Cocaine Use Reduction and Health

• Contingency Management (Behavioral): Subjects will receive payments for providing cocaine negative urine samples.

Primary outcomes

• Endothelin-1 Levels [At baseline.]: Endothelin-1 levels will be measured. They will be recorded in pg/ml.
• Endothelin-1 Levels [Week 6 of study participation]: Endothelin-1 levels will be measured. They will be recorded in pg/ml.
• Endothelin-1 Levels [Week 12 of study participation]: Endothelin-1 levels will be measured. They will be recorded in pg/ml.
• Mean Arterial Pressure [At baseline]: Mean Arterial Pressure is recorded during participant visits and is recorded in mm Hg
• Mean Arterial Pressure [Week 1 of participation]: Mean Arterial Pressure was recorded during subject visits and is recorded in mm Hg
• Mean Arterial Pressure [Week 2 of participation]: Mean Arterial Pressure was recorded during subject visits and is recorded in mm Hg
• Mean Arterial Pressure [Week 3 of participation]: Mean Arterial Pressure was recorded during subject visits and is recorded in mm Hg
• Mean Arterial Pressure [Week 4 of participation]: Mean Arterial Pressure was recorded during subject visits and is recorded in mm Hg
• Mean Arterial Pressure [Week 5 of participation]: Mean Arterial Pressure was recorded during subject visits and is recorded in mm Hg
• Mean Arterial Pressure [Week 6 of participation]: Mean Arterial Pressure was recorded during subject visits and is recorded in mm Hg
• Mean Arterial Pressure [Week 7 of participation]: Mean Arterial Pressure was recorded during subject visits and is recorded in mm Hg
• Mean Arterial Pressure [Week 8 of participation]: Mean Arterial Pressure was recorded during subject visits and is recorded in mm Hg
• Mean Arterial Pressure [Week 9 of participation]: Mean Arterial Pressure was recorded during subject visits and is recorded in mm Hg
• Mean Arterial Pressure [Week 10 of participation]: Mean Arterial Pressure was recorded during subject visits and is recorded in mm Hg
• Mean Arterial Pressure [Week 11 of participation]: Mean Arterial Pressure was recorded during subject visits and is recorded in mm Hg
• Mean Arterial Pressure [Week 12 of participation]: Mean Arterial Pressure was recorded during subject visits and is recorded in mm Hg

