Ketamine Shows Promise in the Treatment of Depression

THE ESSENTIAL GUIDE TO

KETAMINE

(K, Ket, Special K, Vitamin K, Lady K)

 

(±)-2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone
C13H16ClNO

TABLE OF CONTENTS

1. Overview | 2. History & Stats | 3. Pharmacology | 4. Effects | 5. Myths | 6. Therapeutic Use |
7. Personal Growth | 8. Legality | 9. FAQ | 10. Footnotes

 

Disclaimer: Ketamine is a potentially illegal substance, and we do not encourage or condone the use of this substance where it is against the law. However, we accept that illegal drug use occurs, and believe that offering responsible harm reduction information is imperative to keeping people safe. For that reason, this guide is designed to ensure the safety of those who decide to use the substance.

1. OVERVIEW

Ketamine is a general anesthetic with powerful dissociative and psychedelic effects. Although more widely used on animals since its development in the1960s, ketamine has long been used on humans as well—especially in patients with respiratory or circulatory problems. More recently, the drug has been hailed as a breakthrough therapy for depression.

Recreationally, ketamine is either insufflated (snorted) or injected. The drug is most famously associated with the ‘K-hole’ effect, a depersonalized state that many find therapeutic.

Despite its benefits, ketamine remains a controlled substance in the United States and many other countries.

2. HISTORY & STATS

Ketamine was developed in 1962 as an anesthetic to replace PCP (phencyclidine).[1] It was first synthesized by Calvin Stevens of Parke-Davis, Michigan—once the largest pharmaceutical company in the US. Initially known as CI-581, the drug was tested on human prisoners in 1964 and the term “dissociative anesthetic” was coined to describe its effects[2]

Recreational use began around 1965 and became internationally prevalent by the mid-1970s. During this period, psychedelic researchers such as John C. Lilly, Marcia Moore, Stanislav Grof, and D. M. Turner were exploring ketamine’s psychotherapeutic potential. It was also being used by Vietnam veterans with PTSD, having been the field anesthetic of choice during the war. Lilly referred to the drug as “Vitamin K” and once took it for 100 days straight[3]; Grof found it useful and integrative for therapy with LSD.[4]

In the 1980s, ketamine’s popularity shifted to the rave culture of Ibiza and Goa. It was often encountered as a cheaper alternative to another up-and-coming “club drug,” MDMA.

In 1981, the DEA filed a notice of intention to place ketamine in Schedule III of the Controlled Substances Act,, but evidence of actual abuse was too scarce to support the designation. In 1995, the drug was added to the agency’s “emerging drugs list” and finally labeled Schedule III in 1999, making it illegal to possess without a prescription. As a result, it was commonly stolen from hospitals or smuggled from overseas.[1]

CURRENT USAGE

In 2016, ketamine was among the top ten illicit drugs used worldwide, with a global past-year prevalence of 6.72% (compared with 11.75% for psilocybin and 12.89% for LSD).[5]

In 2006, people between the ages of 18 and 25 comprised the age group most likely to use ketamine in the US, at a rate comparable to PCP. An estimated 2.3 million people aged 12 or older had used ketamine at least once in their lifetimes, and around 203,000 had used it in the past year.[6] Between 2000 and 2011, the rate of ketamine use among US high school students steadily declined, never reaching more than 2.6%.[7]

Ketamine is reported to be around five times more prevalent in the UK[8], where 2013 statistics highlight a similar age bracket—20-24-year-olds—as the most likely group to use it. It has also been identified as one of the most likely drugs to be used in combination, with around 50% of UK users mixing it—often with alcohol.[9]

In China, one of the drug’s major manufacturing centers, ketamine has seen a dramatic rise in popularity. In part, this is due to its low production cost.[10]

3. PHARMACOLOGY

Ketamine is a water-soluble PCP derivative. As a chiral molecule, it has two enantiomers: an S(+) isomer, or “esketamine,” and an R(-) isomer, or “arketamine.”[11]

