Trial Outcomes & Findings for Anxiety, Inflammation, Stress, and Cannabinoids (NCT NCT03491384)

NCT ID: NCT03491384

Last Updated: 2025-08-27

Results Overview

The DASS21 is a 21-item scale that measures self-reported change in anxiety, depression, and stress symptoms. Participants are asked to use 4-point severity/frequency scales (higher values indicate greater severity) to rate the extent to which they have experienced each state. Scores for Depression, Anxiety and Stress are calculated by summing the scores for the relevant items. Changes in DASS subscale self-report will be tested in relation to THC and CBD blood levels. For this aim, only the Anxiety subscale was used. Anxiety subscale score range 0-42 Normal 0-6; Mild 7-9; Moderate 10-14; Severe 15-19; Extremely severe 20-42

• Recruitment status: COMPLETED
• Target enrollment: 361 participants
• Primary outcome timeframe: Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration)
• Results posted on: 2025-08-27

Participant Flow

Participant milestones

Measure	Non-Use No use of cannabis	THC Group Participants used THC dominant products	CBD Group Participants used CBD dominant products	THC+CBD Group Participants used products with roughly equivalent proportions of THC and CBD
Overall Study STARTED	44	105	117	95
Overall Study COMPLETED	42	86	92	80
Overall Study NOT COMPLETED	2	19	25	15

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Anxiety, Inflammation, Stress, and Cannabinoids

Baseline characteristics by cohort

Measure	Non-Use n=42 Participants No use of cannabis	THC Group n=86 Participants Participants used THC dominant products	CBD Group n=92 Participants Participants used CBD dominant products	THC+CBD Group n=80 Participants Participants used products with roughly equivalent proportions of THC and CBD	Total n=300 Participants Total of all reporting groups
Age, Continuous	35.3 years STANDARD_DEVIATION 14.4 • n=93 Participants	31.3 years STANDARD_DEVIATION 11.7 • n=4 Participants	29.5 years STANDARD_DEVIATION 10.9 • n=27 Participants	32.3 years STANDARD_DEVIATION 12.5 • n=483 Participants	31.6 years STANDARD_DEVIATION 12.2 • n=36 Participants
Sex: Female, Male Female	27 Participants n=93 Participants	50 Participants n=4 Participants	47 Participants n=27 Participants	45 Participants n=483 Participants	169 Participants n=36 Participants
Sex: Female, Male Male	15 Participants n=93 Participants	36 Participants n=4 Participants	45 Participants n=27 Participants	35 Participants n=483 Participants	131 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=93 Participants	7 Participants n=4 Participants	5 Participants n=27 Participants	4 Participants n=483 Participants	20 Participants n=36 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	38 Participants n=93 Participants	79 Participants n=4 Participants	87 Participants n=27 Participants	76 Participants n=483 Participants	280 Participants n=36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Region of Enrollment United States	42 participants n=93 Participants	86 participants n=4 Participants	92 participants n=27 Participants	80 participants n=483 Participants	300 participants n=36 Participants
Anxiety: DASS 21	9.38 units on a scale STANDARD_DEVIATION 7.71 • n=93 Participants	10.14 units on a scale STANDARD_DEVIATION 6.69 • n=4 Participants	10.46 units on a scale STANDARD_DEVIATION 7.29 • n=27 Participants	10.14 units on a scale STANDARD_DEVIATION 6.69 • n=483 Participants	10.11 units on a scale STANDARD_DEVIATION 6.86 • n=36 Participants

PRIMARY outcome

Timeframe: Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration)

The DASS21 is a 21-item scale that measures self-reported change in anxiety, depression, and stress symptoms. Participants are asked to use 4-point severity/frequency scales (higher values indicate greater severity) to rate the extent to which they have experienced each state. Scores for Depression, Anxiety and Stress are calculated by summing the scores for the relevant items. Changes in DASS subscale self-report will be tested in relation to THC and CBD blood levels. For this aim, only the Anxiety subscale was used.

