When administered in a medically supervised setting, the risk of adverse side effects is very low. However, when used in a non-supervised medical setting, it is difficult to control dosage. As such, the risk of side effects goes up significantly.
In this guide from Pasithea Clinics, we will cover everything you need to know about proper ketamine dosage, in addition to which dosage is “too much.”
What Is Ketamine?
The history of ketamine begins with the synthesis of phencyclidine (PCP), which is also known by its street name “angel dust.” Because general anesthesia at the time significantly depressed the cardiovascular and respiratory systems, chemists were on the lookout for an anesthetic that did not greatly affect these vital functions.
In the 1950s, chemists at Detroit-based Parke-Davis Pharmaceutical Company synthesized PCP. Following animal trials, it was shown to be an effective anesthetic that did not cause cardiovascular or respiratory depression. However, it caused psychomimetic effects in the human participants that it was administered to, which included excitement, delirium, and hallucinations.
The use of PCP was discontinued, and chemists continued their search for an alternative anesthetic. By tweaking the chemical formula of PCP, chemists at Parke-Davis were able to synthesize ketamine — an anesthetic that did not suppress the cardiovascular or respiratory functions while being effective as an anesthetic.
Following ketamine’s approval by the Food and Drug Administration (FDA), ketamine quickly garnered popularity as an anesthetic and analgesic. To this day, it is used to induce anesthesia in many parts of the world, which most notably includes war combat zones. Ketamine can be used to sedate agitated patients or relieve pain in those who may not use opioid medication.
Researchers and clinicians have discovered many other potential benefits of ketamine in recent decades. For instance, it has been shown to be effective in treating the symptoms of various psychiatric conditions, such as treatment-resistant depression (TRD), various anxiety disorders, and post-traumatic stress disorder (PTSD).
Ketamine infusion clinics, such as Pasithea Clinics, administer intravenous (IV) ketamine infusion treatments to their patients for rapid relief. The wealth of research surrounding ketamine infusion supports this therapy. For instance, in treating TRD symptoms, ketamine infusion has an efficacy rate as high as 70% while producing clinically significant effects after just one treatment.
How Does Ketamine Work?
The reason why ketamine is effective in treating symptoms of various psychiatric conditions, unlike conventional treatments, is its multifactorial effects on the central nervous system.
Ketamine is simultaneously an anesthetic, analgesic, and sedative. Its effects result from its mechanism of action, which affects receptors in the brain called N-methyl-D-aspartate (NMDA) receptors. These receptors sit on specialized brain cells called neurons and can be activated by certain chemical messengers called neurotransmitters.
Ketamine is an NMDA receptor antagonist — which means that it blocks NMDA receptors. This increases levels of glutamate in the brain. Glutamate is a neurotransmitter that “excites” neurons. As a result, it can strengthen connections between different brain regions. In addition to NMDA receptors, ketamine is implicated in opioid receptors, which explains its pain-relieving effects.
Ketamine also works by blocking the communication between the prefrontal cortex (which is responsible for higher-order functions), the thalamus (which relays sensory signals to the prefrontal cortex), and the amygdala (which is responsible for emotional processing). This “blocking” of signals prevents the prefrontal cortex from perceiving painful stimuli.
Not only does this mode of action significantly reduce the pain response, but it can induce a state of dissociation when administered at high enough doses. Dissociation is described as a state of disconnect between the self and the external environment. It can produce patients with profound insights, which might explain why ketamine’s dissociative effects are implicated in its ability to produce an antidepressant response.
Physically, ketamine can increase heart rate, breathing rate, blood pressure, and intracranial and intraocular pressure. This makes it ideal for use in patients with asthma, acute bronchospasm, or any other medical condition that impairs the cardiorespiratory system.
How Is Ketamine Administered?
Ketamine can be administered orally, nasally, intravenously (IV), and intramuscularly (IM).
The oral route of administration has the lowest bioavailability — which ranges from about 20% to 30%. This makes oral ketamine significantly less effective than other routes of administration. When administered orally, ketamine has a delayed onset, which can be as long as 30 minutes. In addition, because the entire dosage has to be administered at once, the effects of the oral ketamine are much less predictable.
Intravenous (IV) administration has a 100% bioavailability, making it the preferred administration method for Pasithea Clinics. In addition, it has the most rapid administration, with an onset that ranges from 30 to 60 seconds.
One advantage of IV ketamine is that the entire dosage is not administered at once. Instead, it can be administered over the course of 40 minutes, allowing the clinician to monitor the patient for side effects and stop treatment if any happen to occur.
In some cases, patients may not be administered IV ketamine. This applies especially to severely agitated patients who must be sedated. An alternative route of administration is intramuscular (IM) injection, which has a bioavailability of about 93%.
