Is Ketamine Really Dangerous?

Did it really kill Matthew Perry? Will it make you crazy like Elon? Let’s dig in.

Ketamine seems to be everywhere these days. It can be sprayed up your nose in a club or administered by IV in a clinic, mailed to your doorstep in lozenges, or put up the bum for a longer, more powerful journey. It’s also showing up in Instagram reels about “healing.” Depending on who you ask, ketamine is either a revolutionary treatment for depression—or a recreational substance for folks who want something quicker, floatier and less headache-inducing than ecstasy. Some people blame Elon Musk’s erratic and disturbing behavior on ketamine. Others think the drug itself killed Matthew Perry. What’s the truth?

Like most substances that can be used therapeutically and recreationally, the correct answer is: “It depends.” It depends on the context in which the drug is delivered, the strength of the dose and the purity of the ketamine. (One study analyzing ketamine purchases from cryptomarkets found an average purity of 71.3%, with a range from 27% to 95%. Adulterated street smaples may contain chalk, baking soda, coffee creamer, and gypsum dust mixed in).

Ketamine isn’t “safe” or “dangerous” in the abstract. It’s a potent tool—one that can relieve depression in just one session or just leave you sprawled on the floor feeling like your body has turned to mist. But when it’s abused it can wreck your bladder and maybe your life. Just ask the 1,800 people on the Ketamine Addiction subreddit who describe peeing blood, having seizures, permanent kidney damage and K cramps (agonizing abdominal pain) caused by out of control abuse.

My intention with this post is to take a step back from the healing hype and the fear-inducing headlines to understand what ketamine is, how it works and coldly examine the risk to reward ratio. My perspective is also influenced by my own mostly positive experiences with this drug. I’ll share it below in an effort to demonstrate why context and education is so important to understanding the good the bad and the ugly sides of this fascinating molecule.

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A Short History: From Battlefield to Bedroom

Ketamine was synthesized in 1962 by a Detroit chemist named Calvin Stevens, originally as a safer alternative to PCP (phenylcyclohexyl piperidine, which at the time was a widely used and dangerous anesthetic. Ketamine was a game changer. Unlike PCP, which lowered vital signs to the very thin line between life and death, ketamine numbed pain immediately but didn’t lower breathing rate, heart rate or blood pressure. It was also very flexible: classified as a dissociative anesthetic it mixed well with other medications, worked in humans and animals, and it could be used in the operating room and on the battlefield. During the Vietnam War it was nicknamed the “buddy drug” because soldiers carried a ketamine loaded syringe with them. If a fellow soldier was wounded they could administer it immediately to treat the trauma without other painkillers. By 1970, ketamine was FDA-approved.

“It was an outlier – clinical and recreational uses emerged almost simultaneously.”

It didn’t take long for ketamine to leap from the clinic to the dance floors of the 1980s. Known as “Special K”, “Kit-Kat,” or

…it became the party favor of choice, an-easy-to-use, affordable disssociative that made time stretch and bodies dissolve. Just like that other white powder, cocaine, it came in a small glassene envelope and could be snorted in lines, bumps, and baggie-dips.

By 1999, the DEA had gotten wind of ketamine’s popularity and in an effort to restrict use, classified it as a Schedule III controlled substance, which, of course, drove it to new heights of popularity, especially in Europe. That same year, Time Out London proclaimed “Ketamine is the new E!”

In 2000 researchers at Yale began exploring its antidepressant effects. The findings were startling. Unlike SSRIs, which can take weeks to work (if they work at all — SSRIs are only effective in half the population that use them), ketamine assisted therapy (that’s the drug plus integration, not just the drug alone) lifted depression within hours and kept the therapeutic window of neuroplasticity open for 3 or 4 days following treatment. That’s a relativly short window, so the treatments must often continue over weeks or months if the effects are to hold.

Today, esketamine—a ketamine derivative—has been FDA-approved as an expensive (thanks, Johnson & Johnson!) nasal spray for treatment-resistant depression. Ketamine can also be administered IV, IM, in a lozenge or as a suppository, the latter providing the strongest and longest lasting experience.

