Behavioral Data
Main Effect of Time on the QOLIE-31-P
Descriptive statistics for the QOLIE-31-P are shown in Figure 2.
[Insert Figure 2_QOLIE Descriptive Statistics: QOLIE Descriptive Statistics; Legend: Figure 2 (top) shows the mean and standard deviation for the total score on the QOLIE-31-P for each of the three time points during which data was collected. Means and standard deviations for each of the QOLIE-31-P subscales are also shown. The chart below plots the total score means for each of the three time points, along with 95 % Confidence Intervals.]
The mean QOLIE-31-P TOTAL SCORE at enrollment (TIME 1) was 37.51±17.47 SD, compared to 52.96±19.52 SD at TIME 2, and 63.84±23.04 SD at the end of the study (TIME 3), representing an average increase in QoL scores of 26.33 points over time. Higher scores were indicative of improved QoL. QOLIE-31-P SUBSCALE means also increased over time.
Inferential statistics for the QOLIE-31-P and its subscales are shown in Figure 3.
[Insert Figure 3_QOLIE-31-P Inferential Statistics: QOLIE-31-P Inferential Statistics; Legend: The results of a one-way repeated measures ANOVA on the QOLIE TOTAL SCORE with a factor of TIME (3 levels) are shown, as are the results for Bonferroni-corrected pairwise comparisons. Results for post-hoc one-way repeated measures ANOVAs on the SUSCALES of the QOLIE-31-P are also shown along with the results of Bonferroni-corrected pairwise comparisons.]
A one-way repeated measures ANOVA, with a factor of TIME (3 levels = TIME 1, 2, 3), found a significant main effect of TIME on the QOLIE TOTAL SCORE (2 df, F = 8.042, p = 0.003). This indicates that participants’ TOTAL SCORES increased over TIME. Partial Eta squared was 0.472, which was indicative of a large effect. Pairwise comparisons showed TIME 1 was significantly different from TIME 3 (p = 0.024), but not TIME 2 (p = 0.221). TIME 2 was also not significantly different from TIME 3 (p = 0.124). Therefore, the increase measured in TOTAL SCORE over TIME was largely due to the increase in scores between TIME 1 and TIME 3.
Post hoc one-way repeated measures ANOVAs showed a main effect of TIME on almost all of the QOLIE-31-P SUBSCALES, including: distress (2df, F = 8.687, p = 0.010), cognition (2df, F = 6.046, p = 0.010), seizure worry (2df, F = 8.070, p = 0.014), overall quality of life (2df, F = 5.328, p = 0.015), mood (2df, F = 4.65, p = 0.024), daily activities (2df, F = 4.459, p = 0.027), and energy (2df, F = 3.851, p = 0.041) (Figure 3). Partial Eta’s on significant tests ranged from 0.300 to 0.491, and were indicative of large effects. Two subscales required Greenhouse-Geisser corrections due to sphericity violations (distress and seizure worry). No main effect of TIME was found for medication effects (2df, F = 0.992, p = 0.396). Pairwise comparisons showed TIME 1 was significantly different from TIME 3 for the following subscales: distress (p = 0.036), cognition (p = 0.032), seizure worry (p = 0.041), and daily activities (p = 0.032). No other post hoc tests were statistically significant. While many of the subscale scores increased over time, those that contributed most to the statistically significant difference in TOTAL SCORE found between TIME1 and TIME 3 were: distress, cognition, seizure worry, and daily activities.
Main Effect of Time on the HADS
Descriptive and inferential statistics for the HADS are shown in Figures 4a and 4b, respectively.
[Insert Figure 4_HADS: Hospital Anxiety and Depression Scale; Legend: Figure 4 (top) shows the means and standard deviations for both the anxiety and depression subscales of the HADS for each TIMES 1, 2 and 3. Figure 4 (bottom) shows the results of a two way repeated measures ANOVA on data from the HADS with factors of TIME and SUBSCALE, along with the results of Bonferroni-corrected pairwise comparisons. Figure 4 also shows the results of post-hoc one-way repeated measures ANOVA on each of the two separate SUBSCALES, along with the results of Bonferroni-corrected pairwise comparisons.]
