Sitting on cushions in the corner of a brightly decorated room in Jerusalem’s Shaare Zedek Medical Center, 11-year-old Eitan anxiously watched the sliding door leading to the hallway outside. Each time someone entered the room, he rushed past the hanging mobiles and flowers painted on the walls to make sure the door was shut securely.

Eitan was at the hospital with his parents to receive extracts of cannabis that researchers hope will help treat his severe autism. The project, which will test the effects of cannabinoids on 120 autistic children and young adults, is the first of its kind worldwide, said Dr. Adi Aran, the director of the hospital’s neuropediatric unit. The study is made possible by Israel’s progressive approach to research on cannabis and has generated interest in the scientific community and among families of children with autism.

“Our waiting lists are full. Many, many families want to participate and they come from all over Israel,” Aran said. “They hope and they heard from their friends and other families that it might help.”

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Autism is a neurodevelopmental disorder whose symptoms include impaired communication and social skills, and compulsive and repetitive behaviors. The disease usually appears in infancy or early childhood, and can be debilitating. Eitan, for instance, cannot speak at all. The causes of the disease are poorly understood and there is no known cure. It affects roughly one percent of the population in Israel and worldwide, Aran said.

Most autistic children are currently treated with antipsychotic medications, which are not always effective and can have harmful side effects. Eitan’s father, Aviv, said that Eitan became obese after previous medications caused him to eat compulsively. Some medications aggravate him and cause him to throw tantrums, Aviv said.

The impetus for the current study was prior research on epilepsy and a smaller trial in which Aran administered cannabis extracts to around 70 young people with autism, which saw some positive results. The extracts were found to be safe and effective for the treatment of epilepsy, which also afflicts around 20% of autistic children. Researchers studying the effects of cannabis extracts on epilepsy realized that the compounds helped participants deal with some symptoms of autism as well.

Despite interest from families and the medical community, there was a lack of evidence that cannabis products could be a safe and effective treatment, which made it hard to move forward.

“The dilemma was not only our dilemma,” Aran said. “Many physicians in the world are in the same position, that the families ask for cannabis because they have heard, they read on the internet that it really helps but the physician has no evidence” to support the treatment, Aran said.

The Health Ministry has taken a progressive, scientific approach to medical uses for cannabis, though, opening the door for further research, said Dr. Tamir Gedo, CEO of Breath of Life Pharma, the company producing the cannabis extracts used in the study.

“The Ministry of Health in Israel has channeled a lot of energy here in order to examine all the evidence based medicine, and is willing to take that approach. Other ministries of health around the world are hesitant,” Gedo said.

Aran said it was easier than expected to get approval for the study from the Health Ministry.

Israel also has a critical mass of scientists and clinicians familiar with and open to medical uses for cannabis, a strong biotech industry and researchers in leading medical institutes and universities who support the work, Gedo said.

Breath of Life is able to break down the cannabis plant to extract different chemical compounds, called cannabinoids, for use in research and medicine. There are about 140 cannabinoids, the most well-known of which is tetrahydrocannabinol, or THC, which is the primary psychoactive compound in marijuana.

There are few facilities that can carry out the extraction process worldwide, Gedo said, and most can only do it on a small scale.

“We can basically take all the cannabinoids and isolate and amplify them,” Gedo said said of his company. “It’s not a cannabis facility, it’s a drug facility that by accident is producing cannabinoids.”

There are tens of thousands of strains of cannabis worldwide, including over 100 in Israel, Gedo said, and the variation in the levels of cannabinoids can be huge within a single batch. This makes a precise and reliable extraction process crucial. Clinicians and researchers can test what specific compounds and ratios of compounds are most effective, and regulators will only approve a drug with a consistent chemical profile. Gedo hopes that, if the results of the study are positive, they could receive FDA clearance in about a year or a year and a half.

The researchers at Shaare Zedek are mostly administering a cannabinoid called cannabidiol, or CBD, which is one of the two main cannabinoids in the plant, along with THC. CBD is not psychoactive and acts as an antagonist to THC; in medical strains of cannabis, the level of CBD is relatively high, while in plants used recreationally or sold on the street, THC levels are much higher. Participants in the Shaare Zedek study will receive a mixture of CBD and THC dissolved in olive oil at a ratio of 20 parts CBD to one part THC, which is a level deemed safe for children. A small amount of THC may amplify the effects of the CBD, Gedo said.

It is unclear how CBD and other cannabinoids could positively affect people with autism and other disorders. CBD could be decreasing anxiety and depressive systems by affecting serotonin receptors in the brain, Aran said. It may be more effective when paired with THC because the two compounds work on similar receptors, and when the CBD antagonizes the THC it may prolong the amount of time the compound is affecting the synapses involved.

Cannabinoids’ side effects, which depend on the specific compounds and ratios used, are mild and can include drowsiness, increased sleep and diarrhea.

Participants will receive pure cannabinoids, in other words, THC and CBD isolated from any of the other dozens of cannabinoids, or a whole plant extract, which will also contain CBD and THC in a 20:1 ratio. The whole plant extract, which will include cannabinoids besides CBD and THC in low concentrations, may be more effective due to synergy among the chemical compounds in what is known as the “entourage effect.”

“Nobody knows right now what cannabinoids or what active ingredients are enhancing the others. There are a lot of theories currently. It’s an unknown issue,” Gedo said.

The participants will receive one of the two mixtures, or a placebo, for 12 weeks, then go through a four-week washout period, then take the second mixture or a placebo for another 12 weeks. The placebo will contain only flavored olive oil. Participants are aged 5 to 29 and suffer from moderate to severe autism. Some engage in self-harming behaviors and about 40% do not respond well to existing medication. They will be evaluated before beginning the study, after the first treatment period, after the first washout period, and after the second treatment period. Caregivers and teachers will also report on the subjects’ behavior. It is a double-blind study, meaning neither the participants nor the researchers will know which mixtures the participants are taking during the study. So far, 13 participants have started treatment.

The researchers hope to eventually determine which compounds, and at which ratios, are most effective, and who will benefit most from the treatment.

For families of autistic children in Israel, hopes for the treatment are high. Eitan was at the hospital for evaluation and would be starting to take one of the mixtures, or the placebo, later that day. His father, Aviv, became interested in the treatment after seeing a television show about a similar treatment. The treatment was illegal, and the families and participants had their faces hidden to conceal their identities. Aviv followed up by researching online.

“We have a lot of information from television and news,” Aviv said. “Everyone who spoke, either it didn’t improve them or it was amazing. No one talked about a decline.”

They were referred to the Shaare Zedek study through a psychiatrist. Eitan’s mother, Varda, said psychiatrists had prescribed Eitan a variety of antipsychotic drugs, but they had been ineffective and had caused detrimental side effects.

“It got to the point where, at his school, they didn’t know how to cope,” Aviv said.

The family is from the town of Azor in central Israel and is in touch with other parents of autistic children in Israel.

“Other families are talking about it, in conversations and correspondences and all kinds of forums, in WhatsApp groups this thing is always coming up. How to do it, where to find it, how it’s possible, how to find a permit,” Aviv said.

The families discuss whether to try the treatment legally or illegally, Varda said.

“Me personally, I have lots and lots of hope,” Aviv said. “We have a lot of hope, and if it doesn’t work — we tried.”