Rare diseases There are thousands of disorders out there that have remained understudied due to their rarity and complexity. Cannabis and cannabinoid compounds may provide complex solutions to these complex diseases. Medicinal cannabis programs are now helping to discover these solutions and deliver them to the patients that desperately need them.
Tuberous sclerosis complex
- A rare genetic disorder that causes benign tumours to grow within the brain, eyes, and other vital organs.
- Global prevalence of 10-16 in 100,000
- Usually diagnosed during infancy or childhood.
Tuberous sclerosis complex (TSC) can cause autism, epilepsy, developmental delay, behavioural problems and various other symptoms, although symptoms vary widely between individuals.
In TSC, genetic mutations alter the expression of two proteins, hamartin and tuberin. In healthy individuals, these two proteins work together to control various aspects of cell growth, division and death, and act as tumor growth suppressors. In TSC, the two proteins are inhibited, allowing unchecked cell growth and ultimately the formation of tumours.
The endocannabinoid system is deeply involved in cases of TSC. Research has suggested that children with TSC show abnormally high expression of CB₁-receptors during early brain development. It is well-known that the EC system plays a crucial role in processes related to cell division and death. Furthermore, CBD is an important anti-epilepsy drug that can manage seizures in TSC.
The creators of Charlotte’s Web included a young TSC sufferer, Keegan Streetman in their earliest trials, with good results. Now, GW Pharmaceuticals is undertaking a Phase III clinical trial into the effectiveness of its CBD-based spray Epidiolex for epilepsy caused by TSC.
- A group of genetic disorders affecting the mitochondria, the energy-generating “engines” of cells.
- Global prevalence of around 11-12 in 100,000.
- Children born with MD usually display symptoms by age 10.
MD causes neurological impairment, seizures, chronic pain, muscle weakness, poor hearing and vision, learning disabilities, multi-organ disease and respiratory disorders.
The symptoms of MD may be related to oxidative stress, a buildup of reactive oxygen species within the cell. Thus, existing (limited) treatments include antioxidants able to penetrate the cell membrane.
Recognition of cannabis’ ability to treat symptoms of MD has come primarily from patient groups. Patients state that cannabis oil notably improves management of seizures, and eases chronic pain. In the US state of Georgia, MD is now on the list of approved conditions for medicinal cannabis patients.
It is thought that the antioxidant abilities of some cannabinoids may work directly to improve mitochondrial function. Several studies have investigated this relationship, but research is in its infancy. A discussion of existing studies can be found in the paper Cannabinoid receptor agonists are mitochondrial inhibitors (A. Athanasiou et al., 2007).
- An autoimmune disorder in which the immune system attacks healthy blood vessels, causing inflammation.
- Rare in North America and Northern Europe (1 in 15,000 to 1 in 500,000)
- More common in certain regions of Asia and Africa (80-300 in 100,000 in Turkey, the worst-affected country).
Behçet’s disease (BD) can cause skin and genital lesions, joint swelling, chronic pain, swelling in the brain, blood clots, and aneurysms. It is thought that a combination of as-yet-undetermined genetic and environmental factors cause BD. There is no known cure, but anti-inflammatory drugs may provide some relief, and immunosuppressive drugs are also used.
Several cannabinoids including THC and CBD are known for their anti-inflammatory effect, and some US BD patients have reported subjective relief of symptoms when using cannabis. Indeed, the state of Illinois has included BD on its list of approved disorders.
Neuromyelitis Optica (Devic’s syndrome)
- A rare autoimmune disease that causes recurrent inflammation and demyelination of the optic nerve and spine.
- Global prevalence of 1-2 in 100,000.
- Often mistaken for multiple sclerosis (MS), which causes difficulty in establishing prevalence.
Neuromyelitis Optica (NMO) causes ongoing loss of vision and spinal cord function; the latter can lead to muscle weakness, lack of coordination and bowel/bladder control, and loss of sensation.
NMO is very similar to MS, as the latter is also characterised by inflammation and demyelination of nerve tissue. However, a different autoimmune response is involved. NMO can cause much more rapid physical decline, and around 30% of sufferers die within five years of diagnosis. Conversely, the majority of MS sufferers can expect to live a normal or slightly reduced lifespan. As with MS, there is no cure for NMO, but some medications can ease symptoms.
In a 2013 study into neuropathic pain and hypersensitivity resulting from NMO, the endocannabinoids 2-AG and anandamide were both elevated in patients compared to healthy controls. The authors concluded that these endocannabinoids are released in higher levels in NMO sufferers, in order to reduce pain and sensitivity and prevent hyperalgesia.
- An autoimmune condition causing progressive weakening of the muscles.
- Global prevalence of 5-20 in 100,000.
The main signs and symptoms of myasthenia gravis (MG) include drooping eyelids and facial features, difficulty with chewing, swallowing and speaking, and respiratory difficulty. MG is caused by antibodies that block the normal transmission of acetylcholine, the neurotransmitter responsible for coordinating nerve impulses with muscle movement. There is no cure for MG, but some anticholinesterase medications may have some effect.
Acetylcholinesterase is the enzyme that degrades acetylcholine, so inhibiting the former can effectively raise levels of the latter at the neuromuscular junction (where nerve meets muscle). Higher levels of acetylcholine allow more nerve signals to get through, and improve the response of the muscles.
Various studies have demonstrated THC, CBD and other cannabinoids’ ability to inhibit acetylcholinesterase and reduce the degradation rate of acetylcholine. One US state, Illinois, includes MG on its list of approved conditions, and California-based doctor Allan Frankel has been treating MG patients with a combination of THC, CBD and THC-A, apparently with good results.
