Safety and Efficacy on Spasticity Symptoms of a Cannabis Sativa Extract in Motor Neuron Disease

Inclusion criteria: Subjects must fulfil ALL of the following criteria:

• Written informed consent

• Subject able and willing to comply with all study requirements

• Affected by ALS, either of definite, probable or possible category according to the ElEscorial revised criteria or by primary lateral sclerosis (Pringle's criteria)

• Affected of spasticity, equal or above 1 in the Ashworth Scale for spasticity in 2 ormore muscle groups

• Who will judge spasticity a relevant cause of movements impairment

• Subject has spasticity due to MND of at least three months duration, which is notwholly relieved with current anti-spasticity therapy

• Subject fulfils at least one of the two criteria below. Subject must be either:

1. Currently established on a regular dose of anti-spasticity therapy, or

2. Previously tried and failed, or could not tolerate suitable anti-spasticitytherapy

• Stabilization of factors affecting spasticity: any physiotherapy regimen or medicationlikely to affect spasticity will be optimised before the study and not altered in the 3 weeks before start of treatment

• Subject is willing for his or her name to be notified to the responsible authoritiesfor participation in this study, as applicable. Additional inclusion Criteria to be met at baseline

• Subjects have registered spasticity NRS scores via the personal clinical diary over the 6days (day 2 to day 7) before randomization

Exclusion criteria:

• Any concomitant disease or disorder that has spasticity-like symptoms or that mayinfluence the subject's level of spasticity

• Subjects receiving Botulinum Toxin during the preceding 6 months

• Bedridden and tracheotomised patients

• Fixed-tendon contractures

• Severe cognitive impairment

• Currently using or has used cannabis, cannabinoid-based medications or Acomplia (Rimonabant) within 30 days of study entry and unwilling to abstain for the durationof the study

• Any history or immediate family history of schizophrenia, other psychotic illness,severe personality disorder or other significant psychiatric disorder other thandepression associated with their underlying condition

• Any known or suspected history of a diagnosed dependence disorder, current heavyalcohol consumption, current use of an illicit drug or current non-prescribed use ofany prescription drug

• Subjects with poorly controlled epilepsy or recurrent seizures (Subjects who have hadone or more fits in the year prior to Visit 1 will be excluded)

• Any known or suspected hypersensitivity to cannabinoids or any of the excipients

• Subject has experienced myocardial infarction or clinically relevant cardiacdysfunction within the last 12 months or has a cardiac disorder that, in the opinionof the investigator would put the subject at risk of a clinically relevant arrhythmiaor myocardial infarction

• Subject has a diastolic blood pressure of <50 mmHg or >105 mmHg (when measured in asitting position at rest for five minutes) or a postural drop in the systolic bloodpressure of greater than 20 mmHg

• Personal history suggestive of relevant impaired renal or hepatic function

• Female subjects of child bearing potential, unless willing to ensure that they ortheir partner use effective contraception during the study and for three monthsthereafter

• Female subject who is pregnant, lactating or planning pregnancy during the course ofthe study and for three months thereafter

• Subjects who have received any IMP within the 8 weeks before Visit 1

• Any other significant disease or disorder which, in the opinion of the investigator,may either put the subject at risk because of participation in the study, or mayinfluence the result of the study, or the subject's ability to participate in thestudy

• Unwilling to abstain from donation of blood during the study

• Patients will be asked not to drive while they will be receiving medication