As hypothesized, new medical marijuana users experienced improvements across all domains of HRQoL over the first three months of medical marijuana use for any of the more than 20 qualifying medical conditions for use in PA. Notably, participants endorsed greater than 20% increases in ratings of their role limitations due to physical health problems and emotional problems, and in social functioning after three months of medical marijuana use. The physical health and emotional limitations subscales of the SF-36 capture time spent, amount accomplished, or difficulties encountered when performing work or other activities due to physical health or emotional problems over the past four weeks, while the social functioning subscale assesses the extent to which physical or emotional problems have interfered with normal social activities.[16] We believe that these HRQoL gains represent clinically meaningful change in our participants. According to Wyrwich and colleagues, “clinically significant change in QoL is a difference score that is large enough to have an implication for the patient’s treatment or care” (p. 286).[20] While our study did not ask participants to define this threshold, the moderate effect sizes found in several domains including energy/fatigue, emotional well-being, social functioning, and bodily pain suggest that meaningful change occurred. Further, HRQoL directly relates to clinical outcomes. In individuals with chronic pain conditions, greater severity of pain is associated with greater impairments in HRQoL [21]; however, HRQoL improves as pain levels decline with treatment.[22].

Notably, the changes in HRQoL seen in our study were comparable to HRQoL gains in others evaluating different treatment modalities for the two most common referring conditions, anxiety and chronic pain. A study of HRQoL after 13 weeks of oral analgesic use for chronic knee pain found improvements in bodily pain scores on the SF-36 that were similar to the changes in bodily pain scores in our study after 12 weeks of medical marijuana use.[23] HRQoL has also been evaluated in individuals with generalized anxiety disorder (GAD). A double-blind, placebo-controlled study evaluating HRQoL following treatment with the prescription medication vortioxetine for GAD also found similar gains in social functioning scores after eight weeks as we found after 12 weeks of medical marijuana use.[24] Future studies that employ randomized controlled designs are needed to better understand the effectiveness of medical marijuana on HRQoL compared to other treatments for various conditions.

How the use of medical marijuana may relate to the observed gains in HRQoL, particularly in the domains that increased most, requires further study. For example, levels of energy increased in medical marijuana users as reported in the energy/fatigue subscale; future studies may benefit from examining potential mediators of this effect such as sleep quality and duration. It is also plausible that levels of bodily pain could mediate the gains observed at three months in physical and social functioning, especially given the high number of participants referred for medical marijuana to treat chronic pain. Additionally, the observed social functioning gains may be particularly relevant to individuals referred for medical marijuana for the treatment of anxiety disorders, as the symptoms associated with many anxiety disorders can substantially interfere with interpersonal functioning. The HRQoL gains in our study are similar to those reported in a study of patients with chronic pain [10] and in a smaller study of UK patients over three months of medical marijuana use.[9] Notably, referring condition (i.e., anxiety, chronic pain) was not related to the degree of improvement in HRQoL for any of the domains examined. Older participants in our study, however, reported less robust gains in their physical functioning and pain than younger participants, which may reflect the changes in functioning that normally coincide with older age, or may indicate a possible limitation of medical marijuana use in older adults. Additional studies are needed to clarify this finding.

This study has multiple strengths. To our knowledge, this study is one of the largest longitudinal studies of quality of life in individuals using medical marijuana in the US. This study utilized a well-established and widely used measure of HRQoL in both research and clinical domains, and had a high follow-up rates at month three (91%). The study also had several limitations. Our sample identified as predominantly White and female, limiting the generalizability of our findings to other groups. The reasons why this particular demographic is overrepresented are unclear, but may relate to the higher prevalence of anxiety disorders [25] and chronic pain [26] in women (the two most common referring conditions in this study), the greater likelihood of women to utilize complementary and alternative medicine compared to men, or fears of potentially negative outcomes in racial and ethnic minorities despite the legalization of cannabis use for medicinal purposes.[27] The observational study design did not allow for the attribution of causality in regards to the observed changes in HRQoL and the initiation of medical marijuana use; the current Schedule I designation of products containing tetrahydrocannabinol (THC) in the US limits the utilization of more rigorous study designs.

Individuals seeking medical marijuana for the first time may be experiencing particularly acute, intense or refractory medical conditions that more adversely impact their HRQoL compared to those seeking more evidence-based behavioral or prescription treatment options. It is also important to note that while individuals who enrolled in this study were naïve to medical marijuana use, 25% reported recent recreational use. The rate of recent recreational marijuana use was higher than rates of marijuana use reported in the general U.S. population with medical conditions [28] and could therefore limit the generalizability of our findings. Further, the high number of participants reporting previous experience with marijuana allows for the potential for both expectancy biases and placebo effects surrounding the use of marijuana for medical purposes. Beyond the reasons for declining study enrollment, no additional information was collected regarding the individuals who declined to participate in this study. It is possible that these individuals were different than enrolled participants in meaningful ways and future studies may benefit from obtaining descriptive information on those who decline to participate. While the majority of participants who did not complete three-month assessments were lost to follow-up (> 80%) and therefore the reasons for drop out remain unknown, several participants reported their reasons for dropping to be low remuneration and a high burden of time. Further, the present analyses did not evaluate potentially adverse psychosocial outcomes of medical marijuana use, though Arkell and colleagues found use to be associated with a low risk of serious adverse events.[11] Future studies could evaluate the adverse or unintended consequences of use or the reasons for initiating use, and may benefit from following participants for longer durations. The present study represents interim analyses and future analyses of this ongoing study will help to determine whether the observed gains in HRQoL at three months are sustained over the first year of medical marijuana use.

In conclusion, the use of medical marijuana for three months was associated with improvements in physical, social, emotional and pain-related HRQoL. Ongoing surveillance of HRQoL in individuals with physical and mental health conditions can help to treat the “whole person” and to capture any collateral impact of selected therapeutic approaches as treatment initiates and progresses. Results from this study can help patients, their caregivers, and their providers to make more informed and evidence-based decisions on whether to incorporate medical marijuana into their treatment regimens.