Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study

In a crossover, double-blind RCT comparing nabilone and dihydrocodeine for chronic neuropathic pain, the mean VAS score decreased to a greater extent in the group receiving nabilone first then dihydrocodeine, corresponding to an overall treatment effect of 5.6 mm (95% CI 0.8-10.3, p=0.023).

“The mean VAS score decreased to a greater extent in the group receiving nabilone first then dihydrocodeine, which corresponded to an overall treatment effect of 5.6 mm (95% confidence interval [CI] 0.8-10.3,p=0.023).”

Neither nabilone nor dihydrocodeine reduced pain by a clinically significant amount (>10-mm drop in VAS) in half of the study population.

“Neither treatment at the end of the treatment period reduced pain by a clinically significant amount (i.e., > 10-mm drop in VAS) in half of the study population.”

In the RCT comparing nabilone and dihydrocodeine, improvements in anxiety and sleep were comparable between groups.

“In the RCT comparing NABILONE FOR PAIN MANAGEMENT Tsang and Giudice 281 nabilone and dihydrocodeine, improvements in anxiety and sleep were comparable between groups.15”

Studies evaluating nabilone for pain management excluded patients with a history of psychiatric illness, severe organ disease, epilepsy/seizures, and a history of substance abuse or dependence.

“Studies evaluating nabilone for pain management excluded patients with a history of psychiatric illness (bipolar disorder, schizophrenia, psychosis, depression), severe organ disease (heart, liver, or kidney), epilepsy/seizures, and a history of substance abuse or dependence.[15][16][17][19][20][21]”

Reported adverse drug reactions were generally mild to moderate in intensity, and few serious ADRs were reported.

“Reported adverse drug reactions (ADRs) were generally mild to moderate in intensity, and few serious ADRs were reported.[15][16][17][18][19][20][21][22]25”

Nabilone provides only modest reductions in pain at best.

“Nabilone provides only modest reductions in pain at best [15][16][17][18][19][21][22][23][24]”

Adverse drug reactions are usually mild to moderate in severity and commonly include drowsiness, dizziness, dry mouth, headache, clumsiness, loss of memory, difficulty concentrating, appetite changes, nausea, euphoria or elevation in mood, confusion, and depression.

“Adverse drug reactions are usually mild to moderate in severity and commonly include drowsiness, dizziness, dry mouth, headache, clumsiness, loss of memory, difficulty concentrating, appetite changes, nausea, euphoria or elevation in mood, confusion, and depression 15,[17][18][19][22][23][24]”

Randomized controlled trials using active comparators are lacking, except in two studies.

“RCTs using active comparators are lacking, except in two studies.15,20”

In that RCT, the overall mean ± SD VAS score was 59.93 ± 24.42 mm for nabilone and 58.58 ± 24.08 mm for dihydrocodeine.

“However, the overall mean Æ SD VAS score was 59.93 Æ 24.42 mm for nabilone and 58.58 Æ 24.08 mm for dihydrocodeine, respectively.”

No statistical analysis was conducted for the comparisons of ADRs between nabilone and dihydrocodeine or amitriptyline.

“No statistical analysis, however, was conducted.15,20”

When compared with dihydrocodeine and amitriptyline, patients receiving nabilone had a higher overall occurrence of ADRs.

“When compared with dihydrocodeine and amitriptyline, patients receiving nabilone had a higher overall occurrence of ADRs.15,20”

Nausea and dizziness were more frequent in patients receiving nabilone compared with dihydrocodeine and amitriptyline.

“Nausea and dizziness were more frequent in patients receiving nabilone compared with dihydrocodeine (which caused less frequent nausea) and amitriptyline (which caused less frequent dizziness).15,20”

Patients receiving nabilone had a lower occurrence of nightmares and headaches versus dihydrocodeine and amitriptyline.

“On the other hand, patients receiving nabilone had a lower occurrence of nightmares and headaches versus dihydrocodeine (which caused more frequent nightmares) and amitriptyline (which caused more frequent headaches).15,20”

Other studies gave similar results in neuropathic pain: nabilone versus gabapentin and nabilone versus dihydrocodeine.

“Other studies gave similar results in the management of neuropathic pain: one comparing nabilone and gabapentin used as add-on or mono-therapy in patients with peripheral neuropathy [20] and another comparing nabilone with dihydrocodeine in neuropathic pain [21].”

In a third study, it was concluded that the weak opioid dihydrocodeine was a statistically better treatment for chronic neuropathic pain than nabilone.

“In this latter study,166 it was concluded that the weak opioid dihydrocodeine was a statistically better treatment for chronic neuropathic pain than nabilone.166”

Patients in this study exhibited a mean baseline visual analogue scale rating of 69.6 mm on a 0-100 mm scale; mean ratings were 59.93 ± 24.42 mm for nabilone and 58.58 ± 24.08 mm for dihydrocodeine.

“Patients in this study exhibited a mean baseline VAS rating of 69.6 mm on a 0-100 mm VAS scale; mean VAS ratings were 59.93 ± 24.42 mm and 58.58 ± 24.08 mm for patients taking nabilone and dihydrocodeine, respectively.”

The authors noted that a small number of subjects responded well to nabilone and side-effects were generally mild and in the expected range.

“However, the authors noted that a small number of subjects responded well to nabilone and side-effects were generally mild and in the expected range.166”