Although clinical studies in this area are difficult to do, even in countries where the use of cannabis has been allowed for years, there is a clear role for cannabis products in symptom management for these difficult conditions. The movement disorders are well-known to be worsened in patients who are anxious, but the careful observations reviewed above lead to the conclusion that there is a direct effect of cannabis in various formulations in some conditions, especially hyperkinetic symptoms. Caution in using a potential central nervous system depressant is always required in patients whose neurologic function is already compromised by disease, but larger studies will prove there is a promising role for this class of drug in the therapy of dyskinesias, tics, and possibly dystonia.  It has been hypothesized that CB1 agonists reduce overactivity of the globus pallidus interna (GPi) and improve dystonia by reducing GABA reuptake.73 In support of this idea, the CB1 and CB2 agonist WIN55,212-2 produces antidystonic effects in a mutant hamster model of dystonia, increases the antidystonic efficacy of benzodiazepines and is reversed by rimonabant, a selective CB1 antagonist.74, 75 Animal models suggest that cannabinoids may reduce MS-related tremor, an effect that appears to be selectively mediated by CB1 receptors.92   Dystonias are the result of abnormal muscles tone, causing involuntary muscle contraction, and resulting in repetitive movements or abnormal posture (Breakefield et al., 2008). Dystonias can be primary, for instance paroxysmal dyskinesia, or secondary to other conditions or drug use, such as tardive dyskinesia after prolonged treatment with antipsychotic drugs (Breakefield et al., 2008).

Consroe et al. (1986) were the first to evaluate the effects of CBD alone in movement disorders. In this open label study, the five patients with dystonic movement disorders displayed 20–50% improvement of dystonic symptoms when treated with CBD for 6 weeks. Of note, two patients with simultaneous PD's signs showed worsening of their hypokinesia and/or resting tremor when receiving the higher doses of CBD. However, it should be noted that in two more recent studies with PD patients no worsening of motor function was seen (Zuardi et al., 2009; Chagas et al., 2014b). In accordance, Sandyk et al. (1986) reported improvement of dystonic symptoms in two patients—one with idiopathic spasmodic torticollis and one with generalized torsion dystonia—after acute treatment with CBD.

The effects of CBD on dystonic movements were also evaluated in pre-clinical studies. In a hamster model of idiopathic paroxysmal dystonia, the higher dose of CBD showed a trend to delay the progression of dystonia (Richter and Loscher, 2002). In addition, CBD prevents the increase in vacuous chewing movements, i.e., dyskinesia, promoted by repeated administration of reserpine (Peres et al., 2016). CBD's beneficial effects are also seen in L-DOPA-induced dyskinesia in rodents, but only when CBD is administered with capsazepine, an antagonist of TRPV1 receptors (Dos-Santos-Pereira et al., 2016). These effects seem to depend on CB1 and PPARγ receptors (Dos-Santos-Pereira et al., 2016). In addition, treatment with capsazepine and CBD decreases the expression of inflammatory markers, reinforcing the suggestion that the anti-inflammatory actions of CBD may be beneficial to the treatment of dyskinesia (Dos-Santos-Pereira et al., 2016).

Moreover, Sativex has been used in the treatment of spasticity in multiple sclerosis. Spasticity is a symptom that affects up to 80% of patients with multiple sclerosis and is associated with poorer quality of life (Flachenecker et al., 2014). A significant portion of patients does not respond to the conventional anti-spasmodic therapies, and some strategies are invasive, posing risks of complications (Flachenecker et al., 2014; Crabtree-Hartman, 2018). Recent data point to Sativex as a valid and well-tolerated therapeutic option. Sativex is able to treat the spasms, improving the quality of life, and displays a low incidence of adverse effects (Giacoppo et al., 2017a).  Cannabis has been used as a medicinal plant for thousands of years. As a result of centuries of breeding and selection, there are now over 700 varieties of cannabis that contain hundreds of compounds, including cannabinoids and terpenes. Cannabinoids are fatty compounds that are the main biological active constituents of cannabis. Terpenes are volatile compounds that occur in many plants and have distinct odors. Cannabinoids exert their effect on the body by binding to receptors, specifically cannabinoid receptors types 1 and 2. These receptors, together with endogenous cannabinoids and the systems for synthesis, transport, and degradation, are called the Endocannabinoid System. The two most prevalent and commonly known cannabinoids in the cannabis plant are delta-9-tetrahydrocannabinol (THC) and cannabidiol. The speed, strength, and type of effects of cannabis vary based on the route of administration. THC is rapidly distributed through the body to fatty tissues like the brain and is metabolized by the cytochrome P450 system to 11-hydroxy-THC, which is also psychoactive. Cannabis and cannabinoids have been indicated for several medical conditions. There is evidence of efficacy in the symptomatic treatment of nausea and vomiting, pain, insomnia, post-traumatic stress disorder, anxiety, loss of appetite, Tourette's syndrome, and epilepsy. Cannabis has also been associated with treatment for glaucoma, Huntington's Disease, Parkinson's Disease, and dystonia, but there is not good evidence to support its efficacy. Side effects of cannabis include psychosis and anxiety, which can be severe. Here, we provided a summary of the history of cannabis, its pharmacology, and its medical uses.

Cannabis -vs- Dystonia