Is Ketamine an Opioid?
Understanding the differences between these two types of drugs
Medically reviewed by Lindsay Cook, PharmD
Ketamine is not an opioid. However, it can sometimes be mistaken for one because of the similarities between the two types of drugs.
Like opioids, ketamine does cause sedation (a relaxed and sleepy state). It can also produce dissociative feelings, hallucinations, and amnesia (no memory of events while under the influence of the drug). It is also similar to opioids in that it has a high abuse potential. For that reason, it is a controlled substance.
Ketamine is a non-barbiturate general anesthetic and an NMDA receptor antagonist. It is available as an injectable drug, ketamine hydrochloride, approved for anesthesia in diagnostic and surgical procedures–both alone or in combination with other anesthetic drugs.
Spravato is another ketamine product that contains just one of the two forms of ketamine’s chemical structure, called esketamine, and is a nasal spray approved for treating depression in adults.
This article will discuss the differences between ketamine and opioids, ketamine's uses and legal status, and safety considerations for ketamine.
How Is Ketamine Different From Opioids?
While ketamine shares some characteristics with opioids, such as producing sleepiness and having a potential for abuse, it is a different type of drug from opioids.
Opioids treat pain by binding to mu-opioid receptors in your brain and spinal cord and producing a response that controls the amount of pain you feel.
Ketamine, however, works primarily by binding to a different type of receptor, called an NMDA receptor, and blocking the action of this receptor. This blocking, or antagonism, of the NMDA receptor, results in anesthesia, analgesia (pain relief), dissociative feelings, and some respiratory depression. Apart from NMDA antagonism, ketamine may also bind in a limited capacity to opioid receptors and affect other non-NMDA pathways. Still, these are not the main sources of effects.
Is Ketamine a Controlled Substance?
Ketamine is a Schedule III (3) controlled substance.
Controlled substances are tracked and monitored more closely by the Drug Enforcement Agency (DEA) than non-controlled substances due to their potential to be habit-forming, abused, or overused. Schedule III drugs like ketamine are considered to carry moderate risk for these–more than Schedule IV (4) and V (5) drugs but less than Schedule I (1) and II (2) drugs.
Understanding Ketamine: Approved Uses and Legal Status
The DEA uses Schedules I through V to classify the risk and abuse potential of different drugs, as well as set laws for how tightly different drugs need to be regulated.
Schedule I drugs carry the highest risk of abuse and dependence and are not approved for any medical use. An example of a Schedule I drug is heroin.
Schedule V drugs carry the lowest abuse potential and come with the fewest amount of restrictions, with examples including Lyrica (pregabalin) and some cough medicine products that contain codeine.
Ketamine is classified right in the middle of this scale at a Schedule III, meaning the DEA considers it to carry a moderate to low risk of dependence. The drug does get abused and sold illegally as a street drug.
If you are about to undergo a surgical procedure, either in an outpatient setting or while hospitalized, your healthcare provider administering anesthesia will discuss the medications they plan to use to keep you comfortable and asleep throughout your procedure. This list of drugs may include ketamine. Hospitals and clinics take measures to comply with controlled substance laws, so this is nothing you need to worry about.
Your pharmacy may also practice necessary restrictions if a healthcare provider prescribes you Spravato, the nasal spray containing esketamine, similar to ketamine hydrochloride. The number of refills you can get of this medication within a certain period of time will be restricted depending on the state you live in.
Pharmacies in almost every state also use PDMP, or prescription drug monitoring programs. These programs prevent people from filling controlled substances at different pharmacies repeatedly in a short period. They enable all different pharmacies to see where people have filled controlled substances at other pharmacies and can deny filling the prescription if they feel there are signs of abuse or overuse of controlled substances, including ketamine.
Ketamine for Chronic Pain
The United States (U.S.) Food and Drug Administration (FDA) has not approved ketamine as a pain treatment. However, it is often used off-label for this purpose.
Lower dosing of ketamine is used in pain treatment compared to that needed for surgical procedures to prevent dissociative or other psychological effects that may come with higher dosing.
NMDA receptor antagonism results in analgesia, or pain relief. Other mechanisms of action exerted by ketamine may also contribute to this pain control.
For this reason, ketamine has a high potential for pain management as an alternative to opioids. It is already commonly used off-label for acute or extreme pain seen in emergency departments, such as trauma, fractures, and abdominal or flank pain. Off-label use for treating chronic pain is not unusual either.
What Does "Off-Label" Use Mean?
"Off-label" use is the practice of prescribing FDA-approved medications for a health condition or disease that it is not approved for. This happens when a healthcare provider deems the drug medically appropriate for a particular individual and their condition.
Drugs used off-label may be given for a disease or condition they are not approved to treat, given in a different form, or prescribed in a different dose than what is FDA-approved.
Guidance on Ketamine's Off-Label Use
Organizations containing experts on pain management and anesthesia have responded to requests for guidelines on using ketamine to manage pain, since it is still an off-label use. This use must be guided by the experience and opinion of field experts rather than by the prescribing information that comes with FDA approvals of new indications.
Some organizations that have contributed to these guidelines that will help other providers safely treat pain with ketamine include the:
American Society of Regional Anesthesia and Pain Medicine
American Academy of Pain Medicine
American Society of Anesthesiologists' Committees on Pain Medicine and Standards and Practice Parameters
These groups recognize that more thorough and consistent research is needed. However, they do their best with existing research data to provide standardized recommendations on dosing, indications (uses), pretreatment requirements, necessary personnel to administer infusions, and what indicates a positive treatment response.
Some indications that these committees included in their recommendations include spinal cord injury pain and complex regional pain syndrome (CRPS). Improvement in these conditions is supported by weak or moderate evidence.
The committees only assert weak or no evidence for improvement in pain types such as:
Cancer pain
Headache
Mixed neuropathic pain
Guidelines also assert that ketamine should not be used if you:
Have a poorly controlled heart condition
Have active substance abuse disorder
Have severe liver disease
Are pregnant
More research is needed on the types of pain that ketamine is most effective in treating and the appropriate dosing and criteria for treating these types of pain.
Side Effects and Risks of Ketamine
Some more common side effects of ketamine include:
Nausea or vomiting
Dizziness
Diplopia (double vision)
Drowsiness
Dysphoria (an unpleasant or uneasy mental state)
Confusion
Other possible but less common side effects or risks that can come with ketamine include:
Elevated blood pressure and heart arrhythmias
Nystagmus (rapid eye movement) or increased intraocular pressure (pressure inside the eye)
Muscle spasms
Seizures
Respiratory depression
Anxiety or depression
Dissociative state (lack of control or inability to respond appropriately to verbal commands)
Hallucinations or fear
Summary
Ketamine is not an opioid, but it does share some similarities with the opioid drug class, including its ability to cause sedation and respiratory depression and its tendency to be abused or overused.
Like opioids, it is also a controlled substance. However, it is a Schedule III controlled substance, while most opioids are Schedule II because they carry a higher risk of abuse and dependence.
Ketamine is approved by the FDA to provide anesthesia for surgical procedures and to treat depression in adults (as a nasal spray product containing only one of two forms of ketamine’s chemical structure). It works by blocking NMDA receptors, which, at different doses, causes anesthesia, amnesia, dissociative feelings, sleepiness, and analgesia or pain relief.
Because of this analgesic effect, ketamine has started to be widely used for treating pain despite not having FDA approval for any pain indication.
Based on existing but limited research data, ketamine holds some promise as an alternative pain management treatment. Still, more thorough and consistent research is needed.
Read the original article on Verywell Health.