Secondary outcomes

• Interleukin-10 [At baseline.]: Interleukin-10 levels will be measured throughout subject participation. They will be recorded in pg/ml.
• Interleukin-10 [Week 6 of study participation]: Interleukin-10 levels will be measured throughout subject participation. They will be recorded in pg/ml.
• Interleukin-10 [Week 12 of study participation]: Interleukin-10 levels will be measured throughout subject participation. They will be recorded in pg/ml.
• Total Sleep Time [At baseline]: Sleep time the night before in minutes
• Total Sleep Time [Week 1 of participation]: Sleep time the night before in minutes
• Total Sleep Time [Week 2 of participation]: Sleep time the night before in minutes
• Total Sleep Time [Week 3 of participation]: Sleep time the night before in minutes
• Total Sleep Time [Week 4 of participation]: Sleep time the night before in minutes
• Total Sleep Time [Week 5 of participation]: Sleep time the night before in minutes
• Total Sleep Time [Week 6 of participation]: Sleep time the night before in minutes
• Total Sleep Time [Week 7 of participation]: Sleep time the night before in minutes
• Total Sleep Time [Week 8 of participation]: Sleep time the night before in minutes
• Total Sleep Time [Week 9 of participation]: Sleep time the night before in minutes
• Total Sleep Time [Week 10 of participation]: Sleep time the night before in minutes
• Total Sleep Time [Week 11 of participation]: Sleep time the night before in minutes
• Total Sleep Time [Week 12 of participation]: Sleep time the night before in minutes
• Hamilton Depression Scale Score [At baseline]: Score on the Hamilton Depression Inventory. Higher scores indicate greater depression symptoms. Minimum = 0, Maximum =56.
• Hamilton Depression Scale Score [Week 1 of Participation]: Score on the Hamilton Depression Inventory. Higher scores indicate greater depression symptoms. Minimum = 0, Maximum =56.
• Hamilton Depression Scale Score [Week 2 of Participation]: Score on the Hamilton Depression Inventory. Higher scores indicate greater depression symptoms. Minimum = 0, Maximum =56.
• Hamilton Depression Scale Score [Week 3 of Participation]: Score on the Hamilton Depression Inventory. Higher scores indicate greater depression symptoms. Minimum = 0, Maximum =56.
• Hamilton Depression Scale Score [Week 4 of Participation]: Score on the Hamilton Depression Inventory. Higher scores indicate greater depression symptoms. Minimum = 0, Maximum =56.
• Hamilton Depression Scale Score [Week 5 of Participation]: Score on the Hamilton Depression Inventory. Higher scores indicate greater depression symptoms. Minimum = 0, Maximum =56.
• Hamilton Depression Scale Score [Week 6 of Participation]: Score on the Hamilton Depression Inventory. Higher scores indicate greater depression symptoms. Minimum = 0, Maximum =56.
• Hamilton Depression Scale Score [Week 7 of Participation]: Score on the Hamilton Depression Inventory. Higher scores indicate greater depression symptoms. Minimum = 0, Maximum =56.
• Hamilton Depression Scale Score [Week 8 of Participation]: Score on the Hamilton Depression Inventory. Higher scores indicate greater depression symptoms. Minimum = 0, Maximum =56.
• Hamilton Depression Scale Score [Week 9 of Participation]: Score on the Hamilton Depression Inventory. Higher scores indicate greater depression symptoms. Minimum = 0, Maximum =56.
• Hamilton Depression Scale Score [Week 10 of Participation]: Score on the Hamilton Depression Inventory. Higher scores indicate greater depression symptoms. Minimum = 0, Maximum =56.
• Hamilton Depression Scale Score [Week 11 of Participation]: Score on the Hamilton Depression Inventory. Higher scores indicate greater depression symptoms. Minimum = 0, Maximum =56.
• Hamilton Depression Scale Score [Week 12 of Participation]: Score on the Hamilton Depression Inventory. Higher scores indicate greater depression symptoms. Minimum = 0, Maximum =56.
• Criteria for Cocaine Use Disorder Diagnosis [At Baseline]: Number of criteria met on a Structured Clinical Interview as endorsed yes/no on a series of 11 questions on a scale. Range = 0-11. Higher scores indicate greater severity of Cocaine Use Disorder (e.g., more life problems due to cocaine use).
• Criteria for Cocaine Use Disorder Diagnosis [Week 12 of Participation]: Number of criteria met on a Structured Clinical Interview as endorsed yes/no on a series of 11 questions on a scale. Range = 0-11. Higher scores indicate greater severity of Cocaine Use Disorder (e.g., more life problems due to cocaine use).
• Reactive Hyperemia Index [At Baseline]: Measure of peripheral arterial tonomotry which assesses peripheral microvascular function through changes in amplitude of pulses in fingertips. Reactive hyperemia index (RHI) is "determined by calculating the ratio of hyperemic pressure (RHm) to baseline pressure (BLm) in the measurement and control arms (RHc and BLc respectively)" (Rosenberry and Nelson, 2020). This yields a natural log RHI ratio with higher scores indicating worse microvascular function. Being calculated as a natural log, there range is infinite.
• Reactive Hyperemia Index [Week 12 of participation]: Measure of peripheral arterial tonomotry which assesses peripheral microvascular function through changes in amplitude of pulses in fingertips. Reactive hyperemia index (RHI) is "determined by calculating the ratio of hyperemic pressure (RHm) to baseline pressure (BLm) in the measurement and control arms (RHc and BLc respectively)" (Rosenberry and Nelson, 2020). This yields a natural log RHI ratio with higher scores indicating worse microvascular function. This yields a natural log RHI ratio with higher scores indicating worse microvascular function. Being calculated as a natural log, there range is infinite.

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* Age 18 or older
* Self-report of recent cocaine use verified by a cocaine-positive urine sample
* Meet moderate-severe Cocaine Use Disorder Criteria
* Seeking treatment for their cocaine use
* Able to commit to 12-week intervention, plus 24-week follow up

Exclusion Criteria:

* History of serious physical or psychiatric disease (e.g., physical dependence on any drug requiring medically managed detoxification, unstable angina, uncontrolled cardiac arrhythmia, aortic stenosis, self-reported compromised immune function, extreme hypersensitivity/allergy to candida yeast or similar products, severe diagnosis for other substance use disorder) that would interfere with study participation
* Current physical or psychiatric disease that would interfere with study participation
* Poor veinous access, precluding blood draws

