Ketamine – The Legal Psychedelic


As the psychedelic renaissance continues to heat up and California may be weeks away from legislatively decriminalizing psychedelic substances while a host of other states and jurisdictions have already done so by ballot measure there is one drug that produces a psychedelic experience that already enjoys federal legal status: ketamine. 

“Ketamine is already an FDA-approved drug for treatment-resistant depression and is accordingly classified under Schedule III.”

When most people think of psychedelics they think of the classics like LSD and psilocybin or they think of MDMA commonly known as Ecstasy. There are other psychedelic compounds which produce profound experiences and for those die hard cannabis consumers certain strains of flower can produce a medicinal psychedelic experience as well if consumed intentionally. Although, cannabis does not yet enjoy federal legal status we are hopeful that this will be the administration to correct that long overdue gaffe. 

Yet ketamine can also produce some profound effects and depending on dose can produce mystical experiences that have been linked to positive treatment outcomes.  Ketamine was approved by the FDA for medical use as an anesthetic in 1970. 

“Ketamine is a so-called dissociative anesthetic. Like all good anesthetics, it ensures patients have no body movements, no pain and no memory. What’s more, Ketamine has two important advantages over other anesthetics. First, it doesn’t cause significant drops in blood pressure. And second, it doesn’t cause respiratory depression. These additional features made ketamine the anesthetic of choice for operating under suboptimal conditions, like in the Vietnam War where anesthesiologists, who must monitor vital signs and adjust dosage to keep patients from dying, were rare in the field.”

It is currently listed as a Schedule III compound. Schedule III drugs are classified as drugs that “have less potential for abuse but can still lead to moderate or low physical dependence and high psychological dependence”.  As it happens Tylenol is classified as Schedule III. 

“Aside from its value as a general anesthetic, ketamine is used to directly treat major depressive disorder, generalized anxiety, and post-traumatic stress disorder (PTSD), among other pain-related illnesses and mood disorders.”

When used “off label” by a licenced clinician ketamine has been successful in treating treatment-resistant depression.  And it is legal to do so. 

“Off-label” prescription is when a medicine is used to treat another condition outside of its original medicinal intent.”

How did ketamine come to be used as a treatment for depression? 

“Starting around the year 2000, ketamine has had a revival in the field of psychiatry. It turns out that, in lower doses, ketamine has distinct antidepressant effects. Ever since, psychiatrists have administered ketamine to patients who suffered from severe depression. The clinical use confirmed what studies had previously shown: for many patients, ketamine could immediately relieve symptoms of depression—even with just one dose. This extremely fast onset closed an important gap in the clinical treatment of depression, because modern antidepressants like SSRIs and SNRIs take about two weeks to come into full effect. Acutely suicidal patients can’t wait that long, thus ketamine has gained popularity again, now as a so-called rapid-acting antidepressant.”

What does it feel like and what are the effects?

“Ketamine is fast-acting and has shown impressive clinical efficacy across many conditions. This is likely because ketamine increases neuroplasticity (the ability to create new neural connections) and suppresses the default mode network (DMN), which is often the culprit of negative and ruminating thought patterns.”

“How long ketamine remains active in your system will ultimately depend on your unique physical characteristics. Most patients find that their first infusion of ketamine will provide relief from physical symptoms for several days. With the somatic alleviation comes an uplift in mood that can last months or even years afterward.”

“Ketamine creates a unique experience due to its biological, experiential, and psychological impacts. Ketamine is dissociative, which means it alters your perception of reality. In other words, it can open you up to seeing yourself, and the world, in a whole new light, thereby opening up new possibilities for change.”

“Those who suffer from chronic depression are often held back by self-defeating thoughts that have been ingrained over long periods of time. After one administration of ketamine, patients are relieved of these symptoms for the first time in years, which can have long-term positive effects on one’s well-being.”

What is the difference between ketamine and esketamine?

“Ketamine has widely been used off-label in treating treatment-resistant depression. But in order to be formally approved as an indicated treatment it takes a long, complicated and expensive procedure, which typically only pharmaceutical companies can afford. After 20 years of off-label use, the pharma company Johnson & Johnson changed the game. In 2019 they attained FDA approval for a variant of ketamine—Esketamine—which they patented and sell today as a nasal spray called Spravato. Now that there is an approved treatment available, doctors are compelled to use the proprietary nasal spray over regular ketamine. The catch: a single dose of Spravato is priced in the high 3-digits, whereas a dose of regular ketamine costs less than a cup of coffee.”

So is ketamine effective? And how is it administered? 

All in all, yes, ketamine has a high efficacy rate. And that is what makes this treatment so exciting and the idea that psychedelic medicine in general can be helpful in treating depression, PTSD, and in promoting mental wellness better than classic pharmaceuticals. 

“Ketamine is believed to produce its therapeutic effects through several novel mechanisms of action – increasing production of brain-derived neurotrophic factor (BDNF) and reducing activity in the default mode network (DMN).”

“Multiple routes of administration are used by practitioners treating depression and other psychiatric conditions, each with its own unique pharmacokinetics. These include IV, IM, intranasal (IN), sublingual (SL), anal, and oral delivery. Each has its own rate of absorption and timing of onset. In our practices, new patients tend to begin with the SL method for assessment of sensitivity to the medicine.”

