Can Cannabis Help with Fragile X Syndrome?
By Gleb Oleinik
Feb 16, 2020
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.
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.
The Cannigma content is intended for informational purposes only. It is not a substitute for professional medical advice, diagnosis or treatment. Always consult with an experienced medical professional with a background in cannabis before beginning treatment.
About Fragile X Syndrome
Fragile X syndrome is a common genetic condition that causes behavioral, intellectual, and cognitive disabilities, as well as changes in a person’s physical appearance and health. It’s also sometimes referred to as FXS, fraxa syndrome, fra(X) syndrome, Martin-Bell syndrome, and marker X syndrome.
Fragile X syndrome is when the FMR1 gene on the X chromosome is damaged, so it can’t produce the FMR protein that enables normal brain development. When the X chromosome is examined under a microscope, it looks like part of it is fragile or broken, which is where the term “Fragile X” came from. The part where the FMR1 gene lies is the part that’s missing from the X chromosome.
Fragile X syndrome affects boys more than girls because boys only have one copy of the X chromosome whereas girls have two. Boys who have Fragile X syndrome also usually have more serious symptoms than girls. It’s thought that around one in every 4,000 boys and 1 in every 8,000 girls have Fragile X syndrome.
There’s no cure for FXS, but therapy and medication can help control the symptoms and improve the acquisition of life skills.
There are many symptoms of Fragile X syndrome, but they don’t all become noticeable at the same time. Some people with Fragile X syndrome will have very severe symptoms, while others may not present with any symptoms at all. As a matter of fact, some people may have fragile X syndrome and never be diagnosed at any point due to a paucity of symptoms.
Most males with Fragile X syndrome have a mild to moderate intellectual disability, in contrast to about one-third of females. Women with Fragile X who have an intellectual disability generally only have a mild disability.
The other common symptoms of Fragile X syndrome are:
- Anxiety disorders
- Hyperactivity disorders and ADD
- Features of autism spectrum disorders, like avoiding eye contact and compulsive hand flapping
- Social and communication disorders
- Learning difficulties
- Delays in speech and motor development
Around 15% of males and 5% of females with Fragile X syndrome also experience seizures.
Most boys and some girls who have Fragile X syndrome also have distinctive physical features, including:
- A long, narrow face
- A large head and ears
- A prominent forehead, jaw, and chin
- Loose joints, flexible fingers, and low muscle tone
- When boys reach puberty, they generally have enlarged testicles (macroorchidism)
Some people with FXS also have frequent ear infections, extreme sensitivity to sound and light, dental problems, crossed eyes (strabismus), and heart problems.
Fragile X syndrome is diagnosed by using genetic testing on a blood sample. It can be done before birth, if there’s reason to suspect that the baby might have Fragile X syndrome. During pregnancy, doctors can carry out an amniocentesis, to check a sample of the amniotic fluid for changes in the FMR1 gene. Alternatively, doctors use chorionic villus sampling (CVS) to look for these changes in some cells from the placenta.
Fragile X syndrome isn’t usually obvious from birth. Occasionally, doctors notice that a baby’s head is larger than normal, but otherwise the symptoms only develop later, from around the age of two and onwards, when learning and behavioral problems begin to be apparent.
Fragile X syndrome is caused by a genetic mutation to the FMR1 gene that produces the FMR protein. This protein is vital for nerve cells in the brain to communicate successfully with each other.
Most of the time, the mutation is what’s called a full mutation. This means that the relevant DNA segment, called the CGG triplet repeat, repeats more than 200 times instead of between five and 40 times. This expanded segment turns off the FMR1 gene.
Some people have a premutation, which means that the DNA segment is repeated between 50 and 200 times. People with a premutation usually don’t have all the symptoms of Fragile X syndrome, but can show milder versions of some of the symptoms, and a mild intellectual disability.
People with premutations can develop FXTAS or POI, which are related disorders that appear in adulthood. FXTAS stands for Fragile X tremor-ataxia syndrome, which mostly affects men and causes abnormal movements and tremors. POI stands for primary ovarian insufficiency. It causes early menopause – before the age of 40 – in women.
Fragile X syndrome is always inherited. Sometimes, a premutation can develop into a full mutation when it’s passed down to the next generation. Women are often unwitting carriers of the Fragile X mutation, and it’s only discovered when it’s diagnosed in their children.
There’s no cure for Fragile X syndrome, but the right therapies and medication can improve the quality of life.
Early intervention therapies for children with Fragile X include speech therapy, physical therapy, sensory integration training, and behavioral therapy. Social support can also improve their communication and social interactions. Children with Fragile X syndrome might also need special education support to help them learn necessary life skills.
Research is still going on to try to develop effective medication for Fragile X syndrome. Sometimes, medication is prescribed to deal with some of the symptoms of FXS, like anti-anxiety medications, anti-seizure medications, and medications for ADD and ADHD.