Endocannabinoid Tone and Charcot-Marie-Tooth disease (CMT)

Charcot-Marie-Tooth disease (CMT) is an inherited condition that damages peripheral nerves.
The damage interrupts the signals and commands travelling from the brain to the muscles. It also interferes with sensory information sent from the body to the brain.
According to Charcot-Marie-Tooth UK, about 25,000 have CMT in the UK, and it’s the most common genetically inherited neurological condition.
The first symptoms of CMT usually appear in children between 5 and 15 years old, but occasionally it may take up to middle age before it fully develops.
The progressive nature of CMT means that the symptoms slowly increase in severity throughout a patient’s lifetime.
CMT is caused by a fault in any of the genes that promote the development of peripheral nerves.
These faults can affect the nerves in different places resulting in over 100 types of CMT.
As the nerve cell damage develops, it either attacks the protective myelin sheath around the nerve cell or the axon in the centre.

There are more than 100 different types of CMT, and each patient can be affected differently. Some common symptoms include:
- Difficulty lifting feet from the ground
- Muscle weakness in the feet, ankles and legs
- High arches in the feet
- Unstable ankles
- Loss of feeling in the arms and feet
- Poor circulation in the hands and feet
- Feeling fatigued throughout the day
- Tremors
- A curved spine
- Neuropathic pain.
There is no cure for CMT, and current treatments are designed to minimise the symptoms and make adjustments to allow patients to remain independent for as long as possible. This includes pain medication, physiotherapy, orthotics and even surgery.
CBD and Your Endocannabinoid Tone

CBD works in your body in many different ways, but one of the most vital interactions is how it stimulates the endocannabinoid system (ECS) and raises your endocannabinoid tone:
What is the endocannabinoid system?
The endocannabinoid system is a collection of signal molecules (endocannabinoids), receptors and enzymes.
It's active throughout the body, particularly in the central and peripheral nervous systems.
When the ECS is activated, it makes tiny chemical adjustments that enhance the signalling capacity of cells within your body.
This allows your body systems to communicate effectively and quickly restore a healthy balance following damage or illness.
What is your endocannabinoid tone?

Endocannabinoid tone refers to the level of potential endocannabinoid activity in your body and the ability of your endocannabinoid system to respond to any problems.
This can be affected by a range of factors, including genetics, diet, stress and disease.
If your endocannabinoid tone is low, your endocannabinoid system is unlikely to be able to restore your body systems to a state of healthy balance. As a result, you may feel unwell or experience symptoms related to anxiety.
Regular consumption of CBD can stimulate the action of your endocannabinoid system (ECS) and raise your tone.
To learn more about how CBD raises your endocannabinoid tone, you can read our article: Endocannabinoid Tone and CBD.
Key terms:

CB1 and CB2 – These are the most common endocannabinoid receptors.
- CB1 is found in the central nervous system.
- CB2 is present in the central nervous system, the peripheral nervous system and in immune cells throughout the body.
Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) – These are endocannabinoid signalling molecules present in humans and animals. They can interact with a range of chemical receptors, including CB1 and CB2.
Endocannabinoid Tone and CMT
Current research into the links between CMT symptoms and the endocannabinoid system is limited. There is no indication that the endocannabinoid system can influence CMT-related genetic damage or the corresponding nerve damage.
However, there are two areas where a balanced or naturally high endocannabinoid tone may assist in reducing some of the symptoms. These are:
Neuropathic Pain

Neuropathic pain is pain caused by nerves that are damaged or not working correctly.
It’s usually described as a sharp shooting, stabbing or burning sensation. Researchers studying CMT reported that 71% of patients with CMT suffered neuropathic pain in some form.
It’s usually in the lower limbs, with the most common areas being the lower back, knees and ankles.
The behaviour of the endocannabinoid system related to neuropathic pain has been the focus of several scientific studies and may provide a new avenue to manage the pain symptoms associated with CMT.
Scientists discovered that higher levels of CB1 and CB2 receptors are produced along the pain processing pathways from damaged nerves.
When anandamide (endocannabinoid) binds with CB1 receptors on nerve cells, it activates channels that alter the electrical and chemical activity of the neuron. This doesn’t stop the transmission of pain signals but regulates and adjusts them.
CB2 receptors are found throughout your body in tissues, organs and immune cells. When activated by endocannabinoids, they inhibit the release of several chemical signalling molecules, including cytokines.
Scientists have found that the expression of cytokines is linked to many types of pain, and controlling them is key to effective pain management.
Both receptors also produce a range of other effects that regulate pain when they’re activated by anandamide or 2AG.
This includes the release of endorphins and the regulation of neurotransmitters that control pain processing within the central nervous system.
Muscle spasms

Muscle tightness and spasms can be a feature of CMT for some people.
Research conducted on muscle spasticity (abnormal muscle tightness due to prolonged muscle contraction) in Multiple Sclerosis (MS) patients may also shed some light on how high endocannabinoid tone may reduce CMT muscle spasms.
Synthetic activation of CB1 and CB2 receptors was found to significantly reduce muscle tremors in mice.
Scientists also noticed that mice with spasticity had higher levels of anandamide and 2-AG in their brains.
They concluded that this could be an indication that an increase in endocannabinoids is the body’s natural homeostatic response to attempt to reduce the tremors.
Consequently, a higher endocannabinoid tone is likely to produce a therapeutic effect that could limit the muscle spasms caused by CMT as well as those from MS.