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New analysis claims the FDA rushed ketamine's approval for depression treatment
Clinical trials by Janssen Pharmaceuticals showed troubling results.
- A new analysis in The British Journal of Psychiatry claims the FDA approval process for ketamine was rushed.
- Only one of three clinical trials showed efficacy, while the discontinuation trial produced troubling outcomes.
- Ketamine's side effects include anxiety, poor appetite, delusions, hallucinations, paranoia, rage, and craving.
There was a lot of excitement when the FDA fast-tracked ketamine trials for depression treatment in 2016. The announcement marked a major turning point in our understanding of psychedelics, which were deemed a Schedule 1 substance as part of Richard Nixon's racist 1970 "War on Drugs." Ketamine was approved for use as an anesthetic that same year; due to increasing recreational usage in the 1990s, however, it was deemed Schedule III in America in 1999.
Though ketamine is not a traditional psychedelic—they have an agonist (or partial agonist) effect at brain serotonin 5-HT2A receptors—it falls into this class due to its hallucinogenic and dissociative effects. Recently it has been referred to as a "party psychedelic." Psychedelic therapy advocates were pleased when the FDA approved a nasal spray medication for treatment-resistant depression known as esketamine in 2019. Janssen Pharmaceuticals launched Spravato shortly after.
This move is exciting. Trials of two types of ketamine—racemic ketamine and esketamine—showed early positive results, even though researchers are not exactly sure how it functions in depression treatment. We do know antidepressants and antipsychotics are showing less efficacy and more chronic side effects than previously believed, however.
There is precedent in the psychedelic realm. Psilocybin, ayahuasca, ibogaine, MDMA, and LSD are showing early positive results in treating anxiety, depression, addiction, and PTSD. This does not mean we should rush blindly ahead, however.
That's the consensus reached by Mark Horowitz (writer) and Joanna Moncrieff (editor), whose recent analysis, published in The British Journal of Psychiatry, concludes that we're moving too fast in clinically adopting ketamine. As their data shows, caution is necessary.
Since its discovery in 1962, ketamine has been used broadly as a sedative and anesthetic; to aid in emergency surgeries in war zones; as a bronchodilator for severe asthmatics; to treat certain type of seizures; in postoperative pain management; and now, as a nasal spray to treat depression. Unlike SSRIs and SNRIs, esketamine works immediately—in as little as two hours—making it more attractive to patients and clinicians.
The Experimental Ketamine Cure for Depression
While treatment-resistant depression sounds extreme, Horowitz notes the definition: patients unsuccessful with two different antidepressants, a low bar for the term "resistant." The problem with trying esketamine, he writes, falls back on the FDA fast-tracking of the drug.
"Out of the three short-term trials conducted by Janssen only one showed a statistically significant difference between esketamine and placebo. These were even shorter than the 6–8 week trials the FDA usually requires for drug licensing."
Each trial lasted only four weeks. The FDA normally requires that two such trials show better results than the placebo; in this case, only one achieved this goal. The successful trial showed a four-point margin on a scale that goes to 60.
Failing to provide two effective trials, the FDA allowed Janssen to submit a discontinuation trial as evidence. This 16-week trial let patients either continue or stop treatment. The problem: side effects were treated as evidence of relapse, not withdrawal symptoms.
Ketamine users have a long history of withdrawal issues, including anxiety, poor appetite, delusions, hallucinations, paranoia, addiction, rage, and craving. The discontinuation trial considers such effects as proof of ketamine's efficacy, not as symptoms of withdrawal.
Science writer Peter Simons explains why this is worrisome:
"Perhaps even more concerning is the fact that, within the discontinuation trial, a single site in Poland drove the apparent finding of efficacy. Data from this site suggested that 100% of the placebo group supposedly relapsed (compared with about 33% of the placebo group in all the other sites)—an unlikely result. When data from this suspicious outlier was removed, the study analysis showed no evidence that esketamine was better than the placebo."
Add to this that six people in the esketamine group died during the trials, including three by suicide—two of whom had previously shown no signs of suicidal ideations—and a troubling picture emerges. The FDA accepted Janssen's explanation: the problem wasn't esketamine, but their underlying condition. This is possible, but the company did not provide conclusive evidence.