RECEPTOR BINDING

Ketamine antagonistically binds to, or blocks, NMDA (N-methyl-D-aspartate) receptors.[12]This interaction prevents signals passing between the brain and spinal column and is responsible for the molecule’s analgesic effect. Ketamine also interacts with opioid receptors and the monoamine, cholinergic, purinergic, and adrenoreceptor systems.[11]

SAFETY AND TOXICITY

Ketamine appears to be relatively safe for occasional users. However, frequent use carries the potential long-term risk of neurodegeneration. Prolonged intravenous exposure to the drug (over nine or 24 hours) has led to brain cell death in rhesus monkeys.[13] A similar effect has been seen in neonatal rats.[14] In the monkeys’ case, however, continual exposure to ketamine over a shorter period of three hours had no adverse effects. Likewise, frequent human users have been found to exhibit signs of cognitive impairment affecting thought and memory[15], while occasional users (i.e. those who take ketamine once or twice a month) have not.[16]

 Schizotypal symptoms, including delusions, superstitious thinking, dissociation, and flashbacks, have also been observed in frequent users. Symptoms may persist for some time after ketamine use ceases.[17][18]

Bladder pain is another common complaint among frequent users[19], often accompanied in the long term by reduced bladder volume, incontinence, passing blood in urine, and cystitis.[20]More research is needed to fully determine the relationship between ketamine and urological problems, but in some cases it has been necessary to surgically remove the bladder.[21]

In 2009, there were 529 ketamine-related emergency department visits in the US—compared to 36,719 for PCP and a total of 973,591 for any illicit drug.[22] Only 12 ketamine-related deaths were recorded worldwide between 1987 and 2000, and only three of these involved ketamine alone. The cause of death in each case was an overdose by injection.[23] More often, ketamine-related deaths are caused by interactions with other drugs, leading to respiratory depression and cardiac arrest.[24]

4. EFFECTS

Ketamine is active at 10-15 mg when insufflated or injected into a muscle, while more common doses range between 30 and 75 mg. Effects are usually felt within the first five minutes, but they may take up to 15 minutes after insufflation. Injection has a faster, more intense onset.

Ketamine may also be swallowed by mixing the powder with a little hot water and orange juice. The threshold oral dose is 40-50 mg, but 75-300 mg is more common.[25]

WHAT TO EXPECT

At lower doses, ketamine may cause numbness, a tingling body-high (especially in the hands, feet, and head), jerky movements, rapid breathing, and dizziness. These effects are often accompanied by euphoria, relaxation, a feeling of weightlessness, mild visuals, and blurred or roving vision. Users may also experience introspective thoughts and enhanced appreciation for music. At higher doses, visual, auditory, and even gustatory (taste-oriented) hallucinations are common, with some reporting a metallic flavor in the mouth. Hallucinations may be extremely realistic, including conversations with friends who aren’t there. [26][27][28]

At high-end “K-hole” doses, awareness of the physical environment and body dissolves. Out-of-body or near-death experiences are common, as are vivid internal realities and a distorted sense of time. The K-hole dosage is approximately 0.75 mg/lb injected or 1 mg/lb insufflated.

Some negative effects include paranoia, nausea, amnesia, and depersonalization—some of which may persist after frequent use.

PRECAUTIONS

A sitter is a good idea with ketamine, as it’s important to ensure a safe, comfortable environment. If alone, there should be no lit cigarettes or candles to be dropped or knocked over when bodily control is lost. Physical movement may become impossible, so it’s crucial not to take ketamine while driving, or anywhere near water. Numerous people have drowned in baths after losing physical control—including D. M. Turner[29] and John C. Lilly.[30]

Ketamine should also be taken on an empty stomach to avoid vomiting, which can lead to choking.[31]

5. MYTHS

“KETAMINE IS A CAT OR HORSE TRANQUILIZER AND NOT SUITABLE FOR HUMAN CONSUMPTION”

A common misrepresentation by the media, this myth gives the impression that ketamine use in humans is somehow deviant. But despite its wider use in veterinary medicine, ketamine was originally devised for and tested on humans.[1] Nowadays, it’s perhaps the most effective therapy for treatment-resistant depression, while remaining one of our most reliable anesthetics. In fact, it’s one of only two injected general anesthetics listed on the World Health Organization’s Model List of Essential Medicines—a core list of “the most efficacious, safe and cost-effective medicines for priority conditions.”[32]

6. THERAPEUTIC USE

Because it doesn’t disrupt breathing or circulation to the extent of traditional anesthetics, ketamine is well suited to patients with respiratory problems or heart disease. For the same reason it’s also useful when supplementary oxygen is scarce, making it ideal for the military.

