Medical Cannabis and Cachexia
Medical cannabis and phytocannabinoids like THC and CBD may provide hunger-boosting and anti-anxiety effects that help ensure a healthy appetite and weight maintenance for those with cachexia.
Cachexia, also called “wasting syndrome,” is a disorder that occurs when the patient suffers extreme weight, fat, and muscle loss. It is often associated with eating disorders, but the patient’s weight and appetite loss in cachexia are not always intentional. Cachexia is often associated with cancer or AIDS/HIV treatments, chemotherapy, and anti-retroviral therapy (ART).
What is Cachexia?
Cachexia is a disorder where the patient suffers extreme weight, fat, and muscle loss. Cachexia is usually associated with:
- Cancer and chemotherapy
- Kidney disease
- Rheumatoid arthritis
- Chronic obstructive pulmonary disease (COPD)
- Crohn’s disease
- Cystic fibrosis
- congestive heart failure (CHF)
Those with cachexia are not necessarily purposefully attempting to lose weight or appetite, i.e., their weight loss is involuntary. This makes cachexia different from eating disorders like anorexia or bulimia, where weight loss is intentional. Where appetite loss and food aversion are also a part of a patient’s cachexia, it may be termed “anorexia-cachexia syndrome.” Cachexia affects about 1% of the population.
Cachexia is not a well-understood condition, and the disorder’s mechanism is not well-known. Immune system dysregulation is part of cachexia, particularly the inflammatory tumor necrosis factor (TNF), interferon-gamma cytokines, and interleukin-6 (IL-6). In response to weight loss, ghrelin and adiponectin levels increase.
Brief Summary of Current Treatments
Regarding medications, the most commonly-prescribed drugs are progestogens, namely medroxyprogesterone acetate (MPA, or Depo-Provera) and megestrol acetate (MA, or Megace, which is also used to treat breast cancer). These are hormonal medications that can help increase appetite and reduce muscle wasting.
There is also a cannabinoid-based medication for cachexia called “Dronabinol” (trade name Marinol). Dronabinol is a synthetic version of THC prescribed for the side effects of chemotherapy, including appetite loss, nausea, and chronic pain.
Exercise may be recommended to reduce skeletal muscle loss, but this can be difficult for patients undergoing painful medical procedures and taking medications with severe adverse side effects. Calorie-dense protein supplementation and other nutritional supplements such as glutamine, leucine, and valine may also be woven into a patient’s diet to reduce muscle and bone loss.
How Might Medical Cannabis Help?
A cannabinoid-based medication is already available for prescription for those with AIDS/HIV- or cancer-related cachexia named “dronabinol.” Dronabinol is synthetic THC and does not contain other cannabinoids like cannabidiol (CBD) or cannabigerol (CBG). This means that there is no entourage effect to help battle inflammation. Dronabinol also has longer-lasting results compared to cannabis. This can have benefits and drawbacks, as many people find the products of pure THC overwhelming. Moreover, as dronabinol only contains THC, its therapeutic value is diminished somewhat as it is only effective for a certain number of people.
The main compound in cannabis that stimulates appetite is THC, a partial agonist of CB1 receptors and is more well-tolerated than many current medications, which have side effects like headaches, insomnia, and gastrointestinal (GI) upset. Promoting CB1 signaling can increase appetite and stimulate feeding, and blockading CB1 signaling suppresses appetite.
- THC stimulates appetite via interaction with CB1 receptors.
- Cannabinol (CBN) also interacts with CB1 receptors, albeit slightly milder than THC. CBN has sedative properties as well, which can help battle insomnia.
- High doses of tetrahydrocannabivarin (THCV) can stimulate appetite. Lower doses, however, may suppress appetite as THCV is an agonist of CB1 receptors.
- Some CBD may help boost appetite indirectly by helping reduce nausea, vomiting, and GI upset.
- THC:CBD 1:0
- THC:CBD 1:1
- THC:CBD 2:1
- THC:CBD 3:1
Terpenes and Terpenoids
The following terpenes may boost appetite:
More research must be done to confirm the appetite-boosting potential of these terpenes.
Colorful, flavonoid-rich foods can relieve inflammation and decrease the appetite-suppressing hormone leptin levels. The following flavonoids in cannabis may help stimulate hunger:
Effective Ways of Taking Medical Cannabis for Cachexia
Routes of Administration
A THC-rich formulation is ideal. Too much CBD, CBG, and low doses of THCV may result in appetite loss, so avoid such formulations if appetite gain is your primary objective. Humulene also reduces appetite, so it is also worth avoiding high doses of this terpene.
