In October 2018, Canada became the third nation, and the world’s largest to date, to legalize adult (“recreational”) use of cannabis (marijuana; Cannabis sativa, Cannabaceae). While hinting at this development, the authors write that cannabis is “one of the most widely used illicit substance in Canada, [with] a unique ability to facilitate relaxation and relieve anxiety while reducing pain.”*
Cancer diagnosis is a life-changing event, causing significant stress and anxiety besides the burden of disease. Among patients newly diagnosed with head and neck cancer (HNC), given the central role of the head in function, body image, socialization, etc., diagnosis may be especially likely to cause distress. While quality of life (QoL) issues are recognized in cancer standards of care, treatment for distress related to HNC diagnosis remains problematic. Data are lacking both on the effects of recreational cannabis among patients with HNC and the use of cannabis to treat stress, depression, and anxiety in HNC patients. In this prospective cohort study, patients were enrolled consecutively upon diagnosis with HNC between January 1, 2011–January 1, 2015. Self-identified cannabis users were first screened for eligibility, then case-matched to non-users by age, gender, and tumor subsite, with 74 in each group. All self-identified cannabis users screened met inclusion criteria. Cannabis use was defined as the use of “loose-leaf marijuana” at least weekly. Demographic and QoL data were collected at enrollment and data analysis conducted from November 1–December 1, 2017. QoL instruments were administered by an HNC research assistant before initiation of treatment. Instruments for QoL data collection were the Edmonton Symptom Assessment System (ESAS), a 9-item questionnaire used commonly for QoL measurement in cancer patients, and the EuroQOL-5D (EQ5D), a 5-item health utility instrument. Lower ESAS scores (0-10) indicate better outcomes. On the EQ5D, scores range from 1-3 in each of five dimensions, with 1 indicating no problems; 2, some problems; and 3, extreme problems.
Mean age in the cannabis user group was 62.3 ± 10.3 years; in the non-user group, 62.2 ±10.4 years. Men made up 82% of users (n = 61); 85% of non-users (n = 63). There were no significant differences between groups in tumor subsites, T-N-M staging, treatment modality, or Karnofsky scores. Most common tumor subsite was the oropharynx (64% in both groups); the majority of these patients (96% of cannabis users; 98%, non-users) presented with p16-positive HNC. Groups were matched in income quartiles based on Canadian census data and in employment status. A plurality on both groups was retired, and just over one-third in each were employed full-time.
Univariate analysis found no significant differences in mobility, self-care, or usual activities domains of the EQ5D. Cannabis users had significantly lower scores for anxiety/depression (0.74 difference; 95% confidence interval [CI] 0.56 – 0.93) and pain/discomfort (0.29 difference; 95% CI 0.04 – 1.54). In ESAS results, users had significantly less pain (0.87 difference; 95% CI 0.04 – 1.69), depression (2.47 difference; 95% CI 1.67 – 3.27), and anxiety (4.53 difference; 95% CI 3.97 – 5.09), and significantly better general well-being (1.93 difference; 95% CI 1.13 – 2.74) than non-users Improvements were seen in all ESAS dimensions including nausea (0.49 difference; 95% CI 0.11 – 0.88), tiredness (2.22 difference; 95% CI 1.39 – 3.04), drowsiness (2.12 difference; 95% CI 1.38 – 2.87), and appetite (1.87 difference; 95% CI 1.00 – 2.73).
Cannabis is used medically as an analgesic and antiemetic by patients with cancer, to relieve anxiety and depression by those with post-traumatic stress disorder (PTSD), and as an adjunct for neuropathic pain by those with chronic pain syndromes, among others. Its main phytocannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD), have distinct pharmacological and behavioral effects. THC is involved in regulating fear- and anxiety-related behavior. CBD activates receptors that constrain fear-related and other psychological stress responses. Small uncontrolled studies in patients with PTSD show reduced symptoms with cannabis use. In a large longitudinal study, cannabis was associated with less prevalence of PTSD, anxiety, and depression. In a small study of patients receiving radiotherapy (RT) or chemoradiotherapy (CRT) for HNC, cannabis was associated with a reduction in depression (67%) and anxiety (33%). Patients using cannabis when diagnosed with HNC may face different psychosocial challenges than those with PTSD or other cancers. Despite study differences, similar improvements in anxiety and depression scores are striking. In a systematic review comparing synthetic THC analogs with placebo and other antiemetics among 1366 patients diagnosed with cancer, cannabinoids were found significantly more effective than placebo or other antiemetics in reducing nausea and vomiting, common adverse effects of RT and CRT. This is also similar to results in this study of cannabis use by patients diagnosed with HNC; however, it is unclear what caused their nausea, since RT or CRT had not yet begun. Cannabis’s anti-nociceptive effects in neuropathic pain are thought related to high concentrations of cannabinoid receptors in areas of the brain that modulate pain processing. Their distribution is quite similar to that of opioid receptors. Several clinical trials confirm the benefits of cannabinoid receptor agonists in relieving chronic pain associated with cancer. A trial of a THC/CBD preparation in 177 advanced cancer patients with uncontrolled pain despite opioid use reported a 30% reduction in pain compared to placebo, again similar to this HNC study. Additional studies on long-term effects of cannabis use on QoL scores of oncology patients would be valuable.
* Medical cannabis has been approved in Canada since 2001, administered by Health Canada (HC). Cancer is one of the conditions approved for cannabis use. The authors do not mention the availability of medical cannabis in Canada. Newly-diagnosed patients already using cannabis not obtained through HC thus have been by definition recreational, illicit users. Users in this study were self-identified. Unlike in United States studies, however, there seems no reason to think Canadian users would not tell their doctors of their use.
Zhang H, Xie M, Archibald SD, Jackson BS, Gupta MK. Association of marijuana use with psychosocial and quality of life outcomes among patients with head and neck cancer. JAMA Otolaryngol Head Neck Surg. November 2018;44(11):1017-1022..doi: 10.1001/jamaoto.2018.0486.