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Street use of the anesthetic ketamine is on the rise. Kylie, a 28-year-old professional female, recently told me about her experience snorting recreational ketamine: “I was feeling anxious and I was feeling sad. My friend suggested I try snorting some ketamine crystals she had, and when I did . . . I had the best feeling of my life. The drug made me happier. It made the next hour a fun experience without any sadness, and when the high wore off an hour later my sadness was still gone. It was as if I’d been treated with some antidepressant drug, and the improvement in my mood was more lasting than the initial buzz. Now I see my future using ketamine as a periodic antidepressant. When you read about it on the internet, doctors are prescribing ketamine as a treatment for depression, but the whole medical clinic intravenous treatment is really expensive. It’s a lot easier to do it myself with ketamine I buy on the streets.”
Hmmm. We’re all aware of the dangers of recreational drug use with cocaine or methamphetamine or narcotics. We’re all aware of the dangers of recreational drugs laced with fentanyl, a powerful drug that can stop a person’s breathing and kill them in minutes. In this context, what kind of a threat is street ketamine?
KETAMINE AS AN ANESTHETIC
Ketamine is a powerful general anesthetic drug in an anesthesiologist’s toolbox. In 1962 Calvin Stevens, a professor of chemistry at Wayne State University, synthesized ketamine from phencyclidine (PCP), an animal tranquilizer/anesthetic also known as angel dust, with the desired goal of discovering a safer anesthetic with fewer hallucinogenic effects than PCP.
Anesthesiologists administer ketamine intravenously to produce general anesthesia without utilizing any anesthesia gas. We call ketamine a dissociative drug, because it can distort sensory perception and impart a feeling of detachment from oneself and the environment. The drug can produce bizarre and unpleasant nightmares, so anesthesiologists are trained to pair ketamine with an intravenous benzodiazepine such as Versed to temper ketamine’s potentially frightening dream world. Anesthesiologists are also trained to pair ketamine with an anticholinergic (mouth-drying) medication such as atropine or glycopyrrolate (Robinul), because ketamine can produce excessive salivating, which can lead to a patient choking on a rising tide of saliva.
For anesthesia usage, ketamine is a clear liquid with a concentration of 100 mg/ml or 50 mg/ml.
Because ketamine is an effective general anesthetic in one syringe, it’s included on the World Health Organization’s list of essential drugs. For medical sedation, ketamine is typically diluted and administered intravenously in small boluses of 20 to 30 mg, and titrated to obtain the desired depth of anesthesia. To induce general anesthesia, the intravenous dose is 1 – 4.5 mg/kg, or a mean dose of 2 mg/kg = 100 mg for a 50 kg adult. If it’s not possible to insert an IV line (e.g. if a patient is uncooperative, developmentally delayed, or is a child), a combination of 2 mg/kg of ketamine, 0.2 mg/kg of midazolam, and .02 mg/kg of atropine can be administered as an intramuscular injection into the deltoid muscle of the shoulder or the quadriceps muscle of the anterior thigh. To induce general anesthesia with intramuscular ketamine alone, dosing levels are higher than for intravenous use, for example the intramuscular dose is 6.5 – 13 mg/kg, or a mean dose of 10 mg/kg = 500 mg ketamine for a 50 kilogram adult.
How does medical ketamine affect a patient’s ABCs of airway, breathing, and circulation? Patients typically maintain an adequate airway and breathing during ketamine sedation and anesthesia, which is advantageous in short surgical procedures because this often eliminates the need for a breathing tube. Ketamine causes stimulation of the cardiovascular system, with the potential side effect of increasing blood pressure.
There is no reversal agent for ketamine. If an administered ketamine dose is excessive, a patient’s airway and breathing may become compromised, resulting in inadequate oxygen delivery to the lungs, heart, and brain. Patients who are obese, or who have obstructive sleep apnea, may lose their safe airway and breathing status during ketamine sedation. Ketamine can elevate blood pressure, so vigilant monitoring of the blood pressure is required, and acute treatment for hypertension may be necessary. Because of these risks, ketamine administration is typically limited to anesthesia professionals or physicians who are experts in the emergency management of airways and acute vital sign changes.
KETAMINE AS AN INTRAVENOUS ANTIDEPRESSANT DRUG
Multiple meta-analyses have concluded that IV ketamine is an effective rapid-acting antidepressant for major depressive disorders. Ketamine was first reported to have antidepressant properties in the year 2000, when published data showed that an intravenous administration of a sub-anesthetic ketamine dose resulted in a reduction of symptoms in major depressive disorder (MDD). MDD is a common disorder with significant consequences. A 2012 epidemiological study of mental health in Canada showed the lifetime prevalence of major depressive disorder was 3.9%. The prevalence was higher in women and in younger age groups. Ketamine is a treatment option for patients suffering from treatment-resistant depression (TRD). IV ketamine can exert rapid antidepressant effects as early as several hours after administration. In contrast, traditional oral antidepressant pills usually require several weeks of therapy for a clinical response. Ketamine has a unique mechanism of action on the central nervous system, at the NMDA (N-methyl-D-aspartate) and AMPA (𝛼-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors, rather than at the serotonin and/or noradrenaline neurotransmitters that are the sites of action for traditional antidepressant pills such as Prozac, Paxil, or Zoloft.
