Services


Call us at 703-844-0184 for a consultation for Ketamine, or at email@novahealthrecovery.com. At NOVA Health Recovery We not only treat patients with depression, anxiety, PTSD, and other disorders with Ketamine, but also evaluate and treat root causes of depression. Simple changes in diet, exercise, and supplements can make a huge impact on your life. Dr. Sendi is Board Certified in Addiction Medicine and Obesity Medicine as well and offers pharmacogenomic and nutrigenomic testing which can identify sources of mood disorders and direct their treatment. We offer IV vitamin infusions as well, which can bolster the effects of a ketamine infusion. Call us today! We are open 7 days a week and offer evening infusions even on weekendsCall us at 703-844-0184 | NOVA Health Recovery in Alexandria, Virginia. For those who are afraid of IV’s, we offer intranasal Ketamine and nebulized ketamine treatment plans as well.

Depression, PTSD, Anxiety

Ketamine infusions offer significant impact in diminishing symptoms acutely so you  can lead a more normal life. Infusions are two to three times a week for two weeks, each occurring over a one hour period in the safety of a monitored environment. Therapies can be personalized to fit your best outcome.

Neuropathic pain and CRPS

Ketamine has been an effective agent in decreasing pain  in patients with CRPS and Neuropathy. Infusions can offer rapid pain management in a significant number of patients. Infusions twice a week over a few weeks offersrelief of discomfort as your regularly managed medications take better effect.

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Ketamine Treatment

We offer intravenous Ketamine therapies in a comfortable, monitored medical setting. Treated conditions include depression, PTSD, anxiety, chronic pain conditions, fibromyalgia, neuropathies, CRPS, and several other ailments. Our protocols are based from medical studies that will provide the optimal outcome. See our Ketamine page for more information and research. Of course we are glad to have a complete consultations to assess your personalized care needs!

Introduction

Intravenous (IV) ketamine infusion therapy has emerged as a treatment option for a variety of chronic pain conditions including fibromyalgia, small fiber neuropathy, complex regional pain syndrome (CRPS), reflex sympathetic dystrophy (RSD) and psychiatric conditions including depression, post-traumatic stress disorder (PTSD), suicidal ideation, and obsessive-compulsive disorder (OCD). Dr. Sendi is America’s top doctor offering IV Ketamine Infusion treatment, with multiple treatments performed.

History of Ketamine

Ketamine is not a new drug. It has been used for five decades in human and veterinarian medicine. Ketamine is an anesthetic drug that was introduced into clinical practice in 1970.1  At anesthetic doses it results in a complete loss of consciousness while preserving certain protective reflexes. That has made it attractive to anesthesiologists in selective patients. While it does stimulate opiate receptors, much like morphine, its NMDA receptor antagonism at subanesthetic doses is thought to be much more important in the treatment of chronic pain and psychiatric disorders. Blocking the NMDA receptor and preventing the passage of ions through the channel interrupts pain signal transduction, giving central pain centers a chance to “reboot”. This often requires that a patient undergo a series of low dose ketamine infusions for dramatic or complete elimination of their chronic pain. Ketamine infusions have been most often used when other treatment modalities have failed. Certain types of pain considered to be “neuropathic” in origin have been most studied and are considered to be most responsive to ketamine therapy.

Science

The primary and most well known pharmacological action of ketamine is NMDA antagonism.  This is the main rationale for the use of ketamine infusions to treat chronic pain and psychiatricIV Ketamineconditions that are not responsive to conventional therapeutic options.  Many studies have shown increased NMDA expression and activity in animal models of chronic pain.2-4  Further, subsequent studies have shown that NMDA antagonism is useful in these same models of chronic pain.5-8  The most studied of these NMDA antagonists is ketamine and is the subject of many current CRPS research endeavors.9-12Ketamine exhibits extensive polypharmacology that has yet to be fully understood in the context of CRPS.13  This has led some to regard the drug as “a pharmacologist’s nightmare” because there is not one clear defining mechanism of action.13  However, we believe that the multiple pharmacological actions of ketamine may produce an “entourage effect” that is uniquely beneficial for the management of many treatment-resistant psychiatric conditions, CRPS and other pain conditions that are refractory to opiate therapy or in patients where opiate narcotics are contraindicated.

