Effects of Ketamine on the Human Body

The desire to alter consciousness is a fundamental human trait. From being something impossible to finding numerous chemicals in controlling the mind, the process of discovery has also created opportunities for us to explore the effects and mind-tricks behind it. Just like any other new inventions in technology, there is always a path that leads to a wrong destination. The use of psychoactive drugs has turned into a trend amongst the younger generation, endangering both their own lives and the stability of the society.

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It has been said that this ingenious discover has benefited the forward of our medical industry; yet in our 21st century many have become a tool to escape from stress and reality. These so called “party drugs” are now produced in large amounts and distributed to young people at bars, nightclubs and house parties around the globe. The disastrous impact behind this irresponsible crime has led to thousands of innocent people condemned and forced to dwell in a living hell.
Different people have their own definitions of the term abuse. It is hard to have a universal definition for the word as the bottom line of an individual is drawn upon their own decision. Therefore using the definition published by the World Health Organization, “psychoactive substance abuse” is defined as “a maladaptive pattern of use indicated by …continued use despite knowledge of having a persistent or recurrent social, occupational, psychological or physical problem that is caused or exacerbated by the use [or by] recurrent use in situations in which it is physically hazardous”.  In addition, “chronic abuse” in this context will be defined as “a relapsing disease characterized by compulsive drug seeking and use despite harmful consequences as well as neurochemical and molecular changes in the brain.” , in other words, chronic abuse is addiction. Addiction is mostly dependent on previously exposed rewards such as food, alcohol, sex, and in this case, on the psychoactive drug Ketamine.
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What is Ketamine?
Psychoactive Drugs
Before answering the above question, it is important to know how ketamine is categorized as a psychoactive drug and its evolvement in human history. The term “psychoactive drug” is used to describe any chemical substance that affects mood, perception or consciousness as a result of changes in the functioning of the nervous system (brain and spinal cord).  These drugs are often termed “mind-altering” because they change the perceptions and the behavior of the individual using them.
Psychoactive drugs can be classified into seven different categories: stimulants, depressants, narcotics, cannabis, inhalants, hallucinogens and club drugs. Stimulants are mostly used to relieve tiredness and increase alertness. The most common stimulants are nicotine, which can be found in tobacco products, and caffeine, which is mixed in soft drinks and coffee. The more these drugs are consumed, the more our body will depend on it to maintain the desired effects. Cannabis acts in a similar way, only that it is a plant mainly in forms of marijuana and hashish. Depressants and Narcotics work in the opposite way. They are often used to dull senses and depress the functioning of the central nervous system. These two types of drugs are used medically as anesthetics and analgesics. Small doses of depressants may help more to relax muscles and produce calmness, while larger doses may cause difficulties with reflexes and judgement. Alcohol is a depressant which is widely found in our daily lives, and Narcotics such as opium and heroin are mostly used to relieve pain, yet a long-term dependence on these two may cause addiction and abuse. Hallucinogens and inhalants are synthetic drugs that distort the perception of reality and produce feelings of euphoria. These drugs may cause a short period of excitation and light headedness as it quickly acts on the body as it enters the bloodstream through inhalation. A good example of hallucinogenic drugs is Phencyclidine (PCP), which is mostly used as a sedative in operations before switching to Ketamine. Ketamine is the most common club drug found in the society nowadays. Club drugs have the effect of both stimulants and hallucinogens, and are most popular at party venues such as house parties and nightclubs among the younger generation. Other Club drugs include Ecstasy and Gamma-Hydroxybutryic Acid (GHB). The latter one is odorless and tasteless, therefore gaining the reputation as a date-rape drug as it may cause deep sleep and unconsciousness when administered with high dosage.  