“Depending upon dose, ketamine promotes a time-out from ordinary, usual mind, relief from negativity, and an openness to the expansiveness of mind with access to self in the larger sense. These effects enhance a patient’s ability to engage in meaningful psychotherapy during and after administration. Ketamine is potent for respite, analysis, and meditative presence, and potent for recovery from depression and the lingering effects of trauma.” 

There are three different clinical models of administration which clinicians, researchers, and practitioners utilize when formulating hypotheses about what makes ketamine effective.

“What’s effective is 1) the pharmaceutical substance, versus 2) the combination with psychotherapy, versus 3) the visions themselves.”

“The medical model

Dosage: 0.5mg/kg

Routes of administration: intravenous drip, nasal spray

The medical model operates with small doses, no visions and higher frequency. With low dosages, psychoactive effects can be kept at bay. On the other hand, low doses need to be administered more often in order to achieve a cumulative effect. As mentioned above, ketamine is used as an add-on treatment to conventional antidepressants. The medical model is the status quo in most larger clinics around the world.

Recently however, a new perspective has emerged amongst experts in the field: what if the psychoactive properties aren’t merely an irritating side effect, but are actually responsible for the efficacy of ketamine?

The therapeutic model

Dosage: 0.25-0.75mg/kg

Routes of administration: intravenous drip, intramuscular injection, lozenge

The idea of the therapeutic approach is to use the psychoactive properties of ketamine as lubrication for talk therapy. In other words, to help patients relax and talk about things that are too painful to talk about otherwise. During this approach, patients are fully conscious but feel a bit more disinhibited, which makes it easier for them to open up. 7 This approach has been named Ketamine-Assisted Psychotherapy (KAP) and is offered by smaller treatment centers and individual health care providers.

The psychedelic model

Dosage: 1-2mg/kg

Routes of administration: intravenous drip, intramuscular injection

In the psychedelic model, the patient is lying down and fully giving in to the psychedelic experience which can involve colorful dream-like visions, meaningful insights and full dissociation which manifests as out-of-body experiences. This is the state that recreational users refer to as being in a k-hole. Psilocybin and LSD Studies from the 1960s until today have shown a correlation between such mystical-type experiences and positive treatment outcomes.8 It stands to reason that the same principle could apply to ketamine as well, thus the psychedelic model. But little data has been gathered to confirm this assumption. 

Typically it’s the same providers that offer the therapeutic model, that would also offer the psychedelic model. It’s widely agreed however, that this high-dose approach is not appropriate for many patients. 7

“The experience has also been described as “euphoric,” “calming,” and “mystical.””

What are the side effects of ketamine?

“Even with experiences that may seem negative in the moment, the insights gained are often tremendously valuable.”

“A feeling of dissociation or disconnection from your normal self”

 “A sense of impaired balance and coordination”

“A feeling of drowsiness, mental confusion, and/or slurred speech”  

“Impacts to visual, auditory, or tactile processing, including diminished ability to see, hear, or feel objects accurately”

 “Ketamine can worsen psychotic symptoms in people who suffer from

  schizophrenia or severe personality disorder”

 “Feelings of anxiety, fright, nausea, and/or vomiting”

Is ketamine a club drug and the same as Angel Dust otherwise known as PCP? 

Yes and no. Ketamine is a derivative of PCP. Which I would not suggest anyone go looking for these days. 

Ketamine is a derivative of PCP which some readers may know of as the street drug called Angel Dust.” 

“Outside the lab ketamine is sold as Special-K or Vitamin-K in the form of a snortable powder. Ketamine has detrimental side effects if used frequently, it can lead to addiction and—under unfavorable und unsupervised circumstances—can be lethal.”

So what are the hallmarks of a well run ketamine clinic? Where can someone go for ketamine assisted therapy? And what should someone look for in a ketamine clinic? 

“Phil Wolfson, author of The Ketamine Papers, Director of the Center for Transformational Psychotherapy, and a pioneer in the world of ketamine-assisted psychotherapy, always includes a trained therapist and a medical doctor as part of ketamine treatments. Wolfson’s website cautions against ketamine therapy clinics that take an overly medicalized approach.”

“If a patient is already working with a psychiatrist or therapist, clinics should collaborate with them. Dr. Cristina Cusin, co-director of a ketamine clinic at Massachusetts General Hospital and psychiatry professor at Harvard Medical School, told STAT that her patients are required to have a primary mental health provider to receive ketamine.” 

“The American Psychiatric Association strongly recommends that ketamine clinics assess any patient’s physical and mental health status before, during, and after treatment.” 

“Ethical clinicians will do a thorough pre-treatment evaluation, and take into consideration any medical, psychological or social factors that could affect the treatment. Same-day appointments are another giant red flag.”

“Look for a clinic that includes some type of integration as part of the ketamine treatment plan. While psychedelic integration means different things to different people, it can be defined as taking the time to glean the insights gained from a drug experience, processing those iInsights through journaling, meditation, or talking with mental health professionals or other supportive people in your life, and figuring out how to incorporate those shifts of the experience into daily living.”

For a list of reputable ketamine clinics DoubleBlind has included a “non-exhaustive” list in the following article

I will add the following two names to a non-exhaustive list:

Remember that the medicine is only part of the journey. You want to be comfortable with the team who will be guiding you through from preparation through integration. This is your mental health and the first part of self empowerment is self-care. Please be sure that the team at any clinic has your best intentions front and center.

Author: Sherri Margolin (Dark Matters)

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