least a 30% pain reduction.

Nugent et al, 2017: 13 trials, 246 patients

Nugent et al33 reviewed 13 trials in 246 patients that evaluated the effects of different cannabis-based preparations on either central or peripheral neuropathic pain from various conditions. Actively treated patients were more likely to report a 30% improvement in neuropathic pain. Again, studies tended to be small and brief.

Cochrane review, 2018: 16 trials, 1,750 patients

A Cochrane review34 analyzed 16 trials (in 1,750 patients) lasting 2 to 26 weeks. Treatments included an oromucosal spray with a plant-derived combination of THC and CBD, nabilone, inhaled herbal cannabis, and plant-derived THC.

With cannabis-based treatments, significantly more people achieved 50% or greater pain relief than with placebo (21% vs 17%, number needed to treat 20); 30% pain reduction was achieved in 39% of treated patients vs 33% of patients taking placebo (number needed to treat 11).

On the other hand, significantly more participants withdrew from studies because of adverse events with cannabis-based treatments than placebo (10% vs 5%), with psychiatric disorders occurring in 17% of patients receiving active treatment vs 5% of those receiving placebo (number needed to harm 10).

The primary studies suffered from methodologic limitations including small size, short duration, and inconsistency of formulations and study designs. Further evaluation of long-term efficacy, tolerability, and addiction potential is critical to determine the risk-benefit ratio.

RISKS OF CANNABIS USE

Like any drug therapy, cannabis has effects that may limit its use. Cannabis can affect a person’s psyche, physiology, and lifestyle.

Impaired attention, task speed

Neurocognitive changes associated with cannabis use—especially dizziness, fatigue, and slowed task-switching—could affect driving and other complex tasks. Evidence indicates that such activities should be avoided in the hours after treatment.26,27,32,33

Concern over brain development

Most worrisome is the effect of long-term cannabis use on brain development in young adults. Regular use of cannabis at an early age is associated with lower IQ, decline in school performance, and lower rates of high school graduation.35

Avoid in psychiatric patients

It is unlikely that cannabis can be safely used in patients with psychiatric illnesses. Anxiety, depression, and psychotic disorders can be exacerbated by the regular use of cannabis, and the risk of developing these conditions is increased while using cannabis.36,37

High concentrations of THC (the highest concentration used in the above studies was 9.5%) can cause anxiety, paranoia, and psychosis.

Respiratory effects

Long-term cannabis smoking may cause wheezing, cough, dyspnea, and exacerbations of chronic bronchitis. There is some evidence that symptoms improve after stopping smoking.33,38

SHOULD WE RECOMMEND CANNABIS?

Where cannabis can be legally used, doctors should be familiar with the literature and its limitations so that they can counsel patients on the best use and potential risks and benefits of cannabis treatment.

A recent conceptualization of pain suggests that a pain score reflects a composite of sensory factors (eg, tissue damage), cognitive factors (eg, beliefs about pain), and affective factors (eg, anxiety, depression).39 Physicians should keep this in mind when evaluating patients to better assess the risks and benefits of cannabis. While pharmacotherapy may address sensory factors, cognitive behavioral therapy may help alter beliefs about the pain as well as anxiety and depressive symptoms that might influence subjective reports.

Ideally, patients being considered for cannabis treatment would have a type of neuropathic pain proven to respond to cannabis in randomized, controlled studies, as well as evidence of failed first-line treatments.

Relative contraindications include depression, anxiety, substance use, psychotic disorders, and respiratory conditions, and these should also be considered.

Although current research shows an analgesic benefit of cannabis on neuropathic pain comparable to that of gabapentin,40 further investigation is needed to better evaluate long-term safety, efficacy, and interactions with standard therapies. Until we have a more complete picture, we should use the current literature, along with a thorough knowledge of each patient, to determine if the benefits of cannabis therapy outweigh the risks.

Acknowledgments: We thank Camillo Ferrari, BS, and Christina McMahon, BA, for their helpful comments.

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