Cystic fibrosis Cystic fibrosis is a severe and debilitating genetic disorder that significantly reduces life expectancy and quality of life in sufferers. Now, evidence is emerging of the endocannabinoid system's fundamental role in the disorder.
Cystic fibrosis is a severe and debilitating genetic disorder that significantly reduces life expectancy and quality of life in sufferers. Now, evidence is emerging of the endocannabinoid system’s fundamental role in the disorder.
What is CF?
Cystic fibrosis (CF), also known as mucoviscidosis, is a genetic disorder that affects the lungs and various other organs. Symptoms include difficulty breathing and overproduction of sputum as a result of lung infections.
It is known that CF is associated with a protein known as cystic fibrosis transmembrane conductance regulator (CFTR), the production of which is encoded by the CFTR-gene. Individuals possessing certain single-nucleotide polymorphisms of the CFTR-gene exhibit reduced ability to regulate fluid transport in the epithelial tissues of the lungs, pancreas and various other organs, leading to the development of CF itself.
Now, research is suggesting that this genetic abnormality exerts its effects on the individual via the endocannabinoid system itself.
Fat loss, CF & the EC system
Cystic fibrosis (CF) is associated with abnormal lipid metabolism; progressive fat loss is a common symptom of the disease. The lungs and pancreas are most affected, which typically results in progressive lung damage and “pancreatic insufficiency” (a condition whereby the pancreas is unable to synthesise enzymes in sufficient quantities, resulting in malabsorption of nutrients). As endocannabinoids are fatty acid derivatives, it is thought that the imbalanced EC system seen in CF sufferers may be a result of this factor.
Due to the potential for malabsorption, sufferers of CF have significantly higher caloric requirements than non-sufferers in order to achieve normal growth and development and maintain good overall health throughout life. Furthermore, researchers have known for some time that in CF, pulmonary health is fundamentally linked to nutritional status; thus, maintaining good dietary health significantly improves long-term prognosis and probability of survival.
Therefore, most CF patients follow a specifically tailored, high-calorie diet in order to achieve normal development and maintain pulmonary health. Diets of CF patients should be carefully controlled and monitored to ensure that adequate nutrition is reaching the patient, and if malnutrition should occur, immediate steps must be taken to reverse it.
In some cases, appetite stimulants can be useful for CF patients suffering from malnutrition, although it is vital to ensuring that the malnutrition arises due to insufficient food intake and appetite rather than due to malabsorption. In such cases, treatment with THC could represent an ideal option as it stimulates the appetite while also potentially helping to manage many of the other symptoms of CF.
Pre/postnatal EC dysfunction and CF
Recent research has indicated that the development of CF may be associated with dysfunction in the endocannabinoid system during pre- or postnatal development. The EC system has a fundamental role to play in various aspects of human development, from the very earliest stages.
High levels of cannabinoid receptors, along with high concentrations of the endocannabinoid anandamide, are present in the newly-formed embryo prior to implantation in the epithelial lining of the uterus; a temporary drop-off in anandamide levels is then necessary to ensure successful implantation of the embryo.
Alongside this, the presence of CB1 receptors in white matter regions of the pre- and postnatal nervous system suggests that these receptors play a specific role in brain development. Furthermore, anandamide has been shown to be present in mother’s milk, and there is evidence to suggest that activation of CB1 receptors is crucial to the suckling response in newborn mice. Anandamide has also been shown to exert a neuroprotective effect in the postnatal brain.
Dysfunction at any stage of this process is thought to cause a range of developmental disorders such as CF; potentially, treatment with cannabinoids could mitigate or even reverse such disorders. Crucially, there is evidence to suggest that children may be less susceptible than adults to the the psychoactive effects of THC. Thus, THC and other cannabinoids may represent promising targets for further research into this serious and widespread condition.
How THC administered to at-risk infants may lower the risk of CF Symptoms Developing/Worsening
While there have so far been no studies into the potential for cannabinoids to treat human infants with CF, research into mice has yielded promising results. A 2011 study studied behaviour including motor activity and anxiety levels in mice specifically bred to lack the CFTR gene and exhibit symptoms of CF, with the expectation of finding impairments to the EC system in such mice compared to healthy controls.
The researchers predicted that administration of cannabinoid receptor agonists to CF mice during infancy would restore imbalanced cannabinoid levels and prevent behavioral abnormalities. Thus, CF mice treated with THC were compared to wild-type mice and untreated CF mice for anxiety and motor activity levels. It was demonstrated that CF mice untreated with THC exhibited decreased motor activity and increased anxiety in adulthood compared to wild-type controls, while adult CF mice treated with THC in infancy showed normal motor activity and anxiety.
The study authors suggested that behavioural alterations in CF result primarily from a lack of the CFTR-gene, which causes neural cells to lack an important neurotransmitter signalling system known as the CFTR-channel, and secondarily mediated by fatty acid deficiencies and imbalanced levels of endocannabinoids and their receptors. They furthermore suggested that intensive treatment with cannabinoids during infancy could restore balance to the EC system and mitigate behavioural abnormalities in adulthood.
Cannabis use by existing sufferers of CF
Although overall substance use in CF patients is lower than in the general population, cannabis is used surprisingly frequently. Indeed, some papers have noted a frequency of up to 60% (which is in fact far higher than use within the general population , but it is likely that this figure is somewhat overblown).
A 2001 review stated that there have been “no long-term studies looking at marijuana use in the CF population, but several papers have observed a disturbing prevalence of up to 60%. Some patients may find they obtain transient broncho-dilator effect (sic.) from smoking marijuana, but this benefit is very short-lived and patients need to be aware of the long-term damage from both the tobacco products and the metabolites of the marijuana”. An earlier study found that cannabis “often aggravated chronic pulmonary symptoms, although some patients reported transient relief during use”.
Of course, this review assumes that cannabis is smoked alongside tobacco, and is specifically discussing the dangers of smoking cannabis rather than other forms of consumption. Furthermore, more recent studies have suggested that the health risks from smoking cannabis are far lower than that of smoking tobacco. It is not clear whether smoking cannabis alone could prove advantageous for CF sufferers in a similar manner to the relief anecdotally reported by countless sufferers of asthma; however, it may be advisable for current sufferers to opt for a method of consumption which carries less potential for irritation of lung tissue.
Implications for healthcare
Much research remains to be done before we will have gained a complete understanding of the intricacies of the endocannabinoid system, its importance to human development, and its relationship to many previously mysterious diseases such as cystic fibrosis. However, initial research into the importance of cannabinoid receptor agonists such as THC is highly promising, and no doubt will provide the basis for future targeted therapies.