Long-Term THC/CBD Spray Was Well Tolerated for Cancer Pain With No Loss of Effect Over Time | Research

The takeaway

Cancer patients using THC/CBD oromucosal spray long-term showed sustained pain relief with no evidence of tolerance, no dose escalation, and no new safety concerns compared to the initial trial.

Read this if you or a loved one has cancer-related pain and is interested in cannabinoid-based treatments.

No dose escalation or increased use of other pain medications over long-term use

What the researchers found

Forty-three patients with advanced cancer and pain inadequately managed by strong opioids entered an open-label extension study of THC/CBD spray (nabiximols/Sativex). Thirty-nine used THC/CBD spray and 4 used THC-only spray, self-titrating to symptom relief.

Pain severity and worst pain scores improved from baseline at each visit. Quality of life measures showed improvements in insomnia, pain, and fatigue domains. Critically, patients did not seek to increase their dose over time, nor did they increase their other pain medications, suggesting no development of tolerance. No new safety concerns emerged beyond those identified in the parent trial.

Why it matters

One of the biggest concerns about cannabinoid pain medications is tolerance development. This study provides evidence that THC/CBD spray maintains effectiveness for cancer pain over extended use without dose escalation, which would make it a practical long-term adjunct to opioid therapy.

The numbers in context

43 patients entered (39 THC/CBD, 4 THC-only). Pain severity decreased at each visit. Worst pain decreased at each visit. Quality of life improved: insomnia, pain, fatigue domains. No dose escalation. No increase in other pain medications.

How the study worked

Open-label, multicenter extension study following a three-arm RCT. 43 patients with cancer pain refractory to strong opioids. Self-titrated dosing. Brief Pain Inventory-Short Form and EORTC Quality of Life Questionnaire-C30 measured at regular visits.

What this study cannot tell us

Open-label design with no placebo comparison in the extension phase. Small sample (43 patients). Selection bias: only patients who completed the parent trial and chose to continue were included. Advanced cancer patients have complex and changing pain patterns. No formal analysis of time-to-tolerance.

How to read the evidence

Open-label extension of an RCT; moderate evidence for long-term safety and sustained efficacy.

When this study was published

Published in 2013. THC/CBD spray (nabiximols) has continued through clinical development for cancer pain.

The bigger picture

This study addressed one of the key barriers to cannabinoid use in chronic pain: the fear of tolerance. The absence of dose escalation over extended use, combined with no increase in other pain medications, suggests a sustainable adjunctive role for cannabinoid sprays in cancer pain management.

Questions still open

How long can the effect be maintained? Would tolerance develop eventually with even longer use? Is the absence of dose escalation specific to the spray formulation? Could THC/CBD spray reduce opioid dose requirements?

Common questions

Does the body develop tolerance to cannabis pain medication?

In this study, cancer patients using THC/CBD spray long-term did not increase their dose over time and did not need more of their other pain medications. This suggests tolerance did not develop for pain relief, at least over the duration of this study. This is notable because tolerance is a well-known limitation of many pain medications.

Can cannabinoids replace opioids for cancer pain?

This study tested cannabinoids as an add-on to existing opioid therapy, not as a replacement. All patients were already on strong opioids that were not providing adequate relief. The THC/CBD spray provided additional pain reduction on top of opioids. Whether cannabinoids could reduce opioid doses was not directly tested but is suggested by the stable opioid requirements.

Read the original research

An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics.

Journal of pain and symptom management, 46(2), 207-18

View on PubMed ↗Publisher’s paper ↗

Citation

Johnson, Jeremy R; Lossignol, Dominique; Burnell-Nugent, Mary; Fallon, Marie T. (2013). An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics.. Journal of pain and symptom management, 46(2), 207-18. https://doi.org/10.1016/j.jpainsymman.2012.07.014