The mean value for anxiety symptoms on the HADS anxiety SUBSCALE at TIME 1 was 11.3±3.92 SD. The HADS anxiety subscale scores decreased from 11.3±3.92 SD at TIME 1 to 5.3±3.97 SD at TIME 3, representing an improvement, on average, of 6 points. Levels of depression symptoms at TIME 1 were 7.3±5.01SD. The HADS depression subscale scores decreased from 7.3±5.01 SD at TIME 1 to 3.9±2.85 SD at TIME 3, representing an average improvement of 3.4 points. Mean anxiety and depression scores both decreased over TIME.
HADS data was initially analyzed using a two-way repeated measures ANOVA, with factors of TIME (3 levels = TIME 1, 2, 3) and SUBSCALE (2 levels = anxiety, depression). A main effect of TIME was found (2 df, F = 5.616, p = 0.013). Partial Eta squared was 0.384. A main effect of SUBSCALE was almost significant (p = 0.054). Partial eta was 0.354. The interaction of TIME and SUBSCALE was not significant (p = 0.280). Pairwise comparisons showed TIME 1 was significantly different from TIME 3 (p = 0.013), but not TIME 2 (p = 0.461). Time 2 was not significantly different from TIME 3 (p = 0.407). These results indicated that one subscale was likely primarily responsible for the differences observed in HADS scores between TIME 1 and TIME 3.
HADS data was further analyzed using two separate one-way repeated measures ANOVAs in order to independently assess the effects of TIME on anxiety vs. depression. A main effect of TIME on anxiety was found (2 df, F = 5.718, p = 0.012). Partial Eta squared was 0.388. Post hoc pairwise comparisons showed TIME 1 was significantly different from TIME 3 (p = 0.021) but not TIME 2 (p = 0.251). Time 2 was not significantly different from TIME 3 (p = 0.513). No main effect was found for TIME on depression (2 df, F = 2.859, p = 0.083). Although estimated marginal means confirmed a decreasing trend in depression scores over time, this data indicated that anxiety changed more over TIME than Depression.
Main Effect of Time on the LAEP
LAEP items reported as “always” or “sometimes” a problem at TIMES 1, 2, and 3 are shown in Figure 5.
[Insert Figure 5_LAEP: Liverpool Adverse Events Profile; Legend: This figure shows the frequency of participant endorsement of items on the LAEP at TIMES 1, 2, and 3.]
Some of the most frequently reported problems were: memory problems, difficulty concentrating, and nervousness/agitation. Most problems appeared to decline over the course of the study.
LAEP global scores were calculated by summing all responses to LAEP items that indicated the symptom was “always” or “sometimes” a problem. The mean global scores for the LAEP decreased from 52.1± 8.71 SD at TIME 1 to 38.5±10.80 SD at TIME 3, indicative of an average improvement of 13.6 points.
LAEP global scores were subsequently analyzed using a one way repeated measures ANOVA, with a factor of TIME (3 levels). A highly significant main effect of TIME was found (2df, F= 13.936, p = 0.000). Partial Eta was 0.608, which indicated a very large effect. Estimated marginal means confirmed a decrease in global LAEP scores over TIME. Pairwise comparisons showed TIME 1 was significantly different from TIME 2 (p = 0.007) and TIME 3 (p = 0.005). TIME 2 did not differ from TIME 3 (p = 1.000). This means that there was a significant decrease in adverse medication effects within the first 2.5 months that continued over the course of the study, albeit at a slower rate.
Urinalysis Data:
Cannabinoids and metabolites found in participants’ urine included: THC, 11-OH-THC, THCCOOH, THCCOOH-Gluc, THC-Gluc, CBD, 6a-OH-CBD, 6b-OH-CBD, 7-OH-CBD, 7-CBD-COOH, CBD-Gluc. The only metabolites tested for and not found in any of the urine samples were: CBC, CBN, CBG, THCV, and CBDV.
