Some existing drugs might fight COVID-19. One may make it worse

Scientists are investigating a variety of drugs, including ones for anxiety and allergies, that might prevent the coronavirus from hijacking different cell systems to replicate itself. But one medicine that patients with COVID-19 may be using to treat a symptom of the disease could make things worse, lab experiments hint.

A common ingredient in cough medicines, dextromethorphan, stimulated the growth of SARS-CoV-2 in monkey cells in lab dishes, researchers report April 30 in Nature. Dextromethorphan seems to activate a cellular stress-coping process that is also exploited by the virus for its replication.

“We’re not necessarily recommending that everyone stop taking dextromethorphan,” said Brian Shoichet of the University of California, San Francisco School of Pharmacy.

This work is only in lab experiments, he noted during a news briefing on April 30. In people, cough suppressants have not been shown to make infections worse. But because the lab results demonstrate “a pro-viral effect, it would be wrong not to highlight it, because it could be detrimental,” Shoichet said, noting that more work needs to be done. It’s “something to look out for.”

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Shoichet was part of an international team that mapped interactions between the coronavirus’s proteins and proteins found in human and monkey cells. Lung cells produce more of the proteins involved in these viral interactions, the researchers discovered, which may help explain why the virus causes severe disease in the lungs (SN: 4/27/20).

Scientists tested a battery of drugs to see if any could interrupt those interactions and limit the virus’s growth. Drugs that have shown some promise in lab experiments involving monkey cells include antipsychotics haloperidol and cloperazine; an anxiety and depression drug called siramesine; antihistamines clemastine and cloperastine; and an experimental drug called zotatifin, now in clinical trials testing its efficacy against cancer.

The team also found an experimental compound, PB28, that performed better than hydroxychloroquine at inhibiting the virus’s growth by interfering with certain protein interactions.  Unlike hydroxychloroquine, PB28 doesn’t mess with heart rhythm proteins, so may have fewer side effects (SN: 4/21/20). PB28 also hasn’t been tested in people.

The hormone progesterone also interfered with the virus’s replication, perhaps partially explaining why women are less prone to die from COVID-19 than men (SN: 4/23/20).

Lean, Sizzurp, Purple Drank — What’s It All Mean?

ean, also known as purple drank, sizzurp, barre, and Texas tea, among other names, is a concoction of cough syrup, soda, hard candy, and, in some cases, alcohol. Originating in Houston, Texas, it’s typically served in a white Styrofoam cup.

The term “lean” comes from the position it tends to put you in after drinking it.

Here’s a look at what’s going on behind the Styrofoam.

Healthline does not endorse the use of any illegal substances, and we recognize abstaining from them is always the safest approach. However, we believe in providing accessible and accurate information to reduce the harm that can occur when using.

How did it become so popular?

People have been misusing codeine, a main ingredient in lean, for ages, but lean’s prominence in pop culture has made it more popular than ever.

Rappers (and Justin Bieber) have been singing its praises in songs — and dying or having seizures from it — since the late ’90s (though it seems to have first appeared in the ’70s or ’80s).

Here’s a highlight reel of lean’s more specific claims to fame in pop culture:

  • Reports suggest it’s a major factor in Lil Wayne’s ongoing hospitalizations for seizures.
  • Bow Wow recently opened up about almost dying as a result of his addiction to lean.
  • The late Mac Miller also described dealing with an addiction to lean in 2013.
  • Rapper 2 Chainz was arrested at an airport for possessing promethazine, a key lean ingredient.

Then there are the high-profile athletes whose lean-related suspensions and hospitalizations continue to make the headlines.

What’s in it, exactly?

The most commonly used ingredients are prescription cough syrup that contains the opioid codeine and the antihistamine promethazine.

The cough syrup is mixed with soda and sometimes alcohol. Some people also add hard candies, especially Jolly Ranchers, to the mix.

Others use over-the-counter (OTC) cough syrup containing dextromethorphan (DXM) instead. Since OTC cough syrups no longer contain alcohol, people usually add their own alcohol to the OTC version of lean.