Ketamine
As mentioned above, Ketamine was used to replace Phencyclidine (PCP) as an anesthetic medicine.  PCP was originally tested as a surgical anesthetic in the 1950s.5 It is known as a dissociative anesthetic because it can make a person feel a sense of detachment, as if the mind is separated from the body.  PCP was used in veterinary medicine to anesthetize large animals, but was never approved for use in humans because many patients became agitated, delusional and irrational while recovering from their operations. During 1960s, PCP was widely abused as it could be easily distributed in pill forms. The powdered form of PCP was developed in 1970s, commonly known as “rocket fuel”, “superweed”, etc. which is sprinkled on top of tobacco or marijuana for smoking. PCP can be easily synthesized; as a result it is often sold off on streets as another drug such as mescaline or Lysergic acid diethylamide (LSD).
Due to the worse effects illustrated by patients after the use of PCP, Ketamine was developed in 1962 to replace PCP. It was first known as Cl-581, discovered by scientist Calvin Stevens. Ketamine was then tried in humans as an anesthetic for the first time by Professor Edward Domino, and this is what he said afterwards,
‘Our findings were remarkable! The overall incidence of side effects was about one out of three volunteers. Frank emergence delirium was minimal. Most of our subjects described strange experiences like a feeling of floating in outer space and having no feeling in their arms or legs. ‘  
The successful effects soon encouraged the drug to be patented by the company Parke-Davis for use as an anesthetic in humans and animals. Nonetheless, Professor Domino described Ketamine as a potent psychedelic drug and named it as a “dissociative an anesthesia”. Ketamine was first used in large quantities in the Vietnam War by the USA Army, where it was used as an anesthesia for soldiers on field. Ketamine’s chemical structure, mechanism of action and effects are similar to those of PCP, but it acts for a shorter duration and is less potent than PCP. The drug provides dissociative anesthesia, which is a combination of analgesia with superficial sleep. This state is characterized by spontaneous ventilation, relative preservation of airway reflexes and hemodynamic stability, and explains why Ketamine has remained the anesthetic drug of choice in the developing world and for mass casualties in the field.  Ketamine is tasteless and odorless, so it can be added to food and drinks undetected. Because of this, the drug is sometimes used in sexual abuse at entertainment venues and therefore referred to as “drug rape.” Ketamine is known on the streets as special K, K and cat tranquilizer. Ketamine has plenty of other street names that have changed throughout the years. Originally it was known as “rockmesc” or “mean green”  , and then it evolved to numerous different slang names including Jet, Super K, Vitamin K, New Ecstasy, Honey oil, Mauve, Keller, Bump and Super Acid.
Uses and effects of Ketamine exposure in medicine
One of the most important happenings in the modern society is our breakthrough in the development of effective medicine for clinical procedures. Advances in technology has prospered the birth of new operation methods such as laparoscopic and robotic surgeries, enabling medical practitioners to increase efficiency to max, at the same time lowering the cost and risk of the procedure. These improvements have greatly ameliorated the side effects of conventional open surgery, allowing patients to heal faster with better comfort. Medicine becomes an indispensable need in our daily lives, and the more it improves, the more we rely on it.
I have attended a medical lecture over the summer holidays on the background of surgery. The professor explained the four most important factors behind all the surgeries, namely the 4As: Anesthetics, Analgesics, Antibiotics and Antiseptics. Among these four, Ketamine has already covered two of these factors. Ketamine has several clinically useful properties, including analgesia and less cardiorespiratory depressant effects than other anesthetic agents  ; in fact it causes some stimulation of the cardiovascular system. Ketamine is soluble in water and is prepared with the sodium salt benzethonium chloride as a preservative. It is a basic compound and is dissolved in a solution of pH 3.5-5. The ketamine molecule contains an asymmetrical carbon atom with two optical isomers (enantiomers). The S (+) isomer is about three times more potent and longer acting as an anesthetic than the R (-) isomer. It is believed that the R (-) isomer is the part of the molecule that is the root of the cause of some undesirable side effects.  Studies recently have shown that the S (+) Ketamine isomer is a stronger analgesic with a faster clearance and less side effects than the R (-). It has shown to provide a more rapid motor and sensory block, shorter duration and less motor blockade in elder males.  Ketamine interacts with N-methyl-D-asparate (NMDA), opioid, monoaminergic, muscarinic receptors and voltage sensitive Ca2+ channels. However, unlike other general anesthetic agents, ketamine does not interact with GABA receptors. The NMDA receptor is a member of the glutamate receptor family. It is an example of an ion channel coupled receptor with excitatory properties which has been implicated in the mechanism of general anesthesia, analgesia and also in neurotoxicity. Ketamine is a non-competitive antagonist of the NMDA receptor which interferes with the action of excitatory amino acids  . In addition, at clinically relevant concentrations, ketamine interacts with the phencyclidine (PCP) binding site leading to significant inhibition of NMDA receptor activity. This only occurs when the calcium ion channel has been opened.
