Ketamine: Can a Single Infusion Cure Alcohol or Drug Addiction?
Can you cure addiction with a single infusion of medication? Proponents of ketamine claim that a single treatment or a series of treatments can help people with substance use disorder. What is ketamine and how does it work? What are the risks? What does the science say? We’re going to talk about all this and more today.
First, I need to remind you that nothing I speak about in today’s blog should be considered medical advice. If you have a question about addiction treatment which pertains to an individual situation, consult with a medical professional.
With that out of the way, let’s talk ketamine.
What is ketamine & how does it work?
Ketamine is a drug which was introduced to the US market in 1970 as an anesthetic. When given intravenously, ketamine causes a rapid induction into sedation, but the patient continues breathing on their own. Ketamine is therefore a very useful drug for inducing general anesthesia for surgery and for providing sedation during minor, but painful procedures.
Unlike other anesthetics, ketamine doesn’t cause the obliteration of consciousness but rather induces a mental state known as dissociation. It’s hard to explain the difference between unconsciousness and dissociation, because from the outside, these states look identical.
Dissociated patients may be unresponsive, but they actually perceive their surroundings. Dissociated patients are aware, but their internal consciousness is divorced from their experiences of the outside world.
This means that they experience pain and noxious stimuli but do not perceive them as unpleasant and do not remember what happened while dissociated. Almost like the patient is in a waking dream.
To put it in other words, you become a detached observer, inside your body but separate from it, almost like dreaming. Typically, patients have no memory of the events during dissociation, which lasts 10-15 minutes from a single dose.
Dissociation only occurs when a person receives a large enough dose of ketamine, known as a dissociative dose. This is typically over 1 mg/kg IV or 2 mg/kg IM.
Below this dose, people experience perceptual disturbances and pain relief, but remain alert and aware. This is what doctors call a sub-dissociative dose of ketamine.
With a small enough dose, less than 0.3 mg/kg IV, most people only experience pain relief but no perceptual disturbances. This is sometimes referred to as low-dose or analgesic dose ketamine.
Recreational users typically attempt to reach a dose between the dissociative dose and analgesic dose so they can experience the perceptual disturbances which make ketamine use rewarding and remember the experience.
Others may use large doses of ketamine and enjoy the come down as they proceed through dissociative state into the perceptual disturbances of sub-dissociative dosing.
After a person reaches dissociation, taking more ketamine won’t make them more dissociated, but rather simply prolong the experience. Dissociation is like a light-switch, you either are or you aren’t.
Brain Chemistry
Now that you understand the basics of ketamine dosing, let’s learn how ketamine exerts its effects on the human brain.
Ketamine is an NMDA receptor antagonist. This means that it acts to turn off the signaling of NMDA receptors on brain cells.
These NMDA receptors detect glutamate, which is a signaling molecule in the brain which leads to increased brain activity. When ketamine is administered, it blocks glutamate from binding the NMDA receptors and this interrupts the pathways which transmit pain from the spinal cord and those that help create our experience of consciousness.
The net effect is to block pain and create a dissociated state.
This explanation is a very simple one, as ketamine also has effects throughout the brain and we still are not fully aware of the details.
It also appears that ketamine can improve the symptoms of depression, reduce the severity of chronic pain, and reverse opioid tolerance, at least for a brief period. Scientists are still not certain how ketamine produces these effects.
Alternative Uses of Ketamine
In recent years, ketamine has gained popularity as therapy for treatment-resistant depression and chronic pain. These effects were first observed in patients who were sedated with ketamine for electroconvulsive therapy and pain procedures.
Doctors noticed that patients who received ketamine for sedation seemed to have better results than those receiving other sedatives. Studies have since demonstrated a small, but real benefit for patients with depression and chronic pain.
However, this benefit is only temporary and therefore patients require regular repeat therapy sessions, typically once every few months.
Ketamine is not approved by the FDA for the treatment of depression or chronic pain, but this does not necessarily mean it is ineffective; many drugs are used for conditions other than what their FDA indication states.
To gain FDA approval would take years of expense clinical trials and there is little motivation for drug companies to pay because ketamine has been a generic drug for decades and therefore no single company could profit from a new indication.
The lack of FDA approval for depression and chronic pain treatment has not stopped the numerous ketamine clinics which have opened in recent years to exploit the excitement of ketamine therapy.
Naturally, if ketamine can help patients with treatment-resistant depression and chronic pain, doctors were curious if it might help with substance use disorder. If we could help patients with a single infusion, it would be a tremendous boon.
What does the science say about ketamine treatment for addiction?
The Scientific Evidence
Unfortunately, the evidence for ketamine treatment of substance use disorder is sparse.
As I mentioned previous, there is little motivation for drug companies to fund investigation into generic drugs that they cannot exclusively profit from. Thus, all the trials mentioned are funded by universities or public grants.
