Johnson, J.R., Lossignol, D., Burnell-Nugent, M., & Fallon, M.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, 207–218.

To investigate the long-term safety and tolerability of 9-tetrahydrocannabinol (THC)/cannabidiol (CBD) spray and THC spray in relieving pain in patients with advanced cancer

Patients who had previously participated in a two-week parent RCT to investigate the efficacy, safety, and tolerability of THC/CBD spray and THC spray in patients with cancer-related pain were invited to take part in the long-term, open-label, follow-up study. This study took place at 22 study sites in the United Kingdom and Belgium. Visits occurred at the conclusion of the RCT study or at extension study screening, 7–10 days later, then every four weeks, and at study completion or withdrawal. Adverse events, vital signs, blood sample analyses, changes in medication dosing and in current medical conditions were monitored at each visit. A pump action oromucosal spray was used to deliver the study medication. Each 100 uL actuation of THC/CBD spray delivered 2.7 mg of THC and 2.5 mg of CBD to the oral mucosa. Each actuation of THC delivered 2.7 mg of THC, and each actuation of placebo (in the parent RCT) delivered the excipients plus colorants.

N = 43  

MEAN AGE = 57.5 years for the THC/CBD group, 58.6 years for the THC group

MALES: THC/CBD: 59%, THC: 25%; FEMALES: THC/CBD: 41%, THC: 75%

KEY DISEASE CHARACTERISTICS: Breast (21%), prostate (16%), rectum (16%), lung (7%), and bone cancers (5%)

OTHER KEY SAMPLE CHARACTERISTICS: Those who had participated in the original RCT in Romania were not included in this study. The most commonly reported pain type was mixed pain, affecting more than half of all the patients, followed by neuropathic pain (37%) and bone pain (28%). Exclusion criteria included those with a history of severe cardiovascular, renal, hepatic, convulsive, or psychiatric disorder (other than depression associated with pain), patients currently taking levodopa, those pregnant or lactating or those not using adequate contraception, and those with oral cavity cancers or those whose previous treatments had included radiotherapy to the floor of the mouth.

• SITE: 22 study sites 
• SETTING TYPE: Not stated   
• LOCATION: United Kingdom and Belgium

• PHASE OF CARE: Palliative
• APPLICATIONS: Elder care, palliative care

Patients self-titrated THC/CBD spray (n = 39) or THC spray (n = 4) to symptom relief or maximum dose and were assessed regularly for safety, tolerability, and evidence of clinical benefit.

• Vital signs
• Adverse events
• Blood sample analyses
• Pain assessment
• Changes in medical condition
• Current dose of study medication
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
• Brief Pain Inventory-Short Form (BPI-SF)

The efficacy end point of change from baseline in mean BPI-SF scores for both “pain severity” and “worst pain” domains demonstrated an improvement at each visit in the THC/CBD spray patients. The EORTC QLQ-C30 scores demonstrated an improvement from baseline in the domains of insomnia, pain, and fatigue.

Long-term use of the THC/CBD spray was generally well tolerated. No evidence was seen of a loss of effect for the relief of cancer-related pain with long-term use. Patients who continued the medication did not seek to increase their dose of THC/CBD or other pain medication over time, suggesting a useful benefit of cannabinoids in cancer-related pain.

Small sample (less than 100)

Findings not generalizable

No comparable information with the study group, making drawing conclusions from the results difficult

Discrepancy between patient continuation within the study and the level of satisfaction of clinicians with level of pain relief

For patients with cancer-related pain, pain is a major issue. The adjuvant use of cannabinoids in patient with cancer-related pain could provide a great benefit. The proportion of patients reporting satisfactory analgesia was greater for the THC/CBD spray than placebo overall. The results of this study show that patients and investigators considered that maintenance or treatment with THC/CBD spray was justified by the clinical importance of pain management in patients with cancer-related pain.