Effects of Ketamine on our body
We were always informed with purely the basic consequences of drug abusing. For instance, we were taught that drug abusing may cause serious damage to our body – but what exactly is our body suffering from?
Central Nervous System
Ketamine is the only anesthetic available which has analgesic (pain relieving), hypnotic (sleep producing) and amnesic (short term memory loss) effects. When used correctly it is a very useful and versatile drug.  Clinically, Ketamine has been reported to produce not only general but also local anesthesia. Ketamine’s site of action is primarily in the thalamus and limbic systems. It does not suppress respiratory drive unless high doses are used, or smaller doses given rapidly. Unlike other anesthetic agents, patients who have had ketamine may have their eyes opened and make reflex actions during the operation; therefore it is not suitable for use in eye surgeries. However, use of ketamine increases the intracranial pressure, therefore patients who have recent head injuries should avoid using it to prevent further damage. The reason behind was that the rise in mean arterial pressure caused a rise in cerebral perfusion pressure and therefore intracranial pressure. Moreover ketamine is a very effective analgesia and may be used without other analgesics intraoperatively. Due to the frequent occurrence of hallucinations after operation, the patient may be in agitation during recovery. These can be reduced by premedication and by recovering the patient in a quiet area.  
I recently read several medical research papers on the effect of anesthetics and sedatives for the developing brain. A study performed by Dr. John Olney’s laboratory demonstrated widespread neuronal degeneration following the repeated administration of ketamine in newborn rats, as well as long-term decreases in neuronal density and impaired neurocognitive function in adulthood following an exposure to other anesthetic drugs.  It is further discovered that drugs used to provide clinical anesthesia and sedation are thought to affect proper formation of the central nervous system as it interferes the NMDA-type glutamate receptor function. Moreover, several studies have examined the effects of Ketamine on the developing brain of monkeys and have observed widespread neuronal cell death following the administration of multiple doses up to 75mg/kg.  Another study by Dr. Fredriksson and colleagues demonstrated that a single ketamine exposure of 50mg/kg in new-born mice caused abnormal behavior and impaired learning and memory acquisition in adolescence. Experimental data also indicate that NMDA glutamate receptor agonists and GABA receptor antagonists trigger cell death.  
As laboratory investigation on humans is not allowed, scientists may only conduct their research on rats and monkeys. The potential mechanism of anesthetic neurotoxicity is still under investigation; however, it is further complicated by the lack of understanding of exact mechanisms of consciousness and anesthesia. Therefore these results may only be interpreted as a reference to the effects that relate back to ketamine abuse.
Respiratory System
By using ketamine, the airway is usually well maintained as the airway reflexes and skeletal muscle tone are relatively preserved. Aspiration is a potential hazard despite the retention of protective reflexes. Ketamine is an effective bronchodilator and its action may be mediated either via an increase in blood catecholamine or by its direct smooth muscle relaxant effect.  When ketamine is given slowly respiration is usually well maintained, after rapid intravenous injection the breathing may stop for a short while but usually restarts within a minute.  Because of this, ketamine becomes a very useful anesthetic agent in places where there is only limited oxygen available.
