**4. Discussion**

The purpose of this survey was to assess participants' medical cannabis usage within the Pennsylvania Medical Marijuana Program. The data collected in this survey provide needed information about the demographics, numbers of cannabis products used over time, routes of administration, and concomitant medication use of patients enrolled in a state-run medical cannabis program over the course of the year.

This study highlights the fact that patients take multiple medical cannabis products along with multiple other medications. While the average number of concomitant medications was low, it is important to recognize that patients reported using up to 15 additional medications along with cannabis, and approximately 30% were taking 5 or more medications. Some patients may choose to use cannabis as a sole agen<sup>t</sup> or as an adjunctive treatment to other medications, as evidenced by the proportion of patients concomitantly using opioids, benzodiazepines, and antidepressants. The use of medical cannabis can impact the levels of other medications and may have synergistic effects with patients also taking benzodiazepines, sedative-hypnotics, and opioids [14].

Approximately 40% of study participants did report using vitamins, and nearly 20% reported using complementary and alternative medications along with their cannabis. This may be an indication that some people are seeking more natural ways to treat conditions in addition to or as a replacement for prescription medications [15,16].

Another important aspect of the data is that participants exhibited high rates of starting new cannabis products and discontinuing others at each of the follow-up survey time periods. This could be due to patients needing to experiment with various products to find the one that works best for them, as patients exhibit different sensitivities to cannabis depending on the dose, dosage form, and prior use history [8]. This could also be due to product availability, as cannabis products may or may not be available over time depending on demand or crop production [8].

This study has several limitations. First, this study did attempt to look at the specific information for each MC product that participants reported taking. Unfortunately, it was evident during data collection that patient recall of specific information such as THC/CBD percent or ratios was hard to gather for each individual product. This may be due to the fact that people used various products at different times of the day and had a hard time recalling each one individually and the fact that MC products are often interchanged due to varied product availability over time. Patients were able to express that they use certain forms a certain number of times per day, but they may have had multiple products within the same dosage form. For example, patients could verbalize that they used a tincture multiple times per day, but they may have used one type of tincture in the morning and another later in the day depending on therapeutic effects they were looking to achieve or what types of adverse effects they were trying to avoid. For future studies, the challenge of self-reported data will impact how questions are asked with regard to getting accurate information on the types and composition of MC products used. The lack of participant recall also highlights the challenges of using MC in a clinical sense, in that patients could say they were using MC but did not know much more about the individual products. This also underscores the fact that clinicians who are trying to guide the patient's choice of product may prefer to reference documented objective data (dispensing data) as opposed to self-report if small details are needed to help inform therapy decisions.

Another limitation was that study participants were recruited from dispensaries, which may have led to a sample bias toward those that heavily rely on cannabis for symptom management. This may have also impacted the number of people that stopped using cannabis altogether due to lack of efficacy or intolerable side effects, as a majority of patients continued to use MC products throughout the study. Data from a meta-analysis on the efficacy of cannabis in the treatment of pain found that 10% of participants withdrew due to adverse effects [17]. Other meta-analyses on cannabis in multiple sclerosis and chemotherapy-associated nausea and vomiting also found that study withdrawal rates were higher in those taking cannabis as opposed to a placebo [18,19].

Furthermore, the sample was mostly comprised of individuals who identified as white. This may be due to known differences in cannabis use by race [20]. Future surveys should focus on recruiting more diverse participants from both cannabis dispensaries and non-dispensary locations to ge<sup>t</sup> a sample more indicative of general use. Lastly, this study was conducted during the COVID-19 pandemic, which may have impacted patients' MC and medication use due to potential social, economic, behavioral, physical, and mental health changes incurred as a result of this world-wide event [21,22].
