Like other controlled substances and psychedelics (which unfortunately overlap to a great extent), ketamine is shrouded in myth and mystery. On one hand, some believe ketamine to be dangerous, illicit, and addictive. On the other hand, some think that ketamine is a miracle cure.
Spoiler alert: Ketamine is neither but somewhere between 😏
One belief that I’m 100% confident about is that when people misunderstand something, they tend to:
Today, I’m going to summarize five of the most common (negative) misconceptions about ketamine. In my next post, I’ll summarize three overly optimistic misconceptions. My hope is to reduce misunderstanding about this powerful medicine. The more my patients know about ketamine and ketamine therapy, the more realistic their expectations are. And that’s better for everyone.
Ketamine is on Schedule III of the Controlled Substances Act. This means that Congress believes ketamine has, “a moderate to low potential for physical and psychological dependence,” and the DEA controls who can manufacture, sell, and possess ketamine, among other activities. In other words, as long as it is administered (and prescribed to you) by a licensed medical provider, ketamine is legal.
Not quite. But you may have heard of some medications which are used in both humans and non-humans. They include amoxicillin, Prozac, tramadol, prednisone, ivermectin, and ketamine. Crucially, all of these medicines are formulated and prescribed with different concentrations, inactive ingredients, dosing protocols, and uses.
According to the FDA and anyone with common sense, “Never use medications intended for animals on yourself or other people.” The reverse is also true: Don’t give Fido medicine intended for humans. You can be confident that ketamine administered by a licensed medical provider is fit for humans.
The FDA has approved both ketamine and its enantiomer, esketamine or S-ketamine. The former was approved over 53 years ago on February 19, 1970, under the brand name Ketalar as a fast-acting general anesthetic. Whereas the latter was approved much more recently on March 5, 2019, as a nasal spray under the brand name Spravato for Treatment Resistant Depression (TRD).
The phrase “off label” refers to when a medication is prescribed for a different purpose than what the FDA approved. In other words, its prescribed use literally differs from the package insert or label. Medical providers commonly prescribe drugs “off label” because:
Ketamine is FDA approved and prescribed “off label” when administered by a licensed medical provider to treat conditions like depression, anxiety, and chronic pain. (Its “on label” use is as an anesthetic.) The newer esketamine nasal spray called Spravato which was developed and patented by Janssen (part of Johnson & Johnson) is also FDA approved for TRD.
“Off label” does not imply unsafe or ineffective. In fact, some have argued that because of bad incentives, ketamine—a safe and effective mental health treatment—could be displaced by the less effective but more expensive esketamine nasal spray 😤
Important: There may be drawbacks associated with “off label” use. For example, it may be that an “off label” prescription proves ineffective or brings unwanted side effects. Therefore, always ask your medical provider why they believe an “off label” prescription is right for you. Another issue is that the cost may not be covered by health insurance. So you may need to rely on your FSA or HSA (if you have a HDHP).
In the 1950s, Parke Davis (now a subsidiary of Pfizer) synthesized phencyclidine or PCP while researching its use as an anesthetic. Soon after however, scientists noted that PCP produced a drunken state, delirium, and catatonia in various animals as well as signs of delirium or psychosis in humans. Searching for a shorter duration and less disruptive analog, Parke Davis published its findings related to research drug CL-581 (aka Ketalar and ketamine) in 1965.
In 1983, researchers first discovered that both PCP and ketamine work by blocking the N-methyl-D-aspartate (NMDA) glutamate receptor. However unlike PCP, they found that ketamine was about ten times less potent, therefore less likely to produce unwanted side effects, and shorter lasting.
Lastly, PCP does have a storied reputation, some of which is sensational and some which may have a kernel of truth. Rather than making people more violent or giving them superhuman strength, however, it appears that its users are succumbing to its strong hallucinogenic and numbing effects.
When The Partnership for a Drug Free America (now Partnership to End Addiction) put out this misleading and simplistic public service announcement in the 1980s, it bolstered existing anti-drug sentiment in parents and scared kids like me. Instead of educating us on why people might abuse drugs, legitimate uses of drugs (both legal and not), and ways to prevent or minimize harm, drugs were simply labeled “bad” by government campaigns like Just Say No in 1986 and DARE in 1991. Unfortunately, ketamine got swept up into this and has been fighting to rebrand itself ever since.
Ketamine was first synthesized in 1962 by Calvin Stevens who was working with Parke Davis. Following FDA approval as an anesthetic in 1970, ketamine has been used in emergency and operating rooms worldwide. Ketamine has been on the World Health Organization’s Model List of Essential Medications for decades alongside penicillin, lidocaine, and morphine. This is to say that ketamine has a relatively long history of widespread use which has proven its safety when used properly.
I first learned about ketamine in my surgical residency where we commonly used it to anesthetize and sedate patients in the emergency room. One of the main reasons we relied on ketamine was because like opioids, it is an anesthetic. But unlike opioids, it does not decrease breathing or heart rate. Furthermore:
Unsurprisingly, given its psychoactive properties and purported feelings of euphoria and dissociation, there are reports of ketamine addiction and abuse around the world. Misuse and abuse in the UK, east and southeast Asia, and possibly the US has been reported. When combined with other substances like alcohol, cocaine, or other medications, there is a greater risk of injury or death compared to when misused alone. Without close monitoring by licensed medical providers, addiction is possible.
For these reasons, it is important to use ketamine under the supervision of a licensed medical provider who is trained to prevent and watch for signs of misuse, abuse, and addiction. Licensed medical providers are also equipped to respond to medical emergencies, however rare they may be in a clinical setting where ketamine therapy is practiced.
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