November 13, 2019
Opioid-based plant might not be best solution for those seeking to curb habitual alcohol use
Scientists take closer look at use of ‘drug of concern’ kratom
WEST LAFAYETTE, Ind. – Lawmakers across the United States continue to debate the safety of kratom, an opioid-containing plant that has been listed as a “drug of concern” by the U.S. Food and Drug Administration. Kratom is sold over the counter in specialty stores and online.
Substance use disorders are a major health concern in the U.S. and a growing number of people suffering from these diseases are self-medicating with kratom to help break a cycle of dependence. After tobacco, the most commonly abused substance in the U.S. is alcohol with nearly 15 million people diagnosed with an alcohol use disorder.
A Purdue University-led team published a paper in the Nov. 8 edition of the British Journal of Pharmacology examining the effects of kratom and the potential impacts on people with alcohol use disorder. The cost to individuals and society from alcohol use is estimated at more than $250 billion each year.
“One big challenge is that alcohol use disorder is not adequately treated with currently available medications; in fact less than 10% of patients receive treatment,” said Richard van Rijn, an associate professor in Purdue’s College of Pharmacy, who led the research team. “Few broadly effective drug therapies exist to treat alcohol use disorder, so finding new and better treatments is of critical importance to help people manage their disease.”
The Purdue scientists, in collaboration with researchers at Memorial Sloan-Kettering in New York City and Washington University in St. Louis, studied the potential effects of kratom and its components on the body and in the ability to reduce alcohol consumption.
“Our work shows that kratom may be effective to self-medicate alcohol use disorder but is not entirely safe,” van Rijn said. “Instead, our research provides additional support for other therapies that would not produce the obvious side effects of using kratom, which may be addictive.”
The Purdue team previously focused on a G protein-coupled receptor, called the delta opioid receptor, which is a novel drug target that is different from the receptor in the body that binds prescription opioids. They developed drugs that bind to this new target and selectively activate a particular protein signaling cascade of this receptor.
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G protein-biased kratom-alkaloids and synthetic carfentanil-amide opioids as potential treatments for alcohol use disorder
Anna M. Gutridge, Meridith T. Robins, Robert J. Cassell, Rajendra Uprety, Kendall L. Mores, Mee Jung Ko, Gavril W. Pasternak, Susruta Majumdar and Richard M. van Rijn
Mitragyna speciosa, more commonly known as kratom, is a plant that contains opioidergic alkaloids, but is unregulated in most countries. Kratom is used in the self‐medication of chronic pain and to reduce illicit and prescription opioid dependence. Kratom may be less dangerous than typical opioids because of the stronger preference of kratom alkaloids to induce receptor interaction with G proteins over beta-arrestin proteins. We hypothesized that kratom (alkaloids) can also reduce alcohol intake.
We pharmacologically characterized kratom extracts, kratom alkaloids (mitragynine, 7‐hydroxymitragynine, paynantheine, and speciogynine), and synthetic carfentanil‐amide opioids for their ability to interact with G proteins and beta‐arrestin at mu, delta and kappa opioid receptors in vitro. We used C57BL/6 mice to assess to which degree these opioids could reduce alcohol intake and whether they had rewarding properties.
Kratom alkaloids were strongly G protein-biased at all three opioid receptors and reduced alcohol intake, but kratom and 7-hydroxymitragynine were rewarding. Several results indicated a key role for delta opioid receptors, including that the synthetic carfentanil-amide opioid MP102-a G protein-biased agonist with modest selectivity for delta opioid receptors-reduced alcohol intake, whereas the G protein-biased mu opioid agonist TRV130 did not.
Our results suggest that kratom extracts can decrease alcohol intake, but still carry significant risk upon prolonged use. Development of more delta opioid-selective synthetic opioids may provide a safer option than kratom to treat alcohol use disorder with fewer side effects.