- A group of genetic disorders affecting the skin and the connective tissues of the joints.
- Global prevalence of around 20 in 100,000.
Ehlers-Danlos syndrome (EDS) can cause hypermobile, unstable joints, hyperelastic skin, chronic pain, muscle spasms, deformities of the joint and spine, and cardiovascular complications. EDS is caused by mutations in certain key genes, which control the expression of proteins crucial to collagen production.
EDS sufferers have anecdotally reported subjective relief from neuropathic pain and spasms when using cannabis and cannabinoid-based treatments. The compound palmitoylethanolamide (PEA) has also been used to control neuropathic pain in EDS, and is available under the brand name PeaPure in some countries.
Although not a classical cannabinoid, PEA is known to have affinity for the GPR55 and GPR119 receptors, which are part of the endocannabinoid system, and is also known to augment the effects of anandamide.
- A rare group of autoimmune disorders affecting the skin and the mucous membranes, particularly the mouth.
- Global prevalence of pemphigus is estimated at 10-50 in 100,000.
- Certain ethnic groups (particularly Ashkenazi Jews) are more affected than others.
Pemphigus causes itchy, often painful blisters and sores that can spread to cover a large percentage of the body. If untreated, it can cause runaway infections, which can be fatal. The most common treatments include several high-strength steroids including prednisone, which have a range of serious side-effects including intestinal perforations.
Pemphigus is caused by pathogenic antibodies attacking a protein known as epithelial cell adhesion molecule. Without this protein, cells cannot stick together as normal, and the outer layer of the skin and mucous membranes gradually sloughs off.
Cannabis-based treatments have been shown to be effective against several autoimmune disorders affecting the skin, including psoriasis and epidermolysis bullosa. In general, it is the CB₂-receptors that mediate the immunological and anti-inflammatory effects of cannabinoids – and these receptors are highly concentrated in the epidermis.
Furthermore, cannabinoid treatments (specifically topical creams and ointments) may also confer important antibacterial, antiviral, and antifungal effects, helping to prevent secondary infection. Several patent applications for cannabis-based topicals for pemphigus have been submitted, and there are several anecdotal reports of patients experiencing relief from symptoms.
Myoclonus diaphragmatic flutter
- An extremely rare condition causing rapid, involuntary spasms of the diaphragm.
- Only 50 people worldwide diagnosed thus far.
- Also known as belly dancer’s syndrome.
Myoclonus diaphragmatic flutter (MDF) causes the diaphragm to contract between 35 and 480 times per minute, causing a spasmodic, rippling effect somewhat reminiscent of a belly dancer. This extremely rare disorder may be caused by nutritional disorders, dysfunction of the central or peripheral nervous systems, pharmaceuticals, or possibly even anxiety.
MDF is not generally thought to be fatal, but causes discomfort and difficulty with breathing and eating. There is no standard pharmaceutical treatment, but symptoms can be instantly relieved by temporarily blocking the phrenic nerve that runs past the lungs to reach the diaphragm.
In one celebrated case, a young man suffering from MDF, Chaz Moore, was reported to have found that medicinal cannabis was the only effective treatment for his symptoms. Due to its extreme rarity, there is little research on the disease. However, cannabinoids with antispasmodic and anticonvulsant effects, such as CBD, are likely to be of most interest.
Familial Mediterranean fever
- An inherited inflammatory disorder that particularly affects the chest, abdomen and joints.
- Global prevalence estimated at 10-50 in 100,000; in worst-affected areas prevalence may be as high as 500 in 100,000 (1 in 200).
- Mostly affects Mediterranean populations, particularly Armenians, Greeks, Italians and Sephardic Jews.
Familial Mediterranean fever (FMF) causes attacks of pain, fever and inflammation in the chest, abdomen and joints, which last several hours and recur intermittently. First attacks occur by the age of 18 in 99% of patients.
FMF is thought to be caused by mutations in genes that control expression of a protein known as pyrin, which is deeply involved in regulating inflammatory processes. Analgesics, NSAIDs and certain other drugs including colchicine may have some effect.
Cannabis was first described as a possible treatment for FMF in 1997. In a double-blind placebo-controlled crossover trial conducted on a single patient with FMF, THC was found to markedly reduce the need for opiate-based painkillers. However, it does appear that there has been any further research since then.
- An extremely rare genetic disorder linked to the X-chromosome, causing seizures and developmental delays.
- 167 cases registered worldwide so far.
- Primarily associated with girls.
This rare and recently-discovered condition causes severe seizures, developmental delays, scoliosis, microcephaly, poor motor control, limited speech, and various other abnormalities. It is associated with mutations in the CDKL5 gene, which is located on the X-chromosome.
Very little is known about this disorder thus far, and there have been no formal studies into the potential of cannabis as a treatment. However, several families of children with the condition have reportedly seen great improvements after using CBD. In 2014, an 11-month-old girl was reported to have exhibited improvements in muscle control, eye contact, alertness and overall progress after using CBD.
In 2016, 6-year-old Harper Elle Howard tragically lost her battle against CDKL5. At just two weeks old, she began to experience life-threatening seizures that failed to respond to conventional treatments.
Treatment with CBD caused a rapid and dramatic decline in seizures, and allowed Harper to resume near-normal development for several years. However, the battle to maintain normal life ultimately proved too much for Harper – although her story has directly inspired changes in medicinal cannabis legislation in half a dozen countries.