Inflammation, autoimmune response, demyelination, and axonal damage are thought to participate in the pathogenesis of MS. Increasing evidence supports the idea of a beneficial effect of cannabinoid compounds for the treatment of this disease. In clinical trials, it has been shown that cannabis derivatives are active on the pain related to MS,84,85,95,97,98 However, this is not the only positive effect of cannabinoids in this disease. In rat experimental autoimmune encephalomyelitis (EAE), a laboratory model of MS, THC, given once after disease onset, significantly reduced maximal EAE score. Reduction in the inflammatory response in the brain and spinal cord was also noted in animals treated with dexanabinol (HU-211 a nonpsychoactive synthetic cannabinoid).101 In another trial in rats, all animals treated with placebo developed severe clinical EAE and more than 98 % died, while THC-treated animals had either no clinical signs or mild signs, with delayed onset with survival greater than 95 %.102 WIN-55,212-2, another synthetic cannabinoid, also was found to ameliorate the clinical signs of EAE and to diminish cell infiltration of the spinal cord, partially through CB2.103 Using a chronic model of MS in mice, it was shown that clinical signs and axonal damage in the spinal cord were reduced by the synthetic cannabinoid HU210.104 To more fully inderstand the involvement of the endocannabinoid system in MS, the status of cannabinoid CB1 and CB2 receptors and fatty acid amide hydrolase (FAAH) enzyme in brain tissue samples obtained from MS patients was investigated. Selective glial expression of cannabinoid CB1 and CB2 receptors and FAAH enzyme was found to be induced in MS.105 In mice with chronic relapsing experimental allergic encephalomyelitis (CREAE), a chronic model of MS that reproduces many of the pathological hallmarks of the human disease, a moderate decrease in the density of CB1 receptors in the caudate-putamen, globus pallidus, and cerebellum was found. These observations may explain the efficacy of cannabinoid agonists in improving motor symptoms (spasticity, tremor, ataxia) typical of MS in both humans and animal models.106 Spasticity is a common neurologic condition in patients with MS, stroke, cerebral palsy, or an injured spinal cord. Marijuana was suggested as treatment of muscle spasticity as early as the 1980s.107 In an experiment in mice, control of spasticity in a MS model was found to be mediated by CB1, but not by CB2, cannabinoid receptors.108 In clinical trials, patients treated with THC had significant improvement in ratings of spasticity compared to placebo.109 In one case report nabilone improved muscle spasms, nocturia, and general well-being.110 In another case report, the chronic motor handicaps of an MS patient acutely improved while he smoked a marijuana cigarette.111 THC significantly reduced spasticity by clinical measurement. Responses varied, but benefit was seen in patients with tonic spasms.112 At a progressive stage of illness, oral and rectal THC reduced the spasticity, rigidity, and pain, resulting in improved active and passive mobility.113 However, in other clinical trials, cannabinoids appeared to reduce tremor but were ineffective in spasticity.114,115 Moreover, in one trial marijuana smoking further impaired posture and balance in patients with spastic MS.116 The inconsistent effects noted might be due to dosedependency. Improved motor coordination was seen when patients with MS, seriously disabled with tremor and ataxia, were given oral THC.117 In another study, cannabis extract did not produce a functionally significant improvement in MS-associated tremor.118 Suppression of acquired pendular nystagmus (involuntary movement of the eyes) was seen in a patient with MS after smoking cannabis resin, but not after taking nabilone tablets or orally administered capsules containing cannabis oil.119 There are also findings suggestive of a clinical effect of cannabis on urge incontinence episodes in patients with MS.120 In the treatment of MS, as well as in pain reduction described earlier, there is a preferential effect of a THC+CBD combination (Sativex).121 A mixture of 2.5 mg THC and 0.9 mg cannabidiol (CBD) lowered spasm frequency and increased mobility, with tolerable side effects, in MS patients with persistent spasticity not responding to other drugs.122 Oromucosal sprays of Sativex significantly reduced spasticity scores in comparison with placebo.123 Long-term use of Sativex maintains its effect in those patients who perceive initial benefit.124 Zajicek et al originally reported that cannabinoids did not have a beneficial effect on spasticity; however, there was an objective improvement in mobility and some patients reported an improvement in pain.125 Later the same group also found positive effects on muscle spasticity with prolonged treatment.126  The subject has been thoroughly reviewed.99,127,130  

Cannabis -vs- Cerebral Palsy