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What is Ketamine? 

What is Ketamine Drug? Ketamine belongs to the chemical class of drugs known as arylcyclohexylamines. The first drug of this kind was phencyclidine (PCP), and ketamine was later synthesized in 1962 by the chemist Calvin L. Stevens as he produced a series of PCP derivatives. In clinical settings, ketamine is normally administered intravenously, where it rapidly induces dissociation, sedation, and analgesia. At sub-anesthetic doses. Ketamine infusion therapy helps with a number of psychiatric conditions, but it is most commonly used in those with treatment-resistant depression, a form of major depressive disorder. This begs the question, “Is Ketamine addictive?” and “What is the Ketamine Infusion Cost?”

Ketamine can produce psychedelic experiences. It distorts perceptions of sight and sound and makes the user feel detached and not in control. When a user uses ketamine repeatedly, a physical or psychological tolerance forms, leading to Ketamine addiction. Because of this tolerance, the Ketamine user begins to want the drug, want more of it, and use it more frequently. Several negative outcomes and side effects, such as withdrawal symptoms, long-term side effects, irreversible substance-induced psychosis, or other issues, are possible due to Ketamine addiction. Ketamine, while not generally regarded as addictive, has the potential to produce substantial dependence that needs professional treatment if the user decides to stop using.

Is Ketamine physically addictive? When ketamine is involved, Ketamine addiction is primarily psychological. For instance, cravings and thoughts of Ketamine may occur, but they are not accompanied by severe physical side effects like vomiting or nausea when the drug usage is stopped. This is not to suggest that overcoming psychological dependency on this drug is any simpler than overcoming physical dependence, as any drug dependence, whether physical or psychological, is challenging for the user and can present a number of issues.

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What is Ketamines for Depression?

Ketamine for depression is often reserved for individuals with severe mental health conditions who have tried other medications but found little to no relief. Patients with acute suicidality and treatment-resistant depression have been the subjects of the most extensive research. Patients with mental health disorders such as PTSD, OCD, bipolar depression, anxiety, and eating disorders may also find it helpful. In general, therapeutic ketamine is not a good choice for people with specific illnesses like psychosis.

Ketamine was approved as an anesthetic, but using it to address psychiatric conditions is considered “off-label.” That means it’s legal for a doctor to prescribe, but it’s not approved by the Food and Drug Administration (FDA) for that indication. The exception is esketamine, a nasal spray approved by the FDA in 2019 and marketed as Spravato for treatment-resistant depression and acute suicidal thinking.

Ketamine Dose for Depression

According to the National Center for Biotechnology Information (NCBI) [1], Ketamine, administered in subanesthetic doses, is an effective off-label treatment for severe and even treatment-refractory depression; however, despite dozens of studies across nearly 2 decades of research, there is no definitive guidance on matters related to core practice issues.

Ketamine is most commonly administered in the dose of 0.5 mg/kg, but some patients may respond to doses as low as 0.1 mg/kg, and others may require up to 0.75 mg/kg. The ketamine dose for depression is conventionally administered across 40 minutes; however, safety and efficacy have been demonstrated in sessions ranging between 2 and 100 minutes in duration.

There is likely to be a complex interaction between ketamine dose for depression, session duration, route of administration, frequency of administration, and related practice. Until definitive studies comparing different doses, rates of administration, routes of administration, and other considerations are conducted, firm recommendations are not possible. From the point of view of clinical practicability, subcutaneous, intranasal, and oral ketamine warrant further study.

Is Ketamine for Depression Addictive?

Even though Ketamine has yet to be approved by the Food and Drug Administration or FDA for use in treating depression, patients are flocking to ketamine clinics to receive the off-label ketamine for depression treatment. It may provide fast relief, which is critically important in cases where patients feel suicidal. In addition, for depressed patients who have tried all of the other anti-depressants available with no luck, ketamine for depression treatment may offer new hope.

The FDA hasn’t yet approved ketamine for use as an anti-depressant, but both Esketamine and Rapastinel (developed by Johnson & Johnson and Allergan, respectively) have been fast-tracked as breakthrough drugs. As a result, the demand for these two medications is projected to multiply in the coming years.

Medical professionals can only prescribe ketamine for depression treatment off-label since ketamine has been FDA approved for use as an anesthetic, not as an anti-depressant. Researchers have warned doctors to avoid over-prescribing this medication because patients’ long-term health and well-being could be at risk. Ketamine has a high potential for abuse after all, and experts claim that the evidence does not exist to prove that this drug is safe

How addictive is Ketamine? Higher doses (usually administered as injections) can produce the “K-hole” effect, where the user experiences what is often described as a near-death or out-of-body experience and feels separated from reality. The drug can cause numbness in its user, which increases the risk of accidents and serious injury. Many unintentional overdoses happen when a user tries to reach the “K-hole.” The main reason for death from a Ketamine overdose is respiratory failure.

