Treatment against cachexia - Recent and complementary studies on the beneficence of cannabis in case of cachexia
Cachexia is a profound weakening of the body (weight loss, fatigue, muscular atrophy, etc.) related to a very important undernutrition. Cachexia is not a disease in itself, but the symptom of another. This deterioration reduces patients to a state of immobility due to anorexia, asthenia and anemia, but also by muscle damage by protein hypercatabolism and therefore loss of lean body mass. Endogenous cannabinoids have a stimulating effect on appetite in humans. The same effect has been known since Antiquity on the part of plant cannabinoids, for example that of hemp (cannabis sativa) ...
Cachexia is not only caused by inadequate dietary intake, but is a consequence of the immune and metabolic disturbances that cancer brings. Glutathione and some amino acids are involved in the process: people with cancer lack glutathione and the administration of molecules to restore normal levels of glutathione is therapeutic. Cachexia is treated if one understands the causes ...
The causes of cachexia are due to serious illnesses
- - cancer
- - AIDS
- - celiac disease
- - chronic obstructive pulmonary disease
- - multiple sclerosis
- - rheumatoid arthritis
- - congestive heart failure
- - tuberculosis
- - family amyloid polyneuropathy
- - mercury poisoning
- - the hormonal deficit
This wasting syndrome most often occurs in the first two cases: on terminally ill cancer patients (usually referred to as cancer cachexia), and HIV / AIDS patients. The risk of death increases dramatically over time. Therefore, the treatment must be both against this wasting syndrome and the underlying cause of this syndrome (serious illness). Various appetite stimulants or serotonin antagonists have proven in clinical trials that they can not stop the progressive weight loss associated with cancer cachexia ... The standard treatment for cachexia is not very efficient in itself; because he neglects the secondary condition due to another illness.
Note that since June 2016, a metabolite called the HMB is recommended by professionals to treat the reduction of muscle mass loss in patients with this disorder. Doctors recommend a diet high in protein for patients, and use stimulants to encourage patients to regain their appetite and body mass.
THC & Dronabinol
The appetizing effect of Δ9-tetrahydrocannabinol (THC), the main active ingredient of cannabis sativa, and the partially synthetic THC dronabinol, have demonstrated their stimulating effect on appetite. These substances used as drugs for the treatment of anorexia and cachexia of AIDS patients, are authorized in the United States as antiemetics for cancers.
In the Netherlands, doctors assume that marijuana heals the disease. A study states that Dutch doctors of various specialties prescribe the use of medicinal cannabis against anorexia and cancer cachexia. This study also notes that smoked marijuana is perceived to be more effective than oral administration; this is confirmed by a medicinalgenomics article who points out that dronabinol, a cannabis-based drug, and cannabis cigarettes offer many benefits in the treatment of the syndrome.
Whatever the case, the cannabis-based medication is used to stimulate the appetite to increase body weight. The researchers studied diseases for which marijuana can be useful as a treatment. On the subject of cachexia, they say that cannabis and its active ingredient (THC) can stimulate appetite and increase body weight, but also dronabinol which helps increase appetite and increase weight in patients with AIDS (who suffer from cachexia).
According to the experience of several patients: Synthetic THC dronabinol causes terrible side effects like heartburn.
Cannabis a safe and future value
Cachexia is a complex disorder that in all likelihood will never be adequately treated with only marijuana. However, the known plant of antiquity and its extracts establish a safe and effective value among the drugs beneficial for people suffering from this disease. Weight loss is the main indicator of danger in this wasting syndrome, the effectiveness of cannabis to counteract this effect is a huge advantage.
By increasing appetite and, more importantly, body weight, cannabis can improve patients' quality of life in order to slow down or stop any symptoms of deterioration due to this disease.
The use of cannabis to treat cachexia in cancer patients
La cancer cachexia is caused by loss of body mass, including skeletal and cardiac muscle (myocardium), inflammatory response, changes in protein and energy balance, and changes in body composition that result in net weight loss. Cachexia is a common complication that occurs at terminal cancer stages and is responsible for 22% of deaths.
The role of increased systemic inflammation is mediated by pro-inflammatory cytokines (a substance developed by the immune system, regulating the proliferation of cells) leading to the pathogenesis of cancer. Some of the pro-inflammatory cytokines involved in pathogenesis are TNF-α, IFN-gamma, IL-6 and PGE2. The latter acts directly in the higher centers and plays a mediating role in suppressing the appetite. These molecular pathological events induce anorexia and muscle catabolism, resulting in lean muscle mass loss.
Some of the conventional treatments for cancer-related cachexia are megestrol acetate and medroxyprogesterone, ghrelin, melanocortin antagonists, thalidomide and etanercept to improve weight and anabolism. In addition, dietary supplements (including omega-3), corticosteroids, NSAIDs, beta-2 adrenergic agonists, and physiotherapy are also prescribed to treat cancer cachexia. However, the results of treatment are marginal and the prognosis is generally poor.
The central and psychoactive action of Δ9-tetrahydrocannabinol (THC) is well known and is mediated by centrally expressed CB1 receptors. These receptors are also present in peripheral tissues and transmit various molecular signals. Similarly, CB2 receptors are also widely present throughout the body and participate in the regulation of inflammatory processes.
