Efficacy of Dronabinol for the Treatment of Cervical Dystonia
Efficacy of Dronabinol for the Treatment of Cervical Dystonia
Cervical dystonia (CD) is characterized by abnormal, involuntary sustained cervical muscles
 contractions associated with twisting movements and abnormal postures of the neck that can be
 quite disabling. Currently there are no good oral medications for the treatment of CD. While
 botulinum toxin injections are effective in most, they require repeat injections and there
 are some patients who either stop responding or who never respond at all. Therefore, better
 treatments are needed. While the underlying mechanisms of dystonia are not entirely known,
 there is some information suggesting that it is ude to an underactivity of a chemical
 compound, GABA, that is located in the basal ganglia. Cannabinoids are a compound than can
 enhance transmission of GABA, and thus, may alleviate the symptoms of dystonia. Dronabinol,
 one such cannabinoid, has been widely used to treat anorexia and nausea in chemotherapeutic
 patients. The aim of this study, therefore, is to study the effect of dronabinol on cervical
 dystonia
The study is a double-blind, randomized, placebo-controlled, crossover, phase II study of
 dronabinol versus placebo. Thirty patients with idiopathic cervical dystonia will be enrolled
 in the study. Patients will be randomized to either dronabinol or placebo by a
 computer-generated random numbers table that will be kept in the central pharmacy until the
 end of the trial. Only the central pharmacy will be aware of treatment allocation; all others
 will be blinded for the duration of the trial.

 Regardless of treatment allocation, study participants will begin taking their assigned study
 medications on Day 1, increasing the "dose" (actual increase in dose for dronabinol-assigned
 arm, fictional increase in dose for placebo-assigned arm) every 3 days. At the end of the
 third week, on Day 21, the study participant will complete the first phase of study
 medication and remain off study medication for a period of two weeks, and will have a planned
 study visit. On Day 36, the study participant will have a planned study visit, the new
 medication will be dispensed, and the participant will begin taking the other arm of the
 study medication for a period of 3 weeks, in the same manner as the first arm. At the end of
 the 3 weeks (8 weeks in total), the study participant will discontinue the assigned study
 medication and will attend a planned study visit for study termination. At each visit,
 patients will be assessed with a medical and neurological history and examination and a video
 recording made for post hoc analysis of TWSTRS by a rater blinded to the treatment arm.

 The main issue with compliance to study medication will relate to side-effects. Side-effects
 are mainly dose related and can be minimized with a dose escalation protocol, which is
 planned in this study. Compliance and adverse effects will be monitored by weekly phone calls
 for side effects and pill counts at the end of each treatment arm.
Inclusion Criteria:

 -  18-75 year old male and female patients with idiopathic cervical dystonia -

 Exclusion Criteria:

 -  Secondary causes of dystonia; history of substance abuse, psychosis, ischemic heart
 disease, symptomatic postural hypotension, liver disease (LFTs > 2 times normal),
 renal disease

 -  Women who are pregnant or plan on becoming pregnant during the course of the trial

 -  Use of botulinum toxin as a treatment for cervical dystonia in the preceding 4 months

 -  Use of other GABA mediated drugs including: gabapentin, phenobarbital,
 benzodiazepines, or baclofen

 -  Use of other cannabinoids in the preceding month

 -  Refusal to refrain from use of other cannabinoid compounds during the course of the
 trial

 -  Refusal to refrain from operating heavy machinery or driving during the course of the
 trial