Full-spectrum Medical Cannabis for Treatment of Spasticity in Patients With Severe Forms of Cerebral Palsy

The proposed study is a double-blind, placebo-controlled, cross over study on 60 children aged 5 to 25 years with severe spasticity related to cerebral palsy (CP), level IV and V with full-spectrum medical cannabis product of CBD/THC ratio 10:1.

Test components:

A) Active: Full-spectrum medical cannabis with ratio of CBD:THC 10:1 (HemPhar)

B) Placebo (both of the same producer)

Study Steps

1. Informed consent should be signed by parents/caregivers.
2. Weight of the participant should be determined and an IV line inserted. The following lab tests should be performed: CBC and differential counts, blood electrolytes, magnesium, calcium, phosphorus, urea \& creatinine, liver enzymes (AST, ALT, gGT)
3. ECG performed and analyzed
4. A trained physiotherapist will perform the following motor assessments: spasticity level according to modified Ashworth scale (Bohannon), function/activity assessment with the use of Gross Motor Function Measure scale (GMFM-88) and assessment of muscle power with dynamometer.
5. Randomization of patients into one of the two arms of the study
6. Active substance or placebo are introduced thereafter (as an oral oily solution for oral application) in a starting dose of 0.08 mg/kg body weight (BWt)/day divided in 2 doses (the dose is according to the THC content). The dose is gradually increased, every 3 days for 0.08 mg THC/ kg BWt/day, until the maximum dose of 1 mg THC/kg BWt/day is reached, or else until adverse effects are noted. It is expected that the average dose will be 0.33 mg/kg BWt per day.
7. The parents/caregivers are given questionnaires/scales and also given oral instructions on how to fulfil them (Edmonton scale, Borg scale and Global Impression of Change - GIC) and the paper to take down notes on possible side/adverse effects while taking the preparation (either active substance or placebo).
8. After 6 weeks of taking the substance or at the premature end of the study again the lab tests will be performed as well as the motor assessment by the physiotherapist (as above at inclusion).
9. In patients, who have been receiving placebo for the first 6 weeks, the active substance is given for the next 6 weeks, as described above (under 6). The patients who have been receiving the active substance for the first 6 weeks will continue to do so for the next 6 weeks.
10. Additional blood samples are taken at 6 weeks in both groups for analysis of levels of cannabidiol (CBD) as well as delta-9-tetrahydrocannbinol (THC) - around 4 ml of blood for determination of both levels at time(s) after ingestion: 0, 1, 2, 4, 8 and 24 hours.
11. At the end of the study (after 12 weeks) again repeat:

    1. CBC and differential counts, blood electrolytes, magnesium, calcium, phosphorus, urea \& creatinine, liver enzymes (AST, ALT, gGT)
    2. ECG
    3. Motor assessments by a physiotherapist (Ashworth/Bohannon, GMFM 88, dynamometer)
    4. Pharmacokinetics: 4 ml of blood for determination of phamacokinetics after ingestion of the last dose (as in point 10 above)
12. Evaluation of the questionnaires

NOTE: if severe side/adverse effects are noted, the test compound should be stopped immediately. If mild/moderate side/adverse effects are noted, the test component should be gradually stopped: for 0,08 mg/kg BWt/day, every 3 days.

Eligibility Criteria:
Inclusion criteria:

* With confirmed diagnosis of cerebral palsy (CP) and classified according to the Gross Motor Function Classification System (GMFCS) as level IV or V
* With spastic unilateral or spastic bilateral type of CP
* Those children/young adults whose parents/caregivers were informed about the aims of the study and have signed the Informed consent form

Exclusion criteria:

* Other proven diseases/conditions with the prevalence of spastic type of muscle tone (e.g. neurodegenerative, metabolic, etc.), and children with liver disease
* Other forms of CP (dyskinetic, ataxic)
* History of psychiatric illness/condition in the family