IV Ketamine Procedure

At NOVA Health Recovery, treatment protocols are individually planned depending on the nature of your pain and your responsiveness to initial sessions. Infusion cocktails are prepared in house so that they can be tailored to each patient’s therapeutic needs.  A variety of medications are often used:

  • Lidocaine
  • Ketamine
  • Magenesium

These medications are typically mixed with saline in an IV bag and infused slowly over several hours, depending on the medication and/or protocol being used.  Usually, a series of treatments will be recommended daily for a period of a week or more. The duration of pain relief following one or more ketamine infusions cannot be predicted. The goal is to achieve lasting relief as measured in weeks or months following the last treatment. Most patients who enjoy prolonged pain relief will need to return on occasion for a booster infusion, or continue to take low dose intranasal ketamine at home.

Risks

Ketamine infusion therapy is generally well tolerated and, as such, very few patients need to terminate treatment due of side effects. Still, ketamine is a derivative of phencyclidine (PCP) a known psychedelic and if not combined with sedation can cause hallucinations in many patients. You will be given a benzodiazepine to control this dysphoria. Other possible side effects include nausea and rarely a headache. These side effects can also be managed and often eliminated during the infusion therapy. Following the completion of a daily infusion regimen, patients are usually tired for several hours and need to be accompanied home by a responsible adult. We have yet to observe any long-term side effects that can be attributed to low dose intravenous ketamine therapy. Furthermore, ketamine is not highly addictive like more common FDA approved analgesics like opioids.

References

1.         Domino EF. Taming the ketamine tiger. 1965. Anesthesiology. 2010;113:678-684.

2.         Da Silva LF, Walder RY, Davidson BL, Wilson SP, Sluka KA. Changes in expression of NMDA-NR1 receptor subunits in the rostral ventromedial medulla modulate pain behaviors. Pain. 2010;151:155-161.

3.         Hummel M, Strassle B, Miller S, Kaftan E, Whiteside G. Anatomical localization and expression pattern for the NMDA-2D receptor subunit in a rat model of neuropathic pain. Neuroscience. 2008;155:492-502.

4.         Chapman V, Honore P, Buritova J, Besson JM. The contribution of NMDA receptor activation to spinal c-Fos expression in a model of inflammatory pain.British journal of pharmacology. 1995;116:1628-1634.

5.         Wang Y, Guo Q, Wang M, Wang E, Zou W, Zhao J. [Effect of intrathecal sufentanil and protein kinase C inhibitor on pain threshold and the expression of NMDA receptor/ CGRP in spinal dorsal horn in rats with neuropathic pain]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences. 2012;37:783-789.

6.         Hudspith MJ, Harrisson S, Smith G, Bountra C, Elliot PJ, Birch PJ, et al. Effect of post-injury NMDA antagonist treatment on long-term Fos expression and hyperalgesia in a model of chronic neuropathic pain. Brain research. 1999;822:220-227.

7.         Munglani R, Hudspith MJ, Fleming B, Harrisson S, Smith G, Bountra C, et al. Effect of pre-emptive NMDA antagonist treatment on long-term Fos expression and hyperalgesia in a model of chronic neuropathic pain. Brain research. 1999;822:210-219.

8.         Chu YH, Wong CS, Ho ST, Watkins WD. Epidural coadministration of ketamine and morphine attenuates the neuropathic pain: A case report. Pain Clinic. 1995;8:263-267.

9.         Shirani P, Salamone AR, Schulz PE, Edmondson EA. Ketamine treatment for intractable pain in a patient with severe refractory complex regional pain syndrome: a case report. Pain physician. 2008;11:339-342.

10.        Kiefer RT, Rohr P, Ploppa A, Nohe B, Dieterich HJ, Grothusen J, et al. A pilot open-label study of the efficacy of subanesthetic isomeric S(+)-ketamine in refractory CRPS patients. Pain medicine. 2008;9:44-54.

11.        Kiefer RT, Rohr P, Ploppa A, Altemeyer KH, Schwartzman RJ. Complete recovery from intractable complex regional pain syndrome, CRPS-type I, following anesthetic ketamine and midazolam. Pain practice : the official journal of World Institute of Pain. 2007;7:147-150.

12.        Pickering AE, McCabe CS. Prolonged ketamine infusion as a therapy for complex regional pain syndrome: synergism with antagonism? Brit J Clin Pharmaco. 2014;77:233-238.