Intravenous ketamine clinics are typically supervised by an attending anesthesiologist whose is present is to ensure the safe management of airway, breathing, and circulation during these brief sedation anesthetics. Intravenous ketamine administered in a clinic setting can result in adverse effects during the infusion period and immediately afterward, including nausea, vomiting, drowsiness, dizziness, confusion, dissociation, or an increase in blood pressure.Typically an infusion of 0.5 mg/kg of ketamine (e.g. 40 mg for an 80 kg patient) is administered slowly over 40 – 60 minutes. The patient will remain onsite in a recovery room until the sedative effects have cleared. Patients report positive antidepressant effects within two hours, and these effects last for one to two weeks. Data demonstrate a positive response rate of 44% after six intravenous ketamine treatments in patients with treatment-resistant depression. A series of anesthetics will cost significantly more than one Prozac pill per day, so the use of ketamine as an antidepressant is directed at treatment-resistant depression.
KETAMINE AS AN INTRANASAL ANTIDEPRESSANT DRUG
In 2019 the FDA approved a nasal spray called Spravato (active ingredient esketamine) for major depression that failed treatment with two or more oral antidepressants.
Per the Spravato website:
SPRAVATO® is a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist indicated, in conjunction with oral antidepressant, for the treatment of: treatment-resistant depression in adults, depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior.
SPRAVATO® is intended for use only in a certified healthcare setting.
SPRAVATO® is intended for patient administration under the direct observation of a healthcare provider, and patients are required to be monitored by a healthcare provider for at least 2 hours. SPRAVATO® must never be dispensed directly to a patient for home use.
The advantage of intranasal ketamine is that it does not require an IV, and it requires monitoring by a healthcare provider but does not require an anesthesiologist to supervise its administration.
KETAMINE AS A RECREATIONAL DRUG
To supply the illicit street market, diverted pharmaceutical liquid ketamine is evaporated from its liquid solution into a powdered form.
How popular is recreational ketamine? The number of ketamine seizures by federal, state and local law enforcement in the United States increased from 55 in 2017 to 247 in 2022. The total weight of ketamine confiscated increased by more than 1,000 percent over the five years. The majority of the confiscated ketamine was in powder form. According to the DEA (Drug Enforcement Agency), powdered ketamine is typically packaged in “small glass vials, small plastic bags, and capsules as well as paper, glassine, or aluminum foil folds. . . . powdered ketamine is cut into lines known as bumps and snorted, or it is smoked, typically in marijuana or tobacco cigarettes. . . . Ketamine is found by itself or often in combination with MDMA, amphetamine, methamphetamine, or cocaine. . . . Ketamine produces hallucinations. It distorts perceptions of sight and sound and makes the user feel disconnected and not in control. A ‘Special K’ trip is touted as better than that of LSD or PCP because its hallucinatory effects are relatively short in duration, lasting approximately 30 to 60 minutes as opposed to several hours. . . . An overdose can cause unconsciousness and dangerously slowed breathing.” (bold lettering mine.)
Recreational users call the phenomenon of a deep ketamine high as a “K-hole.” Falling into a K-hole means the drug user is temporarily unable to interact with others or the world around them. Some people refer to a K-hole as an out-of-body or near-death experience. The effects of long-term use of dissociative drugs such as ketamine haven’t been exhaustively studied, but ketamine use is thought to be reinforcing, meaning that individuals find the ketamine high an experience they wish to repeat. Repeated ketamine usage likely leads to some degree of tolerance and physical dependence.
The website The Cut states that “most of the recreational users . . . take K in very small doses, seeking a pleasant buzz that wears off within 30 minutes or can be re-upped as needed. It’s often taken to compliment other drugs — a garnish instead of the main course. For a generation that has less free time for sprawling multi-day psychedelic trips, ketamine has an appealing choose-your-own-adventure quality. . . . Claire says it actually feels like a healthier and more mature lifestyle. ‘People are like: I used to go out and have 16 drinks and do a bunch of cocaine and feel like shit the next day. And then it was this total shift [to ketamine]: Oh, yeah, I can do this. And it still feels like stepping out of my life, but I also feel fine tomorrow.’ At this point, she says: ‘I wouldn’t say that it’s different than like, a bunch of people getting off work and going out for drinks.’”
KETAMINE AS A RECREATIONAL ANTIDEPRESSANT?
Can a layperson use ketamine recreationally to treat themself for depression? The specter of self-treatment reminds one of the saying that a physician who treats himself has a fool for a doctor and a fool for a patient. A corollary of this is: a person who treats his or her mood disorder with recreational ketamine has a fool for a caretaker and a fool for a patient.
Kylie will attempt to titrate ketamine recreationally to treat her depression. But a precise, tailored medical dose is required for patients to experience optimal benefit from ketamine with safety. Individuals who self-administer ketamine expose themselves to serious health risks. Ketamine may make their symptoms worse, or they may even die from the habit. Kylie has no plans to have a healthcare provider present when she self-administers ketamine. Kylie has no idea of the milligram dose she is snorting. Her ketamine is not FDA-approved, and may in fact contain fentanyl at a dose that could cease her breathing and kill her.
How dangerous is ketamine? A meta-analysis of the published medical literature showed a total of 312 overdose cases and 138 deaths from recreational ketamine. There were no cases of overdose or death related to the use of ketamine as an antidepressant in a therapeutic setting. Street ketamine may seem cheaper, as the cost of ketamine on the street is approximately $100 per gram (1000 mg), and a single dose is approximately 100 mg. Medical treatment with 50 mg IV ketamine costs approximately $400-$800 per treatment. But ketamine administered by anesthesiologists in a clinic is safe, while there are legitimate respiratory and cardiac risks involved in the recreational use of ketamine.
If Kylie is depressed and seeks relief, an appropriate action would be to consult a psychiatrist. The alternative of intermittent recreational intranasal ketamine as a self-administered treatment for her depression is a dangerous detour.
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