3.2.3. Sleep Quality

Sleep deprivation is one of the most common comorbidities associated with chronic illness [36]. Quality of sleep, assessed by the Pittsburg sleep quality index (PSQI), was improved following the inhalation of THC-predominant cannabis flowers after 3 months (Figure 2D, N = 344; T = 14.5; *p* < 0.001). This effect was maintained, but not further increased, at the 6-month follow up (Figure 3D, N = 140; X<sup>2</sup> = 74.9; *p* < 0.001). Participants diagnosed with anxiety disorders and chronic pain conditions reported similar basal levels (12.31 vs. 13.51) and no significant differences were found among the average improvement (3.15 vs. 2.72) in the PSQI scores of the two sub-populations (Table 2).

#### *3.3. Indication-Specific Outcome Measures*

Besides general outcome measures, which were collected for all patients, T21 participants are asked to complete health questionnaires specific to their primary indication. Here, we report only results from the main two health conditions, which included more than 85% of all participants (Table 1). Results from other less frequent indications, such as ADHD (N = 24) and PTSD (N = 21), will be disclosed in a separated data review once adequate statistical powering is achieved. Participants diagnosed with a chronic painful condition (N = 174) completed the Brief Pain Inventory-Short Form, a 9-item questionnaire used to evaluate (i) the severity of a patient's pain and (ii) the impact of this pain on the patient's daily functioning. Patients diagnosed with anxiety-related disorders or other mental health issues concomitant with anxiety (N = 107) completed the Generalized Anxiety Disorder (GAD-7), which total score for the seven items ranges from 0 to 21.

## 3.3.1. Pain Severity

Participants reported a 16.2% reduction in pain severity (Figure 4A, N = 174; T = 6.67; *p* < 0.001) from an average baseline value of 5.63 to a mean value of 4.72 at the 3-month follow up, associated with the treatment.

**Figure 4.** Improvement of indication-specific outcome measures at the 3-month follow-up. Analysis of PROMS shows how the inhalation of KHIRON 20/1 was associated with a marked improvement in self-reported ( **A**) pain severity and (**B**) pain interference in patients diagnosed with chronic painful conditions, measured with the Brief Pain Inventory-short form (N = 174). ( **C**) Generalized anxiety measured with the GAD-7 questionnaire was markedly decrease after 3 months of treatment with cannabis flos KHIRON 20/1 (N = 107). \*\*\* *p* < 0.001.
