Cannabinoids in the management of difficult to treat pain

Figures & data

Figure 1 Molecular structures of four cannabinoids employed in pain treatment.

Table 1 Results RCTs of cannabinoids in treatment of pain syndromes ()

Drug	Subject number N =	RCT indication	Trial duration	Results/Reference
Ajulemic Acid	21	Neuropathic pain	7 day crossover	VAS improved over placebo (p = 0.02) (Karst et al 2003)
Cannabis, smoked	50	HIV neuropathy	5 days	Decreased daily pain (p = 0.03) and hyperalgesia (p = 0.05), 52% with >30% pain reduction vs placebo (p = 0.04) (Abrams et al 2007)
Cannabis, Smoked	21	Chronic neuropathic pain	5 days	No acute benefit on pain, average daily pain lower on high THC cannabis vs placebo (p = 0.02) (Ware et al 2007)
Cannador	419	Pain due to spasm in MS	15 weeks	Improvement over placebo in subjective pain associated with spasm (p = 0.003) (Zajicek et al 2003)
Cannador	65	Post-herpetic neuralgia	4 weeks	No benefit observed (Ernst et al 2005)
Cannador	30	Post-operative pain	Single doses, daily	Decreasing pain intensity with increased dose (p = 0.01)(Holdcroft et al 2006)
Marinol	24	Neuropathic pain in MS	15–21 days, crossover	Median numerical pain (p = 0.02), median pain relief improved (p = 0.035) over placebo (Svendsen et al 2004)
Marinol	40	Post-operative pain	Single dose	No benefit observed over placebo (Buggy et al 2003)
Nabilone	41	Post-operative pain	3 doses in 24 hours	NSD morphine consumption. Increased pain at rest and on movement with nabilone 1 or 2 mg (Beaulieu 2006)
Sativex	20	Neurogenic pain	Series of 2-week N-of-1 crossover blocks	Improvement with Tetranabinex and Sativex on VAS pain vs placebo (p < 0.05), symptom control best with Sativex (p < 0.0001) (Wade et al 2003)
Sativex	24	Chronic intractable pain	12 weeks, series of N-of-1 crossover blocks	VAS pain improved over placebo (p < 0.001) especially in MS (p < 0.0042) (Notcutt et al 2004)
Sativex	48	Brachial plexus avulsion	6 weeks in 3 two-week crossover blocks	Benefits noted in Box Scale-11 pain scores with Tetranabinex (p = 0.002) and Sativex (p = 0.005) over placebo (Berman et al 2004)
Sativex	66	Central neuropathic pain in MS	5 weeks	NRS analgesia improved over placebo (p = 0.009) (Rog et al 2005)
Sativex	125	Peripheral neuropathic pain	5 weeks	Improvements in NRS pain levels (p = 0.004), dynamic allodynia (p = 0.042), and punctuate allodynia (p = 0.021) vs placebo (Nurmikko et al 2007)
Sativex	56	Rheumatoid arthritis	Nocturnal dosing for 5 weeks	Improvements over placebo morning pain on movement (p = 0.044), morning pain at rest (p = 0.018), DAS-28 (p = 0.002), and SF-MPQ pain at present (p = 0.016) (Blake et al 2006)
Sativex	117	Pain after spinal injury	10 days	NSD in NRS pain socres, but improved Brief Pain Inventory (p = 0.032), and Patients Global Impression of Change (p = 0.001) (unpublished)
Sativex	177	Intractable cancer pain	2 weeks	Improvements in NRS analgesia vs placebo (p = 0.0142), Tetranabinex NSD (Johnson and Potts 2005)
Sativex	135	Intractable lower urinary tract symptoms in MS	8 weeks	Improved bladder severity symptoms including pain over placebo (p = 0.001) (unpublished)

Abbreviations: MS, multiple sclerosis; NRS, numerical rating scale; NSD, no signifi cant difference; RCTs, randomized clinical trials; VAS, visual analogue pain scales.

Figure 2 Comparison of adverse events (AE) encountered with long term therapeutic use of herbal cannabis in the Netherlands (Janse et al 2004; Gorter et al 2005) and Canada (Lynch et al 2006), vs that observed in safety-extension (SAFEX) studies of Sativex oromucosal spray (Russo 2006; Wade et al 2006).

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