Cannabidiol and Cannabis Concentrate Users

Last updated: February 6, 2025
Sponsor: University of Colorado, Denver
Overall Status: Active - Recruiting

Phase

2

Condition

Substance Abuse

Treatment

Placebo

Broad Spectrum Cannabidiol (bsCBD) 400 mg

Broad Spectrum Cannabidiol (bsCBD) 200 mg

Clinical Study ID

NCT06575751
23-0953
1P50DA056408
  • Ages 25-60
  • All Genders

Study Summary

This study is a randomized, placebo-controlled, dose-ranging trial of plant-derived cannabidiol (CBD) among people who regularly use cannabis concentrates but are not trying to stop or cut down on their use. The main questions it aims to answer are whether CBD, relative to placebo, reduces cannabis concentrate use, the subjective effects of cannabis, or cannabis craving. Participants will take CBD (200 mg or 400 mg per day) or placebo for 4 weeks and will complete three visits during the study medication period, all conducted using a mobile laboratory.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Age 25-60.

  2. Regular use (at least 4 times per week) of cannabis concentrates for the last year.

  3. Not currently seeking to cut down or stop cannabis use.

  4. At least one episode of 3 consecutive days of cannabis abstinence with no experienceof severe withdrawal symptoms (i.e., >=4 DSM-5 Cannabis Withdrawal symptoms rated as "severe"), in the last 90 days.

  5. At least two symptoms of a DSM-5 cannabis use disorder.

Exclusion

Exclusion Criteria:

  1. Use of any illicit substance besides alcohol, nicotine, or cannabis (e.g., cocaine,opiates, methamphetamine, MDMA, benzodiazepines, or barbiturates) in the past 60days, as indicated by self-report and urine toxicology screening at the beginning ofeach study visit.

  2. Use of CBD-containing products other than cannabis concentrates in the past 90 days.

  3. Alcohol use on 3 or more days per week, and/or > 3 drinks per drinking day in thepast 60 days. Participants must also have a breath alcohol level of 0 at thebeginning of each study visit.

  4. Daily nicotine use.

  5. Meets DSM-5 diagnostic criteria for a psychotic disorder (e.g., schizophrenia,schizophreniform disorder, schizoaffective disorder), bipolar disorder, or majordepression with suicidal ideation, or has a history of treatment for thesedisorders.

  6. Current cardiovascular or respiratory disease (e.g., coronary artery disease, severeasthma, chronic obstructive pulmonary disease, etc.)

  7. Current use of any psychotropic (e.g., antidepressants, anxiogenics) or hepatotoxicmedications.

  8. Currently use of anti-epileptic medications (e.g., clobazam, sodium valproate) ormedications known to have major interactions with Epidiolex (buprenorphine,leflunomide, levomethadyl acetate, lomitapide, mipomersen, pexidartinib,propoxyphene, sodium oxybate, and/or teriflunomide) or a history of seizures.

  9. Current use of strong or moderate CYP3A4 inhibitors or inducers (commonly usedexamples not captured by other exclusion criteria include protease inhibitors,macrolide antibiotics [e.g., erythromycin], azole antifungals [e.g., ketoconazole],verapamil, and grapefruit juice).

  10. Current use of strong or moderate CYP2C19 inhibitors or inducers (commonly usedexamples not captured by other exclusion criteria include proton pump inhibitors,prednisone, and norethisterone).

  11. Current or past hepatocellular disease, as indicated by medical history or alanineaminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times the upper limitof the normal range at screening.

  12. For female participants, pregnancy or trying to become pregnant. A positivepregnancy test at the beginning of any study visit will result in exclusion fromongoing study participation.

  13. For female participants, currently lactating.

  14. For female patients of childbearing potential, not willing to use at least anapproved method of birth control while taking the study medication, unless she issurgically sterile, partner is surgically sterile or she is postmenopausal (oneyear).

  15. Current suicidality risk as indicated during the conduct of the C-SSRS withconcurrence after a study physician's or PI evaluation if the response to C-SSRSquestions 1 or 2 is "yes".

Study Design

Total Participants: 120
Treatment Group(s): 3
Primary Treatment: Placebo
Phase: 2
Study Start date:
December 04, 2024
Estimated Completion Date:
June 30, 2028

Study Description

The overarching aim of this proposal is to combine a naturalistic cannabis administration paradigm with a placebo-controlled, dose-ranging randomized controlled trial of plant-derived cannabidiol (CBD) to evaluate CBD effects on cannabis concentrate use, subjective effects, and cannabis cue reactivity. To achieve this aim, 120 adult frequent concentrate users will be recruited to complete a four-week protocol during which they will complete three sessions in a mobile pharmacology laboratory. Up to 200 participants may be consented/enrolled to account for screen failures and attrition. In two of the sessions, participants will use their typical cannabis concentrate on an ad libitum basis. Amount of delta-9-tetrahydrocannabinol (THC) self-administration during these sessions will be quantified by THC blood levels, obtained in the mobile lab immediately before and after use. Subjective drug effects and exogenous and endogenous cannabinoid biomarkers will also be quantified before and after THC use. Immediately after the first mobile lab session, participants will be randomly assigned to take either 200 mg or 400 mg of plant-derived, broad-spectrum CBD or matched placebo (40 participants per group) daily for four weeks. Participants will complete a second mobile lab session after two weeks to provide a blood sample that will be analyzed for cannabinoid levels. At this session, participants will also complete a cannabis cue reactivity paradigm. Participants will complete a second mobile lab session after four weeks of study medication ingestion, during which blood draws and THC self-administration will be repeated.

There are three aims:

Aim 1. Test the effect of CBD, relative to placebo and to baseline, on cannabis use over four weeks and THC self-administration in the mobile laboratory.

Hypothesis 1a. Both doses of CBD, relative to placebo, will reduce THC metabolite levels at weeks 2 and 4.

Hypothesis 1b. Both doses of CBD, relative to placebo and to baseline, will reduce the amount of THC that participants choose to consume in the mobile laboratory, as assessed by pre- vs. post-use THC blood levels.

Aim 2. Test the effect of CBD, relative to placebo and to baseline, on subjective drug effects (intoxication, psychotomimetic symptoms, anxiety, and negative affect) following acute cannabis concentrate use.

Hypothesis 2. Both doses of CBD, relative to placebo and to baseline, will reduce intoxication, paranoia, anxiety, and negative affect following acute use, even after controlling for between-group differences in amount of concentrate used.

Aim 3. Test the effect of CBD, relative to placebo, on cannabis cue-elicited craving and evaluate whether this effect mediates CBD effects on cannabis use.

Hypothesis 3a. Both doses of CBD, relative to placebo, will reduce cannabis craving.

Hypothesis 3b. CBD's effect on craving at week 2 will mediate its effect on THC metabolite levels at week 4.

For all aims, a linear effect of CBD dose is hypothesized, with the greatest effects in the 400 mg CBD group. Successful achievement of these aims will allow determination of an efficacious dose of CBD that reduces high-THC cannabis use, subjective drug effects, and craving, setting the stage for a subsequent RCT of plant-derived CBD to treat these outcomes in treatment-seeking high-THC cannabis concentrate users.

Connect with a study center

  • University of Colorado Anschutz Medical Campus

    Aurora, Colorado 80045
    United States

    Active - Recruiting

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