Anxiety subscale score range 0-42 Normal 0-6; Mild 7-9; Moderate 10-14; Severe 15-19; Extremely severe 20-42

Outcome measures

Measure	Non-Use n=42 Participants No use of cannabis	THC Group n=86 Participants Participants used THC dominant products	CBD Group n=92 Participants Participants used CBD dominant products	THC+CBD Group n=80 Participants Participants used products with roughly equivalent proportions of THC and CBD
Change in Anxiety: Depression Anxiety Stress Scale (DASS21). Baseline	9.38 units on a scale Standard Deviation 7.71	10.1 units on a scale Standard Deviation 6.69	10.5 units on a scale Standard Deviation 7.29	9.85 units on a scale Standard Deviation 6.31
Change in Anxiety: Depression Anxiety Stress Scale (DASS21). 4 Weeks	6.78 units on a scale Standard Deviation 6.63	7.14 units on a scale Standard Deviation 5.57	5.39 units on a scale Standard Deviation 4.73	6.33 units on a scale Standard Deviation 5.6

PRIMARY outcome

Timeframe: Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration)

Population: Participants were included in inflammatory marker analyses if they had biomarkers available for both timepoints (baseline and 4 weeks). Thus, sample size here is not the same as sample size for self-report based outcomes.

Change in inflammation from before to after cannabis use will be tested in relation to THC and CBD blood levels.

The sum concentration of the cytokines IL-1a, IL-1b, IL-6, IL-8, IL-12, and TNFα, which are generally regarded as pro-inflammatory, will be utilized.

The range for these values can be from 0 to infinity. Higher values indicate higher (worse) levels of inflammation.

Outcome measures

Measure	Non-Use n=24 Participants No use of cannabis	THC Group n=44 Participants Participants used THC dominant products	CBD Group n=52 Participants Participants used CBD dominant products	THC+CBD Group n=51 Participants Participants used products with roughly equivalent proportions of THC and CBD
Change in Inflammation: Circulating Levels of Cytokines (Panel of Inflammatory Markers). Baseline	484.38 pg/mL Standard Deviation 1280.36	110.41 pg/mL Standard Deviation 152.31	294.71 pg/mL Standard Deviation 501.34	324.04 pg/mL Standard Deviation 871.24
Change in Inflammation: Circulating Levels of Cytokines (Panel of Inflammatory Markers). 4 Week	62.95 pg/mL Standard Deviation 88.15	125.62 pg/mL Standard Deviation 173.02	218.07 pg/mL Standard Deviation 487.29	338.05 pg/mL Standard Deviation 949.23

PRIMARY outcome

Timeframe: This was administered only once, at the 4 week timepoint, asking participants to reflect on how much change they had experienced over the past 4 weeks.

Patient Global Impression of Change Scale (PGIC) measures self-reported change on a 1-7 scale (i.e. from 1 (very much worse) to 7 (very much improved) in anxiety. Changes in this measure will be tested in relation to THC and CBD blood levels.

Scale possible score range 0-7, with higher scores indicating the largest amount of possible change.

Outcome measures

Measure	Non-Use n=42 Participants No use of cannabis	THC Group n=86 Participants Participants used THC dominant products	CBD Group n=92 Participants Participants used CBD dominant products	THC+CBD Group n=80 Participants Participants used products with roughly equivalent proportions of THC and CBD
Patient Global Impression of Change: Global Impression of Change Scale (PGIC).	4.4 score on a scale Standard Deviation 0.93	5.07 score on a scale Standard Deviation 0.96	5.2 score on a scale Standard Deviation 0.73	5.24 score on a scale Standard Deviation 0.93

SECONDARY outcome

Timeframe: Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration)

Co-outcomes testing multiple domains of thinking, memory, and perception (NIH Toolbox), cognitive impairment in the domains of immediate and delayed recall (ISLT), attention and inhibitory control (FICA). Cognitive outcomes are measured in standard scores (e.g. Range of >70 to >140 (Mean of 100 and SD of 15) with higher scores indicating better performance) and can be averaged to reflect a Standard score of overall cognitive function.

