Unlike conventional psychotropic medications, ketamine’s mode of action is complex. It affects various structures and functions in the brain, explaining why it can produce such profound changes in symptomatology.
If you are curious about what makes ketamine so unique, keep reading this guide from Pasithea Clinics that will explain what ketamine is made of, how it works, and what it is used for.
What Is Ketamine?
Ketamine was first synthesized in 1962 by a Detroit-based pharmaceutical company — Parke-Davis Laboratories.
The invention of ketamine followed the creation of phencyclidine (PCP), which was supposed to be an alternative to general anesthesia. Because general anesthesia — especially at the time — greatly suppressed the cardiovascular and respiratory systems, administering it came with certain risks for the patient.
Although PCP was effective, it caused severe hallucinogenic side effects in patients. As such, clinicians chose to discontinue its use while researchers continued their search for an alternative anesthetic. After the synthesis of ketamine, the search finally ended.
Ketamine was initially used as a veterinary anesthetic, which is how it got its street nickname of “horse tranquilizer.” However, after initial human trials proved successful, the Food and Drug Administration (FDA) approved ketamine for use as a general anesthetic in 1970.
Because ketamine — unlike general anesthesia — does not need to be administered by a licensed anesthesiologist in a surgical suite, it became popular in war zones. For this reason, ketamine came to be associated with the Vietnam War. To this day, it is the anesthetic of choice in remote combat zones worldwide.
Today, ketamine is on the World Health Organization (WHO) “List of Essential Medicines.” It has a variety of uses in medicine, including anesthesia, analgesia, sedation, and the treatment of psychiatric symptoms.
What Is Ketamine Made Of?
Ketamine belongs to a class of synthetic — or man-made — organic compounds called arylcyclohexylamines. This class of drugs is characterized by a cyclohexane ring bound to an aromatic ring with an amine group. Phencyclidine (PCP) is thought to be the original arylcyclohexylamine.
This class of drugs is incredibly versatile and possesses a wide range of pharmacological effects. The latter mainly depends on how their chemical structure is “tweaked.”
This class of drugs acts simultaneously as an NMDA receptor antagonist, dopamine reuptake inhibitor, and μ-opioid receptor agonist. As a result, this class of drugs has anesthetic, analgesic, anticonvulsant, pain-relieving, dissociative, and euphoric effects.
Some of these agents can also cause hallucinogenic and psychotomimetic (psychosis-like) effects.
Ketamine is an equal mixture of two of the same molecules with a different orientation. This type of molecule is called an enantiomer. The two enantiomers that ketamine is made up of are esketamine (a left-sided molecule) and arketamine (the right-sided molecule).
Although these molecules are virtually the same, they exert subtly different effects on various receptors in the brain. Esketamine is a more potent dopamine reuptake inhibitor, while arketamine exerts stronger activity on the NMDA receptor. We will discuss ketamine’s mode of action in more detail below.
How Does Ketamine Work?
Generic ketamine — also known as racemic ketamine — is a dissociative anesthetic. As a noncompetitive N-methyl-D-aspartate (NMDA) and glutamate receptor antagonist, ketamine works by increasing levels of glutamate in the brain.
Glutamate is the central nervous system’s main excitatory neurotransmitter. When its levels in the brain increase, there is a substantial increase in activity between neurons. As a result, neurons can form new connections with each other, which results in improved brain function.
Ketamine also increases brain-derived neurotrophic factor (BDNF). This protein-coding gene allows neurons to grow new axons (structures that receive signals from other cells) and dendrites (structures that send signals to other cells).
Ketamine also affects opioid receptors. For this reason, it produces a significant pain-relieving effect in those to whom it is administered. Aside from its use as an analgesic, ketamine is proving to be a promising therapy in treating chronic pain conditions.
Last, ketamine produces dissociative effects by blocking certain brain regions from communicating with others. Most notably, this occurs between the spinal cord and the prefrontal cortex. As a result, pain signals from the body cannot reach the brain.
Aside from its potent analgesic effect, this mode of action can also explain why ketamine produces dissociation when administered at higher doses. While researchers are still unclear about the therapeutic benefits of dissociation, some believe that it is a vital component of ketamine’s antidepressant effects.
Unlike most anesthetics, ketamine preserves normal cardiovascular and respiratory functions. In some cases, it can even slightly increase breathing and heart rate. For this reason, ketamine can be safely administered to patients who have conditions that cause them to experience low oxygen levels.
What Does Ketamine Look Like?
When synthesized in a laboratory, ketamine is a clear liquid. It is mainly administered as an injection in a vial. It can be administered either intravenously (IV) or intramuscularly (IM).