Ketamine has been used, either topically or intravenously, to treat chronic pain like fibromyalgia and migraine (the latter of which John C. Lilly used the drug for). Since there’s no cross-tolerance between ketamine and opioids, it’s also given to patients who build up a tolerance to other anesthetics. The dissociative effects of ketamine make it especially useful for sedating patients after traumatic emergency procedures such as amputation.[11]

As an antidepressant, ketamine’s S-enantiomer, or “esketamine,” has twice been designated a “breakthrough therapy” by the FDA. In August 2016, it was fast-tracked for development as a viable medication.[33] One of its most promising features, and one that sets it apart from traditional antidepressants, is an extremely rapid onset. Depressive symptoms tend to improve within just 4-72 hours—a revolutionary improvement on the 6-12 week waiting period of other medications.[34]

While it doesn’t work for everyone, ketamine’s success rate of 85% is almost double that of traditional antidepressants (45%).[35] It’s also highly effective in patients with treatment-resistant depression, even if their symptoms have persisted for decades without relief.[36]Furthermore, it shows great promise in quickly and reliably eliminating suicidal thoughts, essentially making ketamine the first emergency “anti-suicide” drug.[37] When administered as an intranasal spray, ketamine’s antidepressant effects may last up to 30 days from a single dose.[38]

While some researchers hope for a non-hallucinogenic analogue to ketamine[39][40], others consider its unique psychedelic effects to be crucial for treatment. Ketamine psychedelic therapy (KPT), for instance, takes advantage of the highly suggestible dissociative state to address the underlying psychology of addiction. Specifically, Evgeny Krupitsky and others have been able to imprint drug addicts and alcoholics with new beliefs and memories about substance abuse, effectively creating a strong inner taboo to prevent relapse. One year after treatment, 66% of alcoholic KPT patients remained sober, while 69% of a non-KPT control group returned to drinking.[26]

Recent studies have linked this effect to ketamine’s antagonism of NMDA receptors, destabilizing and even erasing memories that reinforce drinking.[41][42]

KPT has also helped heroin addicts abstain following release from rehab. Those given regular KPT sessions were far less likely to use heroin again than those who received counseling alone.[43] Importantly, it’s the hallucinogenic doses that have the effect; sub-psychedelic doses of 0.2 mg/kg are found to be ineffective.[44]

Other psychotherapeutic applications of ketamine’s dissociative effect include regression, ego-dissolution, and group healing ceremonies.[4]

7. PERSONAL GROWTH

The “near-death experience,” or ego-dissolution, of ketamine can have profoundly transformative effects on an individual’s worldview. Concurrent with the neuroplasticity effect observed in animal and human studies, many have reported shifts in their awareness or perspective and the fading away of otherwise fixed habits and behaviors.[45]

John C. Lilly was enthusiastic about what he called the “emergent state” on ketamine, more commonly known as the “K-hole.” In this state, he said, time slows to the point of becoming meaningless; and events that shape one’s life, along with the causal relationships between them, become readily available for analysis. Dissociated from personal involvement, one may objectively examine one’s ego, behavior, and motivations. Lilly recommended experimentation with different personality traits, or self “programs” while in the emergent state. He advised “trying them on” to see their consequences before deciding to adopt them for good. He called this “metaprogramming.”[46]

Ketamine has also been found to increase compassion and sensitivity to others, reduce fear of death, and increase joy in living.[47]

8. LEGALITY

Ketamine was designated a Schedule III non-narcotic substance under the Federal Controlled Substances Act in August 1999.[48] This places it in the same category as anabolic steroids, immediate-acting barbiturates, and LSA (d-lysergic acid amide, or ergine).[49] It is illegal to possess ketamine in the US without a prescription[50] and first offenses may be subject to federal fines of up to $250,000 and/or three years in prison—although possession in small amounts for personal use is more likely to be prosecuted at the state level.

