Guanfacine showed trends toward improving mood during cannabis withdrawal but didn't significantly reduce symptoms | Research

The takeaway

In a small pilot study of 7 cannabis-dependent volunteers, guanfacine did not significantly improve withdrawal symptoms, craving, or sleep compared to placebo, though trends toward improved positive mood and reduced compulsive craving were observed.

People trying to quit cannabis, clinicians treating cannabis use disorder, and addiction researchers.

No FDA-approved medications for cannabis use disorder; guanfacine showed only trend-level improvements

What the researchers found

Guanfacine (3 mg/day) showed no significant effects on cannabis withdrawal, craving, or sleep compared to placebo. Trends were observed for increased positive mood symptoms and decreased craving-associated compulsivity. The authors note their subjects had early onset and severe cannabis use, potentially increasing treatment resistance.

Why it matters

No medications are FDA-approved for cannabis use disorder. Even negative results from pilot studies contribute to the field by ruling out approaches and identifying potential signals worth pursuing in larger trials.

The numbers in context

7 participants. Guanfacine 3 mg/day vs placebo, 8 days each. No significant effects on withdrawal, craving, or sleep. Trends for positive mood improvement and decreased compulsive craving. Early onset, long-duration cannabis use in subjects.

How the study worked

Within-subjects crossover pilot study with 7 non-treatment-seeking volunteers meeting DSM-IV criteria for cannabis use disorder. Two 8-day inpatient periods (guanfacine 3 mg/day vs placebo) following standardized abstinence onset (30 mg synthetic THC on day 1).

What this study cannot tell us

Very small sample (n=7). Non-treatment-seeking participants. Short 8-day treatment period. Within-subjects design may have carryover effects. Subjects had severe cannabis use histories that may increase treatment resistance.

How to read the evidence

Preliminary: very small pilot study (n=7) with non-significant primary outcomes.

When this study was published

Published in 2019.

The bigger picture

The difficulty of treating cannabis use disorder pharmacologically is underscored by this and other negative pilot studies. The noradrenergic approach (guanfacine targets alpha-2A receptors) may not be sufficient alone, though the mood improvement trends suggest the pathway is worth exploring in combination approaches.

Questions still open

Would guanfacine work in less severe cannabis users? Could combining guanfacine with behavioral treatment improve outcomes? Would higher doses or longer treatment periods show significant effects?

Common questions

Are there medications to help quit cannabis?

None are FDA-approved. This study tested guanfacine, a blood pressure medication, but found no significant improvement in cannabis withdrawal or craving. The search for effective pharmacotherapy continues.

Why is it so hard to find cannabis withdrawal medications?

Cannabis use disorder involves complex brain pathways. The seven participants in this study had particularly severe, early-onset use, which may have increased treatment resistance. Different medications may work better for less severe cases.

Read the original research

Use of Guanfacine for Cannabis Use Disorder and Related Symptomology.

The American journal on addictions, 28(6), 455-464

View on PubMed ↗Publisher’s paper ↗

Citation

Holst, Manuela; Mathai, David S; Patel, Marguerite M; Rodgman, Christopher; Keller, Jake; Hussain, Mariyah Z; De La Garza, Richard; Kosten, Thomas R; Verrico, Christopher D. (2019). Use of Guanfacine for Cannabis Use Disorder and Related Symptomology.. The American journal on addictions, 28(6), 455-464. https://doi.org/10.1111/ajad.12959