Longitudinal Outpatient Treatment for Cannabis Use Disorder

NCT06107062 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 23-0373
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a placebo-controlled randomized trial comparing the effects of hemp-derived cannabidiol (CBD) with and without Delta-9-tetrahydrocannabinol (THC), relative to placebo, on reducing cannabis use and cannabis use disorder (CUD) symptoms in adult treatment seeking cannabis concentrate users with CUD. Participants enroll in the study for 8 weeks (with telehealth follow-ups at 12 and 16 weeks) and are randomized to either full spectrum CBD, broad spectrum CBD, or placebo. Participants are also engaged in five weeks of psychotherapy treatment for CUD. Blood is collected to quantify investigational drug exposure and cannabis use. Participants also complete self-report measures of medical history, sleep quality, subjective cognitive function, physical activity, psychological functioning, substance use, and acute drug effects.

Conditions

Cannabis Use Disorder

Keywords

Cannabis Use Disorder; CUD; Cannabidiol; CBD

Outcome Measures

Primary Outcomes (4)

• Difference in cannabis use

  The change in the amount of cannabis used by participants as measured by self-report

  8 weeks

• Difference in cannabis use

  The change in the amount of cannabis used by participants as measured by biomarkers of metabolites

  8 weeks

• Difference in symptoms of cannabis use disorder (CUD)

  The change in symptom levels of CUD as measured by the Cannabis Use Disorders Identification Test (CUDIT). This questionnaire was designed for self administration and is scored by adding each of the 8 items: * Question 1-7 are scored on a 0-4 scale * Question 8 is scored 0, 2 or 4. Scores of 8 or more indicate hazardous cannabis use, while scores of 12 or more indicate a possible cannabis use disorder for which further intervention may be required.

  8 weeks

• Difference in withdrawal symptoms

  The change in three facets of withdrawal including affective, physiological, and physical withdrawal symptoms as measured by the Marijuana Withdrawal Checklist (MWC)

  8 weeks

Secondary Outcomes (5)

• Difference in alcohol use

  8 weeks

• Difference in alcohol use

  8 weeks

• Difference in wellbeing and quality of life

  8 weeks

• Difference in emotional states

  8 weeks

• Difference in cannabis use

  8 weeks

Other Outcomes (1)

• Moderators of designated outcomes

  8 weeks

Study Arms (3)

400mg Full Spectrum Cannabidiol (fsCBD)

EXPERIMENTAL

Drug: Cannabidiol - fsCBD

400mg Broad Spectrum Cannabidiol (bsCBD)

EXPERIMENTAL

Drug: Cannabidiol - bsCBD

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Cannabidiol - fsCBD DRUG

Full-spectrum (i.e., fsCBD, 7.8mg THC (3.4mg BID)), plant-derived CBD capsules produced by Ecofibre/Ananda Hemp will be used.

400mg Full Spectrum Cannabidiol (fsCBD)

Placebo DRUG

Placebo arm

Placebo

Cannabidiol - bsCBD DRUG

Broad-spectrum (i.e., bsCBD, 0% THC), plant-derived CBD capsules produced by Ecofibre/Ananda Hemp will be used

400mg Broad Spectrum Cannabidiol (bsCBD)

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Regular use (at least 4 times per week) of cannabis concentrates for at least the last year.
• Meets DSM5 criteria for at least moderate CUD.
• Currently seeking to cut down or stop cannabis use.

You may not qualify if:

• Use of any substance of abuse besides alcohol, nicotine, or cannabis (e.g., cocaine, non-prescription use of opiates, methamphetamine, MDMA, benzodiazepines, or barbiturates) in the past 90 days, as indicated by self-report and urine toxicology screening (Syva Rapid Test) at baseline.
• Use of CBD-dominant products in the past 90 days, as evidenced by self-report of use of a CBD\>THC product or CBD blood levels at baseline of \>= 5 ng/mL
• Alcohol use on 3 or more days per week, and/or \> 3 drinks per drinking day in the past 90 days. Participants must also have a breath alcohol level of 0 at the beginning of each study visit.
• Daily nicotine use.
• 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. Psychiatric disorders will be assessed with the Mini-International Neuropsychiatric Interview (MINI).
• Current cardiovascular or respiratory disease (e.g., coronary artery disease, severe asthma, chronic obstructive pulmonary disease, etc.)
• Current use of psychotropics (e.g., antidepressants, anxiogenics), which may dampen effects of CBD.
• Current 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).
• Current or past hepatocellular disease, as indicated by alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2 times the upper limit of the normal range at screening or a history of liver disease irrespective of AST and ALT at the time of screening.
• For participants assigned female at birth, pregnancy or trying to become pregnant as indicated by a urine pregnancy test administered at the beginning of each study visit.
• History of seizures
• Current use of potent CYP2C19 or CYP3A4 inducers (e.g., Rifampin, apalutamide, carbamazepine, enzalutamide, ivosidenib9, lumacaftor, ivacaftor, phenytoin, St. John's wort, Fosphenytoin, Mitotane, Phenobarbital, Primidone), or strong CYP3A inhibitors (e.g., clarithromycin, HIV protease inhibitors, and most antifungals), 2C19 inhibitors (e.g., fluoxetine, Lansoprazole, Tricyclic antidepressants (TCAs))
• Allergy to study medications (hemp seed oil, hemp extract, gelatin, glycerin)

Sponsors & Collaborators

• University of Colorado, Boulder: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

University of Colorado Boulder

Boulder, Colorado, 80301, United States

RECRUITING

Related Publications (1)

• Bidwell LC, Martin-Willett R, Melendez SN, Rosa L, Giordano G, Hutchison KE, Bryan AD. LOTUS: Protocol for a double-blind placebo controlled randomized trial of hemp-derived cannabidiol for the treatment of cannabis use disorder. PLoS One. 2024 Sep 30;19(9):e0308262. doi: 10.1371/journal.pone.0308262. eCollection 2024.

  PMID: 39348366 DERIVED

Central Study Contacts

Jonathan Lisano, PhD

CONTACT

303-492-9549; Jonathon.Lisano@colorado.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: October 12, 2023
• First Posted: October 30, 2023
• Study Start: May 16, 2024
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: June 19, 2025

Record last verified: 2025-06

Locations

US (1)