Cannabidiol and Cannabis Concentrate Users

Cannabidiol and Cannabis Concentrate Users: A Randomized, Placebo Controlled Study

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.

Study Overview

• Status: Recruiting
• Conditions: Cannabis Use Disorder
• Intervention / Treatment: Drug: Broad Spectrum Cannabidiol (bsCBD) 400 mg; Drug: Placebo; Drug: Broad Spectrum Cannabidiol (bsCBD) 200 mg

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kristen M Raymond, BA; Phone Number: 303-724-3196; Email: kristen.raymond@cuanschutz.edu
• Study Contact Backup: Name: Joseph P Schacht, PhD; Phone Number: 303-724-3773; Email: joseph.schacht@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Anschutz Medical Campus
      • Contact: Kristen M Raymond, BA; Phone Number: 303-724-3196; Email: kristen.raymond@cuanschutz.edu
      • Contact: Joseph P Schacht, PhD; Phone Number: 303-724-3773; Email: joseph.schacht@cuanschutz.edu
      • Principal Investigator: Joseph P Schacht, PhD
      • Sub-Investigator: L. Cinnamon Bidwell, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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 experience of 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 Criteria:

1. Use of any illicit substance besides alcohol, nicotine, or cannabis (e.g., cocaine, opiates, methamphetamine, MDMA, benzodiazepines, or barbiturates) in the past 60 days, as indicated by self-report and urine toxicology screening at the beginning of each 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 the past 60 days. Participants must also have a breath alcohol level of 0 at the beginning 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 major depression with suicidal ideation, or has a history of treatment for these disorders.
6. Current cardiovascular or respiratory disease (e.g., coronary artery disease, severe asthma, chronic obstructive pulmonary disease, etc.)
7. Current use of any psychotropic (e.g., antidepressants, anxiogenics) or hepatotoxic medications.
8. Currently use of anti-epileptic medications (e.g., clobazam, sodium valproate) or medications 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 used examples 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 used examples 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 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times the upper limit of the normal range at screening.
12. For female participants, pregnancy or trying to become pregnant. A positive pregnancy test at the beginning of any study visit will result in exclusion from ongoing study participation.
13. For female participants, currently lactating.
14. For female patients of childbearing potential, not willing to use at least an approved method of birth control while taking the study medication, unless she is surgically sterile, partner is surgically sterile or she is postmenopausal (one year).
15. Current suicidality risk as indicated during the conduct of the C-SSRS with concurrence after a study physician's or PI evaluation if the response to C-SSRS questions 1 or 2 is "yes".

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Broad Spectrum Cannabidiol (bsCBD) 400 mg; bsCBD in a 400 mg dose will be used as described in the study arms.	Drug: Broad Spectrum Cannabidiol (bsCBD) 400 mg; Participants in this Arm will take 400 mg of bsCBD daily. Participants will take medication by mouth with food in the morning and evening.
Placebo Comparator: Placebo; A medically inert placebo medication will be used as described in the study arms.	Drug: Placebo; Participants in this Arm will take a medically inert placebo. Participants will take medication by mouth with food in the morning and evening.
Active Comparator: Broad Spectrum Cannabidiol (bsCBD) 200 mg; bsCBD in a 200 mg dose will be used as described in the study arms.	Drug: Broad Spectrum Cannabidiol (bsCBD) 200 mg; Participants in this Arm will take 200 mg of bsCBD daily. Participants will take medication by mouth with food in the morning and evening.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in blood 11-Nor-9-carboxy-THC (THC-COOH) levels	THC-COOH levels in blood samples collected at baseline, Week 2, and Week 4 of medication ingestion	4 weeks
Difference in blood delta-9-tetrahydrocannabinol (THC) levels	THC levels in blood samples collected before and after cannabis use at baseline and at Week 4 of medication ingestion	4 weeks
Difference in cannabis use	Total number of days of cannabis use during the 4-week medication period as reported on daily diaries	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in cannabis-induced intoxication	Drug Effects Questionnaire score following cannabis use at baseline and at Week 4 of medication ingestion (minimum = 0, maximum = 5, higher scores = greater intoxication)	4 weeks
Difference in cannabis-induced subjective effects	Addiction Research Center Inventory Marijuana score following cannabis use at baseline and at Week 4 of medication ingestion (minimum = 0, maximum = 12, higher scores = greater subjective effects)	4 weeks
Difference in cannabis-induced psychotomimetic symptoms	Psychotomimetic States Inventory paranoia and cognitive disorganization item scores following cannabis use at baseline and at Week 4 of medication ingestion (minimum = 0, maximum = 54, higher scores = greater psychotomimetic symptoms)	4 weeks
Difference in cannabis-induced anxiety and negative affect	Profile of Mood States short form tension, vigor, and elation subscale item scores following cannabis use at baseline and at Week 4 of medication ingestion (minimum = 0, maximum = 60, higher scores = greater anxiety and negative affect)	4 weeks
Difference in cannabis craving	Marijuana Craving Questionnaire-Short Form score before and after the cannabis cue reactivity procedure at Week 2 of medication ingestion (minimum = 12, maximum = 84, higher scores = greater craving)	2 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in blood cannabidiol (CBD) levels	CBD levels in blood samples collected at baseline, Week 2, and Week 4 of medication ingestion	4 weeks
Adverse effects	Adverse effects reported at baseline and Week 4 of medication ingestion	4 weeks

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Joseph P Schacht, PhD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2024
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: August 22, 2024
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 28, 2024

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Marijuana Abuse; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: 23-0953; 1P50DA056408 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will be shared through a NIDA P50 data sharing resource.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No