Oral Ketamine for Depression

Major depression is a recurrent and chronic illness that has a lifetime prevalence of 14% and constitutes a significant worldwide burden. After the pharmacological revolution introduced with fluoxetine (Prozac) in 1987, antidepressants have been one of the most commonly prescribed medicines for major depressive disorder (MDD), with more than 25 US FDA approved anti-depressants available [2].

Despite many advances in the field related to pharmacological and non-pharmacological treatments for depression, strategies to improve refractory depression (ie., patients who fail to respond to 2 or more consecutive treatments) continue to be inadequate.

Ketamine, a non-competitive antagonist which exerts its pharmacological effects on the N-methyl-D-aspartate (NMDA) receptor, has demonstrated rapid antidepressant efficacy in patients with treatment-resistant depression. Ketamine has also been shown to rapidly reduce suicidal thoughts in depressed patients with suicidal ideation.

Oral ketamine for depression is suggested as a more convenient alternative and is widely available. However, oral ketamine has yet to be thoroughly investigated. Low bioavailability of oral ketamine for depression may impact the efficacy of oral ketamine and its comparisons between different routes of administrations and scheduling regimens.

Other concerns have related to the increased possibility of psychiatric adverse events such as addiction since it has been highly comorbid with depression. There has been a controversial debate whether there is merit in recommending oral ketamine to patients with refractory depression. Additionally, a recent meta-analysis examined different routes of ketamine administration demonstrating short-term efficacy for intravenous and intranasal ketamine but limited data analysis for oral ketamine.

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How Much Do Ketamine Infusion Cost?

Patients who respond to ketamine often need multiple treatments to maintain the antidepressant response. Ketamine is not FDA-approved for depression and is usually not covered by insurance, leading to a fairly expensive ($400–500/infusion) treatment [2]. Intranasal esketamine is FDA-approved for Treatment-resistant depression (TRD) but is also expensive. There is limited data regarding the long-term use of ketamine. Patients requiring multiple treatments to maintain efficacy may be at increased potential for tolerance and addiction.

How it Works?

What is the cost of ketamine infusion? Ketamine for depression cost usually starts from $400 to $800 per treatment, and most ketamine clinics perform a series of 6 treatments over 2 to 3 weeks. Some providers offer 4 treatments over 1 to 2 weeks. Ketamines infusion cost will depend on the ketamine infusion dose used per treatment. Some conditions like depression require a lower concentration of ketamine than the concentration for pain conditions. 

In a clinical setting, ketamine patients typically sit in a comfortable chair, listening to music while the treatment is administered. Talk therapy, which often happens after the drug effects end, can also be part of the treatment. Several ketamine clinics will evaluate whether or not the patient responds to the first infusion before proceeding with subsequent infusions. The majority of ketamine providers seem to request an upfront payment for a complete set of 4 to 6 infusions. 

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Other Brain Effects of Ketamine Infusion

Major depressive disorder (MDD) is devastating, serious, and prevalent. Treatment-resistant depression (TRD)—often defined as failure to respond to at least two standard antidepressant treatment trials of adequate dose and duration—encompasses up to 30% of patients with MDD [4].

Not only is TRD highly debilitating for patients and their families, economic strain from Treatment-resistant depression (TRD) accounts for nearly $200 billion dollars a year from lost productivity [4]. The more treatment failures a person experiences, the less likely they are to respond to subsequent treatment trials—perpetuating the cycle of disability. For these reasons, it is crucial to find effective and fast treatments for patients with TRD.

While most commonly used psychiatric medications (e.g. SSRIs, SNRIs, TCAs, MAO inhibitors) require multiple weeks to take full effect, subanesthetic doses of ketamine have rapid (within hours), robust (across a variety of symptoms), and relatively sustained (typically up to one week) antidepressant effects—even in patients with TRD. Clinical studies show that about 50% of patients with TRD have a significant decrease in symptoms within 24 hours of a single intravenous subanesthetic ketamine dose.

Animal models show that ketamine’s antidepressant effects are likely mediated by its antagonism of NMDA receptors through increased AMPA-mediated glutamatergic signaling. This triggers activation of intracellular synaptogenic pathways, most notably in the mTOR signaling pathway, which also has implications in many other psychiatric disorders.

