Figure 1
Schema of the study protocol.
Each participant underwent a baseline assessment and eight follow-up assessments. Each arm of the study period included a one-week titration period, a two-week treatment period, and a one-week tapering period, with a three-week washout period between the two study arms.
Figure 2
Titration and taper schedule of the study drug.
The same titration schedule was used for TN-CT120 LM (each capsule contained THC/CBD 5/100 mg) and identical-appearing placebo capsules. Participants remained on the highest tolerated dose throughout the treatment arm.
Figure 3
CONSORT diagram of randomized, placebo-controlled, crossover trial.
Consent was obtained and participants were screened; eligible participants were randomized in a 1:1 ratio to receive either oral THC/CBD 5/100 mg or placebo first.
Table 1
Baseline demographic and clinical characteristics of the randomized participants (N = 7).
| Age, years | 67.0 (11.3) |
| Sex, male | 7 (100%) |
| Race | |
| White | 7 (100%) |
| Ethnicity, | |
| Non-Hispanic/Latino | 7 (100%) |
| BMI | 27.3 (4.7) |
| Duration of ET, years | 39.5 (19.4) |
| Age at tremor onset, years | 26.7 (20.3) |
| Positive family history of ET | 7 (100%) |
| Alcohol responsive tremors | 6 (85.7) |
| MoCA | 27.4 (1.9) |
| Currently taking other medications for tremor | 1 (14.3%) |
| Previously tried and failed medications for tremor | 5 (71.4%) |
| TETRAS Part 1 | 28.3 (5.0) |
| TETRAS Part 2 | 26.9 (3.2) |
| Baseline tremor amplitude on digital spiral drawing, mm | |
| More affected hand, maximum | 9.4 (4.8) |
| More affected hand, mean | 2.9 (1.2) |
| Less affected hand, maximum | 4.9 (2.7) |
| Less affected hand, mean | 1.48 (0.4) |
[i] Continuous variables are reported as mean (SD); categorical variables are reported as N (%).
Abbreviations: BMI = Body Mass Index; ET = essential tremor; mm = millimeters; MoCA = Montreal Cognitive Assessment; TETRAS = The Essential Tremor Rating Scale.
Table 2
Comparisons of changes in primary outcomes from baseline to time = 100 minutes after dose between treatment arms at visits 4 and 8 at the end of the two-week treatment period for all enrolled participants using paired t-test.
| SPR | PLACEBO ARM T = 100 MEAN (SD) | THC/CBD ARM T = 100 MEAN (SD) | DIFFERENCEa (95% CI) | COHEN’S D (95% CI) | P-VALUE | ADJUSTED P-VALUEb |
|---|---|---|---|---|---|---|
| Amplitude, max (mm) | 4.14 (3.07) | 3.57 (2.98) | –1.02 (–2.41, 0.36) | –0.43 (–1.01, 0.15) | 0.13 | 0.40 |
| Amplitude, mean (mm) | 1.10 (0.57) | 1.20 (0.85) | –0.083 (–0.27, 0.11) | –0.25 (–0.83, 0.33) | 0.37 | 0.73 |
| Power (mm/s)2/Hz | 0.014 (0.019) | 0.018 (0.031) | 0.0004 (–0.0095, 0.0087) | –0.026 (–0.60, 0.55) | 0.92 | 0.92 |
[i] Note: aDifference of change in SPR measures from baseline to time = 100 between the two arms. bp-values were adjusted for multiple related outcomes using the Benjamini-Hochberg method; Abbreviations: SPR = digital spirography; CI = confidence interval.
Table 3
Comparisons of change over time and average change in mean (standard deviation) of digital spiral drawing measures between THC/CBD and placebo arms at each time point after two-week treatment at visits 4 and 8 using linear mixed-effects models by treatment arm.
| OUTCOMEa | χ2 (DF) | P-VALUEb | ADJUSTED P-VALUEc | |
|---|---|---|---|---|
| Change over time (from baseline to time = 230 minutes after dose) | SPR (Amplitude, max) (mm) | 9.64 (7) | 0.21 | 0.63 |
| SPR (Amplitude, mean) (mm) | 3.69 (7) | 0.81 | 0.81 | |
| SPR Power (mm/s)2/Hz | 5.70 (7) | 0.57 | 0.81 | |
| Average change from baseline to the last four time points (60 100, 200, 230 minutes after dose) | SPR (Amplitude, max) (mm) | 2.81 (1) | 0.093 | 0.15 |
| SPR (Amplitude, mean) (mm) | 0.77 (1) | 0.38 | 0.38 | |
| SPR Power (mm/s)2/Hz | 2.71 (1) | 0.10 | 0.15 |
[i] Note: alog10 transformation prior to analysis; bp-value for interaction effect; cp-values were adjusted for multiple related outcomes using the Benjamini-Hochberg method; Abbreviations: SPR = digital spirography; df = degrees of freedom.
Figure 4
Tremor amplitude measured by digital spiral drawing over time.
The digital spiral drawings were repeated at various time points ranging from time = 0 [pre-dose] to 230 minutes after dose at visits 4 and 8 at the end of the two-week treatment period in the THC/CBD and placebo arms. Error bars indicate 95% confidence intervals.