The immunomodulatory role of CB2 receptors and its ligands is established. CB2 receptors act as pleiotropic modulators of TNF-alpha signal transduction and regulate circulatory levels of TNF-alpha in various inflammatory diseases. CB2 receptor activation has been shown to induce anti-inflammatory IL-10 release by activation of Erk1 / 2, thereby attenuating IL-6 and other pro-inflammatory interferons. These pro-inflammatory factors would be involved in the pathogenesis of cachexia and the inhibition of these cytokines by cannabinoids could have therapeutic benefits.
Conventionally, cachexia is treated with intravenous nutrition, high caloric diet and appetizers, including testosterone, growth hormones, and so on. The appetizing effect of cannabis is well known; Cannabinoids bind to its receptors responsible for food homeostasis and induce food intake. Among the natural cannabinoids, THC acts centrally and modulates the neural networks associated with the food intake process and induces appetite significantly in patients with cancer cachexia. The effects of cannabinoids on appetite and body weight stabilization have also been reported in patients with AIDS-related cachexia.
Data also suggests that cannabis may slightly improve mood, physical activity levels and energy, which reduces the risk of muscle atrophy, which may be beneficial for patients with cachexia.
Despite this molecular pharmacological evidence, the research community has not recognized / accepted the therapeutic benefits of cannabinoids in the treatment of cachexia associated with cancer. This may be due to the results of clinical trials, which are equivocal, mixed and even contradictory.
In clinical trials in humans, cannabis has been well tolerated by patients with cancer cachexia. The study found no benefit in terms of improvement of appetite or quality of life at various doses tested. Similar results have been observed in other studies. However, the study did not include a placebo comparison group to determine the efficacy or ineffectiveness of THC and dronabinol. The observed increase in appetite (49% of patients) was unclear whether the effect was attributable to treatment or placebo. In addition, no incidence of psychoactive effects or euphoria has been reported in patients treated with cannabinoids, suggesting that the dose used may be "suboptimal" or lower than the normal dose for treatment. cachexia. In other words, the "no effect" reported in these clinical trials may be related to inadequate dosing and no drug exposure, but no lack of therapeutic effect.
Despite these limitations, the study concluded that megestrol acetate was superior in the treatment of cancer cachexia. From a scientific point of view, poorly designed and evidence-biased studies are inconclusive as to the efficacy of cannabinoids in the treatment of cachexia. These types of poorly designed studies aim to reduce the medical use of cannabis and / or its derivatives. On the basis of these "findings", the regulatory authorities concluded that there was insufficient convincing evidence to support the use of cannabinoids in the treatment of cancer cachexia.
Another survey on 469 cancer patients with anorexia and cachexia reported that megestrol was superior to cannabinoids in terms of improved body weight gain and stabilization, appetite and tolerance. Similar results were reported in another study, that megestrol treated anorexia better - and improved cachexia symptoms - than dronabinol alone. This study focused on the pharmacology of synthetic cannabinoids, but not cannabinoids of plant origin.
In contrast to these findings, daily calorie intake and weight gain among HIV-positive people increased with the amount of marijuana consumed, but with moderate adverse effects. Low doses of THC significantly improved sleep quality, and all these results were comparable to those of dronabinol.
The first tests clinical studies on THC in the treatment of cancer cachexia have revealed the potential therapeutic efficacy of THC with improved appetite and weight gain. Similar results have also been observed in the treatment of cachexia HIV-associated.
One may wonder why there are discrepancies in the results of the study. The possible explanation is that these studies focused on the fixed-dose regimens chosen for all patients recruited without taking into account interindividual and intra-individual variations in the dose-response relationship and treatment outcomes. It is unlikely that a clinical study will be conducted with an individual dosing plan, in which dose adjustments can be made based on patient tolerance and response to treatment. Age and other factors may also affect the pharmacokinetics and pharmacodynamics of cannabinoids; young patients with cancer cachexia may have a different metabolic rate of the drug than older people. Given these questions, it is unlikely that the dosage, efficacy and toxicity will be the same or uniform for all patient populations. Therefore, the same dose can not help everyone and the design of this study is imperfect.
In analyzing currently available research literature, evidence supporting the use of cannabinoids in the treatment of cancer cachexia remains equivocal. A well-informed patient population requires large-scale clinical trials to demonstrate the safety and efficacy of cannabinoids in the treatment of cancer cachexia.
However, it is not possible to do this orally, given the interindividual heterogeneity of the pharmacokinetics of cannabinoids in patients with dysfunctional metabolism and modified body composition. In these individuals, the dose-response relationship and the concentration-effect relationship can not be established - even in well-designed clinical trials - as these effects are not universal in all patient populations. It is possible that the benefits or no reported benefits of cannabinoids in cancer cachexia are due to a person's unique dose-concentration relationship.
Until now, there is a lack of rigorous pharmacokinetic data on patients with cancer cachexia. Before conducting clinical efficacy trials, it is essential to explore and understand the pharmacokinetics and the pharmacodynamics of cannabinoids in this unique cachexic population. In this way, the rationale for the use of cannabis for the treatment of cancer cachexia may be warranted, and the cause of the variable outcomes of treatment may be understood. In the meantime, efficacy should be considered variable and dependent on the patient.
To date, more than 23 States have approved medical cannabis as a treatment for cachexia. In addition, other states, including Georgia, New York, Florida, Ohio, Massachusetts, and Pennsylvania, allow the use of cannabis for medical purposes for cachexia-related illnesses such as HIV / AIDS, cancer and Crohn's disease.