13.        Potter DE, Choudhury M. Ketamine: repurposing and redefining a multifaceted drug. Drug discovery today. 2014.

 

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Intravenous administration has shown to be one of the most common clinical ways to deliver the...

The curious case of ketamine

In 1956, a chemist at pharmaceutical company Parke Davis in Detroit, Michigan was experimenting with synthesizing new compounds in an attempt to find a better anesthetic. A compound called phencyclidine was initially created, and in early animal studies it demonstrated defiantly unusual effects. Some animals exhibited a drunk-like state when administered with it, while others entered states of delirium.

Human tests quickly ruled out the compound as clinically useful with some patients exhibiting major delirious and dissociative states for prolonged periods of time. This was despite the fact the it did seem to function remarkably well as an anesthetic. In later years, phencyclidine hit the streets as a recreational drug, becoming infamous due it its violent side effects. Its street name was PCP, or angel dust.

In the early 1960s, Parke Davis researchers began searching for a phencyclidine derivative that could limit the compounds unmanageable side effects. It was here that ketamine was born and after successful animal tests it was administered to the first human subject in 1964, demonstrating remarkable anesthetic effects.

Initially approved for veterinary uses, ketamine quickly found a place as an effective short-acting anesthetic, officially passed by the FDA in 1970 for human uses. One of its first major human uses was as a battlefield anesthetic in Vietnam. It has been suggested that this initial use in the early 1970s was what led to it moving into recreational circles as veterans returned to the United States and continued using the drug.

Non-medical uses continued throughout the 1970s, culminating in several high profile publications “outing” the drug. Perhaps the most infamous of these accounts came in scientist and psychonaut John C. Lilly’s 1978 autobiography The Scientist: A Novel Autobiography.

John Lilly and his infamous isolation tank

Ketamine, sensory deprivation and alien communication

John C. Lilly is perhaps best known for his work blending LSD, isolation tanks and human-animal communications. After developing the first isolation tank in 1954, Lilly began experimenting with LSD in the tanks in the early 1960s. His extreme work sat at the boundary of conventional science, and the extraordinary 1980 psychedelic film Altered States was significantly inspired by his experiences.

It was the early 1970s, however, when Lilly first crossed paths with ketamine. Lilly had long suffered extreme migraines, almost daily, for much of his life. During an attack, a physician friend suggested ketamine may be helpful. So Lilly jumped into an isolation tank, was injected with a small dose of ketamine, and his migraine disappeared … for 20 minutes. When it roared back his physician friend gave him another injection, this time double the dose. For about half an hour the migraine disappeared, but then it stormed back, so finally the physician again doubled the dose and sent Lilly back into the tank.

After an hour Lilly got out of the tank and his migraine had gone. A month later, with his migraine still yet to return, Lilly became convinced ketamine had somehow reprogrammed his brain in ways that his earlier massive LSD experiences couldn’t. For the next few years Lilly’s personal ketamine experiments became more and more extreme.

Lilly became convinced he could communicate with a network of extraterrestrial entities he dubbed ECCO, or the Earth Coincidence Control Office. ECCO guided Lilly’s research but as he began to consume more and more ketamine he came across another, more malevolent entity called SSI, Solid State Intelligence.

SSI was a massive cosmic supercomputer, with evil intent. At one point, in the midst of an epic nearly month-long physical experiment with ketamine, consisting of injections nearly every hour, Lilly tried to contact President Gerald Ford to warn the world of a potential doomsday scenario. One of the president’s aides intervened before Lilly could reach Ford.

These stories, and others, recounted in the late 1970s, slowly added to the infamy surrounding ketamine, but they also started to pique the attention of the authorities. The peripheral clinical uses of the substance were still pervasive enough for it to not be completely regulated until the United States government moved to make it a Schedule III controlled drug in 1999. This added a degree of regulatory oversight as to how the drug was dispensed but still allowed it to be utilized for clinical purposes.

William Hurt in Altered States, a film loosely based on the experiences of John Lilly

The Russian research

In 1985, two Russian researchers hypothesized that ketamine could be a good drug to utilize in a psychotherapeutic context. It was short-acting, controllable, relatively accessible and known to induce psychedelic experiences. For the next decade, Evgeny Krupitsky and his team at the Leningrad Regional Center for Alcoholism and Drug Addiction Therapy pioneered what they called Ketamine Psychedelic Therapy.

