The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
Phase: PHASE3
Conditions: Autism Spectrum Disorder
Sponsor: Assaf-Harofeh Medical Center

 
The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder 
0281-17-ASF                                                                     ver. 5.2                        23.08.20 
 
Treatment with medical cannabis 
 Cannabinoids are defined as compounds acting on the cannabinoids receptors CB1 and CB2. 
When referring to cannabis treatment, there is not a specific, well defined treatment but a 
variety of compounds with different activity between them, all of them acting on the 
cannabinoids receptors. 
 There are three groups:  
 
Endocannabinoids, produced endogenously from phospholipids in the cell  membrane, 
such as Anandamide and Arachidonoylglycerol. 
 
Phytocannabinoids: terpeno-phenols found mainly in Cannabis plants 
 
Synthetics 
Cannabis was already known in China, before some 5000 years ago. In the Middle ages, it was 
used against vomits, epilepsy and inflammations, much as today. 
During the 20 th century, Cannabis was less used because of the discovery of new drugs. During 
the '70s it became illegal as part of the war against dangerous drugs in the US. 
 In the sixties, Prof. Mechoulam and his team isolated and reported the chemical composition of 
the 2 main compounds:  cannabidiol (CBD) and 19-tetrahydrocannabinol (THC). Both of them 
are neuro-active, THC  is responsible for euphoria feeling and CBD has a calming effect. Today, 
more than 110 compounds are known in Cannabis plants. 
In the meantime, case reports of its benefits in the treatment of refractory diseases began to 
accumulate and there was public pressure to allow it for medical needs. Canada in 2003 was the 
first country to permit medical use and many countries followed after. 
A meta-analysis published in 2015 by JAMA reported 79 studies. 
Some studies have tested the efficacy and safety of cannabinoids in a vast array of indications: 
epilepsy, chronic pain, spasticity, chemotherapy side-effects. 
Knowledge re. long term safety and risks is mainly from experience in recreational cannabis use. 
 The conclusion is that the risks are linked to THC concentration. The higher THC, the higher risk. 
CBD has a protective effect. 
Additional risks are: alcohol and tobacco consumption, family history of schizophrenia. 
 
 
 Treatment of children with cannabis 

Most of the experience with Cannabis treatment in children comes from refractory epilepsy 
treatment. In some of the cases, these children were also diagnosed with ASD and show an 
improvement of some of the autism comorbidities. The drug used was THC:CBD 1:20 oral drops. 
 Treatment of children with autism (ASD) with medical cannabis. 
US figures report an increase in the prevalence of ASD with current numbers around 1 in 59 
children and rates are similar in developed countries. Prevalence has a ratio of ~4:1 male-to-
female 
Children with ASD commonly exhibit co-morbid symptoms such as hyperactivity, self-injury, 
aggressiveness, restlessness, anxiety and sleep and eating disorders.  Conventional medical 
treatment includes various psychotropic medications such as atypical anti psychotics, selective 
serotonin reuptake inhibitors (SSRI’s), stimulants and anxiolytics.  These drugs have many side-
effects. 
Several studies are being conducted worldwide on the use of cannabidiol in children with ASD to 
treat comorbid symptoms. However, there is limited published data on the use of cannabinoids 
in this population A recent review by Poleg, 2019, has suggested cannabidiol as a candidate for 
treatment of ASD.  
A study by Barchel et al, 2019, reported benefits of T:C 1:20 treatment in 53 children with ASD. 
The results show an improvement in the severity of the symptoms for between 40-70% of the 
patients. 
The aim of the present study is to assess efficacy and safety of medical cannabis oil CBD:THC 
20:1 in children and young adults with ASD. 
 
