Medical Research News

Cannabinoid Receptor Expression and Non-Small Cell Lung Cancer

Loren DeVito, PhD
Written by Loren DeVito, PhD

Traditionally, the development of Western medicine starts with the identification of a compound through cellular analysis and pre-clinical (animal) testing before it gets to clinical (human) trials. Due to the draconian laws in the US, cannabis medicine has not followed that path. Even after thousands of years of traditional use across a multitude of different conditions, it was not until just two years ago that the Food & Drug Administration put its seal of approval on a cannabidiol (CBD) formulation to treat types of severe epilepsy.

Therefore, the majority of available data on medical cannabis come from two sources – anecdotes from patients (and case reports from physicians) and pre-clinical studies. While clinical trial data are available for some types of conditions, researchers and physicians must rely on stories of which products patients have benefitted from and the effects of different cannabinoids in non-human models.

However, one specialty of medicine has been very familiar with the effects of medical cannabis for quite a while – and those are the healthcare professionals who treat patients with cancer.

In fact, the FDA approved three different synthetic cannabis-based medicines for nausea associated with chemotherapy, a standard cancer treatment. And this particular symptom is a common qualifying condition for those in states with medical cannabis programs.

As cannabis access has widened across the US, interest and funding has augmented and we are finally starting to learn about the basics of cannabis science, especially when it comes to cancer.

Take for instance lung cancer, a very difficult disease to treat with an expected 228,820 new diagnoses in 2020 alone. The majority of cases are of non-small cell lung cancer, or NSCLC. Despite a wide range of available treatment options available, the 5-year survival rate is just 24%.

A number of pre-clinical studies have found that cannabinoids possess anti-tumor effects to target lung cancer itself, not just associated symptoms – some of these dating back to results published in 1975. [1] But due to federal prohibition, cannabis cancer research slowed dramatically for decades as scientists struggled to get funding. And the majority of clinical trials today continue to focus on cannabinoids as a treatment for symptoms like pain.

So aside from the funding issue, how do we propel research into cannabinoids for the treatment of lung cancer itself into the clinical trial orbit?

Nearly 10 years ago, researchers first demonstrated that cannabinoid 1 and 2 (CB1 and CB2) receptors are overexpressed in cells from patients with NSCLC. [2]  They also found that CB1 and CB2 agonists (agents that increase receptor activity) were able to stop these cancer cells from growing and migrating. Additional experiments demonstrated these effects were indeed specific to the activity of the CB1 and CB2 receptors.

Just recently, another study also looked at tumor samples from patients with NSCLC. [3] As in the prior study, researchers found increased CB1 and CB2 receptor expression. However, they also found that overexpression of these receptors was linked to prolonged survival in patients, suggesting that CB1 and CB2 receptors may represent a biomarker of disease activity for NSCLC. Biomarkers are critical in helping manage disease treatment and in the evaluation of new drugs. This is the molecular equivalent of adjusting medications if your doctor found your blood pressure was too high.

Researchers also went on to demonstrate anti-proliferative effects of CBD and delta-9-tetrahydrocannabinol (THC) and further showed that these results are likely mediated by inhibition of epidermal growth factor receptor (EGFR), the target of a few currently available therapies for NSCLC.

These are the type of results that launch compounds into clinical trial testing. However, we certainly can’t skip a step from cells to humans. Hopefully we will see additional evidence to close the gap between pre-clinical/anecdotal/clinical trial data soon – and not in 20 years – so we can learn more about the potentially powerful effects of cannabinoids on NSCLC and other cancer types.

Image Credit: Clker-Free-Vector-Images

Image Source: https://pixabay.com/vectors/lungs-anatomy-breathing-bronchitis-297492/

References

  1. Abrams DI & Guzman M. Cannabis in cancer care. Clin Pharmacol Ther. 2015;97(6):575-586. Impact Factor: 7.266; Times Cited: 80
  2. Preet A, et al. Cannabinoid receptors, CB1 and CB2, as novel targets for inhibition of non-small cell lung cancer growth and metastasis. Cancer Prev Res (Phila). 2011;4(1):65-75. Impact Factor: 4.444; Times Cited: 78
  3. Milian L, et al. Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation and epithelial-mesenchymal transition in vitro. PLoS One. 2020;15(2):e0228909. Impact Factor: 2.740; Times Cited: 1

About the author

Loren DeVito, PhD

Loren DeVito, PhD

Loren DeVito, PhD is a neuroscientist and science writer with expertise in cannabis science and medicine. She is committed to communicating evidence-based information about cannabis and its healing properties. Learn more about her work at Stickyink.net

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