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From Addictive Drug to Prescription

Ketamine, a drug once popular in the club scene, is now psychiatrists’ secret weapon against depression. Perhaps you’ve heard of it, either from celebrities’ personal stories — such as former NBA player Lamar Odom — or through the many research studies currently underway to assess its effectiveness. 

What you may not know is how the drug works to relieve depression, and why it seems to help patients for whom all other treatments have failed. In that, you wouldn’t be alone. Dr. Steven Levine, a board-certified psychiatrist who developed the protocol for the clinical use of ketamine in 2011, says scientists are still nailing it down. The Food & Drug Administration, which approved a nasal spray version of ketamine known as esketamine in 2019, is too. As the science world continues to explore how a drug that was once used as an anesthetic on the battlefield has revolutionized the mental health world, here’s what you need to know. 

Ketamine offers “a more optimistic model of depression”

Levine says the basic way to explain it is that the drug more or less wakes up the brain and allows it to form new connections. “We think that it affects the glutamate system. Glutamate is a neurotransmitter, [which] are chemical messengers that carry information signals in the brain,” he says. “It enables the brain to heal and change and learn and become more resilient.”

He believes it’s a “more optimistic model of depression” than the one behind drugs like Prozac, which is part of a class of medications known as selective serotonin reuptake inhibitors (SSRIs). The theory behind SSRIs is that depression is caused by a deficit of serotonin, a feel-good chemical, in one part of the brain. Ketamine rests on the idea that depression affects many areas of the brain, inhibiting its “neuroplasticity” — or, “the brain’s ability to reorganize itself by forming new neural connections throughout life.” 

Rebecca Price, associate professor of psychiatry and psychology at the University of Pittsburgh, who researches ketamine, says its ability to affect neuroplasticity may be why patients who benefit from the drug typically feel relief immediately. “Ketamine has quite distinct mechanisms from SSRIs in terms of the brain receptors it acts on,” says Price. “The dominant hypothesis for why ketamine works so quickly, even in treatment-resistant patients, is that it rapidly — within about one day — restores neuroplasticity in key brain circuitry involved in regulating mood, cognition and affect.”

Formerly a club drug, ketamine has become an increasingly popular treatment for depression. (Getty Images)
Formerly a club drug, ketamine has become an increasingly popular treatment for depression. (Getty Images)

The mechanism behind ketamine bears some similarities to the main chemical in cough medicine

Levine, who has pioneered much of the work with ketamine and depression, says his interest began a decade ago when he was tapped to give a second opinion for a patient with severe depression. The woman, who had struggled to find relief from other treatments, revealed she’d been using something unusual to treat her depression: cold medicine.

“It was a serendipitous, funny thing. She pretty guiltily admitted to me that the one thing on earth that ever seemed to help, despite the fact that she’d had really good care and a great psychiatrist, was when she had a cough and would take over-the-counter cold medicine,” Levine explains. “So she found herself — when she was at her worst — taking a little half cap of it to help her feel better.”

Levine became determined to find out the mechanism behind this was and quickly narrowed in on dextromethorphan, the active ingredient in cold medicine. “I was curious … what is it about dextromethorphan’s mechanism that works and then [found] that other medicines shared that mechanism,” says Levine. “It brought me back to some of the papers that were starting to be generated around that time, looking at the repurposing of this really old anesthetic called ketamine for this new purpose.”

Soon after trying out the hallucinogen on a patient, he saw almost immediate results — and for over a decade, treating more than 6,000 patients has seen them again and again. “I really feel very grateful that I’ve had the opportunity to sit with so many people who have shared with me how dramatically changed and improved their life is after [ketamine] treatment,” says Levine. “It’s just, it’s difficult to put into words.”

The treatment can “dramatically change” lives but works for only 50 percent of patients

Levine stresses that while the drug can work wonders, it is by no means a silver bullet. Many people experience a major lift from the drug, but just as many — for reasons that are unclear — do not. “Only about 50 percent will respond to ketamine treatments, maybe 60 to 70 percent will have that sort of lower bar of clinically meaningful results,” says Levine. “So lots of people aren’t going to get this great benefit from ketamine. But I have seen people who really were at the end of their rope, who tried everything under the sun … people who really believe that there was nothing on earth that could help them. I’ve seen some really amazing dramatic responses. I’ve been lucky to get lots of hugs.”