Outcome measures

Measure	Non-Use n=42 Participants No use of cannabis	THC Group n=86 Participants Participants used THC dominant products	CBD Group n=92 Participants Participants used CBD dominant products	THC+CBD Group n=80 Participants Participants used products with roughly equivalent proportions of THC and CBD
Cognitive Impairment: NIH Toolbox Cognitive Battery, Flanker Inhibitory Control Attention Task (FICA) and International Shopping List Test (ISLT). Baseline	108.753 score on a scale Standard Deviation 1.003	107.846 score on a scale Standard Deviation 9.442	109.799 score on a scale Standard Deviation 9.453	108.218 score on a scale Standard Deviation 0.353
Cognitive Impairment: NIH Toolbox Cognitive Battery, Flanker Inhibitory Control Attention Task (FICA) and International Shopping List Test (ISLT). 4 Weeks	112.917 score on a scale Standard Deviation 10.676	112.451 score on a scale Standard Deviation 9.087	114.367 score on a scale Standard Deviation 9.14	112.772 score on a scale Standard Deviation 11.357

SECONDARY outcome

Timeframe: Acute change in affect from before the negative affect induction task to post-breathing

Participants reported levels of negative affect on a novel scale from -50 (worst) to +50 (best) while undergoing a guided rumination to induce negative affect.

Outcome measures

Measure	Non-Use n=41 Participants No use of cannabis	THC Group n=86 Participants Participants used THC dominant products	CBD Group n=91 Participants Participants used CBD dominant products	THC+CBD Group n=80 Participants Participants used products with roughly equivalent proportions of THC and CBD
Self-Reported Affect in the Context of Negative Affect Induction Task Baseline	34.415 score on a scale Standard Deviation 15.56	33.518 score on a scale Standard Deviation 17.097	33.966 score on a scale Standard Deviation 14.184	33.416 score on a scale Standard Deviation 15.25
Self-Reported Affect in the Context of Negative Affect Induction Task 4 weeks	34.805 score on a scale Standard Deviation 11.9	36.687 score on a scale Standard Deviation 14.649	36.193 score on a scale Standard Deviation 14.448	36.147 score on a scale Standard Deviation 14.312

SECONDARY outcome

Timeframe: Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration)

The DASS21 is a 21-item scale that measures self-reported change in anxiety, depression, and stress symptoms. Participants are asked to use 4-point severity/frequency scales (higher values indicate greater severity) to rate the extent to which they have experienced each state. For this aim, only the Depression subscale was used.

Depression subscale score range 0-21 Normal (0 to 4), Mild (5 to 6), Moderate, (7 to 10), Severe (11 to 13), Extremely Severe (14 and above)

Outcome measures

Measure	Non-Use n=42 Participants No use of cannabis	THC Group n=86 Participants Participants used THC dominant products	CBD Group n=92 Participants Participants used CBD dominant products	THC+CBD Group n=80 Participants Participants used products with roughly equivalent proportions of THC and CBD
Change in Depression: Depression Anxiety Stress Scale (DASS21).	10.095 score on a scale Standard Deviation 8.588	9.442 score on a scale Standard Deviation 8.921	8.901 score on a scale Standard Deviation 8.333	8.425 score on a scale Standard Deviation 9.144

SECONDARY outcome

Timeframe: Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration)

Self-report measure across primary domains of diet, assessment of sleep quality, and health-related well-being. Each domain was assessed with the following single items:

Diet: "In general, how healthy is your overall diet? Would you say" (response options 0- excellent; 1- very good; 2- good; 3- fair; 4- poor) Sleep Quality: "During the past 2 weeks, how would you rate your sleep quality overall?" (response options 0- very good; 1- fairly good; 2- fairly bad; 3- very bad") Health Related Wellbeing: "In general, how would you describe your health?" (response options 0- excellent; 1- very good; 2- good; 3- fair; 4- poor)