Participant flow

Outcome results

• Endothelin-1 Levels (Primary), Mean, pg/ml: Control Group 2.15 +/- .784; Low Value Alternative Reinforcer Group 2.063 +/- .699; High Value Alternative Reinforcer Group 1.956 +/- .606
• Endothelin-1 Levels (Primary), Mean, pg/ml: Control Group 1.886 +/- .759; Low Value Alternative Reinforcer Group 1.923 +/- .478; High Value Alternative Reinforcer Group 1.939 +/- .718
• Endothelin-1 Levels (Primary), Mean, pg/ml: Control Group 2.093 +/- 0.673; Low Value Alternative Reinforcer Group 2.083 +/- .772; High Value Alternative Reinforcer Group 2.086 +/- .680
• Mean Arterial Pressure (Primary), Mean, mm Hg: Control Group 96.69 +/- 15.77; Low Value Alternative Reinforcer Group 97.22 +/- 12.94; High Value Alternative Reinforcer Group 97.08 +/- 11.93
• Mean Arterial Pressure (Primary), Mean, mm Hg: Control Group 99.22 +/- 16.45; Low Value Alternative Reinforcer Group 99.66 +/- 13.24; High Value Alternative Reinforcer Group 97.38 +/- 13.18
• Mean Arterial Pressure (Primary), Mean, mm Hg: Control Group 95.92 +/- 15.85; Low Value Alternative Reinforcer Group 99.78 +/- 9.85; High Value Alternative Reinforcer Group 97.07 +/- 14.03
• Mean Arterial Pressure (Primary), Mean, mm Hg: Control Group 97 +/- 13.57; Low Value Alternative Reinforcer Group 100.5 +/- 12.39; High Value Alternative Reinforcer Group 96.18 +/- 12.06
• Mean Arterial Pressure (Primary), Mean, mm Hg: Control Group 97.28 +/- 15.08; Low Value Alternative Reinforcer Group 102.02 +/- 12.99; High Value Alternative Reinforcer Group 98.66 +/- 12.41
• Mean Arterial Pressure (Primary), Mean, mm Hg: Control Group 96.12 +/- 14.78; Low Value Alternative Reinforcer Group 99.72 +/- 14.33; High Value Alternative Reinforcer Group 97.96 +/- 13.18
• Mean Arterial Pressure (Primary), Mean, mm Hg: Control Group 97.46 +/- 13.51; Low Value Alternative Reinforcer Group 100.93 +/- 11.70; High Value Alternative Reinforcer Group 95.40 +/- 13.23
• Mean Arterial Pressure (Primary), Mean, mm Hg: Control Group 94.72 +/- 14.88; Low Value Alternative Reinforcer Group 100.13 +/- 11.28; High Value Alternative Reinforcer Group 92.59 +/- 12.29
• Mean Arterial Pressure (Primary), Mean, mm Hg: Control Group 96.14 +/- 14.84; Low Value Alternative Reinforcer Group 100.05 +/- 14.46; High Value Alternative Reinforcer Group 94.55 +/- 12.38
• Mean Arterial Pressure (Primary), Mean, mm Hg: Control Group 100.02 +/- 16.59; Low Value Alternative Reinforcer Group 100.19 +/- 10.81; High Value Alternative Reinforcer Group 94.46 +/- 12.21
• Mean Arterial Pressure (Primary), Mean, mm Hg: Control Group 99.43 +/- 17.18; Low Value Alternative Reinforcer Group 102.68 +/- 11.80; High Value Alternative Reinforcer Group 95.71 +/- 13.60
• Mean Arterial Pressure (Primary), Mean, mm Hg: Control Group 98.06 +/- 15.53; Low Value Alternative Reinforcer Group 101.31 +/- 12.07; High Value Alternative Reinforcer Group 93.20 +/- 11.05
• Mean Arterial Pressure (Primary), Mean, mm Hg: Control Group 97.98 +/- 14.21; Low Value Alternative Reinforcer Group 102.10 +/- 11.00; High Value Alternative Reinforcer Group 93.05 +/- 11.89
• Interleukin-10 (Secondary), Mean, pg/ml: Control Group .547 +/- .750; Low Value Alternative Reinforcer Group .429 +/- .424; High Value Alternative Reinforcer Group .251 +/- .106
• Interleukin-10 (Secondary), Mean, pg/ml: Control Group .587 +/- 1.23; Low Value Alternative Reinforcer Group .329 +/- .116; High Value Alternative Reinforcer Group .257 +/- .102
• Interleukin-10 (Secondary), Mean, pg/ml: Control Group .384 +/- .663; Low Value Alternative Reinforcer Group .481 +/- .514; High Value Alternative Reinforcer Group .230 +/- .907
• Total Sleep Time (Secondary), Mean, minutes: Control Group 393.81 +/- 135.91; Low Value Alternative Reinforcer Group 379.27 +/- 139.21; High Value Alternative Reinforcer Group 353.18 +/- 118.31
• 29 more outcome measures not shown.

Adverse events

Time frame: 12 week clinical trial participation

Other adverse events by term

• Results publication: Ferretti ML, Regnier SD, Irons JG, Stoops WW. Polysubstance use patterns and risk behaviors among people with cocaine use disorder. Exp Clin Psychopharmacol. 2025 Dec;33(6):586-593. doi: 10.1037/pha0000813. PMID 41343351
• Results publication: Stoops WW, Shellenberg TP, Regnier SD, Cox DH, Adatorwovor R, Hays LR, Anderson DM, Lile JA, Schmitz JM, Havens JR, Segerstrom SC. Influence of cocaine use reduction on markers of immune function. J Neuroimmunol. 2024 Dec 15;397:578470. doi: 10.1016/j.jneuroim.2024.578470. Epub 2024 Oct 28. PMID 39504756
• Results publication: Regnier SD, Shellenberg TP, Koffarnus MN, Cox DH, Lile JA, Rush CR, Stoops WW. Cocaine abstinence during the "critical period" of a contingency management trial predicts future abstinence in people with cocaine use disorder. Drug Alcohol Depend. 2023 Dec 1;253:111030. doi: 10.1016/j.drugalcdep.2023.111030. Epub 2023 Nov 18. PMID 38006674

• Study Protocol and Statistical Analysis Plan (PDF, 2024-01-09)
• Informed Consent Form (PDF, 2024-01-09)

• William W Stoops, Ph.D., Principal investigator, University of Kentucky

NIH grants: R01DA043938