Jennifer Taubert, executive vice president and worldwide chairman of Janssen Pharmaceuticals, Johnson & Johnson, testifies before the Senate Finance Committee on "Drug Pricing in America: A Prescription for Change, Part II" February 26, 2019 in Washington, DC. The committee heard testimony from a panel of pharmaceutical company CEOs on the reasons for rising costs of prescription drugs.
Photo by Win McNamee/Getty Images
According to Horowitz, this is a chronic problem with clinical trials and governing agencies.
"It would seem that themes from history are repeating: a known drug of misuse, associated with significant harm, is increasingly promoted despite scant evidence of efficacy and without adequate longterm safety studies."
He also notes that half of the patients experienced disassociation and one-third experienced dizziness. On this point, allow me to break the fourth wall. I've been experimenting with psychedelics since 1994 and am writing a book on psychedelics in ritual and therapy. I ingested a range of substances during my college years. By far, the most troublesome was ketamine. While I'm now aware of Parecelsus's dictum—what is beneficial in small doses is toxic in large doses—I wasn't measuring it out in the 1990s.
Administered doses in Janssen's trials were considered similar to recreational usage. I recall that a bump provided an energetic lift, yet when I'd occasionally snort a line, all bets were off. After a hearty dose one evening, I laid down, sat up, and stood in succession. I couldn't tell the difference between those three physical positions. Ketamine is the most dissociative substance I've ever taken, and I stopped shortly after that last instance.
Psychedelics are the next wave of mental health treatments—call it a continuation, given their role in traditional rituals. We came to rely on pharmacology too much in the twentieth century; hopefully we're learning from those mistakes. As Horowitz points out, however, it appears we're not.
The important word in psychedelic therapy is ritual. There are environmental and social factors entwined with our health. In the right context, psychedelics have tremendous healing power. And to be fair, some ketamine clinics are taking proper right safety precautions as well as designing treatment rooms to be more conducive to healing than sterile white rooms. Patients are anecdotally reporting success in depression treatment with ketamine. This isn't an either-or situation.
But we cannot make the same mistake we've made with CBD and believe these substances are cure-alls. We also can't afford to designate ketamine under the umbrella term "psychedelics." As Alan Watts wrote, hallucinogen is not a proper definition of the psychedelic experience, though it's fitting when describing ketamine. Conflating substances will only further confusion during a time when we need clarity. If the addictive properties and dangerous side effects of ketamine play out widely, it endangers the entire psychedelic therapy model.
We can hope for a clinically-effective dosage and delivery mechanism of ketamine. We can't, as Horowitz's analysis shows, make the same mistakes over. Pharmacological intervention has a place in psychiatry, but it's come to dominate the industry, often no better than placebo and psychotherapy. We need healing, not more side effects.
- Could Ketamine treat depression and suicide? - Big Think ›
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- FDA approves ketamine-like nasal spray for depression - Big Think ›
Sallie Krawcheck and Bob Kulhan will be talking money, jobs, and how the pandemic will disproportionally affect women's finances.
Can an orgasm a day really keep the doctor away?
- Achieving orgasm through masturbation provides a rush of feel-good hormones (such as dopamine, serotonin and oxytocin) and can re-balance our levels of cortisol (a stress-inducing hormone). This helps our immune system function at a higher level.
- The surge in "feel-good" hormones also promotes a more relaxed and calm state of being, making it easier to achieve restful sleep, which is a critical part in maintaining a high-functioning immune system.
- Just as bad habits can slow your immune system, positive habits (such as a healthy sleep schedule and active sex life) can help boost your immune system which can prevent you from becoming sick.
