NCT02892110

Varenicline Treatment for Cannabis Use Disorder

Completed Phase 2 Results posted Last updated 3 December 2019

What this trial tests

Phase 2 trial testing Varenicline in Substance Use Disorder in 72 participants. Completed in 27 November 2018.

Timeline

13 February 2017

Primary endpoint
8 November 2018

27 November 2018

Quick facts

Lead sponsor	Medical University of South Carolina
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	72
Start date	13 February 2017
Primary completion	8 November 2018
Estimated completion	27 November 2018
Sites	1 location across United States

Drugs / interventions tested

• Varenicline (varenicline) — full drug profile →
• Placebo

Conditions studied

• Substance Use Disorder — all drugs for Substance Use Disorder →

Sponsor

Medical University of South Carolina

Who can join

Adults 18 to 65, any sex, with Substance Use Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Cannabis Withdrawal Symptoms During Active Treatment Primary · 3 weeks (Week 4-6 of active treatment period)

For this outcome, the negative affect subscale items of The Cannabis Withdrawal Scale (items 5 \["I felt nervous\], 6 \["I had some angry outbursts"\], 7 \["I had mood swings"\], 8 \["I felt depressed"\], 9 \["I was easily irritated"\], 15 \["Life seemed an uphill struggle"\], 18 \["I felt physically tense"\], restlessness (item 11, "I felt restless), and/or urge to smoke (items 1 and 10, "The only thing I could think about was smoking some cannabis" and "I had been imagining being stoned") were averaged at Weeks 4, 5, and 6 and for an overall 4-6 week value, with minimum score of the subscale

Overall Week 4-6 average

Group	Value	95% CI
Varenicline	2.23	± 4.65
Placebo	3.94	± 6.23

Week 4

Group	Value	95% CI
Varenicline	2.59	± 6.73
Placebo	4.07	± 5.81

Week 5

Group	Value	95% CI
Varenicline	2.15	± 4.84
Placebo	4.27	± 7.11

Week 6

Group	Value	95% CI
Varenicline	1.96	± 4.65
Placebo	3.47	± 6.07

Number of Participants With Cannabis Abstinence Secondary · 3 weeks (Week 4-6 of active treatment period)

Self reported abstinence from Timeline Followback, verified by urine cannabinoid measures

Week 4

Group	Value	95% CI
Varenicline	5
Placebo	3

Week 5

Group	Value	95% CI
Varenicline	4
Placebo	2

Week 6

Group	Value	95% CI
Varenicline	6
Placebo	2

Cannabis Use Quantity Secondary · 3 weeks (Week 4-6 of active treatment period)

Cannabis use sessions per day measured by Timeline Followback (self-report) at twice weekly visits during Weeks 4, 5 and 6 of the active treatment phase.

Week 4

Group	Value	95% CI
Varenicline	0.93	0.54 – 1.33
Placebo	1.33	0.96 – 1.70

Week 5

Group	Value	95% CI
Varenicline	0.89	0.5 – 1.28
Placebo	1.19	0.82 – 1.56

Week 6

Group	Value	95% CI
Varenicline	0.89	0.5 – 1.29
Placebo	1.21	0.84 – 1.58

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event data were collected from time of consent through last study visit (approximately 8 weeks).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Varenicline

Serious: 1/35 (3%)

Deaths: 0/35

Placebo

Serious: 0/37 (0%)

Deaths: 0/37

Serious adverse events (1 terms)

Reaction	System	Varenicline	Placebo
Cellulitis	Infections and infestations	—	—

Other adverse events (13 terms — click to expand)

Reaction	System	Varenicline	Placebo
Nausea	Gastrointestinal disorders	—	—
Dream disturbance	General disorders	—	—
Headache	General disorders	—	—
Insomnia	General disorders	—	—
Other GI	Gastrointestinal disorders	—	—
Irritability	General disorders	—	—
URI/cold symptoms	Respiratory, thoracic and mediastinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Allergies	General disorders	—	—
Fatigue	Gastrointestinal disorders	—	—
Musculoskeletal	Musculoskeletal and connective tissue disorders	—	—
Dizziness	General disorders	—	—

Most-reported serious reactions: Cellulitis.

Data from ClinicalTrials.gov NCT02892110 adverse events section.

Sponsor's own description

Marijuana is the most commonly used illicit drug. There is high demand for effective interventions for cannabis use disorder, yet few specific treatments for have been developed. This study will evaluate the efficacy of varenicline for reducing marijuana use in people who use marijuana frequently.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Treatment Implications Associated with Cannabis and Tobacco Co-Use.
   McClure EA, Rabin RA, Lee DC, Hindocha C. · · 2020 · cited 49× · PMID 33777645 · DOI 10.1007/s40429-020-00334-8
2. Varenicline as a treatment for cannabis use disorder: A placebo-controlled pilot trial.
   McRae-Clark AL, Gray KM, Baker NL, Sherman BJ, et al · · 2021 · cited 19× · PMID 34655945 · DOI 10.1016/j.drugalcdep.2021.109111
3. Exploring the Utility of a Functional Magnetic Resonance Imaging Cannabis Cue-Reactivity Paradigm in Treatment-Seeking Adults With Cannabis Use Disorder.
   Sahlem GL, Dowdle LT, Baker NL, Sherman BJ, et al · · 2025 · cited 2× · PMID 39326740 · DOI 10.1016/j.bpsc.2024.09.006
4. Sex differences in normative modeling of cortical thickness in cannabis use disorder.
   Martin EL, Campbell LM, Thorn K, Sahlem GL, et al · · 2025 · PMID 39897590 · DOI 10.1016/j.dadr.2025.100318