The drug is helping to push the psychiatry world forward

Price, who is pioneering new research that pairs ketamine treatment with neurocognitive training, confirms that ketamine represents a major breakthrough in the world of mental health treatment. “It was highly significant for us to learn that depression can indeed be reversed this rapidly and profoundly, even in patients who haven’t responded well to existing treatment options,” says Price. “I think the field is more open to the idea that we can and should expect better from our treatments for depression and related conditions. Rapid and profound transformations are possible, and we should leave no stone unturned until we can find safe, effective, efficient and durable approaches to help every single person who’s struggling.”

Still, Price says the psychiatry world still has a long way to go in embracing new ideas. “The promise and potential of that initial discovery has yet to be fully realized clinically, because of a range of barriers to widespread adoption by providers and patients,” she says. “One of the key ones is the lack of well-established, safe, feasible and effective ways to make these rapid effects more enduring in the long term. Rapid relief might be very important in certain clinical situations — for example, perhaps to address a suicidal crisis — but what people ultimately want, need, and deserve is a way to stay well for the rest of their lives.”

Ketamine “brings you to the parking lot”

Those still confused about the way that ketamine works may benefit from thinking about it in terms of analogies. While some have likened it to a “flash mob” in the brain, Levine likes to explain it a different way. 

“One analogy I use when comparing traditional antidepressants to ketamine is that it’s like deciding to go to the supermarket. With traditional antidepressants, you’re starting from home and there are a lot of steps. You have to find your keys, get to your car, open the door, turn on the ignition, drive down the street, make lots of turns, get into the parking lot, get out of your car and then walk in and find the frozen food section,” he says. “There are lots of opportunities for things to go wrong and get in your way. With ketamine, it’s not that it drops you directly into the frozen food section, but it brings you at least to the parking lot. So it’s a much shorter route, and it’s perhaps the reason more people are able to benefit and in a shorter period of time.”

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Minnesota wildfire doubles in size, creates its own weather

A wildfire in northeastern Minnesota more than doubled in size Tuesday, growing to more than 19,000 acres, after it produced pyrocumulous clouds that generated lightning and even raindrops, fire officials said.

The Greenwood Fire’s growth, most of which happened Monday afternoon, prompted firefighters to leave McDougal Lake, about 80 miles south-southwest of Duluth, officials said. Authorities fear that structures might have been destroyed or damaged.

“We had crews embedded, and as this fire took off, it was quite an effort to communicate with forces on the ground so they could get out,” said federal fire incident spokesman Clark McCreedy.

The pullout was a success, and no injuries were reported. However, downed trees and necessary cleanup mean crews have been unable to assess damage around the lake, McCreedy said.

In addition to the firefighter pullout, 159 dwellings were evacuated Monday, according to an update from the National Wildfire Coordinating Group. Cabins, homes and recreational sites remain under threat, the group said.

Patrick Prochaska, a Minneapolis resident who built a cabin near McDougal Lake in 2012, told NBC affiliate KARE that he watched via security camera as flames mostly bypassed his property Monday, causing minor damage.

“I was feeling very scared,” he said. “At the same time, I could see that it was not doing anything to the house, and it was kind of reassuring.”

The fire in and north of Superior National Forest has mostly performed according to the weather, fire officials said. On Monday, with dry fuel on the ground and temperatures in the high 80s, it was an expanding inferno punctuated by strobes of lightning.

“The winds were drawn into the fire from all directions,” the incident’s fire behavior analyst, Michael Locke, said in a video update Tuesday. “It created what we call pyrocumulous clouds. And really high in the atmosphere … you’d see a thunderstorm, and in fact they went high enough to produce a few sprinkles of rain and even some lightning.”

Temperatures dipped into the mid-70s Tuesday, and the blaze mellowed. “The real story was cloud cover and cooler temperatures,” McCreedy said.

More of the same, and possibly rain, was in the forecast, giving officials hope that they might be able to close the book on an unusually active and dry fire season in Minnesota.

Experts have said climate change has set the stage for extreme weather, including an increase in the frequency and intensity of wildfires in the Northern Hemisphere.

Firefighters — 426 were assigned to the Greenwood event — have been confronted with “prolonged, severe drought,” making parts of Minnesota look like the fire-prone West this summer, McCreedy said.

The Greenwood Fire, which was detected Aug. 15, is believed to have been sparked by lightning.