Other variations of purple drank involve a combination of codeine tablets added to cough syrup and soda.

The amount of each ingredient varies. But to get the desired effects, a lot more than the recommended or safe dose is used.https://68415784b25d3aa5b31132fd02863569.safeframe.googlesyndication.com/safeframe/1-0-37/html/container.html

Is it legal?

Yes and no.

The Drug Enforcement Administration classifies codeine as a Schedule II controlled substance when it’s a single ingredient. It remains a lesser, but still potent, controlled substance when mixed with other ingredients.

All products containing it are only available with a prescription due to the risk of misuse. The distribution or manufacturing of it without a license is illegal.

Cough syrups containing codeine fall into the risk of misuse category since Actavis — considered to be the best of codeine cough syrups by lean users — was taken off the market due to its popularized misuse.

DXM cough syrup is available without a prescription, but some states restrict the sale of it to people over the age of 18.

What does it do?

Lean creates a feeling of euphoria and relaxation that makes you feel dreamy, almost like you’re floating away from your body. It acts on your central nervous system (CNS) and slows your brain activity for a sedating effect.

While some people may enjoy the euphoric effect of lean, it can also produce other less than desirable, and even downright dangerous, effects in high doses, including:

What happens if you add alcohol?

Combining alcohol enhances the effects of the codeine and DXM. While it may seem like a good way to get higher, it’s not a great idea.

Short-term effects of adding alcohol to lean include:

  • trouble breathing
  • drowsiness or sleepiness
  • delayed motor skills or reaction time
  • poor judgment
  • brain fog

Plus, your chances of overdosing are a lot higher when you combine alcohol with codeine or DXM.

The most serious potential effect of mixing even a small amount of alcohol with cough syrup is respiratory depression. This reduces the amount of oxygen to your brain. It can lead to organ damage, coma, or death.

What about other interactions?

Lean can also have harmful interactions with other drugs, including some OTC medications.

Lean can intensify and prolong the sedative effects of other CNS depressants, including:

Lean may also interact with herbal remedies and supplements, including natural sleep aids, such as valerian root and melatonin.

Like alcohol, all of these things can intensify the impact of lean on your CNS, resulting in potentially life-threatening side effects.

Does it have any long-term effects?

Quite a few, actually.

Liver damage

Acetaminophen, a common ingredient in cough and cold medications, has been linked to liver damage when you take more than the recommended dose or drink alcohol while taking it.

Remember, lean involves using way more than the recommended dose of cough syrup.

High amounts of acetaminophen and other drugs can prevent your liver from properly metabolizing chemicals, leading to excessive amounts in your liver. According to the Food and Drug Administration (FDA)Trusted Source, prescription and OTC drugs are the leading cause of acute liver failure.

Signs of liver damage include:

On their own, codeine and alcohol can also cause liver damage when you ingest more than the recommended dosage.

Withdrawal symptoms

Purple drank contains ingredients that are habit-forming. This means you can quickly develop a tolerance and dependence to it. In a nutshell, you’ll need more of it to get the desired effects and feel lousy when you don’t drink it.

Common withdrawal symptoms include:

Other long-term effects

Lean can also cause a number of other long-term effects, including:

Is it addictive?

Very.

Just about every active ingredient used in every variation of lean can increase the amount of dopamine in your brain’s reward system and lead to addiction.

Unlike dependence, which involves your body simply getting used to a substance, addiction results in cravings and a complete loss of control over use.

Signs of a lean addiction include the following:

  • You need more of it to get high.
  • You can’t stop drinking it even though it’s negatively affecting your life, like hurting your relationships, schoolwork, job, or finances.
  • You crave it and think about having it constantly.
  • You drink it as a way to cope with your feelings or stress.
  • You have withdrawal symptoms when you don’t drink it.

These withdrawal symptoms include:

Can it kill you?

Absolutely. There are many cases of people who’ve died from lean, either due to overdose or complications caused by long-term use. Some high-profile cases of this include the deaths of rappers DJ ScrewBig MoePimp C, and Fredo Santana.