In the UK, ketamine is a Class B substance, the same category as cannabis, codeine, and most amphetamines. Possession is punishable by up to five years in prison.[51]

Ketamine is also illegal in Canada, Australia, and New Zealand. Most countries, including Brazil, restrict the drug to veterinary use, while others permit it for humans on prescription. Very few countries allow it to be sold over-the-counter.[52]

9. FAQ

CAN IT BE DETECTED IN A DRUG TEST?

Ketamine isn’t usually tested for, but it may be included in some extended screens. Because of its chemical similarities to PCP, it may also trigger a false positive. It’s usually detectable in urine for 2-4 days, but tests looking for ketamine specifically will detect norketamine (the major metabolite) in blood and urine for up to 14 days, or longer in frequent users.[53]

WILL KETAMINE MAKE ME CRAZY?

Frequent users may notice long-term cognitive impairments but occasional users tend not to. In any case, symptoms like perceptual distortion, memory loss, and delusional thinking are likely to fade over time. Nonetheless, it’s easy to feel “crazy” in the dissociative state itself. As with any psychedelic, set and setting are important.

ARE THERE RISKS?

While overdose fatalities are rare, there are certainly risks involved. As a general anesthetic, ketamine heavily impairs physical movement and people have been known drown or otherwise injure themselves as a result. Serious injuries may go unnoticed and therefore untreated because of the analgesic effect. Long-term health risks are associated with frequent use.

WHAT IS THE SAFEST WAY TO TAKE KETAMINE?

Some users prefer intramuscular injection because snorting can lead to blocked nostrils and watery eyes. Injection tends to be more intense, which is a plus for some users but a minus for others. Muscle pain is also common when injecting, especially with lower gauge needles. Intravenous injection is rare among recreational users, as is oral use, perhaps because of the unpleasant taste.

CAN I USE KETAMINE TO MICRODOSE?

A mood enhancement effect has been noticed, particularly among sufferers of depression, with sub-perceptual doses of up to 0.2 mg/kg. However, ketamine is not considered safe for microdosing at the same rate as LSD or psilocybin.

Further information on microdosing with ketamine can be found here.

DOES KETAMINE PRODUCE TOLERANCE?

Tolerance builds up slowly, often over a period of weeks with regular use. It can easily be habit-forming if it’s readily available. Although there’s no risk of physical addiction, it’s a good idea to set personal limits to avoid habituation.

CAN I MIX IT WITH OTHER DRUGS?

Ketamine should never be mixed with drugs that depress breathing. These include alcohol, GHB/GBL, opioids, and tramadol. Doing so increases the risk of unconsciousness and choking (e.g. on vomit). Benzodiazepenes, MAOIs, amphetamines, and cocaine are also risky in combination with ketamine. While the drug appears to be safe with LSD, MDMA, and cannabis, among others, combinations are generally advised against. Find out more here.

10. FOOTNOTES

[1] Jansen, K. L. R. (2001). A review of the non-medical use of ketamine: use, users and consequences. Journal of Psychoactive Drugs, 32(4), 419-33.

[2] Domino, E. F., Chodoff, P., Corssen, G. (1965). Pharmacologic effects of CI-581, a new dissociative anesthetic, in man. Clinical Pharmacology & Therapeutics, 6, 279-91.

[3] Hooper, J. (1983). John Lilly: Altered States. Omni Magazine.

[4] Browne-Miller, A. (Ed.). (2009). The Praeger International Collection on Addictions. Westport, CT: Praeger Publishers.

[5] Global Drug Survey. (2016). What we learned from GDS2016: An overview of our key findings.

[6] SAMHSA. (2008). The NSDUH Report -Use of Specific Hallucinogens: 2006.