Outcome measures

Measure	Non-Use n=42 Participants No use of cannabis	THC Group n=86 Participants Participants used THC dominant products	CBD Group n=92 Participants Participants used CBD dominant products	THC+CBD Group n=80 Participants Participants used products with roughly equivalent proportions of THC and CBD
Health and Wellbeing Baseline Self Reported Diet	1.643 units on a scale Standard Deviation 0.932	1.791 units on a scale Standard Deviation 0.883	1.857 units on a scale Standard Deviation 0.95	1.7750 units on a scale Standard Deviation 0.914
Health and Wellbeing 4 Week Self Reported Diet	1.659 units on a scale Standard Deviation 0.825	1.741 units on a scale Standard Deviation 0.804	1.811 units on a scale Standard Deviation 0.792	1.772 units on a scale Standard Deviation 0.784
Health and Wellbeing Baseline Sleep Quality	1.167 units on a scale Standard Deviation 0.696	1.221 units on a scale Standard Deviation 0.582	1.348 units on a scale Standard Deviation 0.67	1.362 units on a scale Standard Deviation 0.68
Health and Wellbeing 4 Week Sleep Quality	1.167 units on a scale Standard Deviation 0.537	1.14 units on a scale Standard Deviation 0.557	1.066 units on a scale Standard Deviation 0.611	1.2 units on a scale Standard Deviation 0.582
Health and Wellbeing Baseline Health-Related Wellbeing	1.238 units on a scale Standard Deviation 0.726	1.291 units on a scale Standard Deviation 0.81	1.217 units on a scale Standard Deviation 0.724	1.275 units on a scale Standard Deviation 0.675
Health and Wellbeing 4 Week Health-Related Wellbeing	1.463 units on a scale Standard Deviation 0.745	1.338 units on a scale Standard Deviation 0.816	1.618 units on a scale Standard Deviation 0.711	1.614 units on a scale Standard Deviation 0.748

SECONDARY outcome

Timeframe: Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration)

Motor control assessed via dynamic sway, proprioception, and finger tapping rate. Motor outcomes can be aggregated via Z-score to reflect a Z-score of overall motor function. We calculated the sum of Motor Battery Balance (Eyes Open, Eyes Closed, and Head Back) z-scores. A score of 0 means a participant's balance is at the mean for the sample. Higher scores (scores greater than 0) correspond to worse balance compared to the sample. Scores lower than 0 indicate better balance compared to the sample.

Outcome measures

Measure	Non-Use n=17 Participants No use of cannabis	THC Group n=40 Participants Participants used THC dominant products	CBD Group n=43 Participants Participants used CBD dominant products	THC+CBD Group n=45 Participants Participants used products with roughly equivalent proportions of THC and CBD
Motor Battery: Balance and Motor Function Baseline sum Motor Battery Balance score	0.0195 z-score Standard Deviation 0.007	0.0192 z-score Standard Deviation 0.006	0.0173 z-score Standard Deviation 0.005	0.0202 z-score Standard Deviation 0.014
Motor Battery: Balance and Motor Function Change in Balance score at 4 weeks	0.0214 z-score Standard Deviation 0.011	0.0201 z-score Standard Deviation 0.006	0.0182 z-score Standard Deviation 0.005	0.0195 z-score Standard Deviation 0.007

SECONDARY outcome

Timeframe: 4 weeks

Physical activity via objective daily data on wearable watch as measured by average minutes of moderate to vigorous physical activity (MVPA).

Outcome measures

Measure	Non-Use n=29 Participants No use of cannabis	THC Group n=62 Participants Participants used THC dominant products	CBD Group n=67 Participants Participants used CBD dominant products	THC+CBD Group n=49 Participants Participants used products with roughly equivalent proportions of THC and CBD
Objective Physical Activity/Exercise	1711.07 minutes Standard Deviation 1055.73	1751.97 minutes Standard Deviation 1075.78	1487.81 minutes Standard Deviation 1060.91	1712.53 minutes Standard Deviation 1114.56

SECONDARY outcome

Timeframe: 4 weeks

Physical activity via subjective self-report data using the Stanford Leisure-Time Activity Categorical item with 6 item responses (L-CAT; 1-6). Scores are reported as a mean between 1 and 6, larger numbers correspond to higher levels of activity.

Outcome measures

Measure	Non-Use n=42 Participants No use of cannabis	THC Group n=86 Participants Participants used THC dominant products	CBD Group n=92 Participants Participants used CBD dominant products	THC+CBD Group n=53 Participants Participants used products with roughly equivalent proportions of THC and CBD
Physical Activity/Exercise Baseline scores on L-CAT	3.476 score on a scale Standard Deviation 1.234	3.523 score on a scale Standard Deviation 1.326	3.571 score on a scale Standard Deviation 1.367	3.612 score on a scale Standard Deviation 1.392
Physical Activity/Exercise Change in scores at 4-weeks on L-CAT	3.415 score on a scale Standard Deviation 1.224	3.5 score on a scale Standard Deviation 1.299	3.4 score on a scale Standard Deviation 1.234	3.481 score on a scale Standard Deviation 1.357

SECONDARY outcome

Timeframe: Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration)

The DASS21 is a 21-item scale that measures self-reported change in anxiety, depression, and stress symptoms. Participants are asked to use 4-point severity/frequency scales (higher values indicate greater severity) to rate the extent to which they have experienced each state. For this aim, only the Stress subscale was used.