CNS depression from drinking high amounts of lean can slow or stop your heart and lungs. The risk of a fatal overdose is even higher when you mix it with alcohol.

Warning signs

Unlike some other drugs, there aren’t many ways to make using lean less risky. If you or someone you know are planning on using lean, you need to know what overdose signs and symptoms to watch for.

Overdose signs and symptoms

Call 911 right away if you or someone else experiences:

You may be scared to call for help if you’ve been taking an illegal substance, but early treatment could prevent permanent damage or even death.

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Getting help

Developing an addiction to lean is totally possible. Remember, one of its main ingredients, codeine, is an opioid. This is a type of drug with a high potential for dependence and addiction.

If you’re concerned about your drug use, there’s help available. You can bring it up to your healthcare provider if you feel comfortable. Keep in mind that patient confidentiality laws will prevent them from reporting this information to law enforcement.

You can reach out to one of the following free and confidential resources:

Fentanyl and geopolitics: Controlling opioid supply from China

Since 2013, China has been the principal source of the fentanyl flooding the U.S. illicit drug market—or of the precursor agents from which fentanyl is produced, often in Mexico—fueling the deadliest drug epidemic in U.S. history. Both the Obama and Trump administrations devoted significant diplomatic capital to persuading China to crack down on the supply of fentanyl from China to the United States, with China finally announcing in April 2019 that the production, sales, and export of all fentanyl-class drugs are prohibited, except by authorized firms which the Chinese government has granted special licenses.

The issue at stake now is whether and how effectively China will enforce this new regulation both with regard to finished fentanyl and the large quantities of fentanyl precursors transshipped to Mexico. The enforcement challenge is formidable since China’s pharmaceutical and chemical industries involve tens of thousands of firms and hundreds of thousands of facilities, and China lacks adequate inspection and monitoring capacity. This policy paper draws on lessons from several sets of regulatory domains in China to identify the conditions under which China enforces its regulations. The explored regulatory domains include illicit methamphetamine production in China and its anti-trafficking collaboration with Australia; wildlife trade and the enforcement of anti-wildlife trafficking regulations since the early 1990s, including in the wake of the Severe Acute Respiratory Syndrome (SARS) and COVID-19 epidemics; and the evolution of the tobacco industry.

The following pattern emerges: The government of China at first tends to deny the existence of a problem. Under international or strong domestic pressure, it eventually moves to tighten regulation. But its enforcement tends to be limited and subverted by powerful vested interests of industry representatives, officials of line ministries charged with regulating or promoting the industry, and government officials. Geostrategic interests also trump other considerations, such as enforcement of regulatory compliance.

Despite the fact that China prides itself on having a strong counternarcotics stance and reputation, China is highly unlikely to mount counternarcotics cooperation with the United States approaching the level of its collaboration with Australia on methamphetamines unless it starts experiencing its own synthetic opioid epidemic. Moreover, the significant deterioration of U.S.-Chinese relations may further undermine China’s willingness to diligently enforce the new fentanyl regulation.

Still, the United States should seek to strongly incentivize Beijing to diligently enforce its new regulations on fentanyl, adopting a four-pronged approach to opioid supply from China:

  • With respect to the government of China, the United States should seek to delink counternarcotics policy and its enforcement from the U.S.-China global rivalry and encourage broad international cooperation with the United Nations, the European Union, and other countries concerned about synthetic drugs and their precursors produced in China;
  • With respect to Chinese pharmaceutical companies, the United States can mandate that all companies seeking to sell legal fentanyl in the United States institute transparent and verifiable monitoring (such as through close-circuit TV systems) of their production facilities, follow best practices developed in the pharmaceutical sector, and contribute samples of fentanyl and other opioids they produce to U.S. and possibly also international drug databases;
  • With respect to prominent Chinese pharmaceutical and chemical industry officials, the United States can develop packages of leverage; and
  • With respect drug traffickers, the United States should continue gathering legal indictment portfolios.

UF Study Suggests Kratom Could Treat Opioid Addictions

UF study suggests kratom, a plant native to southeast Asia, could be an all-natural treatment for opioid addictions.