What are the Pros and Cons of Taking Medical Cannabis for Cachexia?
- THC is an appetite stimulant.
- There are many flavonoids in cannabis that may boost appetite while at the same time providing an anti-obesity effect.
- Medical cannabis can relieve other issues that may occur alongside cachexia, like headaches, insomnia, and chronic pain.
- The phytocannabinoids in cannabis can trigger “hungry hormones.”
- Although CBD and CBG may suppress appetite to some extent, they may also boost appetite by relieving nausea and GI upset.
- Progestogens can have several adverse side effects and “only increase adipose tissue and have not been confirmed to augment lean body mass.”
- Some cannabinoids and terpenes, like CBG, humulene, and low doses of THCV may curb appetite to some extent.
- Some people may feel nauseous, tired, and/or faint after using cannabis, especially THC-rich products and strains (more accurately called “cultivars” or “chemotypes”).
- Several meta-analyses show that cannabis did not help with weight gain and insignificant appetite increases between the cannabis treatment group and the control group.
Useful Anecdotal Information
Barry, Kevin. “Three additional medical conditions moved to expert review for Ohio’s medical marijuana.” News 5 Cleveland. Feb. 12, 2020.
“Medical Cannabis – Should It Be Part Of Your Cancer Care?” Rethink Breast Cancer. Apr 20, 2016.
Scientific Data Overview and Studies
- Total Studies = 17
- Positive Studies = 13
- Inconclusive Studies = 3
- Negative Studies = 1
- 14 Meta-analyses (10 positive, 3 inconclusive, 1 negative); 1 animal study (positive); 1 human trial (positive); 1 lab study (positive)
- 7 studies include CBD (5 positive, 1 inconclusive, 1 negative); 6 studies include THC (5 positive, 1 inconclusive); 1 study includes CBG (positive); 1 study includes a 1:1 THC:CBD ratio (positive).
- Possible Overall Efficacy: Moderate
Quotes from Studies
“Of 24 patients who signed the consent form, 17 started the cannabis capsules treatment, but only 11 received the capsules for more than two weeks. Three of six patients who completed the study period met the primary end-point. The remaining three patients had stable weights. In quality of life quaternaries, patients reported less appetite loss after the cannabis treatment (p=0.05). Tumor necrosis factor-α (TNF-α) levels decreased after the cannabis treatment but without statistical significance. According to patients’ self-reports, improvement in appetite and mood as well as a reduction in pain and fatigue was demonstrated.”
Source: Bar-Sela G, Zalman D, Semenysty V, Ballan E. “The Effects of Dosage-Controlled Cannabis Capsules on Cancer-Related Cachexia and Anorexia Syndrome in Advanced Cancer Patients: Pilot Study.” Integr Cancer Ther. 2019 Jan-Dec;18:1534735419881498. doi: 10.1177/1534735419881498. PMID: 31595793; PMCID: PMC6785913.
“Of 289 patients screened, 243 were randomly assigned and 164 (CE, 66 of 95 patients; THC, 65 of 100 patients; and PL, 33 of 48 patients) completed treatment. At baseline, groups were comparable for age (mean, 61 years), sex (54% men), weight loss (32% ≥ 10%), PS (13% ECOG = 2), antineoplastic treatment (50%), appetite (mean VAS score, 31/100 mm), and QOL (mean score, 30/100). Intent-to-treat analysis showed no significant differences between the three arms for appetite, QOL, or cannabinoid-related toxicity. Increased appetite was reported by 73%, 58%, and 69% of patients receiving CE, THC, or PL, respectively. An independent data review board recommended termination of recruitment because of insufficient differences between study arms.”
Source: Strasser, Florian; Luftner, Diana; Possinger, Kurt, et al. “Comparison of Orally Administered Cannabis Extract and Delta-9-Tetrahydrocannabinol in Treating Patients With Cancer-Related Anorexia-Cachexia Syndrome: A Multicenter, Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial From the Cannabis-In-Cachexia-Study-Group.” Journal of Clinical Oncology 24, no. 21 (July 20, 2006) 3394-3400. DOI: 10.1200/JCO.2005.05.1847
Although there is a solid theoretical framework for using medical cannabis for cachexia, systematic reviews suggest that the quality of evidence for its efficacy is low. However, the fact that there is a synthetic version of THC available on prescription for managing AIDS- and cancer-related cachexia, besides the vast number of anecdotal reports, shows that cannabis certainly can help induce “the munchies” in patients who need it.
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