Over the next decade, ketamine was used to treat more than 1,000 patients for an assortment of drug dependencies, primarily alcoholism. In a systemic study of the work, published in 1997, the researchers reported that the KPT process they developed resulted in zero major side effects, such as protracted psy­choses, flashbacks, agitation, or ketamine abuse. It also proved to be extremely effective in helping patients, with total abstinence rates for more than one year in KPT-treated alcoholic patients hitting around 65 percent compared to conventional treatment which was only successful in 24 percent of patients after one year.

For an extended period of time across the 1980s and early 1990s, this Russian team were extraordinarily the only researchers in the world investigating the therapeutic outcomes of ketamine. Krupitsky suggested this could be because Russia was not suffering from a culture of recreational psychedelic usage, which helped allow his work to continue for so long with no authoritative challenge.

“It seems to be an especially powerful tool in Russia, where there was no psychedelic revolution in the 1960’s and almost nobody knows what “psychedelic” means or can even imagine that this drug can be used for recre­ation,” the researchers concluded in their ten-year report.

Ketamine is known for generating a profoundly dissociative out-of-body experience

The 21st century resurgence

In the early 2000s, ketamine began to reemerge in Western research circles as a potential therapeutic agent, initially for depression. A very small studypublished in 2000 highlighted the drug’s impressive antidepressant qualities, but it was a 2006 study that really turned the tide.

The study, from the National Institute of Mental Health (NIMH), highlighted the remarkably rapid anti-depressant effects of ketamine. It was a small but strong piece of research involving a cohort of patients diagnosed with major, treatment-resistant depression. Two small doses of ketamine were administered, one week apart, and by the end of the first day 71 percent of subjects in the ketamine group reported a nearly 50 percent decline in their symptoms. Even more remarkable, after a week nearly a third of the ketamine group reported complete remission of their depressive symptoms.

This kind of rapid and immense effect was unheard of and the study hit the mainstream media, propelling ketamine into the news for something other than an illicit street use for the first time in years.

The rapid anti-depressant effect of ketamine has been a fundamental and exciting area of research in recent years with scientists slowly homing in on the extraordinarily unique qualities of how the drug operates on the brain. A 2017 study from Columbia University Medical Center revealed impressive results when examining patients suffering from acute suicidal thoughts.

The study, composed of 80 patients with clinically significant suicidal thoughts, displayed a major reduction in reducing such thoughts within 24 hours of a single low-dose infusion. A six-week follow up also found the effects impressively held for an extended duration, especially when compared to a control-group that were administered a sedative called midazolam.

A model of the ketamine molecule

But how does it work?

How the drug actually works to achieve its rapid anti-depressant effects is a hot area of research. While it has been known for several decades that ketamine blocks a protein receptor in the brain called N-methyl-D-aspartate (NMDA), it hasn’t been understood exactly where in the brain this mechanism could be operating.

A recent study from Zhejiang University in China excitingly revealed that this mechanism could be concentrated in the lateral habenula, an area of the brain often referred to as our “anti-reward center.” Overactivity in the lateral habenula has been strongly related to depression and the new study revealed that ketamine directly reduces neuronal activity in that region.

Ketamine’s broad use as a pain- and depression-relieving agent is finding burgeoning uses in treating other conditions peripherally connected to those symptoms. A growing body of anecdotal patient-driven evidence is suggesting the drug could be effective in treating fibromyalgia and chronic fatigue syndrome, two chronic conditions that are somewhat linked by widespread feelings of pain and fatigue.

In regards to fibromyalgia, some small studies have found ketamine to be incredibly effective in reducing acute pain related to the condition. The effects were frustratingly short-lived, unfortunately, but some patients have reported single infusions dulling pain for up to three weeks.

The use of ketamine to treat chronic fatigue syndrome is still in the nascent research stages, but a 2016 study revealed a fascinating insight into the drug as an anti-fatigue compound. While fatigue and depression are profoundly interlinked, the broader NMDA-blocking effects of ketamine are convincingly hypothesized to potentially improve the symptoms of patients suffering from chronic fatigue.

