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Indlæg: 06 mar 2019 14:37 
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Esketamine
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WASHINGTON (AP) — A mind-altering medication related to the club drug Special K won U.S. approval Tuesday for patients with hard-to-treat depression, the first in a series of long-overlooked substances being reconsidered for severe forms of mental illness.

The nasal spray from Johnson & Johnson is a chemical cousin of ketamine, which has been used for decades as a powerful anesthetic to prepare patients for surgery. In the 1990s, the medication was adopted as a party drug by the underground rave culture due to its ability to produce psychedelic, out-of-body experiences. More recently, some doctors have given ketamine to people with depression without formal FDA approval.

The Food and Drug Administration approved Spravato as a fast-acting treatment for patients who have failed to find relief with at least two antidepressants. Up to 7.4 million American adults suffer from so-called treatment-resistant depression, which heightens the risk of suicide, hospitalization and other serious harm, according to the FDA.

The drug will cost between $590 and $885 depending on the dosage and before various insurance discounts and rebates.

There have been no major pharmaceutical innovations for depression since the launch of Prozac and related antidepressants in the late 1980s. Those drugs target the feel-good brain chemical serotonin, and can take weeks or months to kick in.

Ketamine and J&J’s version work differently than those drugs, targeting a chemical called glutamate that is thought to restore brain connections that help relieve depression.

When the drug works, its effect is almost immediate. That speed “is a huge thing because depressed patients are very disabled and suffer enormously,” said Dr. John Mann, a psychiatrist and researcher at Columbia University. If the drug doesn’t work, physicians can quickly switch to other options, he noted.

The FDA approved Spravato, known chemically as esketamine, based on study results that showed patients taking the drug experienced a bigger improvement in their depression levels than patients taking a sham treatment, when measured with a psychiatric questionnaire.

The drug is designed to be lower-dose and easier to use than ketamine, which is normally given as an intravenous infusion.

Robin Prothro, 60, began taking antidepressants more than 20 years ago. But she says none of the five medications she tried relieved the depression that has stymied her personal and professional life.

Since enrolling in a Spravato trial two years ago, Prothro says her depression has lifted and she’s returned to hobbies she abandoned years ago, like gardening.

She takes the drug every two weeks at her psychiatrist’s office while reclining in a comfortable chair.

“You can feel it coming on, it’s a strong drug,” she said, describing colors and shapes that drift before her eyes. “I just let the drug work. I close my eyes and my mind is amazingly quiet.”

PSYCHEDELICS RECONSIDERED

The ketamine-like drug is the first of several psychoactive substances making their way through the U.S. regulatory process as physicians search further afield for new therapies. Researchers are conducting late-stage trials of psilocybin, the active ingredient in magic mushrooms, and MDMA, a euphoria-inducing club drug, as potential treatments for depression and post-traumatic stress disorder.

“Substantially different agents are only rarely appearing from pharmaceutical companies or other laboratories,” said Dr. Paul Summergrad, a psychiatrist at Tufts University. “That’s prompting people to investigate other compounds.”

Unlike ketamine, psilocybin and MDMA have no legal medical use. Classified in the same category as heroin and LSD, they are tightly restricted by the federal government. But the FDA’s approval of esketamine could smooth their path.

BURDEN OF DEPRESSION

Depression is among the leading causes of disability in the U.S. and is being closely monitored by health authorities amid rising suicides nationwide. In 2017, the U.S. suicide rate rose to 14 deaths per 100,000 people, the highest rate in at least 50 years, according to federal records.

Government officials haven’t suggested an explanation for the trend, though academic researchers point to the nation’s widening income gap, financial struggles and divisive politics.

J&J’s drug will be subject to a number of restrictions due to its abuse potential, side effects and lingering safety questions.

The drug will only be given by accredited specialists who must monitor patients for at least two hours after administration, due to its trippy, disorienting effects. Additionally, all patients will be tracked in a registry to monitor long-term safety and effectiveness.

The immediate impact of ketamine is thought to last just four to seven days and there’s no consensus yet on how long patients can benefit from ongoing treatment.

Still, there are few other options for patients who fail to respond to antidepressants. The most effective treatment in such cases, electroshock therapy, requires patients to be fully sedated and can cause persistent memory loss.

Wall Street has high expectations for J&J’s medication, with analysts predicting more than $600 million in annual sales by 2022. But J&J will face competition in the marketplace.