The onset of action for IM ketamine is about three to five minutes. The effects peak at about 15 minutes, with recovery occurring as quickly as an hour following administration.
Last, ketamine may be administered intranasally. Esketamine (a derivative of ketamine)—sold under the brand name Spravato—is sold as a nasal spray. This mode of administration has bioavailability that ranges from 35% to 50%. The onset of effects ranges from five to 20 minutes.
Street ketamine, which most often comes in an off-white powder, is also ingested intranasally. Unlike medically-administered ketamine, it is difficult to control dosing, increasing the risk of overdose. In addition, street ketamine may be “cut” with other illicit substances, such as cocaine and amphetamine. This significantly increases the risk of adverse reactions.
What Is the Right Ketamine Dosage?
Ketamine may be administered to treat a wide range of conditions. As such, in the first place, the dosage depends on the treatment goals. Other factors to consider are patient age, weight, and metabolism.
Although there are clinical guidelines for ketamine administration, it is just as important for the administering clinician to use their judgment in selecting the correct dosage.
In the case of intravenous (IV) ketamine infusion — which is most commonly used to treat symptoms of treatment-resistant depression (TRD) — the recommended dosage is about 0.5 milligrams per kilogram of body weight for adults.
Currently, there is limited research on the effects of IV ketamine in patients younger than 18 and older than 64. For this reason, there are currently no guidelines for treating symptoms of TRD in children, adolescents, and older adults.
Sometimes, it takes only one IV ketamine infusion to produce clinically significant results. However, patients may wish to come back to maintenance treatments. In this case, according to clinical guidelines, IV ketamine infusion can be administered one to three times per week for a maximum of six doses.
At Pasithea Clinics, our standard treatment consists of biweekly infusions over the course of three weeks.
Which Ketamine Dosage Is Too Much?
Although there are clinical guidelines on the necessary dosage to produce certain effects, such as anesthesia, analgesia, or sedation, there is limited information on the maximum dosage. It is up to the administering clinician to consider the individual factors of the patient being treated and the maximum dose they will administer to them.
When considering ketamine dosage, it is important to consider any medical conditions that the patient may have. For instance, although it is relatively rare, some patients may be hypersensitive to ketamine. For these patients, any dose of ketamine may be too high.
Because ketamine may raise blood pressure, it is also important to consider ketamine dosage in patients with a history of hypertension, aneurysm, or stroke. Double-blind experiments show that IV ketamine infusions—since they are administered at subanesthetic doses (0.5 mg/kg)—do not significantly affect blood pressure.
However, some ketamine infusion clinics — such as Pasithea Clinics — may choose not to administer IV ketamine to patients with a history of hypertension to reduce the risk of adverse side effects.
Amongst ketamine’s physical side effects is increased intraocular or intracranial pressure. As such, the dosage must be carefully monitored in patients with a history of head trauma, ocular trauma, intraocular pressure, intracranial mass lesions, intracranial bleeding, or hydrocephalus.
Another physical side effect of ketamine is an increase in heart rate, which enhances the heart’s muscular contraction and oxygen consumption. For this reason, patients with a history of cardiac disease should have their dosage individualized while being closely monitored during treatment.
Ketamine infusion, when administered at low doses, can be used in many patients while resulting in very few adverse side effects, aside from mild dizziness, drowsiness, and nausea. However, the illicit use of ketamine, which is administered at much higher doses, is associated with various adverse reactions.
Street ketamine, also known as “Special K,” “Vitamin K,” or “Kit-Kat,” is not administered in a medically-controlled dosage. As such, it is possible to ingest a dosage as high as 200 mg or higher. This can result in an extreme change to consciousness, including the infamous “K-hole.” This is described as extreme detachment from the outside world, which can be a terrifying experience.
Over time, ingesting high doses of street ketamine can lead users to develop a psychological dependence on the drug. In addition, some users may experience tolerance and withdrawal.
Because street ketamine is sold as an off-white powder, it can be mixed with another illicit substance. As such, no dosage of street ketamine is a safe dosage. To decrease the risk of adverse side effects, it is important for ketamine to be administered in a medical setting by a licensed clinician.
When administered in a medically supervised setting, ketamine dosage is low, significantly reducing the risk of side effects.
At Pasithea Clinics, our highly credentialed infusionists administer intravenous ketamine at 0.5 mg/kg, which can be discontinued at any moment.
If you wish to discuss any concerns about this novel treatment, schedule a free consultation with us today.
- Efficacy of ketamine therapy in the treatment of depression | NCBI
- The role of dissociation in ketamine’s antidepressant effects | Nature Communications
- Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists | NCBI
- The Case of Ketamine Allergy | NCBI
- Blood pressure safety of subanesthetic ketamine for depression: A report on 684 infusions | NCBI