Can Cannabis Help with Fragile X Syndrome?

Cannabis presents a promising treatment option for Fragile X syndrome (FXS). As a matter of fact, researchers have recently discovered that dysfunction of the body’s endocannabinoid system, as evidenced by reduced endocannabinoid activity in the brain, plays a significant role in this condition.

There’s early evidence that CBD-rich cannabis products are remarkably effective at relieving the wide-ranging symptoms of FXS, including anxiety, irritability, hyperactivity, compulsive behaviors, seizures, as well as deficits in cognition, motor skills, communication, and social skills.

Better yet, CBD seems to provide these multifaceted benefits without the same serious side effects of standard pharmaceutical treatments. Indeed, CBD has only been associated with relatively minor, temporary side effects, such as diarrhea, dry mouth, tiredness, and dizziness.

While researchers stress the need for high-quality clinical trials of CBD in FXS, current findings support its therapeutic potential.

How Cannabis Works on Fragile X Syndrome

The endocannabinoid system (ECS) exists in all vertebrates and helps regulate crucial functions such as sleep, pain, and appetite. The human body produces its own cannabinoids, which modulate and activate its various functions, but as its name suggests, the endocannabinoid system can also be modulated and activated by cannabinoids found in the cannabis plant.

The ECS plays a crucial role in regulating brain function. Poor regulation of it seems to be involved in a wide range of mental disorders, including both anxiety and depression.

It’s therefore not surprising that recent research has uncovered a link between ECS dysfunction and cognitive abnormalities seen in FXS. Studies in mice show that the absence of the FMR protein — the central feature of FXS — results in abnormal endocannabinoid levels and reduced activity of endocannabinoid receptors in the central nervous system.

For starters, a 2010 mouse study of FXS mice found that their brains use endocannabinoids in an abnormal way, contributing to the excessive neuron activity that characterizes the disorder.

A similar 2010 study found that NAGL, one of the enzymes that make the body’s endocannabinoids, functions abnormally in FXS. This also changed how endocannabinoids interacted with GABA receptors, which play the main role in preventing excessive brain cell activity.

Meanwhile, a 2012 study found that the brains of FXS mice produced less 2-AG, one of the two main endocannabinoids, and had decreased activity of cannabinoid type-1 (CB1) receptors.

These findings show that the endocannabinoid system doesn’t work properly in those with FXS and that therapies that enhance its function can improve the symptoms of the condition. One such promising therapy is cannabis.

Research on Fragile X Syndrome and Cannabis

Recent studies indicate that cannabis — specifically formulations rich in the non-intoxicating cannabinoid CBD — can be effective at improving FXS symptoms.

One possible reason why CBD in particular seems to be so effective is that it acts not only on the endocannabinoid system but also on GABA receptors, which produce anxiety-lowering, calming effects by reducing neuron activity, and serotonin receptors, which also regulate anxiety.

A 2019 study found that a transdermal CBD gel improved FXS symptoms in children and teenagers. A total of 20 participants were given the gel regularly for 12 weeks, resulting in improved measures of anxiety, social avoidance, irritability, hyperactivity, compulsive behavior, inappropriate speech, psychosocial health, and emotional functioning. The study reported only minor, passing side effects.

A 2019 review paper described the cases of three people with FXS who improved their symptoms by taking full-spectrum, CBD-rich cannabis products with low (0.03%-3.4%) levels of THC.

The first patient was a three-year-old boy whose parents and therapists reported improved eating behavior, motor coordination, speech, language and developmental skills, eye contact, social interaction, sensory sensitivity (e.g., to loud noises), willingness to explore new places, and less hyperactive behavior. When the parents stopped giving him CBD and switched to a standard pharmaceutical drug, the boy experienced increases in anxiety, meltdowns, and sleep issues.

The second patient, a 26-year-old man, saw improvements in social anxiety, language skills, and sleep. The third patient was a 22-year-old woman who noted a reduction in anxiety and panic attacks, so that she became more social and improved her work performance. Much like the boy, her symptoms returned when she stopped taking CBD during a vacation.

Also, in a 2019 study of 15 people with autism, a disorder which presents similar symptoms to FXS, reported improvements of attention deficit and hyperactivity issues, behavioral disorders, sleep, seizures, and deficits in motor skills, autonomy, cognition, communication and social interaction after treatment with CBD-rich cannabis.

CBD might also help with the seizures that occur in about 15% of male and 5% of female FXS sufferers. Research shows that CBD is so effective at improving seizures that the CBD-based drug Epidiolex was recently approved by the FDA for treating Dravet and Lennox-Gastaut syndromes, two specific types of epilepsy. The research findings in this area have been very encouraging:

A 2017 trial reported that CBD coupled with antiepileptic drugs significantly improved seizures in children with Dravet syndrome
A 2018 study found that CBD plus antiepileptic medication significantly improved seizures in Lennox-Gastaut syndrome sufferers
A similar 2018 trial reported that CBD taken with antiepileptic drugs improved Lennox-Gastaut syndrome seizures

Such research suggests that CBD may be an effective treatment option for Fragile X syndrome. Unlike standard pharmaceutical medications, CBD not only seems to provide relief for multiple symptoms of the condition but also produces fewer and milder side effects.

Potential side effects of cannabis use

Cannabis ingestion is known to have psychoactive side effects, such as impaired memory and reaction time. These are caused by tetrahydrocannabinol (THC), its main psychotropic component.

However, the CBD-rich cannabis preparations shown to be effective in FXS have relatively low (0.03–3.4%) THC levels.

CBD is a non-intoxicating cannabinoid that has only been associated with minor side effects. For example, the previously mentioned study of CBD in FXS sufferers reported adverse effects such as skin dryness, dizziness, and lethargy. However, these symptoms were considered minor and it wasn’t clear whether they were caused by CBD.

Other studies have also reported that CBD can cause low blood pressure, dry mouth, diarrhea, sleepiness, lightheadedness, and changes in appetite. However, these side effects were only reported in studies using extremely high CBD doses (300 mg and up).

That said, it’s always best to consult with your doctor before trying CBD oil or related products for FXS.

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