Anorexia-cachexia syndrome is a common clinical problem that significantly impacts upon the quality of life (QoL) and survival of many palliative care patients. Anecdotal reports and numerous small scale clinical trials suggest that cannabis has both appetite stimulant and anti-nausea/vomiting effects. (1,2). Conversely, the endocannabinoid system is also under investigation as a pharmacological target for obesity management due to the role it is believed to play in appetite regulation and metabolism (3).

 In a questionnaire based study completed by 523 HIV patients, a lack of appetite was reported as the most frequently experienced symptom (111 out of 523) and 97% experienced improvement with cannabis use (n = 79 reporting “much better”, while n = 18 reported a “little better”) (4). In a placebo controlled within-subject study, smoked cannabis, oral dronabinol (synthetic THC) and placebo were assessed across a range of behaviours including, appetite, mood and sleep. Smoked cannabis and dronabinol were found to be well tolerated and efficacious as both treatments were seen to increase daily calorie intake and weight in a dose dependent manner (2).

Furthermore, dronabinol, a synthetic version of THC, has been FDA approved in the US for the treatment of nausea and appetite loss associated with HIV and cancer.

 Efficacy and Safety Data

 Dronabinol as a Treatment for Anorexia Associated with Weight Loss in Patients with AIDS. Beal et al 1995 (5).

Objective: A multicenter, double-blind, placebo-controlled, parallel-group trial to study the effects of dronabinol (synthetic THC), on appetite and weight in AIDS-related anorexia.

CohortTotal n = 139.  Dronabinol (2.5 mg bd.) n = 72. Placebo n = 67

Results: Dronabinol was associated with a statistical significant improvement in appetite, nausea and mood: increased appetite above baseline (38 % vs 8 % for placebo, P =0.015), decreased nausea (20% vs 7%; P = 0.05) and improvement in mood (10% vs-2%, P =0.06). Dronabinol treatment resulted in a mean increase in weight (0.1 kg) whereas the placebo group had a mean loss of 0.4 kg.

Safety: Overall dronabinol was well tolerated. Incidence of nervous system events: 35% in dronabinol group vs 9% in placebo group. The adverse events (AEs) were mostly mild to moderate and resolved without discontinuation of treatment. Most common nervous system AEs in the dronabinol group were (i) euphoria (n = 9), (ii) dizziness (n = 5), (iii) thinking abnormalities (n = 5), and (iv) somnolence (n = 4).

Conclusion: Dronabinol was deemed a safe and effective treatment for anorexia in patients with AIDS.

 Long-Term Efficacy and Safety of Dronabinol for Acquired Immunodeficiency Syndrome Associated Anorexia. Beal et al 1997 (6).

ObjectiveA multicentre, open-label, follow up study to investigate the long-term effect of synthetic THC for anorexia associated with weight loss in patients with AIDS.

Cohort: Patients were eligible if they had previously taken part in a 6-week placebo vs synthetic THC study (Beal et al 1995). In current study, all patients were treated with synthetic THC treatment (90% received 2.5 mg dronabinol bd, remaining 10% received 2.5 mg once daily). Of these, 38% modified their own dose by either increasing or decreasing the dose. Total enrolled n = 94 (previously received: synthetic THC n = 46, placebo n = 48). Completed full 12 months n = 22.  Average duration of therapy: 5.8 ±4.38 months

Results: Using the visual analogue scale for hunger (VASH), dronabinol treatment was associated with improvement in mean appetite. Patients previously treated with dronabinol or placebo exhibited improvement in mean appetite as measured by VASH (previous dronabinol: percent change from baseline of 48.6 - 76.1% at each month, previous placebo: percent change from baseline of 27.3% to 69.9%).

Safety:  At least 1 treatment related AE was reported in 44% of participants. Most AEs were mild to moderate, while 2 patients reported a severe AE. Central nervous system related AEs occurred in 38% of patients, these included anxiety, confusion, depersonalization, dizziness, euphoria, somnolence, and thinking abnormality).

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. Strasser et al 2006 (7).

Objective: To compare the effects of whole plant cannabis extract (CE), THC and placebo on appetite and QoL in patients with cancer-related anorexia-cachexia syndrome.

Cohorts: Completed treatment (6 weeks): total n = 164 (out of 243). Completed placebo n = 33 (out of 48). Completed CE (2.5mg THC, 1mg CBD bd) n = 66 (out of 95). Completed THC (2.5mg bd) n = 65 (out of 100).

Results: Treatment was not found to significantly increase appetite in comparison to placebo, however, a large placebo affect was also noted (increased appetite was reported by 69% in the placebo arm, 73% in the CE arm and 58% in the THC arm).

Safety: Both CE and THC treatments were well tolerated.

 A Phase II Study of Delta-9-tetrahydrocannabinol for Appetite Stimulation in Cancer-associated Anorexia. Nelson et al. 1994 (8).

Objective:  To investigate the appetite stimulation properties of THC in advanced cancer related anorexia.

Cohort: Total n =18 (THC 2.5 mg three times a day.)

Results: Overall 13 out of 18 participants reported an improvement in appetite (slight improvement n = 10, major improvement n = 3). Of the 6 patients weighed pre- and post-study, 3 gained weight, 2 maintained weight while 1 patient lost weight.

Safety: Four patients reported side effects (grade I) and 3 withdrew from the study.            

Of note, a recent survey performed in Canada on 271 patients registered to purchase cannabis from Tilray, perceived cannabis to be an effective treatment for appetite loss (n = 79) and nausea (n = 79) (9).

Products most prescribed for this condition:
  1. Foltin, Fischman and Byrne. Effects of Smoked Marijuana on Food Intake and Body Weight of Humans Living in a Residential Laboratory. Appetite, 1988; 11:1-4
  2. Haney, Gunderson, Rabkin, Hart, Vosburg, Comer and Foltin. Dronabinol and Marijuana in HIV-Positive Marijuana Smokers Caloric Intake, Mood, and Sleep. J Acquir Immune Defic Syndr Volume 45, Number 5, August 15, 2007
  3. Cheng and Pang. Endocannabinoids and obesity Vitam Horm. 2013;91:325-68.
  4. Woolridge, Barton, Samuel, Osorio, Dougherty, and Holdcroft. Cannabis Use in HIV for Pain and Other Medical Symptoms. Journal of Pain and Symptom Management. Vol. 29 No. 4 April 2005
  5. Beal JE, Olson R, Laubenstein L, et al. Dronab- inol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage 1995;10:89-97.
  6. Beal, Olson, Lefkowitz, Laubenstein, Bellman, Yangco, Morales, Murphy, Powderly, Plasse, Mosdell, and Shepard. Long-Term Efficacy and Safety of Dronabinol for Acquired Immunodeficiency Syndrome-Associated Anorexia. J Pain Symptom Manage 1997;1:10:7-14
  7. Strasser F, Luftner D, Possinger K, Ernst G, Ruhstaller T, Meissner W, Ko YD, Schnelle M, Reif M, Cerny T. 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. J Clin Oncol. 2006 Jul 20;24(21):3394-400.
  8. Nelson, Walsh, Deeter, and Sheehan. A Phase II Study of Delta-9-tetrahydrocannabinol for Appetite Stimulation in Cancer-associated Anorexia. J of Pall Care. 1994; 14-18
  9. Lucasa, Walsh. Medical cannabis access, use, and substitution for prescription opioids and other substances: A survey of authorized medical cannabis patients. International Journal of Drug Policy 42 (2017) 30–35
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