So far, firefighters have scored no containment, and areas including McDougal Lake, Sand Lake and the Highway 2 corridor have been under mandatory evacuation orders. The federal Boundary Waters Canoe Area Wilderness was closed Saturday “due to active and increasing fire activity, extreme drought, limited resources,” the National Forest Service said in a notice.

Officials set a goal of Sept. 1 for full containment.

“We’re probably going to get more of that moderating weather for the rest of the week,” McCreedy said. “That opens the door for fire crews to make progress on the ground.”

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Hiker survives grizzly bear attack at Denali National Park

A tourist from Indiana was attacked and injured by a grizzly bear at Denali National Park and Preserve in Alaska on Monday night, park officials said.

The 55-year-old tourist, whose name was not released, was hiking alone in dense fog in the Thoroughfare Pass area when a mother bear and multiple cubs charged him from nearby bushes, the National Park Service said in a statement Tuesday.

He had puncture wounds to a calf, his left ribs and his left shoulder, the agency said.

The victim used bear spray that might have cut the attack short, the park service indicated. He walked 1.5 miles to a visitor’s center where “medical personnel” vacationing at Denali treated him as a park bus driver called 911, it said.

The hiker was taken to a medical center near the park before he was transferred to Fairbanks Memorial Hospital, about 120 miles away, park officials said. He was stabilized at the Fairbanks hospital, they said.

“Due to the apparent defensive nature of this attack, there are no plans to locate the bear involved,” the park service said. “Female bears with cubs are naturally defensive of their young, especially when surprised. There is no indication that this bear is unusually dangerous.”

Grizzly bears are federally protected as a threatened species in the lower 48 states. According to the National Wildlife Federation, fewer than 1,500 grizzlies are left in the lower 48, but they thrive, comparatively, in Alaska, where they have a population of about 31,000.

The backcountry area of the attack is closed for one week as a precaution, the park service said.

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House passes John Lewis voting rights bill, sends measure to Senate for tougher fight

House Democrats on Tuesday passed a sweeping voting rights bill named after Rep. John Lewis, D-Ga., the late civil rights icon.

The John Lewis Voting Rights Advancement Act was approved 219-212. All Republicans voted against the legislation.

The bill is part of congressional Democrats’ broader campaign to strengthen voting laws at the federal level to fight restrictive voting laws passed in Republican-led states, such as Texas and Georgia. However, it faces steep opposition in the Senate, where Democrats hold a wafer-thin majority.

The House returned from its recess this week to take up the bipartisan infrastructure bill and a resolution for Democrats’ $3.5 trillion budget package, which includes funding for much of President Joe Biden’s legislative agenda. The procedural motion used to pass the multitrillion-dollar resolution paved the way for the House to vote on the voting rights bill, which was re-introduced last week by Rep. Terri Sewell, D-Ala.

The legislation would require states with recent histories of discrimination to get federal “preclearance” to change their voting laws, which directly addresses the Supreme Court’s 2013 ruling in Shelby County v. Holder. The ruling gutted the preclearance system in the Voting Rights Act of 1965, which civil rights advocates argue was successful in blocking proposed voting restrictions in states and localities with histories of racial discrimination.

House Speaker Nancy Pelosi, D-Calif., said in a statement last week that Congress had “not only an ironclad Constitutional mandate, but a moral responsibility” to pass the bill.

Shortly before its passage, Pelosi said on the House floor that the bill would honor Lewis’ legacy.

“We should have the right to vote and shouldn’t be diminished by anyone. It is unpatriotic to undermine the ability of people who have a right to vote, who have access to the polls,” she said. “As John knew, this precious pillar of our democracy is under attack from one of the worst voter suppression campaigns since Jim Crow.”

It isn’t the first time House Democrats have tackled election law. In March, House Democrats passed the For the People Act, a sweeping bill that seeks to change campaign finance, voting and ethics laws.

The bill would expand access to the ballot box by creating automatic voter registration across the country by registering eligible voters whenever they interact with government agencies, restoring the voting rights of the formerly incarcerated, expanding early voting and modernizing the country’s voting systems.

However, Senate Republicans filibustered the voting rights legislation in June, and the vote to advance an amended version of the For the People Act split along party lines 50-50, short of the 60 votes needed. All Democratic-aligned senators voted to begin debate, and Republicans unanimously voted to block the bill.

Passage of the voting measure was the final vote of the week for the House, whose members are leaving Washington and won’t return until Sept. 20.

Haley Talbot contributed.

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