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“It’s like putting your brain on airplane mode.”

Ketamine doesn’t act on the same neurotransmitters as other psychedelics. Instead of interacting with serotonin, dopamine, or norepinephrine, it primarily blocks NMDA receptors. This boosts the production of glutamate and BDNF (brain-derived neurotrophic factor). Neuroscientists call BDNF “Miracle-Gro for your brain.” It increases the connectivity between neurons, which theoretically leaves the body/mind more amenable to the benefits of therapy, meditation and emotional processing.

Its dissociative effect is also what makes ketamine feel so different from other psychedelics. LSD and psilocybin heighten sensory perception, allowing more inputs to flood the mind. A higher dose ketamine psychedelic state feels very different. It’s more like “putting your brain on airplane mode,” says Dr. Leonardo Vando, an addiction psychiatrist and Medical Director of Mindbloom, one of several home delivery ketamine-in-a-box services operating in the US. “Your mind maintains some functions but it’s largely disconnected from all the noise of the outside world and your own inner world.”

That sense of detachment can offer distance and real relief—especially for people stuck in cycles of rumination, anxiety, trauma or depression. As Dr. Allison Wells, owner of Lone Star Infusion, in Houston Texas, who has administered well over 900 ketamine treatments, adds, “Over the long term I think ketamine makes people less reactive. When you’re soaked in adrenaline and cortisol, your synapses are really pared down and you may get stuck in fight or flight loops and rumination. With more pathways open, you have more flexibility."

Another benefit: ketamine doesn’t cause the side effects – weight gain, loss of libido, and flat affect – that SSRIs do. But unlike psilocybin or LSD, the window of neuroplasticity is relatively short, a few days rather than a few weeks, which is why treatment must continue on a regular basis. More recently ketamine has also received attention as a treatment for stubborn post traumatic stress disorder. The drug is also being investigated as an agent to reduce alcohol, cocaine, or opioid dependence.

That’s a quick take on the clinical story. But head to any club or festival and you’ll likely see people with a beer in one hand and a keybump of ketamine in the other. What makes ketamine such a popular recreational substance?

My Own Story: Context and Dose Really Matter!

Prohibition may limit public discussion about the positive aspects of drug use but it also keeps common problems hidden from the public eye. This is why I’m a staunch advocate of education before medication and recreation. The more you know about a substance, the better decisions you can make that maximize benefits, minimize risks or help you decide that even just trying it once isn‘t for you.

My own brief history with K illustrates how context and dosage can drive the outcome.

In the summer of 1989, cocaine was, for some reason, in short supply. Suddenly every anesthesiologist in Fire Island seemed to be showing up with a stash of K, and this is when I and thousands of others first encountered it.

I had been drinking and dancing to the beats of Frankie Knuckles when someone nearby slid a mountain of K under my nose. Being an obedient and somewhat oblivious young thing, I took a big snort followed by another and another. All I knew about ketamine was that it was a horse tranquilizer (it is still used widely in veterinary practices). The drip burned familiar down the back of my throat and I awaited the jolt. But 10 minutes later I was off my head and way off balance. The dance floor lurched and fell below my feet and I couldn’t stand up. I knuckled my way to a seat, where I spent the next wobbly hour, head down between my legs. This one unhappy experience made it easy to stay away from K for decades.

We were reacquainted a few years ago under very different circumstances. This time I was guided by an experienced practitioner at the now defunct Cardea Healing Center in NYC. I took a powerful dose nasally and was guided to a comfy bed draped with blankets and pillows. My practitioner sat on the floor beside me playing the sound bowls, tuning the frequency to my bodily movements. The result was a joyous journey that transported me to another galaxy for an hour (or a lifetime) but when it was over, landed me gently back on earth. No 5-HTP, no aspirin, no recovery time required.