Population of the trial 
Children and young adults from all over Israel diagnosed with ASD based on DSM IV (American 
Psychiatric Association, 2000) or DSM V (American Psychiatric Association, 2013) criteria, 
between 5 and 25 years of age will be included.  
PURPOSES 
Main 
To assess the effect of medical cannabis oil treatment on the comorbidities of ASD 
To compare between 2 products with same CBD:THC ratio 
To assess the effect of treatment on cognitive function 
 To measure levels of cannabinoids in the blood of the participants 
 
Secondary 

 To detect side-effects and reasons for failure 
To assess if high CBD conc. oil is effective in treating sleep and behavior problems in patients 
with ASD. 
 To detect changes in biochemical and hormonal profile during treatment 
 
Methods 
 Parents of children and young adults with ASD will be interviewed at the Clinical Pharmacology 
Unit, Shamir MC. If recruited, they will sign ICF and will fill in questionnaires. Medical history and 
concomitant drugs will be recorded. 
 There will be 3 visits with the patients: before treatment, after 3 months and after 6 months of 
treatment. 
The treatment length will be of 6 months for each participant. A  group of specialists including a  
pediatrician, a pediatric neurologist specialized in ASD,  a psychologist and a speech therapist,  
 will assess the effects of the treatment using specific tools such as ADOS and questionnaires.  
 Efficacy and adverse effects will be recorded during the phone follow-ups. 
 ASD comorbid symptoms to be evaluated are: hyperactivity, aggression, anxiety, 
sleep problems, eating problems, communication problems  and social problems. 
For each comorbid symptom, the evaluations will mark improvement, no change, or worsening 
of symptoms, as compared to the baseline, according to the parent’s reports. 
Parents will received a license for pediatric use of medical cannabis oil from the Israeli 
Ministry of Health.  
The cannabinoid oil solutions will be manufactured at Nextar for Seach  Sarid LTD and at Panaxia 
for Canndoc Ltd. at  concentration of 30% and 1:20 ratio of CBD and THC for each of the 2 arms. 
Treatment and dosage 
Treatment will start at one drop/day and dose will increase as per physician or CRA instructions 
(titration) until improvement is seen in at least one of the symptoms or until failure is decided 
upon.  
Recommended daily dose of CBD is 16 mg/kg (maximal daily dose 600 mg), and for 
THC- daily dose of 0.8 mg/kg (maximal daily dose of 40 mg). 
 
 
 

Sample size  
One of the symptoms of ASD is self- aggression.  Supposing 65% reporting self-aggression before 
treatment started, and 40% during treatment, 65 participants will be needed (5% significance, 
80% power). Taking into account dropout, 100 participants will be recruited into each arm (total 
of 200 participants) in order to attain significant results. 
Visits 
 
First visit before treatment start (may be divided into 2 different days) 
Patients will undergo weight and height measurements, Cognitive evaluation, 1 hour EEG test, 
Social and communication evaluations ADOS, adaptive behavior, blood tests.  
Parents will fill in questionnaires and have teacher fill in Conners questionnaire 
At the end of the visit, parents will receive cannabis oil and instructions about their use. 
 
Middle-term visit 
Patients will undergo weight and height measurements, neurologist evaluation, blood tests.  
Parents will fill in questionnaires and have teacher fill in Conners questionnaire 
 
 
Third visit(end of treatment) 
Patients will undergo weight and height measurements, Cognitive evaluation, 1 hour EEG test, 
Social, skills and communication evaluations  
Parents will fill in questionnaires and have teacher fill in Conners questionnaire 
 
In-between the 3 visits, there will be biweekly phone follow-up. 
 
 Early termination visit 
Patients not willing to complete the 6 months of the trial will be asked to  be present at a 
conclusion visit, in the format of third visit. 
Dosage reducing will be gradual and take 1 week. 
 
Sleep quality 
Sleep quality will be measured using electronic devices and questionnnaires. 
 
Video filming of the participants 

Participants will be taped during ADOS test for later analysis of repetitive behavior and facial 
movements. 
Other aspects 
 Female of bearing age will be asked to use contraceptives or to declare they will not have 
sexual activity during the time of the trial. 
Participants taking other drugs will be asked not to make any changes without prior consent of 
the trial  team.  
Criteria for participation ceasing 
Significant side-effects, Psychosis or depression, pregnancy 
Contraindications 
Primidone, Phenobarbital, Carbamazepine, Rifampicin, Rifabutin, troglitazone, Hypericum 
perforatum 
Total trial length: 3 years 
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