Antidepressant Effects of Ketamine in Depressed Patients

In terms of major depressive disorder (MDD), decreased glutamate has been noted in various prefrontal regions, including the dorsolateral prefrontal cortex (dlPFC), dorsomedial PFC (dmPFC), and the anterior cingulate cortex (ACC) when compared to controls. This makes ketamine an ideal treatment for MDD; by creating a surge in glutamate levels in regions of the brain that suffer from a glutamate deficit, ketamine may provide some normalization of glutamate levels in patients with MDD.

However, the glutamate surge hypothesis is met with some controversy. Neuroimaging studies specifically examining how ketamine modulates glutamate and gamma-aminobutryic acid (GABA) have been reviewed. Despite the immediate glutamate surge during infusions, it is unclear if glutamate levels remain elevated post-infusion.

Multiple studies attempted to find a correlation between antidepressant response and glutamate/GABA levels before, during, and after infusion. Multiple studies attempted to find a correlation between antidepressant response and glutamate/GABA levels before, during, and after infusion. It is possible, then, that ketamine is acting indirectly to produce its antidepressant effect. Further research is necessary to uncover ketamine’s antidepressant mechanism of action.

What are the side effects of ketamine treatment for depression? Commonly reported ketamine treatment for depression side effects associated with single-dose IV ketamine infusion for TRD include psychotomimetic symptoms (e.g. dissociation, hallucinations), sympathomimetic symptoms (e.g. hypertension, tachycardia), and vestibular symptoms (e.g. nausea, vomiting, headache, dizziness). Relatively little is known about ketamine’s longer-term effects, including increased risks of abuse and/or dependence.

Is Ketamine Safe for Depression?

In 2019, the FDA approved a form of the drug ketamine to treat depression [5]. Ketamine is a fast-acting antidepressant that relieves depressive symptoms in hours instead of the weeks or longer that previous drugs required. In addition to being a major advance in treatment, ketamine provides an opportunity for researchers to investigate the short- and long-term biological changes underlying its effects on depression.

Treatment with ketamine for depression rapidly relieved the abnormal behaviors in the stressed mice. The drug also quickly restored the coordinated activity of prefrontal neural circuits that were disrupted by chronic stress. However, the researchers found that ketamine didn’t work by halting the stress-induced spine loss. Instead, the drug led to formation of new functional spines.

The initial effects of ketamine on mouse behavior occurred independently of its effects on spine formation. While the drug affected behavior within three hours, formation of the new spines took 12 to 24 hours. Formation of spines in the mice correlated with their behavior two to seven days after treatment. Further experiments showed that the newly formed spines were crucial for sustained reversal of the negative effects from stress. When the ketamine-induced spines were eliminated, the mice again showed depression-like behaviors.

What Does Ketamine Therapy Feel Like?

What does ketamine infusion feel like? Patients say that therapeutic ketamine can feel like floating outside one’s body, pleasantly leaving your physical self behind. Some individuals gain a heightened sensory awareness; colors may seem brighter.

When used under medical supervision and with careful patient screening, most medical practitioners consider ketamine for depression treatment to be generally safe, with the caveat that all medications carry some risks. They note that ketamine remains a controlled substance regulated by the Drug Enforcement Administration (DEA) and is subject to strict safety controls because of its potential for abuse. Certain medications and conditions make ketamine therapy too risky for some patients, physicians say, so a full mental health and medical history is critical before embarking on Ketamine for depression treatment.

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Are Ketamine Spas Legal? 

The straightforward answer is “Yes”. So why are we asked this so often? Perhaps it’s because of Ketamine’s history as a horse tranquilizer, club drug, and off-label use, which confuses many individuals regarding its legality. Ketamine was first synthesized in the 1960’s for use as a general anesthetic. It’s been traditionally used in emergency departments and operating room for pain control and sedation. Ketamine has also been known to be used in veterinary medicine as a “horse tranquilizer” and even a recreational club drug of abuse. 

Recently, there has been a rising trend of more ketamine spas and clinics opening up in the United States. Because of ketamine’s history, there may be some confusion about its legal status when used “off-label.” To answer it simply, yes, ketamine clinics are legal. What does “off-label” mean? When a drug becomes approved by the United States Food and Drug Administration (FDA), it usually has an indication for a specific use. Ketamine is being used “off-label” for the treatment of various mood and pain disorders in an outpatient setting.

Ketamine is categorized into Schedule III, meaning that it has a low to moderate potential for physical and psychological dependence. This is the same category as Tylenol with Codeine, buprenorphine, and testosterone. To obtain ketamine from a pharmacy, the clinic/doctor must have a DEA license. Also, to open a ketamine clinic it has standard outpatient requirements like state medical board licenses, OSHA standards, insurance coverage, ability to store controlled substances, and county/city licensing.  