The 2016 study was small, and limited to patients being treated with ketamine for bipolar disorder during an episode of acute depression. It found that ketamine significantly improved symptoms of fatigue when compared to patients in the placebo group, with the anti-fatigue effects most prominent 48 hours after the initial infusion event. The study concludes by suggesting ketamine’s NMDA receptor inhibition could be a novel target for anti-fatigue interventions in a variety of conditions, including chronic fatigue syndrome.

The urban myth of ketamine as a horse tranquilizer became prominent as the drug moved into...

The rise of the ketamine clinic

Unlike other more restricted drugs, ketamine is still available for medical uses. This has led to the recent upsurge of ketamine clinics in the United States. Ketamine is legally approved for use as an anesthetic, but its off-label use for other conditions is not illegal.

Since around 2015, it is estimated that well over 100 ketamine clinics have opened up in the US. These clinics target patients looking for an alternate way to treat their depression. For up to US$1,000 a dose, patients can receive an infusion of ketamine either weekly or monthly. Different clinics have different treatment processes, from specific 10-week programs to more casual dose-by-dose appointments.

It’s the wild west of medical treatments out there, with no clear science on how long these treatments last, or how safe long-term ketamine use like this actually is. The CEO of Actify Neurotherapies, a chain of 10 treatment centers, said recently “It scares the hell out of me that this is still unregulated.”

Actify Neurotherapies is actively resisting the term “ketamine clinic,” recently rebranding itself as a mental health clinic that happens to also provide off-label ketamine treatments. While Actify is positioning itself at the more credible end of the off-label ketamine provider spectrum, it is still part of a troubling, unregulated industry with the science yet to offer real clarity on the best way this drug should be delivered.

Well over 100 ketamine clinics are operating in the United States

A little less psychedelic?

The giant hurdle facing most ketamine research is trying to find a way to overcome the often unpleasant dissociative psychedelic effects of the drug. While NMDA-receptor antagonism is looking like an exciting new pathway to treat a whole host of conditions, the side effects of ketamine are proving tricky to manage when implemented into broader clinical applications.

A recent Australian trial into a ketamine nasal spray for treating depression had to be aborted after several participants started to experience psychotic-like side effects. One of the researchers suggested the dose problems stemmed from inconsistencies in the nasal-delivery method.

“We saw a range of tolerance levels and we think it’s because one person’s blood vessels in the nose can be so different to the next person’s, and when you spray, it crosses the thin lining, gets taken into the blood and straight to the brain. Some people got huge hits.”

Several researchers are now racing to develop compounds chemically similar to ketamine that still act on NMDA receptors but can reduce the psychoactive side effects. One of the most promising new alternatives is called esketamine, and it is currently at the tail end of Phase III clinical trials.

Esketamine is an isomer of ketamine, and reportedly has slightly less dissociative characteristics compared to its sibling. It is thought to be twice as potent as ketamine, which means it is suggested that lower doses could have similar NMDA-inhibiting effects to ketamine without the equivalent hallucinogenic result.

Despite the FDA offering esketamine a breakthrough designation in 2016, suggesting the compound is highly effective and will be rapidly pushed through the trial process, results have been decidedly mixed over the past few years. Most recently, some of the early Phase III results suggest the compound is only mildly effective, and in some cases barely better than the placebo control.

Ketamine + therapy = success?

Of course, some researchers are finding ways to work with the compound’s extremely hallucinogenic properties. An exciting new trial currently underway at the University of Exeter and University College London is directly inspired by Evgeny Krupitsky’s 1980s research in Russia. The trial is called KARE – Ketamine for reduction of Alcoholic Relapse, and it is setting out to examine how well ketamine, in conjunction with psychotherapy, can reduce alcohol dependence and promote abstinence.

The rigorous study, which is double blind and placebo-controlled, involves subjects being administered one dose of ketamine a week for a period of three weeks, alongside seven sessions of cognitive behavioral therapy. The study has a six-month follow-up phase to better understand the long-term effects of this kind of ketamine-assisted psychotherapeutic treatment.

Unlike the attempts to create a less psychoactive compound, this research suggests the holistic effect of ketamine could be vital to its absolute efficacy. The often unwanted hallucinogenic effects may very well be important. And unlike some of the ketamine clinics popping up around the US, this trial offers ketamine within the context of a controlled series of psychotherapy sessions helping patients integrate their experiences into positive outcomes.