The primary metabolites for CBD excretion detected in participants’ urine were CBDCOOH and CBD-Gluc (See Figure 6).
[Insert Figure 6_Urinalysis: Urinalysis; Legend: Figure 6 (top) shows the levels of THC and CBD metabolites (THC-COOH, THCCOOH-gluc, CBD-COOH and CBD-gluc) present in participants urine in ng/mL during each of the three time points when data was collected. A key below shows the lower limits of quantification (LLOQ) and upper limits of quantification (ULOQ) for each of the cannabinoids/metabolites tested. ]
The median concentration of CBDCOOH at TIME 1 was 0.00 ng/mL; the mean was 3.11 ng/mL; the range was (0.00 – 24.84 ng/mL). The median concentration of CBDCOOH at TIME 2 was 1.39 ng/mL; the mean was 22.09 ng/mL; the range was (0.00 – 157.18 ng/mL). The median concentration of CBDCOOH at TIME 3 was 4.184 ng/mL; the mean was 24.76 ng/mL; the range was (0.00 -126.82 ng/mL).
The median CBD-Gluc concentrations detected in participants' urine at TIME 1 was 0.00 ng/mL; the mean was 7.25 ng/mL; the range was (0.00 – 32.52 ng/mL). The median CBD-Gluc concentration at TIME 2 was 162.52 ng/mL; the mean was 180.20 ng/mL; the range was (24.192 – 473.70 ng/mL). The median CBD-Gluc concentration at TIME 3 was 77.16 ng/mL; the mean was 173.55 ng/mL; the range was (7.75 – 547.27 ng/mL).
The primary metabolites for THC excretion detected in participant’s urine were THCCOOH and THCCOOH-Gluc. The median THCCOOH concentration detected at TIME 1 was 0.25 ng/ml; the mean was 2.20 ng/mL; the range was (0.00 – 9.11 ng/mL). The median THCCOOH concentration detected at TIME 2 was 0.00 ng/mL; the mean was 12.70 ng/mL; the range was (0.00 – 106.54 ng/mL). The median THCCOOH concentration detected at TIME 3 was 0.94 ng/mL; the mean was 26.38 ng/mL; the range was (0.00 – 248.75 ng/mL).
The median THCCOOH-Gluc concentration detected at TIME 1 was 0.00 ng/mL; the mean was 153.36 ng/mL; the range was (0 – 1196.96 ng/mL). The median THCCOOH-Gluc concentration detected at TIME 2 was 18.07 ng/mL; the mean was 635.46 ng/mL; the range was (0 – 5478.00 ng/mL). The median THCCOOH-gluc concentration detected at TIME 3 was 9.766 ng/ml; the mean was 1309.71 ng/mL; the range was (0 -12529.83 ng/mL).
Levels of metabolites varied widely from below the lower limits of quantification (LLOQ) to above the upper limits of quantification (ULOQ) and differed across participants for different metabolites. The ULOQ was exceeded in 9/30 samples across five different people. Five of thirty possible urine samples were missing or not tested.
All ten participants reported no cannabinoid use in the last 30 days. However, five of eight participants tested were positive for cannabinoids/metabolites at TIME 1. Two of these five participants tested positive for both THC/metabolites and CBD/metabolites (#’s 6, 8). Three of these five participants tested positive for THC/metabolites only (#’s 2, 3, 6). One of these five participants reported a substantial history of smoking cannabis (# 3), but no cannabis or CBD use within the thirty days prior to enrolling in the study. One of these participants (# 6) reported some previous CBD use, but not within the thirty days prior to enrolling in the study. One participant (# 8) reported previous CBD use, but not within the ninety days prior to enrolling in the study. Two of these five participants reported no history of use, but reported exposure to second hand cannabis smoke (# 2, 7).