In most of these studies, patients were given sub-dissociative doses of ketamine. Many were performed in a hospital setting. Most are short term studies with no long term follow up. All involve small numbers of patients.
I’m going to break this into research on alcohol, cocaine, and opioid use disorders.
Cocaine
Beginning with cocaine use disorder: two studies from the same research team, Dakwar et al, studied ketamine infusions in hospitalized patients with cocaine use disorder.
These patients received a single infusion of intravenous ketamine. Afterwards, the researchers studied a number of outcomes to determine if the ketamine had any effect on their cocaine cravings.
The first study tested two different doses of ketamine and a control medication; the low dose infusion was 0.41 mg/kg, the high dose infusion was 0.71 mg/kg, and the control medication was midazolam, a benzodiazepine.
This was a crossover study, meaning that the same patients all received both treatment doses and the control medication in a series of treatments.
After ketamine infusions, patients had improvements in their cocaine cravings when exposed to visual stimuli to use, but there was no different in efficacy between the two doses of ketamine.
In the follow up study, the researchers compared the high dose ketamine infusion to the midazolam control. This time, they measured efficacy by offering the patient the choice of $11 or 25 mg of pharmaceutical cocaine.
As an aside, how did they get IRB approval to offer cocaine to hospital patients!? My friend wants to know where to sign up!
Patients were more likely to choose the cash over cocaine after a ketamine infusion.
Bottom line, ketamine seems to help cocaine cravings in the short term, but we don’t know how long the effect lasts. More research is necessary.
Alcohol
Again, two studies; one about long-term outcomes for people with alcohol use disorder and one about treating alcohol withdrawal in the hospital.
The first study by Krupitsky et al treated patients in a residential treatment program with a single ketamine psychotherapy session and followed their progress over a year. In this case, the patients not only received ketamine infusions but also participated in a therapy session during the infusion, followed by ongoing treatment.
The control group did not receive the ketamine therapy session and only participated in routine follow-up.
At one year, the ketamine group had an abstinence rate of 65.8% compared to the 24% of the control group. However, the ketamine group received additional on-going therapy sessions, which means we cannot attribute this benefit completely to the ketamine.
The second study by Wang et al asked if ketamine infusions can help patients with severe alcohol withdrawal but reducing the amount of benzodiazepines needed for treatment of that withdrawal.
Currently, benzodiazepine drugs like Ativan (lorazepam) and Valium (diazepam) are the standard of care for severe alcohol withdrawal. These patients were experiencing very severe withdrawal, with 75% of them in delirium tremens at the time of the study.
Delirium tremens is a condition caused by severe alcohol withdrawal which manifests as psychosis and altered consciousness. There was a trend towards decreased need for benzodiazepine medications, but it was not statistically significant, which is a fancy way of saying that ketamine had no effect.
Bottom line, ketamine may help patients stay sober long term, but it does not seem to help with alcohol withdrawal. The evidence is poor and we need more studies.
Opioids
Three studies this time; two pertaining to long term outcomes in people with opioid use disorder and one pertaining to treatment of opioid use disorder.
The first two studies are also from the Krupitsky et al group (man these guys really like ketamine!).
In the first, patients with heroin use disorder received either a single high dose ketamine injection of 2.0 mg/kg or a single low dose ketamine injection of 0.2 mg/kg.
The ketamine treatment was followed by therapy at regular intervals over two years. At one year, the high dose ketamine treatment patients had an abstinence rate of 24% compared to 6% in the low dose group.
As a follow up study, Krupitsy et al studied the effect of multiple ketamine treatments compared to a single treatment. They only administered the “high-dose” of 2.0 mg/kg IM injection in all the patients. Patients who received multiple doses of ketamine had an abstinence rate of 50% at one year compared to 22% among the low dose treatment group.
For the third study on opioids, Jovasia et al ketamine infusions for the treatment of opioid withdrawal in patients undergoing anesthesia assisted rapid opioid detoxification. If you aren’t familiar with this procedure, see my video on the topic—link should appear up here or here.
They gave patients either an infusion of 0.5 mg/kg ketamine IV or saline while patients were sedated and measured various levels of physiological stress.
Patients who received ketamine had lower measurements of heart rate, blood pressure, and cortisol, a stress hormone, during their withdrawal.
They also measured long term outcomes for four months, but found no improvement in treatment retention, abstinence from opioids, physical health, or social functioning.
Bottom line, ketamine may help patients who are already receiving treatment for their opioid use disorder and might help the immediate symptoms of physical withdrawal, but it should not be viewed as a cure to addiction.
Risks
Ketamine is a comparatively safe medication, but it does have risks. The side effects of ketamine include rapid heart rate, high blood pressure, nausea, vomiting, and increased salivation.
