Are there any cannabis-derived drugs approved to treat autism or related conditions?
To date, the U.S. Food and Drug Administration has approved only one cannabis-derived drug: Epidiolex. It is a liquid cannabis extract containing purified CBD that can decrease seizures in people with Dravet syndrome or Lennox-Gastaut syndrome — severe forms of epilepsy that are sometimes accompanied by autism — and in those with tuberous sclerosis complex. It is available only by prescription, and only for these three conditions.
GW Pharmaceuticals, the company that makes Epidiolex, is conducting a trial of the drug for Rett syndrome, a neurodevelopmental condition related to autism. The Rett syndrome trial is not focused on alleviating seizures, but on improving cognitive and behavioral problems. The company is also recruiting autistic children and teenagers for a phase 2 trial of cannabidivarin, another component of cannabis. That trial will examine cannabidivarin’s effect on a range of traits in autistic children, including repetitive behaviors, and on quality of life.
How might cannabis help autistic people?
Epidiolex’s success has spurred many parents to try marijuana and cannabis extracts for seizures, behavioral issues and other autism-related traits in their children, but experts warn that these drugs remain largely untested for such purposes. Some studies on cannabinoids have shown promising results in animal models and in early-stage clinical trials, but this research does not yet support their widespread use.
Cannabis’ active ingredients are thought to exert their effects by binding to proteins called cannabinoid receptors in the brain: THC activates the CB1 and CB2 receptors, whereas CBD seems to block them.
Both types of cannabinoid receptors are located in neurons in the brain and throughout the body. The brain contains more CB1 than CB2 receptors, and the activation of each receptor type affects a range of ion channels and proteins involved in cell signaling. The ultimate effects of cannabinoid receptor activation depend on which body system they belong to. For instance, the activation of CB1 receptors in the brain can either increase or decrease neuron excitability, depending on which kind of neuron a cannabinoid binds to; activation of CB2 receptors in the digestive system can decrease inflammation.
Blocking the CB1 receptor can relieve seizures and memory issues in a mouse model of fragile X syndrome, a condition related to autism, according to a 2013 study in Nature Medicine. A 2018 clinical trial of a synthetic CBD drug by the drug maker Zynerba showed significant improvements in anxiety and other behavioral traits in people with fragile X. Cannabinoid receptor activation has also been shown to lead to memory improvements in fragile X mice.
Research has also demonstrated that CBD alleviates seizures in children with CDKL5 deficiency disorder, an autism-linked condition that is characterized by seizures and developmental delay. CBD also lessens seizures and improves learning and sociability in a mouse model of CDKL5 deficiency disorder.
Complicating the picture, CBD alone may not be sufficient for cannabis’ therapeutic effects. A 20-to-1 ratio of CBD to THC relieves aggressive outbursts in autistic children, a 2018 study suggests. This same ratio of compounds significantly improved quality of life for some children and teenagers with autism in a 2019 study. Specifically, researchers observed significantly fewer seizures, tics, depression, restlessness and outbursts. Most participants reported improvements, and about 25 percent of participants experienced side effects such as restlessness.
Cannabis may have effects that go beyond the cannabinoid receptors, too. Mice that ingested CBD over extended periods of time displayed changes to DNA methylation in sections of the genome associated with autism, a 2020 study showed. The researchers suggested that epigenetic changes may be at least partly responsible for CBD’s behavioral effects, though they did not directly examine the mice’s behavior.