Stress subscale score range 0-33 Normal (0 to 14), Mild (15 to 18), Moderate, (19 to 25), Severe (26 to 33)

Outcome measures

Measure	Non-Use n=42 Participants No use of cannabis	THC Group n=86 Participants Participants used THC dominant products	CBD Group n=92 Participants Participants used CBD dominant products	THC+CBD Group n=80 Participants Participants used products with roughly equivalent proportions of THC and CBD
Change in Stress: Depression Anxiety Stress Scale (DASS21).	13.714 score on a scale Standard Deviation 8.572	13.023 score on a scale Standard Deviation 7.631	12.374 score on a scale Standard Deviation 7.136	12.4 score on a scale Standard Deviation 7.99

OTHER_PRE_SPECIFIED outcome

Timeframe: One survey per day for 30 days (at the start of the 4 week study)

Brief self-report from participants on anxiety and sleep in the past 24 hours. These are all 1-item novel questions in a daily, text based survey. Anxiety and sleep are on a scale of 1-10, with higher numbers being more anxiety or better sleep. Score is an average rating over 30 days.

Outcome measures

Measure	Non-Use n=42 Participants No use of cannabis	THC Group n=85 Participants Participants used THC dominant products	CBD Group n=92 Participants Participants used CBD dominant products	THC+CBD Group n=80 Participants Participants used products with roughly equivalent proportions of THC and CBD
Exploratory: Daily Follow-Up Messages Sleep Quality Rating	5.687 units on a scale Standard Deviation 1.785	5.72 units on a scale Standard Deviation 1.74	5.63 units on a scale Standard Deviation 1.818	5.455 units on a scale Standard Deviation 1.773
Exploratory: Daily Follow-Up Messages Anxiety Rating	3.457 units on a scale Standard Deviation 2.386	3.394 units on a scale Standard Deviation 2.102	3.51 units on a scale Standard Deviation 2.167	3.133 units on a scale Standard Deviation 2.066

OTHER_PRE_SPECIFIED outcome

Timeframe: 5 months (post-study completion)

Self-report from participants on anxiety (DASS anxiety subscale), sleep (novel sleep quality question ranging from 1-10 and 10 being best sleep), subjective cognitive functioning (perceived cognitive ability from the Functional Assessment of Cancer Therapy-Cognitive Function scale as was already reported in secondary measures- see for full description), and general health health (novel health question as was also reported in secondary measures- see for full description).

Outcome measures

Measure	Non-Use n=40 Participants No use of cannabis	THC Group n=57 Participants Participants used THC dominant products	CBD Group n=63 Participants Participants used CBD dominant products	THC+CBD Group n=53 Participants Participants used products with roughly equivalent proportions of THC and CBD
Exploratory: Monthly Follow-Up Surveys Anxiety	3.246 units on a scale Standard Deviation 3.267	3.067 units on a scale Standard Deviation 3.15	2.844 units on a scale Standard Deviation 2.974	3.216 units on a scale Standard Deviation 3.153
Exploratory: Monthly Follow-Up Surveys Sleep	6.145 units on a scale Standard Deviation 1.671	5.763 units on a scale Standard Deviation 1.79	5.837 units on a scale Standard Deviation 1.708	5.595 units on a scale Standard Deviation 1.626
Exploratory: Monthly Follow-Up Surveys Subjective Cognitive Impairment	4.657 units on a scale Standard Deviation 11.058	5.756 units on a scale Standard Deviation 10.222	4.88 units on a scale Standard Deviation 7.918	7.718 units on a scale Standard Deviation 14.185
Exploratory: Monthly Follow-Up Surveys General Health	1.455 units on a scale Standard Deviation 0.779	1.367 units on a scale Standard Deviation 0.893	1.606 units on a scale Standard Deviation 0.745	1.588 units on a scale Standard Deviation 0.777

Adverse Events

Non-Use

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

THC Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

CBD Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

THC+CBD Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. L. Cinnamon Bidwell

University of Colorado Boulder

Phone: 3037355180

Email: CUChange@Colorado.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place