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Cannabis Use DisorderPhase 2LOTUSNCT06107062

Longitudinal Outpatient Treatment for Cannabis Use Disorder

A Phase 2 study testing Cannabidiol - fsCBD and Cannabidiol - bsCBD in people with Cannabis Use Disorder, run by University of Colorado, Boulder at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 21 years and older
Conditions the study is for
Cannabis Use Disorder
What is being tested?
Cannabidiol - fsCBD and Cannabidiol - bsCBD
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
165 participants
Where
1 siteUnited States
Study dates
26 Jul 2024to 31 Mar 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.)
Show all 13Show fewer
  • 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)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Jonathan Lisano, PhD contact

303-492-9549

Jonathon.Lisano@colorado.edu

United States1 site, 1 recruiting

  • University of Colorado Boulder

    Boulder, Colorado, 80301

    Devon Rapken, devon.rapken@colorado.edu

    Recruiting

Other trials in United States

About this study

Official title: Hemp-derived Cannabidiol for the Treatment of Cannabis Use Disorder: A Double-blind Placebo-controlled Randomized Trial

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.

Read the detailed description

As cannabis legalization continues to spread across the United States, average Δ9-tetrahydrocannabinol (THC) concentrations in recreational products have significantly increased, with THC levels as high as 90-95%. The investigators' preliminary data suggest that concentrate use elicits blood THC levels more than twice as high as cannabis flower use, and that concentrate use is associated with greater withdrawal, tolerance, and Cannabis Use Disorder (CUD), prompting concern about the risks of these high potency products in relation to problem use and CUD. No prior study has evaluated effective treatments to reduce cannabis use in this high risk group.

Several previous studies have found that the non-intoxicating cannabinoid cannabidiol (CBD), which may antagonize the effects of THC on CB1 and CB2 receptors, reduces cannabis use and CUD-related symptoms, such as affective disturbance and withdrawal. Results of these studies are promising, but limited to synthetic or isolated forms of CBD that are not widely available. There have been no tests of the hemp-derived CBD that is widely available without a prescription across the U.S. Importantly, hemp-derived CBD comes in two forms, one with a small amount of THC (7.8mg (3.4mg BID) THC, full spectrum; fsCBD) and one without THC (0% THC; broad spectrum; bsCBD). It is possible that a small amount of THC may confer additional benefits with respect to withdrawal and related affective disturbance, and in turn be beneficial for reducing THC use overall. Consistent with this hypothesis, pilot data from the investigators' lab suggest that CBD, that also contains low levels of THC, reduces THC drug reward, withdrawal, anxiety, and overall THC use in heavy concentrate users, supporting the potential for hemp-derived CBD to reduce THC use and mitigate withdrawal in this high risk group. However, no placebo-controlled trial has been conducted comparing hemp-derived CBD with and without THC on reducing THC use.

This study is a placebo-controlled RCT comparing the effects of hemp-derived CBD (fsCBD vs. bsCBD vs. placebo) on reducing THC use in concentrate users with CUD. 150 adult treatment-seeking concentrate users with DSM5 CUD will be recruited to complete an eight-week protocol. Participants will be randomly assigned to take 400 mg of either hemp-derived bsCBD (contains no THC), hemp-derived fsCBD (contains low levels of THC), or matched placebo daily for eight weeks. All participants will receive a five-session empirically supported psychological intervention to support cannabis use reduction during the trial. Participants will be assessed for changes in THC use [self-reported mg of THC used and levels of THC's metabolite 11-nor-9-carboxy-Δ9-THC (THC-COOH)] and CUD symptoms, as well as levels of CBD and CBD's metabolite, 7-Carboxy-Cannabidiol (CBD-COOH) to monitor medication adherence. Primary outcomes include reduction in THC exposure [via self-reported amount used and urine THC-COOH (standardized for creatinine)], CUD symptoms, and withdrawal symptoms, including affective, physiological, and physical symptom facets, across the 8-week study.

Being tested
Cannabidiol - fsCBD, Placebo, Cannabidiol - bsCBD
Keywords
Cannabis Use Disorder, CUD, Cannabidiol, CBD

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cannabidiol - fsCBDDrug

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

  • PlaceboDrug

    Placebo arm

  • Cannabidiol - bsCBDDrug

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

Study groups in NCT06107062
Study groupRoleWhat they receive
400mg Full Spectrum Cannabidiol (fsCBD)ExperimentalNot described
Receives: Drug: Cannabidiol - fsCBD
400mg Broad Spectrum Cannabidiol (bsCBD)ExperimentalNot described
Receives: Drug: Cannabidiol - bsCBD
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Difference in cannabis use

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

    Measured: 8 weeks

  2. Difference in cannabis use

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

    Measured: 8 weeks

  3. 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.

    Measured: 8 weeks

  4. 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)

    Measured: 8 weeks

Secondary outcomes (5)

  1. Difference in alcohol use

    The change in alcohol use as measured by the Alcohol Use Disorders Identification Test (AUDIT)

    Measured: 8 weeks

  2. Difference in alcohol use

    The change in alcohol use as measured by the Timeline Follow-back

    Measured: 8 weeks

  3. Difference in wellbeing and quality of life

    The change in wellbeing as measured by the Health Related Quality of Life survey

    Measured: 8 weeks

  4. Difference in emotional states

    The change in emotional states as measured by the Depression Anxiety and Stress Scale (DASS). Each of the three DASS-21 scales contains 7 items, divided into subscales with similar content (Depression, Anxiety, and Stress). Scores range from 0-42 for each subscale (0-126 for the total scale), with higher numbers reflecting more negative emotional states over the past week.

    Measured: 8 weeks

  5. Difference in cannabis use

    Difference in cannabis use as measured by the DSM-5 Cannabis Use Disorder diagnostic criteria

    Measured: 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Oct 2023
  2. Study start26 Jul 2024
  3. Primary completion31 Mar 2028 (estimated)
  4. Study completion31 Mar 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
165 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06107062
Sponsor's protocol ID
23-0373
Acronym
LOTUS
Status last verified
Jun 2025
First submitted
12 Oct 2023
Last updated
12 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 39348366

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cannabidiol - fsCBD and Cannabidiol - bsCBD in people with Cannabis Use Disorder, run by University of Colorado, Boulder at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 12 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jonathan Lisano, PhD (303-492-9549, Jonathon.Lisano@colorado.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Difference in cannabis use (time frame: 8 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06107062, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2026.

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