Researchers found that kratom tea alleviated some withdrawal symptoms, such as difficulty breathing in morphine-addicted mice, said Jay McLaughlin, a project researcher and UF pharmacy professor. So far, kratom has also provided pain relief with less addiction withdrawal symptoms than morphine.

A five-year, $3.4 million grant from the National Institute on Drug Abuse is funding the study, which is overseen by graduate assistant Lisa Wilson and Chris McCurdy of the UF College of Pharmacy. The study tested anecdotal claims that kratom reduces the opioid addiction symptoms, such as difficulty breathing, McLaughlin said.

Kratom can be purchased at gas stations, kava bars and smoke shops in Florida and all but six other U.S states. The plant has been contested out of concerns that it may be addictive and harmful.

At 17, Ian Mautner began consuming kratom tea at a kava bar in Delray Beach, Ian’s mother Linda Mautner said. After struggling and being treated for a three-year kratom addiction, he committed suicide in July 2014, Mautner added.

“Kratom became number one in his life,” Mautner said.

While struggling with addiction, Ian would not shower and lost about 20 pounds, Mautner said. Sometimes, she said she would find his bed soaked with sweat.

“I told him I can’t live like this, I can’t watch my son die right before my eyes,” Mautner said.

When Ian went to a drug treatment clinic, Mautner said he told staff that his kratom tea was altered by another substance.

“He felt that he was tricked, that someone laced his drink,” Mautner said.

The Centers for Disease Control and Prevention reported that 91 out of 27,338 overdose deaths between July 2016 and December 2017 were related to kratom. All but seven of the kratom-related deaths involved other drugs, such as fentanyl and heroin. The Drug Enforcement Agency attempted to make kratom a Schedule I drug, which would make it fall under the same classification as heroin, LSD and marijuana.

Kratom advocates, like the American Kratom Association, pushed back against kratom’s scheduling, said Mac Haddow, senior fellow of public policy at the association. The potential danger of kratom does not lie with the plant itself, Haddow said. Instead, the synthetic chemicals and other drugs added to kratom products are often unregulated.

Another study conducted by McCurdy found that some kratom products were altered with synthetic components, such as 7-Hydroxymitragynine, a compound naturally found in kratom, but synthetically increased in some of the commercial samples.

While Mautner said she respects McCurdy’s research, she is concerned that some people will read his work and purchase a kratom product altered by synthetic components.

“If he has a component to help the opioid epidemic, my feelings about that are ‘Yay, let’s do it,’” Mautner said. “But the alteration of the product, that is going to happen until regulation is in place.”

The AKA is working to further kratom regulations, Haddow said. It is advocating to pass a bill called the Kratom Consumer Protection Act that would place restrictions on kratom sales in all states that pass it in their legislatures.

The bill would prohibit synthetic additives, require labels and set age restrictions on all kratom products, Haddow added. Versions of the bill were passed with overwhelming support in UtahGeorgiaArizona and Nevada. Twenty-one other states are currently considering the bill, Haddow said.

Despite the UF study’s findings, more research is required, McLaughlin said.

Other forms of kratom need to be tested, he said. The alkaloids, or drug-like molecules inside the plant, vary depending on the conditions kratom is grown in.

Early results of studies of different alkaloid makeups suggest there are similar results across different natural products, he said. This is only the case if there are no other substances added to kratom.

“It would appear that we can see consistently beneficial responses from a wide variety of kratom sources, but we are still working on that,” McLaughlin said.

He added that he hopes the result of UF’s kratom research provides new therapies for people addicted to opioids.

“Given the fact that we are probably looking at least 72,000 deaths to opioid overdoses this year alone, it is really important that we find a solution soon to help these people as fast as possible,” McLaughlin said. “That work is right underway here at UF; hopefully, we can find some results that can help.”

