Autism is challenging to treat pharmacologically because there’s no single cause. Autism can be caused by genetic factors, environmental factors (e.g., pesticide exposure) or a combination of both. Depending on the underlying cause, the severity of symptoms ranges across a spectrum, thus leading to the classification of autism as a spectrum disorder.
But a recent study suggests that cannabidiol (CBD) could offer relief for people on the spectrum. Here's why.
A Broken Gate
Autism Spectrum Disorder (ASD) is characterized by communication deficits, aberrant social behavior, and restricted and repetitive motor behaviors. In many cases, ASD symptoms are the result of reduced inhibition in the brain. For instance, genetic causes can lead to the reduced activity of inhibitory brain cells, thus tipping the brain’s balance towards excitation. This is reflected in hypersensitivity to stimuli, such as to lights, odors, noises, or tactile stimuli that makes the individual act “abnormally” in social situations.
The individual who retreats from a social situation may be doing so because they’re overwhelmed by a strong odor, anxious from direct eye contact, or a host of other reasons brought on by an insufficient inhibitory gate in the brain. In about a quarter of ASD cases, the reduced brain inhibition is so profound, and the resulting increase in brain excitation so great, that seizures result. These cases, in which epilepsy and ASD co-occur, generally reflect the severe end of the spectrum and what scientists are seeking to treat.
Restoring inhibition in the brain thus seems like a reasonable approach to treatment. In mice that were genetically altered to express autism-like behaviors, scientists from Stanford University used a technique called “optogenetics” to increase the brain’s level of inhibition. The researchers could activate inhibitory brain cells by turning on a light-emitting diode (LED) in the brains of mice. When the light was off, the mice avoided social interaction. However, when they flipped the light on, the mice engaged in normal social behavior. Unfortunately, at this point we can’t use optogenetics in humans yet. So we need a new strategy to restore the brain’s inhibition.
CBD to the Rescue
Our research team at the University of Washington sought to similarly treat a mouse model of autism, but instead of using light, we used CBD. CBD has gained recognition and respect in the medical community for its success in treating seizures in children with Dravet Syndrome, a severe childhood epileptic disorder characterized by frequent seizures and autism. While these clinical trials showed that CBD was an effective anti-epileptic in these patients, they never investigated CBD’s effects on ASD. In fact, no clinical study has ever looked at the potential for CBD to treat ASD. To date, there’s only one clinical study being conducted in Israel, but it’s not expected to be completed until 2019. And there’s never been a study of CBD in animal models of autism…until now.
Nearly a decade ago, our lab created a genetic mouse model of Dravet Syndrome by mutating the same gene that causes the disorder in humans. And just like humans, mice have spontaneous seizures and exhibit autism-like behaviors. My colleagues and I used these mice to test whether CBD could treat not only seizures, but autism as well.
Autism is a human disorder, so how do you test autism in mice? Of course, there’s no perfect test, but scientists can model certain common aspects of autistic behavior such as preference to engage in social interaction along with the quality of that interaction. In one test, a mouse chooses between interacting with another mouse or an inanimate object. Generally, mice prefer spending time with the other mouse over the object. But autistic-like mice, such as our Dravet Syndrome mouse, are indifferent, and spend an equal amount of time interacting with the mouse as the object. We gave these mice CBD and the amount of time they spent interacting with the other mouse shot way up (notably, we only needed to give them 10-20% of the anti-epileptic dose to achieve this effect).
Looking at the quality of the social interactions, we found that our autistic-like mice tended to dart away from a social interaction and huddle in the corner of their testing box. This escape can be thought of as social anxiety, perhaps because they’re overcome by socially-related sensory stimuli. However, CBD reduced the frequency of these escapes and improved the quality of their social interaction. So in both of our measures of autistic-like social behavior in mice, CBD improved performance.
To understand how CBD was treating autistic-like behavior in our mice, we recorded the electrical signals in individual brain cells. We found that CBD increased brain inhibition and restored balance by blocking a brain receptor called GPR55, which affects how brain cells communicate with one another. GPR55 is one of CBD’s many brain targets which makes it such a diverse therapeutic tool for treating everything from pain to autism.
Social behavior in mice remains an imperfect model of ASD in humans. But as long as the federal government cannabis classifies alongside heroin as a Schedule I drug — a classification reserved for dangerous substances that have no accepted medical use — then it’s unlikely that we'll see large-scale human trials of CBD and ASD in the United States anytime soon. So for now, we hold our breath as we await the results of Israel’s clinical trial, but can sleep easier knowing that we’re finding success…at least in mice.