[7] The University of Michigan. (2011). Monitoring the Future.

[8] Daly, M. (2016). Why Do the British Love Ketamine So Much? Vice.

[9] ACMD. (2013). Ketamine: a review of use and harm.

[10] Hatton, C. (2015). The Ketamine Connection. BBC News.

[11] Kurdi, M. S., Theerth, K. A., Deva, R. S. (2014). Ketamine: Current applications in anesthesia, pain, and critical care. Anesthesia Essays and Researches, 8(3), 283-290.

[12] Mion, G., Villevieille, T. (2013). Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings). CNS Neuroscience & Therapeutics, 19(6), 370-80.

[13] Zou, X. et al. (2009). Prolonged exposure to ketamine increases neurodegeneration in the developing monkey brain. International Journal of Developmental Neuroscience, 27(7), 727-731.

[14] Yan, J., Huang, Y., Chen, J., Jiang, H. (2014). Repeated administration of ketamine can induce hippocampal neurodegeneration and long-term cognitive impairment via the ROS/HIF-1α pathway in developing rats. International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 33(6), 1715-32.

[15] Morgan, C. J.,

Integral Transpersonal Psychiatry - Carlos Warter, MD

Allows for a humanistic, transcendent and holistic view of people.

The basis of the theory is seeing patients not just in terms of their symptoms or dysfunctional aspects, but instead in terms of their potential and internal resources that they do not even are aware that they possess.

I firmly believe that within a human being there is nothing wrong "per se". There are just un-evolved, small aspects of dysfunction or misinformation within each person.  If one can accept them compassionately, these aspects can be modified and functionally integrated.

 I invite the patient to expand their self-awareness, using self-observation in the here and now, to realize their own behavior patterns thus connecting with their true core structure.

In order to do this, one must first become aware of the mandates and conditionings that govern one´s being from the moment of birth.

What is this conditioning?

When you see a newborn baby she feels as close to perfection as a human being can ever be.

All potentialities are within the child.  Yet when environment and parents take the baby in their arms for the first time, they do so not only with all their love but also with all of their values, beliefs, and unsatisfied desires.  The baby absorbs it all but especially the unresolved conflicts with which the parents identify.  This begins to shape the baby in a “personal” way.  The parent’s teach the baby with their "shoulds" and "oughts" and when they say, "This is you", of course, the baby believes it.

As the baby grows, becoming a child, an adult and finally an elder the person believes everything his parents, teachers, family and society said was his true persona or his true self. This belief makes it impossible to change.  The person still does not realize that what he knows is true about himself is only a biased point of view that was learned. Of course, the person acted according to that belief and confirmed every day, in every act, every thought the false personality. Suffering emerges, as the person continuously stumbles on the same stones, not wanting to make a mistake and at the same time, never learning to act differently. From this interplay, what we call symptomatology arises.

As we are all born with a great need for love and acceptance from our parents, we incorporate these mandates as our own (we identify with them) coming to believe that we really are what we were told.

In this process we exile the essential aspects that do belong to us, covering up in the shadows of our consciousness the immense potential with which we were born.

Over the years, we no longer need outside punishment if we respond differently than expected because we become our own self-censors and self-punishing automatic machines.

We quarrel with those parts of ourselves that do not conform to the ideal of what we want to be (or what we think others want us to be) and end up self-mutilating, sometimes physically or most of the time psychologically.  This produces symptoms and pain that accompanies our lives, creating signs that show us that there are things in our life that we can not handle. Symptoms of the most diverse order: fear, anguish, anxiety, phobias, panic attacks, eating disorders, psychosomatic symptoms, stress, etc.

How can we break this sickening circle?

Transpersonal Psychology shows us that the only way is to develop what is called the Witness Consciousness Of the Essential Self.

We progress by expanding our consciousness through self-observation in the here and now.

Understanding the past that created us but acting in the present to modify the automatic responses  which were acquired.

We need to become able to restrict without criticizing, without judging, and learn something we were never taught: to accept ourselves compassionately for who we are and what we truly are.

