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Natural supplements could help ease opioid withdrawal

Scientists found a natural compound called oleanolic acid decreased withdrawal symptoms associated with morphine addiction in mice.

Image Credit: Photo by Towfiqu barbhuiya on Unsplash

Opioid addiction is a global health problem. Although opioid drugs are meant to treat pain, they are also highly addictive. When addicts stop taking opioids, they experience symptoms like irritability and insomnia, a condition called withdrawal syndrome. Researchers have shown they are also likely to start using opioids again, or to relapse.

Drug addiction starts in our brains. Nerve cells in our brains are connected in systems called neural circuits that interact with each other to influence drug cravings and addiction. The hormone in our brains that makes us feel happy is called dopamine. Addictive drugs increase dopamine in users’ brains, making them feel happy. Therefore, drug addiction is impossible without the region of our brains that regulates dopamine.

Scientists have found herbal medicines like oleanolic acid can help remove toxins in the bloodstream from alcohol and drugs. Oleanolic acid is a naturally occurring chemical found in the roots of some vegetables and fruits, such as olives and avocados. Researchers have shown it has antidepressant-like effects because it increases a chemical that balances emotions, called serotonin.

A team of researchers from China recently investigated the effects of oleanolic acid on opioid addiction in rodents. They tested 160 male rats and 70 male mice. In the rats, they tested whether oleanolic acid helped ease withdrawal symptoms during both spontaneous withdrawal and medication-assisted withdrawal. The scientists gave rats undergoing medication-assisted withdrawal a medicine called Naloxone that reverses opioid symptoms. They did not give the rats undergoing spontaneous withdrawal any Naloxone. 

The researchers injected some of the rats with morphine continuously for 28 days. They injected the remaining rats with saline for a control group. After 28 days, the researchers stopped the morphine injections. They treated some of the rats with a mixture of oleanolic acid tablets dissolved in warm water for 5 days. The rest of the rats were either given no treatment, or were given two other drugs commonly used to treat opioid addiction.

Next they looked at how oleanolic acid affected withdrawal symptoms in the rats. They found the rats undergoing spontaneous withdrawal had improved symptoms 1, 3, and 5 days after taking oleanolic acid. These rats had less diarrhea, less salivation, and higher body weight than rats without treatment. 

They also observed rats undergoing medication-assisted withdrawal with Naloxone had less withdrawal symptoms. These rats lost less weight, had less diarrhea, and were less irritable than rats without treatment. The scientists interpreted their results to mean oleanolic acid reduced the negative effects of morphine withdrawal in the rats.

In the mice, the researchers investigated whether oleanolic acid had any effect on their behavior. When an animal prefers a location that was paired with rewarding events over another location, this behavior is called conditioned place preference, or CPP for short. The researchers investigated the impact oleanolic acid had on the CPP behavior of the mice. 

Before the morphine experiment, the researchers let the mice choose between a darker black box and a brighter white box. Since most mice went to the black box, the researchers labelled that box as the preferred side. During the experiment, they injected one group of mice with morphine, and gave the rest a saline injection. Both mice groups received 1 injection every day for 5 days. They placed the morphine group in the white box and the saline group in the black box. Afterwards, they found mice that received oleanolic acid at different dosages still preferred the black box. They interpreted this result to mean oleanolic acid can significantly reduce morphine dependence in mice as well.

Finally, the researchers measured dopamine levels in the rodents’ blood using a technique that detects hormones, called an assay. They found rodents that received oleanolic acid for morphine addiction had dopamine levels approximately four times lower than morphine rodents that didn’t. They concluded oleanolic acid can improve the withdrawal symptoms of rats and mice while decreasing dopamine release in the brain. 

These scientists have shown oleanolic acid can help decrease withdrawal symptoms, improve neurotransmitter levels in the brain, and reduce weight loss. They suggested their findings should help other researchers develop new methods to ease the effects of opioid addiction. Oleanolic acid could one day play a key role in the treatment of drug addiction.

Study Information

Original study: Oleanolic Acid Attenuates Morphine Withdrawal Symptoms in Rodents: Association with Regulation of Dopamine Function

Study was published on: August 24, 2021

Study author(s): Zhiqi Shi, Shugang Pan, Luolin Wang, Sha Li

The study was done at: Changzhou Institute of Industry and Technology (China), Wuxi Hospital of Traditional Chinese Medicine (China), Nanjing University of Science and Technology (China), Guangdong Provincial Institute of Traditional Chinese Medicine (China)

The study was funded by: Natural Science Foundation from Education Department of Jiangsu Province, China, Changzhou Science and Technology and Information Bureau

Raw data availability: Available on request

Featured image credit: Photo by Towfiqu barbhuiya on Unsplash

This summary was edited by: Melisa Yashinski