Notes on Ketamine - Why Big Business & Pharma wants regular Ketamine to go away. Autism & Ketamine. Safety & Ketamine. OCD & Ketamine. Ketamine derives from a plant source.
Ketamine in the Plant World
Ketamine, a potent dissociative anesthetic, is a fascinating compound that sparks curiosity about its natural origins. Although primarily known for its pharmaceutical applications, ketamine can indeed be found naturally in certain environments.
Within the vast and diverse plant kingdom, a few species have been discovered to contain trace amounts of ketamine. These plants, often native to specific regions, possess the remarkable ability to synthesize ketamine. One such plant species that produces ketamine is the enigmatic Ketaminacea. Native to the rainforests of South America, this plant synthesizes ketamine as a defense mechanism against herbivores. The presence of ketamine in its leaves acts as a deterrent, causing discomfort or even mild hallucinogenic effects in potential predators. Another fascinating example is the Ketaminophyllum, a rare flowering plant found in the remote valleys of the Himalayas. This extraordinary plant has developed a metabolic pathway that allows it to produce ketamine as part of its growth and development.
https://duramedical.us/where-is-ketamine-found-naturally/
Big Pharma and Business and Ketamine
These passages are from the New York Times reports on Ketamine in 2010 and 2014:
It has been known for several years that small doses of the drug, ketamine, can relieve major depression.
A common refrain among ketamine advocates is that questions about its safety are emanating from drug companies, which have no financial incentive to develop ketamine because it is generic but see it as a threat to their proprietary products.
“Let’s trash ketamine to justify producing something patentable and turn it into a blockbuster,” said Dr. Glen Z. Brooks.
Drug company executives say that ketamine itself has too many problems to ever gain wide acceptance for long-term use, especially as an off-label treatment.
There is clearly a need for new drugs. “Almost half of depressed patients are not being treated adequately by existing drugs,” said Dr. Sheldon H. Preskorn, a professor of psychiatry at the University of Kansas School of Medicine-Wichita.
Ketamine would represent a new mechanism of action. It is believed to work mainly by blocking receptors in the brain for N-methyl-D-aspartate, or NMDA, which interact with a different neurotransmitter called glutamate. The blockage sets off a cascade of changes that are not yet completely understood.
He dismissed any suspicions that people are simply getting high and not experiencing a true antidepressant effect, saying the lifting of depression occurs after the side effects end.
To stretch the time between visits, some clinics are now providing ketamine that patients can inject themselves at home.
One of his patients, Maggie, said that when she got her first infusion, she was aware enough to change the tunes on her iPod, albeit slowly, but was “transported into a completely different dimension.” She added, “Everything there is completely vibrant or molten.”
The trip ended quickly, but within hours, a lifetime of depression began to lift. “Never ever ever before have I felt like that,” said Maggie, 53, who lives in Orange County, Calif. says, “I woke up the next morning, and I didn’t take an antidepressant for the first time in 20 years.”
“I look at the cost of not using ketamine — for me it was certain death,” said Dennis Hartman, 48, a businessman from Seattle.
He said that after a lifetime of severe depression, he had chosen a suicide date when he entered a clinical trial of ketamine at the National Institutes of Health two years ago. His depression lifted and since then he has gone to a clinic in New York every two months or so for infusions. He started the Ketamine Advocacy Network to raise awareness of the treatment.
It has been known for several years that small doses of the drug, ketamine, can relieve major depression.
Important research relevant to Ketamine, Psychedelics, & Autism:
Here's a 3-minute video about a UK research group starting a psilocybin project for autistic individuals.
Here’s a group dedicated to the advocacy of psychedelics and autism.
https://www.autisticpsychedelic.com/
Chapter 4 in The Revolutionary Ketamine
Research Important and relevant to Ketamine and OCD:
https://nihrecord.nih.gov/2023/01/06/new-treatments-ocd-show-promise
https://stanmed.stanford.edu/carolyn-rodriguez-ketamine-ocd/
Safety and Ketamine
From NIH on safety:
“RESULTS: Ketamine is most commonly administered in the dose of 0.5 mg/kg, but some patients may respond to doses as low as 0.1 mg/kg, and others may require up to 0.75 mg/kg. Safety and efficacy have been demonstrated in sessions ranging between 2 and 100 minutes in duration. Bolus administration is safe and effective when the drug is administered intramuscularly or subcutaneously. Whereas the intravenous route is the most commonly employed, safety and efficacy have been described with other routes of administration, as well; these include oral, sublingual, transmucosal, intranasal, intramuscular, and subcutaneous routes. Patients may receive a single session of treatment or a course of treatment during the acute phase, and treatment may rarely be continued for weeks to years to extend and maintain treatment gains in refractory cases. When so extended, the ideal frequency is perhaps best individualized wherein ketamine is dosed a little before the effect of the previous session is expected to wear off.”
Studies involving more than 70,000 scientific articles demonstrate the safety of Ketamine. Please see The Revolutionary Ketamine book.
Other studies of interest:
How Ketamine-based clinics are improving veterans’ mental health (militarytimes.com)
New study maps ketamine's effects on brain | ScienceDaily
Business Insider magazine article into which I’ve inserted comments...
A depression drug that researchers have called 'the most important discovery in half a century' just got a big lift.
Ketamine is emerging as a potential new drug for depression - the first of its kind in 35 years.
Johnson & Johnson plans to file for FDA approval of a nasal spray formula called esketamine this year.
On Saturday, they presented new research suggesting the drug worked well alongside a traditional antidepressant for a month.
Other companies are also going after ketamine-inspired antidepressants.
Ketamine, which has been called "the most important discovery in half a century," just got a step closer to becoming the first new depression drug in 35 years.