A decades-old drug, ketamine is already used off-label to treat depression by some doctors. At least 150 clinics around the U.S. provide treatment with various forms of the drug, which is available as a low-cost generic. Patients often pay hundreds or thousands of dollars for intravenous infusions of the drug over several weeks or months. Such therapies are generally not covered by insurance because they haven’t been approved as safe and effective by FDA regulators.

Some doctors plan to offer both ketamine and the new J&J drug.

Dr. Steve Levine says having FDA-approved standards for dosing and administering the new drug should raise standards in the field and drive out some of the bad actors who are not qualified to treat depression.

“This is going to bring in some standards, regulation and it’s going to make it safer and more accessible to patients,” said Levine, who serves as vice president of the American Society of Ketamine Physicians, a group representing doctors, nurses and others using ketamine for treating depression or other nonapproved uses.

Kilde:https://apnews.com/6bf8d3dbe4c2411894635f11418b74dc?fbclid=IwAR0oWAwFNYusiN0sJR4tMneZw5Eu3nPdVHWQ8SS0l0CbjOF0vqaKEL5j0vY


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Indlæg: 06 mar 2019 18:46 
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Takker, god oplysning. Jeg har lidt af depression i et utal af år, først da jeg fik en MAO hæmmer (Marplan) lettede depressionen.

Som jeg kan forstå på sitet her og har set dokumentarer om, så er Ayahuasca og diverse andre psychedelia også MAO hæmmere (tager jeg fejl?). DVS de forhindrer nedbrydningen af dopamin, noradrenalin og serotonin, sådan at mængden af stofferne øges i hjernen

Omvendt med stoffer som fx. kokain der øger mængden af samme stoffer, men ved en direkte tilførsel

Nogle gange er forskellen mellem rekreative stoffer og medicin, især psykofarmaka, meget lille eller ikke eksisterende som i opiaternes tilfælde.

Apropos opiater, sidder jeg lige nu og fejrer udsigten til to fridage med en lille smule opium og en halv flaske vin.

Opium blev brugt som antidepressivt og angstdæmpende middel for små hundrede år siden og så langt tilbage man har kilder. Jeg har et par 150 år gamle (tomme) apotekerflasker med opium og en enkelt med laudanum (opiumdråber) hvor der stadig er halvdelen tilbage.


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Indlæg: 06 mar 2019 23:33 
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(jeg skriver lige to indlæg her)
Det er S-ketamin der er tale om, altså den ene enantiomer af ketamin. Så i og for sig har DR mere ret end denne artikels overskrift når de skriver at det er ketamin. De fejler så ved at kalde det "hestebedøvelse", og undgår behændigt at nævne de anvendelser som ketamin allerede har på mennesker.


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Indlæg: 06 mar 2019 23:39 
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@kryddersnaps, Ayahuasca består af to komponenter - en 5-HT2A agonist og en MAO-hæmmer. Den MAO-hæmmer der findes i ayahuasca hedder tetrahydroharmalin, og den og/eller dens analoger findes også i tobak. Man mener så vidt jeg ved både at det indgår i den subjektive oplevelse af rygning og at det er med til at gøre det svært at stoppe.


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Indlæg: 07 mar 2019 09:18 
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Tak for info, mdmaimedicine2 ... Manglede der ikke et link til DR's artikel, her er den i hvert fald. Jeg håber virkelig det er et stof der er svært at misbruge, ellers ville det vel heller ikke blive godkendt.

https://www.dr.dk/nyheder/udland/usa-go ... -i-danmark


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Indlæg: 08 mar 2019 03:56 
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kryddersnaps skrev:
Tak for info, mdmaimedicine2 ... Manglede der ikke et link til DR's artikel, her er den i hvert fald. Jeg håber virkelig det er et stof der er svært at misbruge, ellers ville det vel heller ikke blive godkendt.

https://www.dr.dk/nyheder/udland/usa-go ... -i-danmark


Hvordan virker ketamin i høje doser?

Jeg er ikke medicinsk uddannet, og har ikke anden baggrund end at have været bruger af de her og en masse andre antidepressive stoffer, men det her lyder stort:

Glutamate works not only as a point-to-point transmitter, but also through spill-over synaptic crosstalk between synapses in which summation of glutamate released from a neighboring synapse creates extrasynaptic signaling/volume transmission.[3]

Det lyder som om de har fundet en måde at lindre depression på, der er mere overordnet... Jeg har aldrig prøvet ketamin, selvsagt ikke i høje doser, men er det ikke rigtig at det giver en form for uvirkelighedsfornemmelse (dissociation)?

