Guanfacine-ER for Cannabis Use Disorder

Overseen By Daniel Brooks, LCSW

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: New York State Psychiatric Institute

Must not be taking: Alpha 2 agonists, others

Disqualifiers: Schizophrenia, Pregnancy, Violent behavior, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests guanfacine-ER, a medication, to determine if it helps reduce cannabis use and manage withdrawal symptoms. The study also examines the medication's effect on impulsivity (acting without thinking). It includes both in-person and virtual sessions, providing flexibility for participants. Individuals with Cannabis Use Disorder, a THC-positive drug screen, and who are actively seeking to reduce or stop cannabis use may be suitable for this trial. Participants should also have internet access and be able to receive mail for study materials. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot participate if you are taking certain medications that interact with guanfacine, like some antihypertensives and specific drugs such as rifampicin, ketoconazole, St. John's Wort, and amitriptyline. If you are stable on psychotropic medication for at least 2 months and it is compatible with guanfacine, you may still be eligible.

Is there any evidence suggesting that guanfacine-ER is likely to be safe for humans?

Research has shown that guanfacine-ER is generally safe for individuals with cannabis use disorder. In past studies, participants mostly experienced minor side effects, such as slight drops in blood pressure, indicating the treatment's likely safety. Other studies, including those for ADHD, reported similar mild side effects. While no treatment is entirely risk-free, guanfacine-ER has demonstrated safety for many individuals. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Cannabis Use Disorder?

Unlike the standard treatments for Cannabis Use Disorder, which often include behavioral therapies and medications like N-acetylcysteine or gabapentin, Guanfacine-ER offers a different approach. Guanfacine-ER is unique because it acts on the alpha-2 adrenergic receptors in the brain, which are involved in regulating stress and impulse control. This mechanism could potentially address the underlying neurological aspects of cannabis dependence more directly than current options. Researchers are excited about Guanfacine-ER because it might enhance the ability to manage cravings and withdrawal symptoms, providing a new avenue for treatment where existing medications have limited effectiveness.

What evidence suggests that guanfacine-ER might be an effective treatment for Cannabis Use Disorder?

This trial will compare Guanfacine-ER with a placebo for treating Cannabis Use Disorder (CUD). Studies have shown that Guanfacine-ER might help treat CUD by reducing withdrawal symptoms and improving behavioral control. Some studies also found that Guanfacine-ER may lessen the cognitive and memory issues caused by THC, the main active ingredient in cannabis. While more research is needed to confirm these findings, early results are promising for those aiming to reduce cannabis use. ^{1 2 3 4 6}

Who Is on the Research Team?

Christina Brezing, MD

Principal Investigator

NYSPI

Are You a Good Fit for This Trial?

This trial is for individuals who have a cannabis use disorder, are seeking treatment to reduce or stop their use, and can give informed consent. They must test positive for THC, be able to receive mail, and have internet access. Excluded are those with certain mental health conditions, on incompatible medications or treatments, pregnant or not using contraception if at risk of pregnancy.

Inclusion Criteria

Meets DSM-V criteria for a current cannabis use disorder

I can receive packages by mail for study needs.

Capable of giving informed consent and complying with study procedures

Exclusion Criteria

Legally mandated to participate in a substance use disorder treatment program

Any medical or psychiatric conditions that in the investigator's judgment would interfere with safe participation in the study will be exclusionary

I am not pregnant, breastfeeding, and I use effective birth control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive guanfacine-ER or placebo, starting at 1mg nightly and increasing to a maximum of 4mg, with a tapering phase starting in week 11

12 weeks

4 visits (in-person), multiple virtual visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Guanfacine-ER

Trial Overview The study tests whether guanfacine-ER helps people cut down or quit cannabis by reducing impulsivity and withdrawal symptoms. Participants will either get the actual drug or a placebo without knowing which one they're taking. The trial includes both in-person visits and virtual check-ins.

How Is the Trial Designed?

Group I: Guanfacine-ER Experimental Treatment 1 Intervention

Participants will start on guanfacine-ER 1mg nightly for 1-week (week 1) and slowly increase by 1mg/per week to a max dose of 4mg per day or maximum dose as tolerated. Medication taper to discontinuation will begin in week 11 and continue into week 12 until complete by end of study, decreasing the dose by 1mg every 4 days until stopped.

Group II: Placebo Placebo Group 1 Intervention

Placebo will be taken nightly and titrated and tapered similar to the active arm.

Who Is Running the Clinical Trial?

New York State Psychiatric Institute

Lead Sponsor

Trials

481

Recruited

154,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

In a 9-week study involving 461 children and adolescents with ADHD, guanfacine extended release (GXR) significantly improved ADHD symptoms when added to a stable dose of psychostimulants, outperforming placebo.

GXR treatment did not introduce new safety concerns, with most adverse events being mild to moderate, and showed only small decreases in blood pressure and pulse, indicating it is a safe adjunctive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled trial of extended-release guanfacine and psychostimulants for attention-deficit/hyperactivity disorder. Wilens, TE., Bukstein, O., Brams, M., et al.[2022]

In a phase 3 safety study of guanfacine extended release (GXR) involving 215 children and adolescents with ADHD, the treatment was well tolerated, with 82.7% experiencing some treatment-emergent adverse events, primarily somnolence and headache.

GXR significantly reduced ADHD symptoms over the 2-year study, with a mean decrease of 19.8 points in the ADHD-RS-IV total score, indicating its efficacy in managing ADHD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of guanfacine extended release in children and adolescents with ADHD. Huss, M., Dirks, B., Gu, J., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6949416/

Guanfacine extended-release for cannabis use disorder This trial suggests that G-XR is a feasible option for treating CUDs, and deserves further evaluation in an efficacy trial.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01467999

Open-Label Pilot Study of Guanfacine-Extended Release ... The purpose of this study is to determine whether guanfacine represents a tolerable, potentially effective pharmacotherapy option for cannabis dependence.

3. researchgate.net researchgate.net/publication/334663349_Guanfacine_extended-release_for_cannabis_use_disorder_a_pilot_feasibility_trial

Guanfacine extended-release for cannabis use disorder Guanfacine treatment was shown to reduce the cognitive impairment induced by THC (Mathai et al., 2018), and new data suggest that it may be ...

4. tandfonline.com tandfonline.com/doi/abs/10.1080/00952990.2019.1620259

Guanfacine extended-release for cannabis use disorder Guanfacine extended-release (G-XR) could be useful in the treatment of CUDs by mitigating withdrawal and improving behavioral control.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6191371/

Guanfacine Decreases Symptoms of Cannabis Withdrawal ... Guanfacine had no significant effect on capsule ratings during abstinence, but increased ratings of capsule strength on days of cannabis administration ...

6. withpower.com withpower.com/trial/phase-2-marijuana-abuse-3-2022-fff63

Guanfacine-ER for Cannabis Use Disorder In cannabis use disorder trials, it was generally well tolerated with minor side effects like small decreases in blood pressure. In ADHD studies, common side ...