These minor effects are temporary in duration, and they can be addressed with other medications.
The more significant risks of ketamine are respiratory depression and laryngospasm, both of which are potentially lethal without immediate skilled medical intervention. Most patients receiving ketamine will continue breathing on their own and will require no assistance aside from monitoring.
A small number, however, will start to breathe slowly or stop breathing all together. Without careful monitoring, this can be missed until it is too late, and the patient’s heart stops beating, known as cardiac arrest.
Laryngospasm describes a situation where the vocal cords start to contract involuntarily, and this leads to obstruction of the airway. The cords clamp down and no air can pass into the lungs.
Naturally, this condition is an emergency and requires skilled intervention to avoid cardiac arrest. The treatment for laryngospasm is to inject paralytic drugs, which break the spasm of the cords and then insert a breathing tube to provide artificial respirations.
Without the proper tools and skills, laryngospasm can create a scenario known as “can’t intubate, can’t ventilate” which is something all doctors dread; it is a guaranteed death sentence for the patient.
Such a scenario is how Joan Rivers died while receiving anesthesia at an outpatient surgery center.
The unpredictable nature of laryngospasm makes patient monitoring mandatory and requires that a professional skilled in airway management, like an anesthesiologist, be present at all times during ketamine administration.
Thankfully, most ketamine clinics are run by anesthesiologists or other doctor knowledgeable in airway management.
It’s important to check the qualifications of the staff at the center before agreeing to any ketamine treatments. Ask who will be present during your treatment and what their qualifications are. You are looking for an anesthesiologist, nurse anesthetist, or emergency medicine trained person who will be physically present during the infusion.
Also ask what monitoring is utilized; the gold standard is end-tidal capnography, which displays a continuous waveform of the concentration of exhaled CO2 and can detect changes in respirations immediately.
Finally, make sure that the clinic has the drugs and equipment available to respond to airway emergencies; they should have a “crash-cart” or “airway box” which contains these tools. This is not something that you want to eyeball or leave to chance because seconds count in an airway emergency.
Conclusions
Ketamine is a rising star of alternative treatment, not only for addiction, but also depression and chronic pain. Like mushrooms after the rain, a bounty of clinics offering various forms of ketamine therapy have opened in recent years; the industry is so popular that it supports consulting firms which exist to train doctors and nurses how to open their own ketamine clinics.
Despite the popularity of ketamine, the clinical evidence supporting its use is sparse, especially regarding addiction treatment. That does not necessarily mean that ketamine is ineffective, because there is often little evidence for the use of older drugs and off-label prescribing is the rule, rather than the exception for this reason.
That said, what evidence does exist suggest that ketamine alone is not a silver bullet. There is evidence that it can reduce the severity of opioid withdrawal and it might also help long term recovery. It should be used in combination with ongoing therapy, as ketamine treatment alone seems ineffective.
Regarding alcohol use disorder, ketamine does not seem to reduce alcohol withdrawal symptoms, but it might improve long term outcomes in conjunction with ongoing therapy, as is the case with opioid use disorder.
When it comes to cocaine use, there is no evidence for long-term benefits, but it seems to reduce cravings in the short-term.
These results are promising but more data are necessary. There are ongoing trials regarding this exact topic for opioid use disorder. I look forward to the results as we desperately need new treatment options.
For now, I don’t specifically advise my patients to seek out ketamine therapy. The cost is rather high, and the benefits are uncertain.
Since no insurance company reimburses ketamine therapy, nearly all patients pay cash out of pocket. Clinics offering ketamine therapy market to people with disposable income and single session cost hundreds, if not thousands of dollars.
If a patient has a budget for their treatment, it’s best to spend that money on proven therapies first.
If they have money to burn or other treatments have failed, then ketamine is an option to consider. However, at this time, I consider ketamine an ancillary treatment, after standard medications, psychotherapy, and support groups.
If you or someone you love is suffering from problematic drug or alcohol addiction use and is seeking treatment, contact the clinic by calling or clicking the “Get Started” button in order to schedule a discovery call and initial evaluation, both of which are free.
We are here to help.
North Tampa Executive Health Clinic is directed by Dr. Jack McGeachy. He provides confidential and comfortable addiction treatments and therapy for opioid and alcohol use disorder. Rather than a rehab or detox, meaning that each patient is cared for one-on-one by a medical doctor, in contrast to other treatment programs. Heed Help? Book your in office appointment in the Tampa office or via video conferencing today.
Helping patients with addictions in Tampa Florida, Temple Terrace, Brandon, Bloomingdale, Carrollwood, Thonotosassa, Town N Country, Lutz, Wesley Chapel, Land O Lakes, St. Pete, Clearwater, Oldsmar, Westchase, Palm Harbor, Tarpon Springs and surrounding areas.