The story of ketamine is a curious one, defiantly unlike other psychedelic substances being co-opted for medical uses. Ketamine is essentially legal, prescribable, yet still wholly experimental. It works on the brain in a completely novel way and we are only just understanding its broad potential uses.

With the rise of ketamine clinics, a strange kind of clinical practice has jumped ahead of research, giving rise to a wild west of drug providers administering the compound as a magic bullet for anything and everything in an unregulated landscape. More research undeniably needs to be done before we understand this deeply mysterious and unique drug, but it is looking like it will certainly become a fundamentally important compound in a bright future of psychedelic medicine.

How ketamine relieves depression by suppressing the brain’s “anti-reward” center

A breakthrough study has revealed the potential mechanism behind how ketamine rapidly relieves symptoms of depression

he anti-depressant qualities of ketamine, initially developed as an anesthetic before drifting into recreational circles due to its hallucinogenic properties, have been a booming topic of research over the past few years. Anecdotal evidence of the drug’s effects have been so strong that “ketamine clinics” have popped up all over the US, delivering experimental treatments to patients for hundreds of dollars a dose. Researchers at Zhejiang University in China have now uncovered exciting new insights into a mechanism that may finally explain how ketamine has such a rapid anti-depressant effect.

Research from Columbia University Medical Center has recently clinically verified the drug’s ability to rapidly reduce major depressive symptoms in a matter of hours, but the actual mechanism underlying these effects has been unclear. It’s been known for some time that ketamine blocks a protein receptor in the brain called N-methyl-D-aspartate (NMDA), and it is this process that some have suspected is the cause of the drug’s fast-acting anti-depressant qualities. But until now it hasn’t been clear where in the brain this process is occurring.

The new research focused on a very small area deep in the center of the brain called the lateral habenula. This area is commonly referred to by researchers as the “anti-reward center,” as it’s known for suppressing nearby reward areas of the brain that release dopamine and serotonin. Following growing evidence suggesting that overactivity in the lateral habenula is related to depression, the researchers examined how ketamine directly affects activity in that region of the brain.

Using rodent models, they found that certain patterns of rapid bursts of neuronal activity in the lateral habenula resulted in major depressive behavior in the animals. This correlation was verified by genetically engineering rats to enhance this particular type of brain activity, confirming that it did indeed promote symptoms of depression. The next part of the research revealed that this particular bursting neuronal activity in the lateral habenula was dependent on NMDA receptors, and knowing that ketamine was an NMDA receptor blocker led the researchers to examine if this could be the elusive mechanism behind the drug’s rapid anti-depressant effects.

Administering ketamine directly into the lateral habenula of rats resulted in a very quick reversal of depression-like behaviors in the animals. A second experiment using a more specific NMDA receptor antagonist achieved the same reduction in burst activity and associated anti-depressant effects, suggesting that this is the probable mechanism behind ketamine’s rapid positive effects.

The researchers do note that while this study addresses the rapid effects of ketamine, it doesn’t account for the long-term anti-depressant qualities of the drug. However, suppressing burst activity in the lateral habenula does look like a promising area for new antidepressant research. A second accompanying research paper from the same team examined what could be causing this overactivity in the lateral habenula and suggests a potential protein target that could be manipulated to block it.

While there is a growing amount of research into the use of ketamine for depression, the drug’s strong psychoactive effect and potential for abuse will certainly limit its widespread application. This research into how ketamine works on the brain will hopefully direct scientists toward the development of new ketamine-inspired drugs that target these same brain areas without the other negative psychoactive effects.

The study was published in the journal Nature.

Breakthrough study finds new mechanism explaining ketamine’s antidepressant effects

The same mechanism explaining how SSRI antidepressants function has been found in the activity of ketamine

A team at the University of Illinois at Chicago has uncovered a new mechanism that helps explain the remarkably rapid, and long-lasting, antidepressant effects of the controversial drug ketamine. The exciting research reveals the drug operates in a similar way to conventional SSRI antidepressants, except is it significantly more effective.

For decades, there has been a growing body of anecdotal evidence suggesting ketamine has extraordinarily rapid antidepressant effects. Originally developed as an anesthetic, before moving into recreational circles due to its psychedelic and dissociative qualities, the drug is now being seriously investigated for its uniquely novel effects on the brain.