En tanke: Når ketamin mht kommunikationen mellem hjernecellerne virker på et mere overordnet niveau, påvirker det det os så på en mere grundliggende måde - hvem vi er, istedet for hvordan vi sanser os selv?

Og kan det, derfor, i høje doser, give en oplevelse af større og mindre sammenhæng mellem krop og bevidsthed? (uvirkelighed/dissociation)

Derfor bruger folk det på at få et trip (og andre bruger det lykkeligvis også på at lave et mærkeligt antidepressivt stof)

Hvordan virker ketamin i høje doser?


Senest rettet af kryddersnaps 08 mar 2019 04:57, rettet i alt 1 gang.

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Indlæg: 08 mar 2019 04:42 
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Aner det ikke. Beklager.


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Indlæg: 08 mar 2019 05:15 
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Prøv at læs nogle triprapporter om det Kryddersnaps :)

Sådan overordnet set, så virker s-ketamin og andre psykedeliske stoffer ved at det skaber/genskaber (nye) baner i hjernen, og hvis man har dygtige folk omkring sig til at støtte de nye mønstre, så manifesteres de langsomt ind i hverdagen. Dvs. man kan bryde ud af sit depressions mønster mm.

Typisk er det der sker ved en normal (omkring 100mg) dosis s-ketamin, at man glemmer lidt at kroppen eksistere, og får derfor lov til at udforske sin bevidsthed, i en drømmeligende tilstand. Flere taler om ud af kroppen oplevelser, og det er også min egen erfaring, hvis man ligger sig ned og lukker øjnene.

Ketamin er noget nemmere at misbruge end klassiske psykedelika, men til den pris det lyder til de vil sælge det bliver det nok ikke aktuelt for de fleste.


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Indlæg: 08 mar 2019 13:05 
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Selvfølgelig, Fritzie, måske skal jeg heller ikke skrive komplicerede, filosofiske tråde midt om natten efter at have kommet hjem godt overrislet fra byen.

NÅ, men nu har jeg læst dem, meget af det lyder skræmmende, det er jo selvfølgelig et spørgsmål om dosis, måske i endnu højere grad for det her stof end andre, lyder det som. Undrer mig stadig over at det virker antidepressivt, læste lidt videre og stødte på det her:

https://www.futurity.org/ketamine-depression-1860752/

Hvor der står, at man har fundet ud af det måske virker på de opioide receptorer. Under alle omstændigheder lyder det som om de som sædvanligvis ikke er helt sikre på hvorfor det virker som det virker:

"The researchers say the findings from the new study may explain why ketamine works so quickly as an antidepressant: It activates the brain’s opioid receptors during its first phase of activity....

Revealing the role of the opioid system in the antidepressant effects of ketamine is critical in the effort to develop new antidepressants, the researchers say. For instance, glutamate receptor blockers may not have rapid antidepressant effects unless they also involve the opioid system, Williams says.

“THERE IS TRULY A LINK BETWEEN DEPRESSION, PAIN, AND OPIOID USE. YOU CAN’T GO AFTER ONE WITHOUT ADDRESSING THE OTHERS.”

“Psychiatry used opioids, barbiturates, and high doses of stimulants to treat depression 50 or 60 years ago,” Schatzberg says. “We have to properly examine the risks associated with using drugs of abuse—even in low doses—to treat depression. It’s not limited to ketamine; other antidepressant drugs that target the opioid system are in development now, too.”

While a standard opioid like morphine initially has an antidepressant effect, it promotes depression after repeated use, Williams says. People who are depressed take as much as 2.4 times as many opioids immediately after painful surgeries than those who aren’t depressed, he says. “There is truly a link between depression, pain, and opioid use,” Heifets says. “You can’t go after one without addressing the others.”

Det sidste er ikke helt min erfaring, hvis man holder pause i sit brug, har jeg ikke oplevet at opiater bevirker depression. Omvendt har jeg hørt det fra mange heltidsmisbrugere, at de bliver depressive/melankolske af det i længden


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Indlæg: 08 mar 2019 13:34 
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Opiater har helt sikkert antidepressive effekter, men det er symptombehandling i min optik. Det kan sikkert også virke på langt sigt, men det er nærmere manglen på opiater der på et tidspunkt kan eskalere en depression, end direkte brug :P


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