IV administration has a 100% bioavailability rate, which means that the body will absorb all of the substance. However, some patients — such as those in an extreme state of agitation — can only be given ketamine through the IM route. IM ketamine has a slightly lower bioavailability rate of 93%.
Recently, the Food and Drug Administration (FDA) approved an esketamine nasal spray sold under the brand name Spravato. This mode of administration has a much lower bioavailability, which is no greater than 50%.
Ketamine is also prevalent as a street drug. When synthesized for street use, ketamine usually comes in an off-white powder form. Sometimes, it is “cut” with other drugs, such as cocaine or methamphetamine. This form of ketamine is usually “snorted” intranasally.
What Are the Effects of Ketamine?
The effects of ketamine begin almost immediately after intravenous (IV) or intramuscular (IM) administration and peak at about 20 minutes. When administered in a therapeutic setting, the effects of ketamine last about one or two hours.
Initially, you should feel an overwhelming sense of calm and relaxation. Many people describe the sensation as being in a dream-like state.
It is possible to experience mild-to-moderate dissociation at higher doses, which is a feeling of being detached from the body and the outside world. Although rare, it is possible to experience hallucinations on ketamine.
Of course, when street ketamine is used, it is possible to experience profound effects such as the notorious “K-hole.” Users describe this as a complete detachment from reality in which it feels like they are in a “hole” that they cannot escape. For this reason, it is important to have ketamine administered only by a health care professional, such as our highly-credentialed infusionists.
When administered therapeutically, the side effects of ketamine are fairly mild. You may experience slight dizziness, drowsiness, and foggy thinking. In some cases, you may also feel slightly nauseous. However, these side effects should subside completely several hours after administration.
Last, it is possible to experience a slightly elevated heart rate, blood pressure, and breathing rate. For this reason, our highly-credentialed infusionists will monitor you during the entire duration of your treatment to ensure that your vital signs remain in the normal range.
How Long Do Ketamine Side Effects Last?
How long the side effects of ketamine last depends on the dosage you were administered, your body weight, your age, your metabolism, and any other drugs that you may also take.
If administered intravenously (IV) or intramuscularly (IM), the side effects of ketamine should peak at about one hour and subside completely just several hours after administration.
That said, it takes about 12 hours for your body to clear the ketamine out of your system completely. Furthermore, ketamine will be detectable in your urine for several days after administration.
For this reason, it is important to avoid consuming any other substances before or after your ketamine infusion treatment. Not only can doing otherwise interfere with the effects of your treatment, but it can be seriously dangerous to your health. For instance, mixing alcohol and ketamine can severely depresses the central nervous system (CNS), potentially leading to a medical emergency and even death.
What Is Ketamine Used For?
Ketamine is a safe drug with a variety of medical uses. It can be administered as early as three months of age. Because children are faster metabolizers of ketamine than adults, they can be administered higher doses of ketamine.
In the first place, ketamine is used as an anesthetic in situations where general anesthesia is either unavailable (in remote corners of the world) or undesirable (such as with patients with certain medical conditions, like asthma). Because it does not greatly suppress the cardiovascular and respiratory systems, there is relatively little risk of ketamine causing complications.
There is increasing evidence that shows that ketamine can be used to treat various pain conditions. In the first place, it is a valuable alternative to opioid medications for those who cannot be administered traditional painkillers. This is especially important for those with a prior history of opioid abuse or addiction.
Ketamine can also be used in the treatment of neuropathic chronic pain conditions that do not respond to traditional treatment approaches. This includes low back pain, fibromyalgia, diabetic neuropathic pain, acute pain, and trauma. Ketamine may be safely mixed with other nonsteroidal pain-relieving medications, including opioids.
Ketamine is also a potent sedative. It can be administered to those in a severe state of agitation or those who have experienced psychological trauma.
In the recent decade, clinicians have been using ketamine “off-label” to treat symptoms of various psychiatric conditions, which most notably includes treatment-resistant depression (TRD).
Unlike conventional antidepressant treatments, ketamine has a much higher efficacy rate, which is approximately 64%. In addition, ketamine begins working almost immediately after administration — unlike conventional antidepressants, which may take weeks to produce any effects.
Ketamine can also be used to treat symptoms of post-traumatic stress disorder (PTSD), panic attacks, agoraphobia, social anxiety, bipolar disorder, and countless others.
Ketamine belongs to a class of synthetic organic compounds called arylcyclohexylamines. It is a blend of two enantiomer molecules called arketamine and esketamine. Ketamine has a complex mode of action, which makes it incredibly effective in treating symptoms of various psychiatric conditions.
If you are suffering from treatment-resistant depression (TRD) — in addition to any other psychiatric condition — you may be a candidate for intravenous (IV) ketamine infusion therapy. Schedule a free assessment with Pasithea Clinics today to discover everything you need to know about this novel treatment approach.
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