Lesson 1: Dancing on a dissociative (or even standing up) = not good for me. Lesson 2: Laying horizontally on ketamine = much better. Lesson 3 (learned after the fact): Laying naked in bed with someone = extremely agreeable. This what I mean by context determining how you use something. Not everyone finds K-sex appealing (one friend called it “unsexy and totally confusing”) but the blurring of the boundaries between bodies was the closest I’ve come to a metaphysical state of merging. Not knowing where your body ends and another’s begins is fun fuckery of the senses, and this is especially apparent with penetrative sex. The first time I tried it I lost track of who was inside of whom. It was sex but inside out and upside down. Try it if you have a consensual relationship with your partner/s. I’d be curious to hear your response.

So… Is ketamine dangerous?

The World Health Organization says overdoses are rare and that ketamine has a lower dependence potential than caffeine, marijuana, MDMA, and alcohol. Most of the stigma seems to come from the lore of the “K-hole” — that full dissociative experience that limits your ability to speak, ravages your motor functions and lay you flat. Whether this is pleasurable or painful depends on your taste in altered states. As Fatboy Slim said in a 1998 Muzik article: “Get the quantity right and it’s incredible. Get it wrong and you feel like you’re dying.”

Also…ketamine and a lot of alcohol are uneasy bedfellows — and often a recipe for a night of puking – nor is it a good idea to mix it with benzodiazepines or other meds that slow your heart.

Used wantonly, ketamine can put you in scary situations, However, in the last 7 decades over 500+ studies have been conducted with ketamine and they conclude that it is by and large, safe. As Dr. Allison Wells of Northstar Wellness put it squarely: “Ketamine, when used properly, is a very safe drug, unless you do something stupid on it.”

“The danger isn’t what ketamine does to your body. It’s what your body does while you’re on ketamine.”

In other words pharmaceutical safety isn’t the whole story. And this is where the concept of behavioral toxicity comes in. The term refers not to a drug’s direct effects on your organs, but to what can happen while you’re altered. People on ketamine have drowned in bathtubs. They’ve fallen asleep face-down and suffocated on pillows. Others have wandered into traffic, or mixed ketamine with too much alcohol and blacked out.

And as Elon taught us, excessive use can indeed cause bladder damage (painful) or a leaky bladder (messy), cognitive issues, psychological dependence, and in some cases, a worsening of depression and anxiety. So, if you have a propensity toward dependence on any drug or alcohol, if you feel an overwhelming craving for K, if your nose is bleeding from snorting too much, or if you're having trouble focusing, ketamine may be a poor choice for you.

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Did Ketamine Really Kill Matthew Perry?

Actually, it was water.

In December 15, 2023, the NYT reported: “Matthew Perry Died of “Acute Effects of Ketamine.” The headline ricocheted around the world but the facts are more complicated.

Yes, Perry was using ketamine-assisted therapy, and yes, the drug was found in his system at the time of death. But the amount in his system wasn’t a therapeutic dose—it was ten times the clinical dose. He was also taking buprenorphine (a potent opioid-reversal medication) and had cardiovascular disease. He was found alone, face-down in his hot tub, a place no one should ever be when using ketamine. Federal officials have charged five people, two of them doctors, alleging they overprescribed and illegally provided the drugs to Perry.

“The scenario was more lethal than the drug.”

Perry’s death wasn’t caused by ketamine toxicity in the pharmacological sense. It was a classic case of behavioral toxicity: altered consciousness, impaired movement, and no one around to intervene when his head toppled into the water.

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So Where Does this Leave Us?

Compared to many other pharmaceuticals, ketamine isn’t very dangerous. But it can be. Just like your car, your credit card, or your relationships, it depends on how you use it.

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What about Kitty Flipping?

When mixed with other drugs, ketamine is often more a garnish than main course. The primary example of this is Kitty Flipping – mixing a small dose of ketamine with MDMA.

