Cannabinoids & Dystonia
Dr Joshua Watt MBBS BSci
Dystonia is a medical condition characterised by involuntary muscle contractions. This can lead to abnormal patterns of movement or postures, which in addition to interfering with daily life, can be extremely uncomfortable. These contractions can be generalised, affecting the whole body, or can be focal and affect specific muscle groups. Common forms include orofacial dystonia involving the mouth and lips, and focal dystonias of the hand which can often affect sportspeople or musicians. Dystonic reactions can also occur as part of other neurological disorders like Parkinson’s disease, or as a side effect to their treatment, such as the abnormal posturing seen in some patients treated with antipsychotics. Treatment is limited, traditionally relying on sedative muscle relaxants or botox injections to selectively paralyse the dysfunctioning muscles.
While we don’t know the exactly how dystonia occurs, we know that it must involve the motor pathways of the brain. Proper movement requires precise communication between neurons to make our actions as smooth and accurate as possible. One of systems involved in modulating these pathways is the endocannabinoid system, at which compounds extracted from cannabis such as THC and CBD have their effect. Cannabinoids have been used with some success for the treatment of other movement disorders such as spasticity in multiple sclerosis, and to reduce the motor excitability in certain forms of epilepsy. Clinicians and patients have reasonably asked whether this effect might extend to the treatment of dystonia.
There does exist some evidence to show that cannabis preparations might be useful. Early case studies showed patients reported significant relief of painful neck dystonia (known as torticollis) with smoked cannabis1. A small pilot study by Consroe and colleagues in 1986 found that orally administered cannabidiol was effective in reducing dystonic symptoms in a dose-dependent fashion (meaning that the effect was stronger at higher doses of the drug). However these higher doses also exacerbated Parkinson disease type symptoms.2 Other case studies have shown positive effects using dronabinol (a preparation containing THC) in patients with multiple sclerosis3.
A study in monkeys showed anti-dystonic effects of a CB1 agonist (a synthetic analogue with effects similar to THC) in animals pre-treated with a drug designed to mimic the side effects prolonged antipsychotic use. This is promising given relatively few treatments exist for this condition, and their side effects are often quite severe4.
While animal studies can be useful to point us in the right direction, the gold standard for demonstrating effectiveness in the scientific community is the randomized controlled trial. Fox (2002) investigated the effects of nabilone, a THC prepration, in 15 patients with primary dystonia. This trial didn’t show any significant effect in reducing dystonia - however the authors note this could be due to the dose being inadequate or to the wrong cannabinoid preparation entirely being used5. Another study investigated the treatment of cervical dystonia with nabilone. While well tolerated, no effect was seen over a 3 week trial. The authors suggest caution interpreting the results due to the small sample size6. Taken together these small trials, while not showing any immediate positive results, leave plenty of room for refinement.
In summary movement is an immensely complex function that we are only just beginning to understand at a cellular level. As can be seen above, studies involving cannabis are rarely standardised. Cannabis contains well over 60 active compounds, making it difficult to tease out which of these might be useful for dystonia, not to mention what ratio they might need to be delivered in for optimal effect. In addition, dystonia has not received as much as attention as other conditions like epilepsy, chronic pain or Parkinson disease, for which we have a much clearer understanding of the underlying neurobiology. Nonetheless given the role of the endocannabinoid system in movement, there is a strong theoretical rationale for trialing cannabis compounds in dystonia. At present, more clinical trials need to be done before we can say with assuredness the role cannabis will play.
- Koppel, B. (2015). Cannabis in the treatment of dystonia, dyskinesia, and tics. Neurotherapeutics, 12, 788-792.
- Consroe, P., Sandyk, R. & Snider, S. R. (1986). Open label evaluation of cannabidiol in dystonic movement disorders. International Journal of Neuroscience, 30(4), 277-282.
- Deutsch, S. I., Rosse, R. B., Connor J. M. et al. (2008). Current status of cannabis treatment of multiple sclerosis with an illustrative case presentation of a patient with MS, complex vocal tics, paroxysmal dystonia, and marijuana dependence treated with dronabinol. CNS Spectrum, 13, 383-403.
- Madsen, M. V., Peacock, L. P., Werge, T., Andersen M. B., Adreasen, J. T. (2011). Effects of cannabinoid CB1 receptor agonism and antagonism of SKF81297-induced dyskinesia and haloperidol-induced dystonia in Cebus apella monkeys. Neuropharmacology, 60(2-3), 418-422.
- Fox, S. H., Kellet, M., Moore, A. P., Crossman, A. R., Brotchie, J. M. (2002). Randomised, double-blind, placebo-controlled trial to assess the potential of cannabinoid receptor stimulation in the treatment of dystonia. Movement Disorders, 17(1), 145-149.