Alzheimer's Drug May Help Treat Opioid Addiction

Megan Brooks

June 11, 2019

The cholinesterase inhibitor galantamine (Razadyne, Janssen) has shown promise as a treatment for opioid addiction, preliminary research suggests.

A secondary analysis of a randomized controlled trial showed reduced opioid use with the cognitive enhancer. Galantamine is thought to have a dual mechanism of action, increasing levels of acetylcholine in the brain and binding to nicotinic receptors, which play a role in addiction to nicotine and other substances.

"My colleagues and I are excited about these preliminary findings, as they could point to new strategies for helping those with opioid use disorder. We hope to pursue this in future research," principal investigator Kathleen Carroll, PhD, Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, said in a news release.

The results were published online June 4 in The American Journal on Addictions.

Anti-Addictive Effect?

Previous clinical research showed galantamine-associated reductions in heavy alcohol and cigarette use. In addition, in preclinical studies, cholinesterase inhibitors reduced self-administration of cocaine, opioids, and nicotine.

This led the investigators to hypothesize that galantamine, or more generally cholinesterase inhibitors, have an 'anti-addictive' effect through a common mechanism shared by different drugs of abuse.

To investigate, the researchers conducted a secondary analysis of a randomized, placebo-controlled trial testing the efficacy of galantamine (8 mg daily extended-release) and computerized cognitive behavioral therapy (CBT) as a treatment for cocaine use disorder in patients stabilized on methadone for co-occurring opioid use disorder (OUD). 

A total of 120 patients participated (mean age, 38 years; 67% men; 52% white) in the 12-week trial that also included a 6-month follow-up period.

The main findings of the trial showed a significant reduction in frequency of cocaine use over time for galantamine vs placebo and CBT vs standard methadone treatment alone.

The secondary analysis found a "significant main effect" for galantamine vs placebo in terms of the percentage of urine specimens testing negative for opioids, both during treatment (77% vs. 62%; P = .027) and during the 6-month follow-up period (81% vs. 59%, P = .001).

The benefit of galantamine on reduction in opioid use was seen early in treatment, with patients on placebo submitting the first opioid-positive urine specimen much sooner than patients on galantamine (median day, 15 vs. 53; P = .02).

Novel Treatment for OUD

In an accompanying commentary, Scott Moeller, PhD, and Anissa Abi-Dargham, MD, of the Department of Psychiatry, Renaissance School of Medicine at Stony Brook University in Stony Brook, New York, note the study authors "appear to have uncovered a novel and potentially impactful therapeutic for OUD, a disease that is devastating the United States."

"While the behavioral mechanism remains elusive," they note, "this report nonetheless suggests numerous exciting directions for future research. Future investigations have the potential to yield valuable information on galantamine as a medication to push forward clinical practice, as well as yield valuable scientific knowledge on the brain cholinergic system and its involvement in OUD and other addictions.

"If the Carroll et al results are replicated and extended in future trials and clinical laboratory studies, and given that galantamine has shown efficacy in other addictions such as alcohol and cigarette smoking, it is possible that galantamine may emerge as an exciting, next‐generation adjunctive medication for improving clinical outcomes in OUD," Moeller and Abi-Dargham conclude.

The study was supported by a grant from the National Institute on Drug Abuse. Carroll is a member of CBT4CBT LLC, which makes validated forms of CBT4CBT available to qualified clinical providers. Moeller and Abi-Dargham have disclosed no relevant financial relationships.

Am J Addict. Published online June 4, 2019. Abstract, Editorial

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