Research over recent years has generally focused on ketamine’s effect in blocking a protein receptor in the brain called N-methyl-D-aspartate (NMDA). This action, unique to ketamine, is what has generally been thought to be the primary mechanism behind the drug’s rapid antidepressant effects.

Mark Rasenick and his team at the University of Illinois at Chicago College of Medicine initially started their research by investigating the neurological mechanisms behind SSRI drugs, the most common antidepressant medication. The research revealed that patients with depression have larger volumes of G proteins held inactive in “lipid rafts” on cell membranes in the brain. These G proteins are vital in helping nerve cells signal effectively and suppressing their activity could lead to many hallmark symptoms of depression.

Traditional antidepressant drugs such as SSRIs were found to release these locked up G proteins, effectively resulting in their antidepressant effects. A mouse study found that this SSRI activity, releasing these G proteins out of the lipid rafts, took several days to manifest, which possibly explains why antidepressants are so slow to take effect.

Rasenick subsequently set out to investigate whether ketamine resulted in a similar effect on the brain, and the results were compelling. Ketamine did indeed result in a similar mechanism to SSRIs, releasing the G proteins from the cell membrane, except with this drug it occurred at an incredibly rapid rate.

Within 15 minutes of administration, the researchers identified the G proteins being redistributed out of the lipid rafts. And not only that, but the administration of ketamine seemed to result in the G proteins moving back to their inactive state much more slowly. This compelling observation could offer an insight into the observation of ketamine’s long-lasting effects, weeks after the drug has left a person’s system.

“When G proteins move out of the lipid rafts, it allows for better communication among brain cells, which is known to help alleviate some of the symptoms of depression,” says Rasenick. “Whether they are moved out by traditional antidepressants or ketamine, it doesn’t matter, although with ketamine, the G proteins are very slow to move back into the lipid rafts, which would explain the drugs long-term effects on depressive symptoms.”

Another interesting discovery from the research was that when the team directly knocked out the NMDA receptor, classically thought to be the primary mechanism by which ketamine works, the effect on G protein activity was still prominent. This suggests ketamine’s rapid antidepressant qualities aren’t solely mediated through the mechanism of NMDA blocking.

The study offers a fascinating direct correlation between the way SSRIs work and the antidepressant qualities of ketamine. It is not only further proof that ketamine is an incredibly effective antidepressant compound, but it offers researchers new insights into neurological mechanisms that can be better exploited for future treatments.

The new research was published in the journal Molecular Psychiatry.

Ketamine found to rapidly reduce suicidal thoughts and depression

A new study has found ketamine to be more effective in rapidly reducing acute suicidal thoughts...

After recently drifting into recreational circles due to its hallucinogenic properties, ketamine is now being re-evaluated among medial researchers for its powerful anti-depressant qualities. A new study has now revealed the drug can be effective in rapidly reducing suicidal thoughts in patients.

For the last decade a vanguard of scientists has been researching the unexpected anti-depressant effects of ketamine, an old drug initially developed as an anesthetic in the 1960s. The rapid anti-depressant effects of ketamine have been so anecdotally strong that a number of “ketamine clinics” have popped up in the US to deliver the drug to patients, for a price.

This new study, from Columbia University Medical Center, homes in on the drug’s rapid anti-depressant qualities, and examines its effects on patients with acute suicidal thoughts. It is the first study to focus explicitly on suicidal patients, as opposed to prior studies that have looked at more general depression symptoms.

“Currently available antidepressants can be effective in reducing suicidal thoughts in patients with depression, but they can take weeks to have an effect,” explains study leader Michael Grunebaum. “Suicidal, depressed patients need treatments that are rapidly effective in reducing suicidal thoughts when they are at highest risk. Currently, there is no such treatment for rapid relief of suicidal thoughts in depressed patients.”

The study took 80 patients with “clinically significant suicidal thoughts” and assigned them either a low-dose infusion of ketamine or a sedative called midazolam, commonly prescribed to reduce acute suicidal thoughts in at-risk patients. Twenty-four hours after the infusion the ketamine group displayed a major improvement in the reduction of suicidal thoughts compared to the midazolam group.

Perhaps the most compelling part of the study was the six-week follow up showing that the effects of the ketamine seemed to hold strong for an extended duration. The ketamine group reported an overall improvement in mood, depression and fatigue, indicating the drug had a major anti-depression effect as well as a rapid effect on reducing suicidal thoughts.