$2.4M will support novel opioid research at the University of Minnesota Medical School

MINNEAPOLIS, MN — A new $2.4 million grant from the National Institutes of Health (NIH) Chemical Countermeasures Research Program (CCRP), administered via the National Institute on Drug Abuse (NIDA) “Countermeasures Against Chemical Threats (CounterACT)” program, will aid researchers at the University of Minnesota Medical School in identifying better ways to treat acute intoxication by fentanyl and fentanyl-like drugs. These opioids, according to the World Health Organization and the U.S. Department of Homeland Security, are considered public health threats and potential chemical weapons.

Led by Marco Pravetoni, PhD, an associate professor in the Medical School’s Department of Pharmacology and member of the Medical Discovery Team on Addiction, the grant supports the development of antibody-based medical countermeasures against toxicity and death after exposure — whether deliberate or accidental — to fentanyl and fentanyl-like drugs, including alfentanil, acetylfentanyl and carfentanil.

“Fentanyl is a synthetic opioid that is 100 times more potent than morphine and can be used therapeutically to treat severe pain,” Pravetoni said. “Unfortunately, fentanyl is also manufactured and distributed illegally and is associated with recent, dramatic increases in opioid-related fatalities in the U.S. and worldwide. There is growing concern that other potent fentanyl analogs, such as alfentanil, acetylfentanyl and carfentanil, which can be 10,000 times stronger than morphine, could pose a risk to national security. Originally developed as a large animal painkiller, carfentanil’s extreme lethality has led the U.S. and other governments to consider its potential as a chemical weapon.”

Pravetoni, a leading expert in the development of biologics for the treatment of substance use disorders, has already created a series of first-generation monoclonal antibodies effective in counteracting respiratory depression (depressed breathing) and bradycardia (depressed heart rate) induced by fentanyl, oxycodone and heroin in animal studies (10.1124/jpet.120.000124). Monoclonal antibodies act by selectively binding to the target opioid and preventing its toxic effects associated with poisoning and overdose.

Under this new grant, Pravetoni, Carly Baehr, PhD, first-author of the peer-reviewed article and a postdoctoral fellow at the U of M Medical School, and their multi-institutional team, including David AuCoin, PhD, with the University of Nevada Reno; Marie Pancera, PhD, with the Fred Hutchinson Cancer Research Center; Saadyah Averick, PhD, with Allegheny Health Network; and Charles France, PhD, with UT Health San Antonio, will develop a series of next-generation monoclonal antibodies targeting the fentanyl-like family of chemicals.

“This grant will pave the way for future clinical evaluation and commercialization of these medical interventions,” Pravetoni said. “Our team is committed to developing antibodies as countermeasures in both pre- and post-exposure scenarios, involving both accidental and deliberate poisoning and overdose.”

Their anti-drug antibodies would not interfere with the use of life-saving medications, such as the opioid antagonist naloxone, which is the prime opioid overdose rescue agent or antidote. In addition, antibodies could possibly be used in combination with naloxone or another approved medication to provide longer-lasting protection, decrease hospitalization and increase survival upon exposure.

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The grant supports Pravetoni’s research until July 31, 2023. Research activities will be supported under Award Number U01DA051658, funded through the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases and the Office of The Director, National Institutes of Health. The research reported has also been supported by a CounterACT Administrative Supplement to U01DA038876. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

About the University of Minnesota Medical School

The University of Minnesota Medical School is at the forefront of learning and discovery, transforming medical care and educating the next generation of physicians. Our graduates and faculty produce high-impact biomedical research and advance the practice of medicine. Visit med.umn.edu to learn how the University of Minnesota is innovating all aspects of medicine.

About the Chemical Countermeasures Research Program

The CCRP was established in 2006 by the National Institute of Allergy and Infectious Diseases (NIAID/NIH) to lead the civilian research and early development of novel or improved medical countermeasures (MCMs) to enhance the nation’s medical response capabilities during and after high consequence chemical emergencies. The CCRP provides multiple extramural grant and cooperative agreement research funding opportunities under the NIH-wide CounterACT program. Awarded projects are subsequently administered/managed by the various trans-NIH Institutes and Centers partners depending on the proposed areas of interest (10.1002/ddr.21707).

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