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Neuropathic pain is difficult to treat. First line treatment includes tricyclic antidepressants (notably amitriptyline), mixed serotonin and norepinephrine reuptake inhibitors (duloxetine for diabetic peripheral neuropathic pain), antiepileptics (gabapentin and pregabalin) and topical agents (lidocaine plasters for postherpetic neuralgia). These drugs can be subsequently associated in case of partial response to monotherapy. Opioids and tramadol are only considered second/third line, alone or in combination with first line drugs.

Neuropathic pain remains difficult to treat. Treatments with established efficacy in several neuropathic conditions include tricyclic antidepressants, gabapentin, pregabalin and strong opioids. Duloxetine and venlafaxine, both antidepressants, and tramadol, an opioid agonist, are also known to be effective in painful polyneuropathies, while lidocaine patches produce analgesic effects, mainly in postherpetic neuralgia. Studies show that pregabalin, gabapentin and duloxetine have positive effects that improve quality of life, and anxiety, depressive, and sleep disorders.

Despite the recent discovery of the potential mechanisms underlying the analgesic effects of cannabis, few clinical studies have so far assessed its analgesic effects, notably in the treatment of chronic non-malignant pain. All the studies used administration of cannabis alone. The aim of this open, pilot, study was to assess the efficacy and side effect profile of oral dronabinol (tetrahydrocannabinol - THC) in the treatment of refractory neuropathic pain.Seven patients (3 women/4 men), aged 60 +/- 14 years, suffering from chronic refractory neuropathic pain, received oral THC titrated to the maximum dose of 25 mg/day (mean dose: 15 +/- 6 mg), during an average of 55,4 days (range: 13-128). Various components of pain (continuous, paroxysmal and brush-induced allodynia) were assessed using VAS scores. Health-related Quality of Life (HRQL) was evaluated using the Brief Pain Inventory, and the Hospital Anxiety and Depression scale was used to measure depression and anxiety.THC did not induce significant effect on the various pain, HRQL and anxiety and depression scores. Numerous side effects (notably sedation and asthenia) were observed in 5 patients out of 7, requiring premature discontinuation of the drug in 3 patients.The present study did not reveal any significant efficacy of THC in a small cohort of patients with chronic refractory neuropathic pain, but underlined the unfavorable side effect profile of the drug. These results may partly relate to the fact that oral dronabinol exhibits a poor therapeutic ratio (efficacy at the price of side effects). The development of new and better tolerated cannabinoids is warranted.