Novel cannabinoid could treat cancer-related anorexia

A synthetic cannabinoid product could offer a new treatment for late-stage cancer patients with anorexia.

California-based pharmaceutical company, Artelo Biosciences is investigating the efficacy of its synthetic cannabinoid product, as a much-needed therapy for cancer patients experiencing anorexia and weight loss.

Anorexia affects over 60 percent of later-stage cancer patients, but there are currently no approved medicines for the condition.

A weight loss of more than five percent can predict a poor outcome for cancer patients and a lower response to chemotherapy.

Artelo Biosciences has developed the novel ART27.13, designed to target the endocannabinoid system’s (ECS) CB1 and CB2 receptors in gut, without crossing the blood barrier.

This means that despite being more potent, it causes fewer side effects than naturally occurring cannabinoids such as THC. 

The company announced last month that the first patient has been dosed in its Phase 1/2 Cancer Appetite Recovery Study (CAReS), taking place at the University of Edinburgh, in the UK. 

Professor of pharmacology and scientific advisor to Artelo biosciences, Saoirse O’Sullivan spoke to Cannabis Health about the significance of the study and its potential benefits for cancer patients and others with a range of conditions. 

Saoirse O’Sullivan, PhD, professor of pharmacology

Cannabis Health: What is cancer-related anorexia, and why is it in need of more awareness?

Saoirse O’Sullivan: Anorexia affects over 60 percent of late-stage cancer patients. Anorexia and the resulting weight loss in cancer patients compromises health, weakens the immune system, causes discomfort and dehydration, ultimately reduces the patient’s prognosis and quality of life. 

No medicines are currently approved for treating cancer anorexia, but Megace (Megestrol acetate), THC compounds (Dronabinol), and steroids (dexamethasone) are used off label with limited efficacy and often intolerable side effects. Therefore this remains a significant unmet need in a considerably vulnerable patient group.

CH: How could the drug being developed by Artelo Biosciences could help patients?

SO: ART27.13 is a CB1/CB2 receptor agonist that doesn’t effectively cross the blood brain barrier and therefore does not cause activation of the CB1 receptor in the brain. This means that there are potentially few central nervous system-mediated side effects like paranoia, memory loss and psychosis. 

ART27.13 was originally developed by Astra Zeneca as a pain medication, but the programme was terminated because it was not effective in people after a molar extraction. However, in otherwise healthy subjects who participated in a Phase 1 pain study it was observed that low doses of ART27.13 rapidly increased body weight of more than three percent that was not explained by fluid retention and without serious or persistent side effects. 

With the knowledge that activation of the CB1 receptor in the periphery can increase appetite and weight loss, ART27.13 represents a novel therapeutic strategy to stimulate appetite and weight gain known to arise from CB1 receptor activation that could significantly benefit patients with cancer-associated anorexia without CNS side effects.

CH: What makes it different from naturally occurring cannabinoids? 

SO: The major differences between ART27.13 and THC are that ART27.13 is more potent and it doesn’t easily cross into the central nervous system.

CH: ART27.3 is said to specifically target receptors in the gut, could you explain how it works?

SO: ART27.13 will activate CB1 receptors in the periphery which impacts the overall energy balance of mammals in a number of different ways; inhibiting satiety (feeling full) and nausea, increasing food intake, altering the levels hormone that control appetite, altering taste sensation, slowing gastrointestinal motility, decreasing lipolysis (fat break down) and increasing lipogenesis (fat generation). The combined effect of peripheral CB1 activation is to promote appetite, and energy storage and preservation.

CH: Could this potentially be helpful in other patients with anorexia, not related to cancer? 

SO: Yes it is possible that ART27.13 could positively impact other types of patients with anorexia by the same mechanisms of action. Positive data from our CAReS trial in cancer patients would help to support that idea.

CH: And what about its potential in other conditions?

SO: While oncology is the main focus of Artelo Biosciences, there are many other indications for which a peripherally restricted CB1 agonist could be beneficial, for example in muscle spasticity, neuropathic pain, anti-tumoural effects, and gastrointestinal disorders.