This does not mean being self-patronizing, or having self-pity.

It means accepting gently and lovingly, even those things we do not like about ourselves.

With new ways of seeing things, we can achieve true self-acceptance, thus taking the first essential step to change.

Quantum physics has amply demonstrated how the observer changes the observed reality.

Therefore, facts we least want to observe in ourselves when consciously accepted, become transformed. 

When this occurs, we have in our hands a basic tool to build our life: the power of choice.

We can choose -  at any time -  to return and repeat the past that hurts us, or conversely, shift by looking within for more creative outlets of expression and behavior. A new strength emerges when we realize that we can respond differently and discover that disease is to choose what is not good for us.

So the ultimate meaning of the therapist is to accompany the person on this wonderful journey of self-discovery. To provide the necessary tools to have better links with one´s self and with the environment. To use wisely the power of choice so as to initiate contact with one´s true spirituality which then translates into a meaningful life, existentially helpful, always tending towards self-realization.

 

 

 

On the Primary Season by Carlos Warter MD

We need compassionate approach towards those in society who are being manipulated, recognizing their pain as legitimate and their desire for a very different kind of world as legitimate even if we disagree with the strategies they've temporarily adopted to address their deep and legitimate needs to feel valued and cared for.  

We need a new vision of the world that would fulfill those needs without engaging in the hateful policies or behaviors that  demagogues encourage and support. 

We need an embrace of true "homeland security" -- replacing the failed Strategy of Domination with a Strategy of Generosity.  Our security and well being depends on the well being of everyone else on this planet as well as on the health of the planet itself.

An important way to manifest this caring is through a Global  Plan that would dedicate 1-2% of the U.S./EU/ JAPAN/ CHINA /SWITZERLAND annual Gross Domestic Product , each year,  for the next twenty years to eliminate domestic and global poverty, homelessness, hunger, inadequate education, health care and repair damage done to the environment by 150 years of ecologically irresponsible forms of industrialization and “modernization” throughout much of the world.

This Plan that includes

  • Participation in planning and fund-distribution decisions by the recipient cities and countries’ most talented and ethically sensitive leaders as well as activists from local communities representing the poor and outstanding figures in the ethical, cultural, religious and non-profit sectors of relevant societies.

  • Methods for ensuring that the monies are used in the most effective, environmentally sustainable and culturally sensitive ways.

  • Safeguards to guarantee that the monies are not siphoned off by governments or local elites or primarily for creating the infrastructure for large corporations, but actually reach the people in need.

  • Amending all existing and future trade agreements to ensure that they serve the economic well-being of the poor and not just the interests of the wealthy nations or local elites in countries with high levels of poverty.

  • Retraining the military to build and rebuild vital infrastructure.

  • Global leadership by the United States to start this effort and encourage other advanced industrial societies to join the plan.

Approaching this initiative with a spirit of humility, not only because of the legacy of colonialism and self-interested Western trade policies which contributed to the underdevelopment in poor countries, but because we can learn much from the cultures and spiritual heritage of other societies—recognizing that their economic poverty does not signify a poverty of wisdom.(be it intra nationals like hopi, navajo, cheyenne, etc) or extranational in other continents living in tribal settings. Generosity of spirit as well as financial generosity are an integral part as a central component in any rational plan to achieve “planetary homeland security,” but also because it reflects a commitment to recognize every human being on this planet as equally valuable and deserving of care. thus getting money out of the business of politics not only by requiring public funding of elections while banning all other sources of campaign contributions, but also by requiring corporations to prove a satisfactory history of social and environmental responsibility once every five years to a council of elder citizens who will hear testimony from people all around the world whose lives have been impacted by the policies, behaviors, products and/or services thus creating a New Planetary Bottom Line.

In order to reach a full understanding of that vision of the world that liberals, conservatives as well as progressives ought to be be addressing, a  sophisticated psycho-spiritual approach to social transformation is needed  led not only by people in every religious tradition but also by atheists and secular humanists of every variety, understanding that we are spiritual beings having a material existence.

C. Warter M.D.

Founder WHFDP