How masturbation affects your brain...<p>Orgasms are a very common human phenomenon. The physical and mental health benefits have been researched frequently as a result, and yet, there is still so much to be learned about how our bodies and brains react to the chemicals and hormones released during and after experiencing this type of sexual release.</p><p>"The amount of speculation versus actual data on both the function and value of orgasm is remarkable" explains Julia Heiman, director of the <a href="https://kinseyinstitute.org/" target="_blank">Kinsey Institute for Research in Sex, Gender, and Reproduction</a>.</p><p>Masturbation causes a rush of <a href="https://www.webmd.com/mental-health/what-is-dopamine" target="_blank">dopamine</a>, which is a chemical that is associated with our ability to feel pleasure. Along with the rush of dopamine that is released during an orgasm, there is also a release of a hormone called <a href="https://www.livescience.com/42198-what-is-oxytocin.html" target="_blank">oxytocin</a>, which is commonly referred to as the "love hormone."<br></p><p>This concoction of chemicals does more than just boost our mood, it also can play a key role in decreasing stress and promoting relaxation. Oxytocin decreases <a href="https://www.webmd.com/a-to-z-guides/what-is-cortisol" target="_blank">cortisol</a>, which is a stress hormone that is usually present (in high volumes) during times of anxiety, fear, panic, or distress. </p><p>According to BDSM and fetish researcher <a href="https://www.psychologytoday.com/us/therapists/dr-gloria-brame-colbert-ga/278388" target="_blank">Dr. Gloria Brame</a>, an orgasm is the biggest non-drug induced blast of dopamine that we can experience. </p><p>By boosting the oxytocin and dopamine levels and subsequently decreasing our cortisol levels, the brain is placed in a more relaxed, euphoric, and calm state. </p>
Masturbation boosts your immune system and raises your white blood cell count.<p>How do those effects on the brain from reaching orgasm translate to boosting our immune system and making our body healthier?</p><p>The increase of oxytocin and dopamine that causes a decrease in cortisol levels can help boost our immune system because cortisol (well-known for being a stress-inducing hormone) actually helps maintain your immune system if released in small doses. </p><p>According to <a href="https://www.health24.com/Sex/Great-sex/incredible-health-benefits-to-masturbating-20181030-2" target="_blank">Dr. Jennifer Landa</a>, a hormone-therapy specialist, masturbation can produce the right kind of environment for a strengthened immune system to thrive. </p><p><a href="https://www.ncbi.nlm.nih.gov/pubmed/15316239" target="_blank">A study</a> conducted by the Department of Medical Psychology at the University Clinic of Essen (in Germany) showed similar results. A group of 11 volunteers were asked to participate in a study that would look at the effects of orgasm through masturbation on the white blood cell count and immune system.</p><p>During this experiment, the white blood cell count of each participant was analyzed through measures that were taken 5 minutes before and 45 minutes after reaching a self-induced orgasm. </p><p>The results confirmed that sexual arousal and orgasm increased the number of white blood cells, particularly the natural killer cells that help fight off infections. </p><p>The findings confirm that our immune system is positively affected by sexual arousal and self-induced orgasm and promote even more research into the positive impacts of sexual arousal and orgasm. </p>
Masturbation can ease and prevent pain, which allows you to achieve the restful sleep that helps your immune system stay strong and healthy.<p>The benefits of masturbation have long been debated, but the more research that is done on the topic the more we understand that there are many positive reactions that happen in our bodies and brains when we orgasm.</p><p>Orgasms can help prevent or mitigate pain, which boosts the immune system, preventing cold and flu symptoms. </p><p>According to neurologist and headache specialist Stefan Evers, about one in three patients experience relief from migraine attacks by experiencing sexual activity or orgasm. Evers and his team <a href="https://www.livescience.com/27642-sex-relieves-migraine-pain.html" target="_blank">conducted an experiment</a> with 800 migraine patients and 200 patients who suffered from cluster-headaches to see how their experiences with sexual activity impacted their pain levels. </p><p>The study showed that 60% of migraine sufferers experienced pain relief after participating in sexual activity that resulted in orgasm. Of the cluster-headache sufferers, about 50% said their headaches actually worsened after sexual arousal and orgasm. </p><p>Evers suggested in his findings that the people who did not experience pain relief from migraines of headaches during their sexual activity did not release as large amounts of endorphins as those who did experience pain relief. </p><p>According to <a href="https://www.sharecare.com/health/chronic-pain/chronic-pain-affect-immune-system" target="_blank">rheumatologist Dr. Harris McIlwain</a>, people who suffer from chronic pain have immune systems that are simply not functioning at full capacity - therefore, alleviating pain (through orgasm, as an example) can help boost the immune system. </p><p>Orgasms can also promote relaxation and make it easier to fall asleep. Serotonin, oxytocin, and norepinephrine are all hormones that are released during sexual arousal and orgasm, and all three are known for counteracting stress hormones and promoting relaxation, which makes it much easier for you to fall asleep.</p><p>There are <a href="https://www.ncbi.nlm.nih.gov/pubmed/1233384" target="_blank">several studies</a> showing that serotonin and norepinephrine help our body cycle through REM and deep non-REM sleeping cycles. During these sleep cycles, the immune system releases proteins called <a href="https://www.sleepfoundation.org/articles/how-sleep-affects-your-immunity" target="_blank"><span id="selection-marker-1" class="redactor-selection-marker"></span>cytokines<span id="selection-marker-2" class="redactor-selection-marker"></span></a>, which target infection and inflammation. This is a critical part of our immune response. Cytokines are both produced and released throughout our bodies while we sleep, which proves the importance of a good sleep schedule to a healthy immune system.</p>
Masturbation promotes a high-functioning immune system; a healthy immune system prevents cold and flu.<p>The immune system is a balanced network of cells and organs that work together to defend you against infections and diseases by stopped threats like bacteria and viruses from entering your system. While there are many things we need to do to keep our immune systems functioning at optimal levels, masturbation (or other means of achieving orgasm) has proven to have positive effects on the immune system as a whole.</p><p>Just as bad habits (such as an inconsistent sleep schedule or harmful chemicals in your body) can slow your immune system, positive habits (such as a healthy sleep schedule and active sex life) can help boost your immune system. </p>
Health officials in China reported that a man was infected with bubonic plague, the infectious disease that caused the Black Death.
