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Lastly, a small independent investigator-initiated non-randomized study of 10 MS patients with neuropathic pain showed that 4 weeks’ treatment with THC:CBD oromucosal spray (nabiximols) significantly reduced the pain rating from baseline (assessed by VAS; p = 0.001) and improved quality of life measures. Interestingly, the clinical effects observed with THC:CBD spray (nabiximols) were paralleled by an increase in fronto-central γ-band oscillation and pain-motor integration strength. 91
Use of herbal cannabis (smoked, vaporized, orally ingested), at present at least, is not suitable to manage pain or other medical conditions. Aside from practical issues such as restricted availability as regulated by national or regional health authorities, risks of herbal cannabis include variability in cannabinoid type and potency, potential for misuse/dependency, and possible future mental health-related consequences in young people. 57
Chronic pain is a common and frequently debilitating condition that carries a large individual and societal burden. Numerous etiological factors contribute to its development. Discovery of the endocannabinoid system and its role in pain control and habituation to stress suggested that cannabinoids may be useful to manage pain conditions. Activation of cannabinoid receptors has multiple analgesia-associated effects mediated by the peripheral and central nervous systems.
Treatment of Chronic Neuropathic Pain
Notes: † Mean pain 0–10 NRS score in patients completing 2 years’ follow-up; § 0–10 Box Scale score; ‡ Pain 0–10 NRS score decreased over time from a mean of 6.9 points (baseline in the parent studies) to a mean of 5.5 points (end of parent studies), to a mean of 4.2 points (end of open-label treatment) in remaining patients.
Notes: Adapted with permission from Attal N, Cruccu G, Baron R, et al. European Federation of Neurological Societies. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010;17(9):1113–e88. 32 †Tramadol may be considered first line in patients with acute exacerbations of pain especially in combination with acetaminophen. § Lidocaine is recommended in elderly patients.
During clinical development of THC:CBD oromucosal spray (nabiximols) for MS spasticity, the most common treatment-related adverse events were mild to moderate transient episodes of dizziness, fatigue or somnolence. 38 , 78 Less commonly, mucosal irritation was reported. 38 To date, THC:CBD oromucosal spray (nabiximols) has not been associated with drug tolerance or a withdrawal syndrome 79 and there has been no evidence of drug misuse or abuse. 38 The estimated total post-marketing exposure of THC:CBD spray (nabiximols) at the end of 2018 was more than 120,000 patient-years. 80
Mechanism of Action of Cannabinoids
In preclinical rodent models, activation of cannabinoid receptors reduced neuropathic and chronic inflammatory pain. 35 , 40 , 48 Recently, in a well-established nerve injury model of neuropathic pain, treatment with CBD for 7 days normalized impaired serotonergic (5-HT) neurotransmission, reduced mechanical allodynia and decreased anxiety-like behavior. 56 The findings are important since they show that the effects of CBD relate not only to a reduction in pain intensity and modification of pain quality, but especially to a change in anxiety-related behavior.
Other phytocannabinoids containing multiple different cannabinoids (eg Bedrocan ® ) have yet to undergo clinical trial development or receive approval for a first official indication. A plant-derived medicine containing single purified CBD (cannabidiol oral solution, Epidiolex ® ) was recently approved by the US Food and Drug Administration and European Medicines Agency for treatment of the rare epileptic syndromes, Lennox–Gastaut and Dravet. 67 , 68 Dronabinol (Marinol ® , Syndros ® ) is a synthetic THC indicated for treatment of anorexia associated with weight loss in patients with AIDS, and treatment of severe refractory nausea and vomiting associated with cancer chemotherapy. 69 , 70 Nabilone (Cesamet ® , Canemes ® ) is a THC analog indicated for treatment of severe refractory nausea and vomiting associated with cancer chemotherapy. 71