Kitty flipping is popular for several reasons. Not only is it accessible and affordable, but the opposing forces of the two substances the combination in the right doses can be a revelation. MDMA is an energizer for love and connection; it enfolds you in a bubble of bliss. With its sedative properties Ketamine reduces tension and excitability. You connect to the universe. Music sounds incredible. You grind less. Of course, what happens depends on dose, set and setting and purity of your substances, but most kitty flippers agree: ketamine used wisely can soften the hammering of the MDMA comedown.

If you are going to Kitty Flip it’s wise to:

-have tried each substance individually so you understand what you’re in for

-test your powders for purity

-begin with a light-to-moderate dose of MDMA [80-100 mg]. Once you reach “peak” (approximately two hours), take a small bump or spray of ketamine to see how you feel. Don’t overuse K. Most people wait 30-60 mins between bumps.

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News Flash: Mushrooms ARE a secret to youth!

A few weeks back I wrote a semi-facetious headline about how microdosing magic mushrooms and LSD are an unheralded secret to youth. It turns out I was prescient. Last week, researchers at Emory University released a study, “Psilocybin treatment extends cellular lifespan and improves survival of aged mice,” which validated my click-baity contention.

The Emory team found that psilocin, the main byproduct of consuming psilocybin, actively delays aging in cells and organisms. It extended the cellular lifespan of human skin and lung cells by more than 50%. It’s in a petri-dish, so take it with a grain of salt.

But in parallel, researchers also conducted the first long-term in vivo study examining the systemic effects of psilocybin in older mice of 19 months, the equivalent of 60–65 human years. Those that received a low dose of psilocybin of 5 mg, followed by a high dose of 15 mg for 10 months, had a 30% increase in survival compared to mice who hadn’t received any. These mice also showed healthier physical features – improved fur quality, fewer white hairs and hair regrowth.

“These mice weren’t just surviving longer — they experienced better aging.”

In the last two decades psilocybin has been researched for its mental health benefits, but this study suggests that it can slow aging by reducing oxidative stress, improving DNA repair responses, and preserving telomere length. Telomeres are the ends of a chromosome that protect it from damage that could lead to age-related diseases such as cancer, neurodegeneration or cardiovascular disease. These processes are foundational and they influence human aging and the onset of some chronic diseases.

“Most cells in the body express serotonin receptors, and this study opens a new frontier for how psilocybin could influence systemic aging processes, particularly when administered later in life,” says Louise Hecker, PhD, senior author on the study.

Adds Dr. Ali John Zarrabi, director of psychedelic research at Emory's Department of Psychiatry: “This study provides strong preclinical evidence that psilocybin may contribute to healthier aging — not just a longer lifespan, but a better quality of life in later years. As a palliative care physician-scientist, one of my biggest concerns is prolonging life at the cost of dignity and function. But these mice weren’t just surviving longer — they experienced better aging.”

Surprisingly, this article did not end with the pro forma warning that psilocybin is a powerful psychedelic and should never be used without supervision. Let the de-aging begin!

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And if you’re interested in microdosing…

In June, at the Psychedelic Science 2025 Conference, I came upon a group called Mycrodrops.com, “an e-commerce based, woman-owned mycrodosing support company that makes ayurvedic-inspired formulas that are synergistic with the most common forms of mycrodosing substances.” (Their intentional “myspelling” is an effort to avoid those annoying bots that scan and ban psychedelic content on social media channels.)

Me with Alice Teapot, founder of Mycrodrops, at Psychedelic Science 2025.

If that all sounds a bit vague, I invite you to check it out. Within their site you’ll also find a private club, hosted on Patreon, called the MycroVerse, which gives members expanded menu access and educational mycrodosing support content. Once you join the club, you’ll find a vast selection of supplements and meet a number of interesting members, mycrodosing coaches, massage therapists and other wellness affiliates.

If you order, be sure to use the ModPsy10 affiliate code at checkout for $10 off your first purchase. Rest assured that any pennies I receive as an affiliate will be used to support this free Substack series.

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Final final thought: If you find this episode of help/interest, I’d appreciate you passing it along to other likeminded folks and urge them to buzz about it on their social media channels. And please send me any questions about psychedelics that may come up. I’ll do my best to find a wise answer.