- The case was reported in the city of Bayannur, which has issued a level-three plague prevention warning.
- Modern antibiotics can effectively treat bubonic plague, which spreads mainly by fleas.
- Chinese health officials are also monitoring a newly discovered type of swine flu that has the potential to develop into a pandemic virus.
Bacteria under microscope
needpix.com<p>Today, bubonic plague can be treated effectively with antibiotics.</p><p style="margin-left: 20px;">"Unlike in the 14th century, we now have an understanding of how this disease is transmitted," Dr. Shanthi Kappagoda, an infectious disease physician at Stanford Health Care, told <a href="https://www.healthline.com/health-news/seriously-dont-worry-about-the-plague#Heres-how-the-plague-spreads" target="_blank">Healthline</a>. "We know how to prevent it — avoid handling sick or dead animals in areas where there is transmission. We are also able to treat patients who are infected with effective antibiotics, and can give antibiotics to people who may have been exposed to the bacteria [and] prevent them [from] getting sick."</p>
This plague patient is displaying a swollen, ruptured inguinal lymph node, or buboe.
Centers for Disease Control and Prevention<p>Still, hundreds of people develop bubonic plague every year. In the U.S., a handful of cases occur annually, particularly in New Mexico, Arizona and Colorado, <a href="https://www.cdc.gov/plague/faq/index.html" target="_blank">where habitats allow the bacteria to spread more easily among wild rodent populations</a>. But these cases are very rare, mainly because you need to be in close contact with rodents in order to get infected. And though plague can spread from human to human, this <a href="https://www.healthline.com/health-news/seriously-dont-worry-about-the-plague#Heres-how-the-plague-spreads" target="_blank">only occurs with pneumonic plague</a>, and transmission is also rare.</p>
A new swine flu in China<p>Last week, researchers in China also reported another public health concern: a new virus that has "all the essential hallmarks" of a pandemic virus.<br></p><p>In a paper published in the <a href="https://www.pnas.org/content/early/2020/06/23/1921186117" target="_blank">Proceedings of the National Academy of Sciences</a>, researchers say the virus was discovered in pigs in China, and it descended from the H1N1 virus, commonly called "swine flu." That virus was able to transmit from human to human, and it killed an estimated 151,700 to 575,400 people worldwide from 2009 to 2010, according to the Centers for Disease Control and Prevention.</p>There's no evidence showing that the new virus can spread from person to person. But the researchers did find that 10 percent of swine workers had been infected by the virus, called G4 reassortant EA H1N1. This level of infectivity raises concerns, because it "greatly enhances the opportunity for virus adaptation in humans and raises concerns for the possible generation of pandemic viruses," the researchers wrote.
The word "learning" opens up space for more people, places, and ideas.
- The terms 'education' and 'learning' are often used interchangeably, but there is a cultural connotation to the former that can be limiting. Education naturally links to schooling, which is only one form of learning.
- Gregg Behr, founder and co-chair of Remake Learning, believes that this small word shift opens up the possibilities in terms of how and where learning can happen. It also becomes a more inclusive practice, welcoming in a larger, more diverse group of thinkers.
- Post-COVID, the way we think about what learning looks like will inevitably change, so it's crucial to adjust and begin building the necessary support systems today.