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8. The therapeutic effects of cannabinoids
8.4 Cannabinoids and neurological disorders
Historically one of the commonest medical uses of cannabis preparations has been as an anti-convulsant. O'Shaughnessy (1842), for example, recommended the use of cannabis to control seizures in epilepsy, tetanus and rabies (Nahas, 1984). Animal studies have provided some support for this use in showing that THC has dual effects on convulsions, i.e. they can produce convulsions in susceptible animals, and suppress the maximum severity of convulsions from a variety of causes, while cannabidiol (CBD) appears to be a potent anti-convulsant (Chesher and Jackson, 1974; Consroe and Snider, 1986; Institute of Medicine, 1982).
Despite this animal evidence, there is very limited evidence on the therapeutic effects of cannabinoids in humans with epilepsy. There are a small number of case studies of individuals with epilepsy in which the recreational use of cannabis appeared to enhance the anti-convulsant effects of more traditional anti-convulsant medication (e.g. Consroe et al, 1975; Grinspoon and Bakalar, 1993). There is a single randomised placebo controlled study of the administration of CBD in 15 patients with epilepsy that was not well controlled by conventional anti-convulsants. Four of the eight patients who received CBD in addition to their usual anti-convulsant drugs were free of seizures throughout the study period, and three were improved. By contrast, only one out of seven patients in the placebo condition showed any clinical improvement (Cunha et al, 1980). Despite this suggestive evidence of efficacy in epilepsy, CBD has not been widely used in clinical management. Perhaps this is not surprising given the absence of evidence of its efficacy, the existence of other effective anti-convulsant drugs, and concerns about the safety of chronic use in the management of a chronic disease. It is perhaps more surprising that there has been no further research on the anti-convulsant properties of CBD, especially as it has no psychoactive side effects (Nahas, 1984).
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Cannabinoids have been used in an empirical way in the management of some patients with movement disorders, a variety of syndromes that have in common a deficit in non-pyramidal motor control function, which is expressed in usually one or more of the non-epileptic, abnormal involuntary movements, such as those found in Parkinson's disease, Huntington's disease, multiple sclerosis, and spasticity. Although a number of drugs may be of benefit in the management of these conditions, they are not always effective, and may produce troublesome side-effects (Consroe and Snider, 1986).
There has been some animal evidence which indicates that THC and its analogues produce a broad spectrum of neurological effects, which include alterations in motor function, and changes in muscle tone and reflexes. The acute motor effects in normal humans - ataxia, tremulousness and subjective weakness - also suggest a potential for therapeutic effects in some movement disorders (Consroe and Snider, 1986).
The evidence that cannabinoids have therapeutic effects in patients with movement disorders is largely anecdotal. Grinspoon and Bakalar (1993), for example, present four case histories of individuals with multiple sclerosis whose condition improved while they smoked marijuana, and deteriorated after they stopped smoking. Meinck et al (1989) report a case history of a young man with multiple sclerosis with severe limb and gait ataxia who complained of erectile impotence. After smoking marijuana his gait improved sufficiently to be able to walk unaided, and he was able to achieve and sustain an erection. When cannabis was withdrawn under medical supervision, the patient's motor function deteriorated to the point where he was unable to walk without assistance.
There has been one controlled study by Clifford (1983) who examined the effects of THC on tremor in eight patients (four male and four female) with advanced multiple sclerosis who had ataxia and tremor. Five patients reported subjective benefit from THC and there was objective evidence of benefit in two of these cases. Single-blind placebo challenge in these cases produced evidence that their clinical condition deteriorated when given placebo and improved with the reinstatement of THC.
Grinspoon and Bakalar (1993) described several case histories of individuals with paraplegia and quadriplegia who reported that cannabis use helped to reduce muscle spasm. The experiences of these individuals were supported by similar reports obtained from a survey of 43 individuals with spinal cord injuries, 22 of whom reported that they used cannabis to control their muscle spasm.
The only controlled trial of a cannabinoid in a movement disorder has been an evaluation of the effects of CBD on severity of chorea in patients with advanced Huntington's disease (Consroe et al, 1991). This study was prompted by the authors' observation that CBD had improved the condition of an individual with Huntington's disease (Sandyck et al, 1988). In this study 19 Huntington's patients were enrolled in a double-blind controlled trial in which they received six weeks administration of CBD or placebo in a cross-over design. The outcome was the severity of chorea, as assessed by blind clinical ratings, patient self-report, and a variety of measures of motor function. Although the study had sufficient statistical power to detect a relatively small clinical benefit, there was no evidence of improvement in chorea on any of the clinical, self-report or motor measures. In the light of Consroe et al's failure to replicate the earlier favourable single case, further controlled trials are warranted before any of the cannabinoids can be routinely used in treating movement disorders.