Cannabinoids for anorexia and cachexia

Cannabinoids for anorexia and cachexia

This time we will talk about cannabinoids for anorexia and cachexia. Serious diseases such as cancer, chronic infections or autoimmune diseases deplete the body and cause weight loss. Therefore, experts also speak of diseases of consumption. Medical cannabis is known to increase appetite as a side effect. Studies show that cannabinoids may be an important option in the treatment of anorexia and cachexia in cancer and HIV patients.

Cachexia and anorexia: what is it?

Cachexia is a multifactorial syndrome that occurs in various chronic diseases and is associated with severe weight loss. In contrast to a state of starvation, in which mainly fat reserves are burned, the body also loses vital organ and muscle tissue in cachexia. Patients become weaker and weaker. Dietary changes alone cannot stop this process. Cachexia not only reduces the quality of life in the face of serious illness. The weakening of the body can even aggravate the underlying disease and negatively influence recovery.

While cachexia has another underlying disease, anorexia does not. Anorexia is the medical term for loss of appetite. Anorexia nervosa (anorexia) refers to loss of appetite due to psychological causes.

Knowing the disease – Consequences of cachexia and anorexia

Anorexia-cachexia syndrome (ACS) occurs with particular frequency in cancer patients. From 50 to 80 percent of patients are affected depending on the type of tumor. Cachexia not only reduces quality of life, but is responsible for at least 20 percent of deaths among cancer patients and reduces the effectiveness of chemotherapy. The highest risk of cachexia is with pancreatic and gastric tumors (80%). However, 40% of lung and prostate cancer patients are also affected.

The symptoms of tumor cachexia can have different degrees of severity. In the case of precachexia, there is a slight weight loss, which is often not yet noticed by the affected person. The symptoms can develop into severe muscle atrophy. Due to the loss of strength, the patient’s independence becomes increasingly impaired.

Cachexia also occurs as an accompanying symptom in other serious diseases along with inflammation. Examples are:

  • Cancer diseases (tumor cachexia).
  • Multiple sclerosis
  • HIV infections (wasting syndrome)
  • chronic obstructive pulmonary diseases (COPD)
  • Cardiovascular diseases
  • Tuberculosis
  • Chronic renal failure
  • Rheumatoid arthritis
  • Diabetic neuropathy

What causes cachexia and anorexia?

In cachexia, inflammatory processes cause disturbances in the body’s energy supply. Food intake is usually reduced, while resting energy consumption (basal metabolic rate) increases. This results in a negative energy balance, in which more energy is consumed than is supplied, with the result that patients lose weight.

Some causes of tumor cachexia:

  • Tumor energy consumption: tumor cells grow out of control and require large amounts of glucose and amino acids.
  • Activation of inefficient metabolic pathways (Cori cycle): in the liver, glucose formed from lactate is metabolized back to lactate in the tumor cell.
  • Muscle breakdown: increased protein degradation leads to muscle atrophy.
    Influence on the central nervous system: due to the disturbance of the hormonal system, patients lose their appetite. In addition, patients taste and smell worse.
  • Insulin resistance: the body’s cells react with less sensitivity to the hormone insulin.
  • Therefore, the cells can absorb less glucose. However, glucose is an important building material for the construction of proteins and fat reserves.
  • Conversion of white to brown adipose tissue: while white blood cells serve as energy stores, brown adipose tissue is responsible for heat production. As a result, energy is consumed unnecessarily.

How cachexia develops in HIV-infected individuals is less well researched. A study in an animal model showed that T-CD8+ T cells play an important role. These immune cells normally kill infected cells, but they also disrupt fat tissue. This causes fat stores to break down. Future research should further decipher the connection between cancer, infections and cachexia in order to discover new methods of therapy.

Cannabinoids to increase appetite

The endocannabinoid system (ECS) controls food intake, metabolism and the body’s energy balance. The goal is to establish a balanced energy budget, i.e. perfect energy homeostasis. Tetrahydrocannabinol (THC), the psychotropic active ingredient of the cannabis plant, activates CB1 receptors. These are formed not only in the brain, but also in organs such as the gastrointestinal tract, liver, fatty tissue, muscles and pancreas. The CB2 receptor, on the other hand, is mainly found in immune cells and is stimulated by cannabidiol (CBD).

THC is responsible for the appetite-enhancing effect. The active ingredient activates the body’s own reward system. This promotes the feel-good factor when eating. In 2015, scientists discovered that so-called proopiomelanocortin nerve cells (POMC cells) trigger this feeling of happiness. Normally, these cells produce a satiety hormone (alpha-melanocyte-stimulating hormone) after a good meal, which reduces hunger. However, in the presence of THC, these cells produce endorphins that increase the desire to eat, even when the person is full.

By binding to peripheral CB1 receptors in the stomach, a hunger hormone (ghrelin) is also produced. This increases the desire for especially tasty, fatty or sweet foods. Maturation of fat cells is also promoted by cannabinoid receptors in adipose tissue.

10 out of 11 cancer patients report a significant increase in appetite

In a 2019 pilot study, the effect of THC / CBD capsules on appetite was investigated in 17 male and female cancer patients with cachexia and anorexia. During the course of the study, six of the individuals discontinued treatment due to side effects or cancer progression. In total, 11 people completed the study. The researchers remarked on the success of the treatment by weight gain of at least 10 percent of the initial weight.

All five people (100 percent) who were treated for 4.5 months reported an increase in appetite. Four people lost weight because their cancer worsened and required adjustment of tumor therapy, associated with side effects due to chemotherapy. The remaining person’s weight remained stable.

The remaining six participants took THC/CBD capsules for 6 months. Of these cancer patients, three achieved the therapeutic target defined by the research team, i.e., a weight gain of at least 10 percent of their initial weight. One person even achieved a weight gain of 21.6 percent. Another person gained only slightly, while the body weight of two patients remained unchanged. Subjectively, however, five (83.3 percent) of the six patients reported an increase in appetite. In half (50 percent) of these six, pain was also reduced and sleep improved. In addition, blood levels of the inflammatory marker TNF-alpha were reduced in four of the six patients. Adverse side effects reported included dizziness and anxiety.

However, the investigators concluded that the significance of the study is limited due to the numerous interruptions in therapy. Nevertheless, in 3 of the 11 patients, good success was achieved with an average weight gain of 17.6 percent. Therefore, a larger study with cannabinoid capsules will be conducted in the future.

Conclusion

Loss of appetite and wasting is a major problem in critically ill patients. Since the weakened body can no longer fight the disease well, treatment should be administered as soon as possible to stop or slow down muscle atrophy.

Since even experts do not yet fully understand what happens in the body during cachexia, the complex inflammatory processes must be investigated further. This will help scientists to develop new therapeutic approaches. Current studies show that tetrahydrocannabinol may be a good option. THC may help people with cancer or HIV infection to have more appetite and a better quality of life. As studies are scarce so far, larger studies are needed to further investigate the role of ECS in energy metabolism.

Sources:

[1]        Aktuelle Ernährungsmedizin 2013; 38(02): 97-111 DOI: 10.1055/s-0032-1332980 DGEM-Leitlinie Klinische Ernährung, Georg Thieme Verlag KG Stuttgart · New York



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