Overview

Amyotrophic Lateral Sclerosis (ALS) is a fatal type of motor neurone disease that leads to progressive degeneration of nerve cells in the spinal cord or brain. This neurodegenerative disorder affects muscle and nerve function. It is not contagious and usually affects individuals aged 40-70, however, it can occur in people who are younger the two main types of ALS include sporadic which occurs randomly without any genetic cause and familial which is the type of ALS which is inherited and affects a small number of people there is ongoing research on the causes of ALS with genetic causes are being considered more important and environmental factors are being investigated as causes for ALS.¹

The role of nutrition is seen as being very important in the management of ALS. Maintaining good nutrition is essential for individuals due to the following reasons:

• To meet the increased energy requirements for individuals with ALS (up to 15% more)
• To slow down the process of muscle breakdown
• To help maintain immunity
• To individuals with ALS a sense of well-being and improved quality of life

For individuals with ALS, maintaining a good quality of life may be more challenging due to symptoms experienced by individuals such as a decrease in appetite, increased stress levels and trouble chewing and swallowing which can affect food intake. These challenges in nutrition are discussed further along with potential therapeutic treatments to manage the symptoms of ALS.² 

Medical cannabis can be described as any sort of cannabis-based medicine which is used to relieve symptoms Cannabis may have therapeutic benefits to relieve symptoms of ALS due to its pleiotropic pharmacological activity.³ The most common compounds have been used for medical purposes for many years Medical cannabis can be used to ease symptoms for individuals with ALS including pain, depression, loss of appetite and muscle spasms, thus serving as an alternative therapy for ALS.⁴

Challenges in Appetite and Nutrition in ALS 

There are many challenges in appetite and nutrition faced by individuals with ALS which include problems related to swallowing and hypermetabolism. The muscles which are used in swallowing are affected for individuals with ALS hence, this leads to swallowing impairment which prevents them from gaining adequate nutrition leading to symptoms like malnutrition. These issues are further worsened due to issues such as hypermetabolism as the resting expenditure increases by 20% for patients with ALS as compared with healthy individuals.⁵

Dysphagia which refers to a swallowing disorder or swallowing impairment. Dysphagia can occur in any of the stages of swallowing and is a common symptom of ALS. PEG or Percutaneous endoscopic gastrostomy tubes are used as a route of feeding a means of nutritional support for patients who have a functioning gastrointestinal system and require long-term enteral nutrition. This route of feeding is common for chronic neuromuscular disorders such as ALS to ensure that patients can overcome challenges in maintaining adequate nutrition which is even more essential to help them recover from ALS.⁶

Furthermore, there are numerous metabolic challenges faced by individuals with ALS which include hypermetabolism. This occurs as people living with ALS have an increased resting expenditure and this can lead to weight loss as there is a higher amount of energy being used than taken in. Due to the heterogeneity of ALS, it is challenging to develop new therapies which would lead to the overall improvement in the quality of life of individuals with ALS. Hypermetabolism has been seen in individuals with ALS and weight loss has been seen to be associated with worsening of symptoms. Thus, weight management is seen as being very crucial for individuals with ALS due to the different metabolic challenges.⁷

The main focus of treatment of ALS is targeted at the slowing of symptoms and managing symptoms like weight loss and malnutrition. The nutritional parameters are typically shown to worsen after disease progression, highlighting the importance of weight loss management. Previous research has focused on challenges in nutrition. Recent studies have highlighted the importance of ALS-specific knowledge of nutrition, psychosocial aspects of eating and drinking, early management and psychological adjustment.⁸  

Mechanisms of Medical Cannabis in Appetite and Nutrition

Cannabis is a complex plant with major compounds such as delta-9- tetrahydrocannabinol and cannabidiol which have opposite effects, the research which has led to the discovery of the compounds of cannabis has allowed for the discovery of the neurotransmitter system known as the endocannabinoid system. ⁹ The neurodegeneration changes like dysregulation in the endocannabinoid system can contribute to the pathological processes in ALS and they can even act as pharmacological targets for the neuroprotective effects of cannabinoids and their effects on these changes.¹⁰

The compound THC which is one of the main active ingredients in cannabis is responsible for cannabis to partially bind to and activate the cannabinoid receptor 1 and THC increases appetite. The activation of the CB1 receptor by THC involves different mechanisms which are as follows:

• The decrease of the peptide tyrosine tyrosine levels (PYYL) increases the levels of ghrelin and increases the appetite
• It activates the mTOR (mammalian target of the rapamycin pathway which also increases the levels of ghrelin and hence the appetite
• It activates a subset of neurons which are called proopiomelanocortin neurons (POMCs these neurons can suppress hunger(primary pathway) and can also increase appetite (secondary pathway) 

Recent research has also revealed that a synthetic form of THC known as dronabinol is capable of stimulating the secondary pathway without having to stimulate the first one. The method of intake of THC can affect the caloric intake and influence the food choice. The two factors that influence the differences in appetite stimulation include differences in potency and rate of absorption.¹¹

Furthermore, it has been suggested that cannabinoids (CBD) may be useful in the treatment of difficult symptoms such as nausea and anticipatory nausea these symptoms are less well controlled by pharmaceutical agents These anti-nausea and anti-emetic effects of cannabinoids can be mediated by the indirect activation of somatodendritic 5-HT1A receptors in the dorsal raphe nucleus, thus cannabinoids may be used for treating nausea and emetic effects for therapeutic treatments.¹²

CBD has been found to be useful for various medical and psychiatric conditions such as depression, anxiety, post-traumatic stress disorder, Alzheimer's and other cognitive illnesses such as pain. These findings suggest that CBD can be used for conditions such as depression and anxiety which could develop in patients with ALS and hence, help aid in increasing appetite and overcoming the nutritional challenges.¹³

Practical Considerations for Cannabis Use in ALS

There are many practical considerations which need to be considered for patients with ALS regarding their symptoms such as swallowing impairment and other nutritional challenges. The consistency of food has to be taken into account to ensure that the food is edible for patients with ALS and the consistency can be defined in terms of different types of food. For example, a steak consistency diet would refer to no consistency whereas a cream consistency diet would refer to enteral feedings. These terms are hence used to determine the consistency of the food which should be given to patients with ALS depending on the severity of the symptoms to ensure that adequate nutrition is being consumed.¹⁴

Furthermore, the practical considerations which need to be taken into account also include the dosage at which the medical cannabis is being given to patients with ALS. This is due to the side effects of cannabis in patients with ALS and some of the common ones include weakness, dizziness, fatigue and dry mouth. Thus, taking these side effects into consideration it is important to start with low doses.¹⁵

Challenges, Limitations and Future Directions

There are many challenges and limitations for the use of medical cannabis which is important to understand to establish future directions in this growing area of research. Some of the challenges in using cannabinoids include their side effects which have to be taken into consideration when administering doses to patients Furthermore, there is currently limited clinical evidence and hence, there is a need for further research to be conducted to further understand the effects on cannabinoids in managing the symptoms of ALS, particularly regarding improving nutrition and appetite. Thus, further research in the translational development of cannabinoid-based therapies would help to further manage symptoms and delay the progression of the disease.¹⁰ 

Summary  

Thus, there are many nutritional challenges for patients with ALS which includes  Recent research that has offered great hope emphasising the use of cannabinoids in the improvement of symptoms of patients with ALS, particularly regarding the improvement of appetite and nutrition.

However, there is a need for further research to be conducted to understand the safety, efficacy and long-term impacts of using cannabinoid-based therapies for managing symptoms of ALS in helping patients improve their overall well-being and quality of life.