“This study shows that ketamine offers promise as a rapidly acting treatment for reducing suicidal thoughts in patients with depression,” says Grunebaum. “Additional research to evaluate ketamine’s antidepressant and anti-suicidal effects may pave the way for the development of new antidepressant medications that are faster acting and have the potential to help individuals who do not respond to currently available treatments.”

With several studies looking into ketamine as a viable new treatment for depression disorders this is yet another fascinating glimpse into the unexpected effects of a drug that has been used in a variety of ways, both medically and recreationally, for over half a century.

The study was published in the American Journal of Psychiatry.

 

Dual studies highlight ketamine’s potential to treat anxiety and addiction

New evidence suggests ketamine can reduce anxiety related to major depression, and substance abuse depression

Two new studies suggest the psychiatric benefits of ketamine treatment may extend beyond just the targeting of depression. The research demonstrates ketamine may be helpful in targeting both anxiety- and substance abuse-related depression.

Although ketamine is a relatively old drug, originally developed in the 1950s as an anesthetic, over the last decade a growing body of research has affirmed its unique, and rapid, antidepressant effects. The anecdotal effects of the drug on depression have raced ahead of scientific research so quickly that ketamine clinics have popped up all across the United States, where the drug can be administered for up to US$1,000 a dose.

Much is still unknown about how efficacious ketamine actually is for depression. We don’t know ideal dosages, how long the treatments last, or how safe long-term usage is. Two newly published studies are adding to our knowledge about ketamine’s psychiatric uses, adding weight to the drug’s burgeoning new potential.

The first study, led by a team from Massachusetts General Hospital and Harvard Medical School, set out to study how effective ketamine is at treating patients with anxiety-based treatment-resistant depression. This is an important question to resolve, as many traditional antidepressants do not consistently improve anxiety-based symptoms in cases of major depression.

The study took 99 subjects with treatment-resistant depression, half of whom suffered from high anxiety and half of whom displayed no anxious symptoms. The study randomly administered subjects either one of four different intravenous ketamine doses, or midazolam, a general sedative that could serve as a control.

As well as demonstrating ketamine’s novel antidepressant qualities, the study revealed the drug worked equally well in both anxious and non-anxious subjects. This suggests that ketamine’s antidepressant effects are uniquely effective across different types of treatment-resistant depression, something that cannot be said for many major antidepressant drugs.

“In contrast to reports from monoaminergic antidepressants, our data suggest that patients with anxious depression respond equally as well to ketamine compared to those with non-anxious depression,” write the researchers in the published study.

The second new study comes from a team at Yale University School of Medicine. This research investigated whether ketamine could be effective in treating addiction-related depression when administered in tandem with naltrexone.

A study in 2018 offered a small but significant finding, revealing that ketamine was ineffective in treating depression when administered alongside naltrexone. These results were important because they suggested that part of ketamine’s antidepressant effects may be related to the activation of opioid receptors, which would mean long-term ketamine use may potentially result in problems with addiction, something that many researchers have long argued against.

Naltrexone, an opioid receptor blocker, is often administered effectively to combat serious substance abuse problems, so if it rendered ketamine ineffective then that would cast doubt on much research into how ketamine actually works to reduce symptoms of depression. The new Yale research was small, with a sample of only five patients, but its results strongly suggest ketamine and naltrexone do not cancel each other out.

All five subjects suffering from alcohol use disorder and depression displayed significant depressive relief from ketamine dosages despite long-term naltrexone consumption. Senior author on the study, John Krystal, says although larger studies still need to be completed the research does suggest ketamine and naltrexone may be a complimentary combination that helps treat substance abuse and its related depression.

“[The results] raise the possibility that for people who have depression complicated by substance abuse disorders, the combination of ketamine and naltrexone may be a strategy to explore in the effort to optimally treat both conditions,” says Krystal.

Although this new study only consisted of five subjects, the prior research linking ketamine to the opioid system was generated from just 12 subjects. So we are still in uncharted territory regarding ketamine’s mechanistic effects of the brain. But the Yale research should assuage some fears that ketamine may be, “merely another opioid in a novel form.”

The ketamine anxiety study was published in the journal Depress Anxiety.

The ketamine naltrexone study was published in the journal JAMA Psychiatry.