Johnson & Johnson, one of the pharmaceutical companies pursuing the drug's fast-acting antidepressant qualities, presented some promising new research on Saturday that could raise the drug's profile as a potential treatment for the condition.
It's a dramatic departure for a compound that most people know either as a surgical anesthetic or a party drug. And it's a seemingly welcome one, according to physicians and psychiatrists who say they've grown tired of giving patients the same mediocre drugs for the past four decades.
Johnson & Johnson isn't the only drugmaker that's hot on the ketamine trail. Allergan is in the last phase of clinical trials with a drug that acts on the same receptor as ketamine, and San Francisco drugmaker VistaGen is studying a similar ketamine-inspired drug.
J&J's version of ketamine is a nasal spray made with a compound called esketamine, the chemical mirror image of ketamine.
[This is the typical trick of Pharma companies: It's the exact same compound, made anew so as to get a new patent and charge a lot - a truly dark little game given that an even more effective compound is 100% available. No wonder this article is in Business Insider Magazine.]
In its latest clinical trial, the company's neuroscience partner, Janssen Research, wanted to show that the spray was safe, well tolerated, and superior to both a placebo and a traditional antidepressant.
[Most disturbingly, they are creating an outcome where there is a DAILY-USE product to sell, when there is already something available right this minute in which literally one dose is effective for a very, very long time.]
To do it, the researchers had 236 adults with treatment resistant depression - known as one of the hardest forms to treat - take a traditional antidepressant for four weeks alongside a nasal spray. Only half of them got a spray with J&J's drug in it; the other half got a placebo.
Their results were promising: The people who got the real spray saw significantly better improvements in their depressive symptoms than those who got the placebo, over the course of 28 days. More importantly, it is also the first time a novel treatment has come out on top even when compared to a traditional antidepressant drug.
The findings come roughly a month after J&J published the results of a small, preliminary version of this study which suggested that over the course of a single day, the spray and traditional antidepressant combo was better than a placebo and traditional antidepressant combo. That study, however, suggested the results diminished over the course of four weeks, while the longer and larger study suggests they might not.
Depression is one of the world's leading causes of death [in more ways than one]. Current treatments for depression, which take roughly five weeks to begin to take effect, may not work well in up to 80% of the people who get them.
That stunning sentence bears re-reading: Current treatments for depression, which take roughly five weeks to begin to take effect, may not work well in up to 80% of the people who get them.
Most existing antidepressants, from Abilify to Zoloft, work by plugging up the places where our brain takes up serotonin, a chemical messenger that plays a key role in mood. The result is more free-floating serotonin and, in some people, relief from a dark curtain of depressive symptoms.
Ketamine doesn't work this way. It capitalizes on a different mechanism in the brain and affects key switches called NMDA receptors which affect the glutamate and GABA neurotransmitters.
In fact, researchers don't know how either drug actually works - these vague descriptions of mechanisms are hypotheses that are always part of Pharma's narrative on SSRI.
Potentially because of depression's damaging effects on brain switches, it appears to cause our synaptic branches to “shrivel up” and in some cases even to die. Scientists think existing antidepressants send help to those branches indirectly over time by way of serotonin. Ketamine, by contrast, delivers its aid directly to the source, plugging up NMDA receptors like a cork in a bottle, and nipping depressive symptoms within hours.
A 2012 study published in the journal Science analyzed ketamine's rapid ability to reduce depressive symptoms in people who'd failed to respond to other drugs. The authors called ketamine "the most important discovery in half a century." Five years later, researchers concluded in a study in the American Journal of Psychiatry that the drug's antidepressant effects appeared to last at least a month.
[but note Johnson & Johnson is creating a daily use product, when the single dose product is known to be more effective]
Still, like any drug, ketamine has a range of side effects, the most troublesome of which appears to be its tendency to produce what are known as dissociative, or "out of body," experiences.
[This "side effect" is literally a key aspect of its value. This "side effect" is what was inspirational and life-improving for many many people easily found in even cursory research on ketamine.]
Experts worry those effects could lead patients to either react negatively to the experience and not want to repeat it, or react positively and want to repeatedly use, potentially leading to a drug-use disorder.
[Pharma companies should literally write comedy. Since it's rarely addictive in a clinical setting, and yet enormously effective, J&J wants the already-available single dose ketamine to be illegal and unavailable... so they are calling an overly positive reaction a "drug use disorder." For these companies, the biggest fear is always that some drug will delivers true benefit in a single dose, such as a psychedelic compound can do, as in the case of that NY Times story about the man and the wound from his father leaving when he was 4 years old... a single dose improved the rest of his life.]
In J&J's most recent study, patients reported other side effects as well, including dizziness, headache, blurred vision, and nausea.
[This too is comedy, because NONE of these effects is an issue with the currently available method of one dose, and every one of these side effects is a problem only in their daily-dose scheme! Sad comedy.]
Besides its immediate side-effects, some researchers approach ketamine with hopeful caution for another reason.
Without a good number of long-term studies on ketamine for depression, it's tough to know what the drug's effects might look like over the course of several months or years. Its beneficial effects, for example, could wear off; other negative side effects could emerge as well -- meaning negative side effects haven't emerged at all.
Allergan and VistaGen are currently doing long term studies of their new drug candidates, which act on the same pathway as ketamine but appear to have substantially fewer side effects; results from those trials are expected in the next two years.
[during this bullshit two-year process, millions of people will continue suffering and dying - when there is a demonstrably effective compound already available and expensively]
J&J is also pursuing more research on its nasal spray ketamine formula, some of which will include longer trials. Company representatives told Business Insider that in addition to the research they've presented so far, they also have plans to study the nasal spray formula in teens with major depression who are at imminent risk for suicide.
Thank you for this analysis. I’d like to learn more about daily use studies, as I feel this is a great danger to the progression of safer once weekly treatments.