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Is At-Home Ketamine Therapy an Option?

There has been a recent proliferation of online healthcare businesses that offer at-home ketamine therapy through virtual visits to individuals suffering from a variety of mental health conditions. Ketamine is a dissociative drug with abuse potential. The dissociative and altered state seen with ketamine may play an important role in its therapeutic benefits.

Increased attention on social media on ketamine for depression treatment alternative, as well as a tool to facilitate psychotherapy through its mind-expanding properties, has led more individuals to seek out this potential at-home ketamine therapy, with or without their HCP’s (health care provider) consent.

Access to ketamine as a treatment option can be challenging to interested individuals. Many health care professionals are reluctant to suggest or use ketamine since it is not approved for psychiatric conditions. Psychiatrists more accepting of ketamine as a treatment option may not have the training, staff, space, or equipment to administer the medication in their offices.

What is the cost of ketamines for depression? Ketamine therapy can be costly since it is often not covered by insurance. Esketamine has some similar pharmacodynamic and pharmacokinetic properties to ketamine since it is an isomer of the medication and is FDA approved for treatment resistan depression (TRD) and major depression with suicidal ideation.

Access to esketamine is limited since many insurances are reluctant to approve this treatment. Few mental health practitioners offer this treatment since they do not have the office space, comfort level, or ability to navigate the complex insurance obstacles restricting payment.

At-home ketamine treatment initiated by an online provider presents many clinical, legal, and ethical challenges to health care providers and potential risks to patients. Some legal questions are whether online prescribing of ketamine, a Schedule III medication, meets criteria for the looser rules of prescribing a controlled substance without an in-person examination. Particularly if ketamine is being used for a mind-expanding, emotionally cathartic purpose. The existing law states that the prescription must be for a legitimate medical purpose by a practitioner in their usual course of their professional role.

What is Ketamine Psychosis?

Ketamine recreational users and abusers frequently experience a range of symptoms that resemble psychosis or a psychotic episode. A ketamine user experiencing a psychotic episode may speak, believe, or act in ways that are inconsistent with reality. After taking the Ketamine, they were more likely to have disorganized thinking and may have had trouble trying to finish simple words.

Loss of connection to reality is a hallmark of psychosis. It’s possible for someone to have incorrect beliefs or delusions that are based on hallucinations. Their ability to perform at work, in the home, and in society is substantially impacted by ketamine psychosis. Psychosis sufferers frequently have poor physical conditions. The greater the psychotic symptoms are, the higher the related level of impairment.

People frequently have difficulty telling the difference between psychotic disorders like bipolar disorder or other similar disorders and drug-induced psychosis. In the case of ketamine psychosis, intervening as quickly as possible with treatment provides the best long-term solution for the patient.

Depression Treatment

People who suffer from depression can experience severe sadness that lasts weeks or even months at a time. It’s common for those battling mental illness to also struggle with substance abuse. Sometimes it can be difficult to determine which condition came first. People faced with prolonged periods of profound sadness may reach for drugs or alcohol to ease the pain, feelings, and other symptoms.

In the general population, the prevalence of a current substance use disorder in persons with Major depressive disorder (MDD) ranges from 8.5 to 21.4%, with a lifetime prevalence of comorbid SUDs ranging from 27 to 40% [6]. Co-occurring depression has an adverse effect on the course of SUDs. Current depression predicted poorer treatment response and higher rates of relapse.

The mental health field has long discussed whether these conditions are independently occurring disorders or are overlapping illnesses intertwined by common etiologic and vulnerability factors. The initial presentation of depression can be obscured by the overriding symptoms or side effects of a substance use disorder (SUD).

However, substance use can actually make depression symptoms more severe. Clinical depression alone increases the risk of accidental injury, suicide, and other forms of self-harm. Add in drugs or alcohol, and the threats to the person’s mental and physical health can be extreme.

To determine the most effective ways to treat depression and substance abuse comorbidity, it’s crucial to first get an accurate assessment of all the symptoms. When the symptoms have been evaluated by a mental health professional, it may be determined that another form of mental condition is present and needs a particular type of treatment. 

Some of the many modalities applied and practiced within our residential treatment facility are:

If you or a loved one are struggling with long-term drug abuse and a co-occurring mental health condition such as major depressive disorder (MDD), contact one of our helpful treatment specialists today. We Level Up NJ can provide information on dual diagnosis and medical detox programs that may fit your specific needs.

At We Level Up NJ, we prioritize removing the stigma and temptations for relapse and applying an air of recovery into every component of the treatment timeline. We find that clients living in a supportive community, especially during their early recovery process, can genuinely focus on what matters most: their recovery. 

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