Cardiovascular System
Ketamine is able to increase both blood pressure and heart rate. These variables reach a peak 2-4 minutes after an intravenous injection, then slowly decline to normal values over the next 10-20 minutes. Ketamine produces its cardiovascular effects by stimulating the central sympathetic nervous system and, to a lesser extent, by inhibiting the reuptake of norepinephrine at sympathetic nerve terminals. Individual responses may vary occasionally as there can be a large rise in blood pressure. This risk is not related to a preoperative history of hypertension, but related to the usage of ketamine. This may increase the workload of the heart; hence ketamine should be avoided in those patients with ischemic heart disease.
Induced bladder dysfunction
Bladder dysfunction associated with ketamine abuse was first voiced out in 2007 by researchers in Canada and Hong Kong. Dr. Shahani and his team presented a series of 9 patients who are all daily ketamine users presented with dysuria, frequency, urgency and frank hematuria. The CT scans revealed a thickened bladder wall, small capacity bladder and perivescicular stranding.  Dr. Chu and his team presented a series of ten patients with severe bladder dysfunction following regular ketamine abuse. From the statistics of their research, all patients had severe lower urinary tract symptoms and small functional bladder capacity varying from 20 to 200mls.  A scan of the bladder (cystoscopy) also revealed that the epithelial layer of the bladder has inflammation.  These reports were from Hong Kong and Canada where ketamine is a popular drug. Dr. Cottrell and his team reported nine patients presenting with similar urinary symptoms and cystoscopy findings following chronic ketamine usage.  These symptoms are currently left unexplained, but with increasing popularity of the drug in the younger generation, more and more ketamine users could present with ketamine induced bladder dysfunction.
As we can see from the above effects, ketamine is already able to induce a lot of problems for our body and affects the whole body system when it responses to the drug in medical uses. Some may be beneficial, but most can cause severe damage to our body, so why is ketamine still on the streets endangering our future generations?
Ketamine in our society
Back in Hong Kong, I often hear reports from the public media reporting that the police force discovers another drug dealing club/bar with underage drinking and drug abuse. Although we were educated with the basics of the consequences of drug abuse, one simply will not be able to know thoroughly about the essential damage that the drug does to the body. Take smoking as an example: Tobacco has existed for centuries, and people nowadays have beautifully wrapped cigarettes packed in delicate boxes. They can easily gain access to buying one of this highly toxic substance back home for their own enjoyment and pleasure. Putting aside the lack of awareness in the old days, nowadays all the education systems around the globe include the effects of smoking into our classes, no matter taught in Liberal Studies or specifically Biology, most people who have received education are equipped with the basic knowledge of the harmful effects of smoking. Even packages of cigarettes are posted with photos of the disastrous effects of smoking, for example, a photo of a dissected lung of a chronic smoker, still does not stop smokers from getting on with their habit.
In the 1970s, the drug was approved by the FDA to be used clinically on children and adults, yet at the same time it also started to flow into drug markets in public. Most of them were firstly sold by hospital staff; later on it became trendy to produce it in large amounts to divert ketamine into wider population. Over the past 20 years, Ketamine has emerged as a testing replacement for PCP to one of the most popular party drugs at underground parties and raves. In the late 20th century, the drug has already gained its reputation around the globe as one of the mainstream dance culture drugs in society.
In the year 1999, The Drug Enforcement Agency in the United Sates made ketamine a schedule three drug. This means that this particular drug is illegal to buy or sell without a prescription.  Ketamine is considered to be a Class C drug in the UK and Mexico, the equivalent of a schedule three in the United States; and schedule one in Canada. It was legal to possess ketamine in England, Scotland and Wales before 2006. Most countries currently have ketamine under controlled substance act in which it can be used as a medication but not recreationally, for instance ketamine is regulated under Schedule 1 of Hong Kong Chapter 134 of Dangerous Drugs Ordinance. It can only be used legally by health professionals, for university research purposes, or with a physician’s prescription.  
Taking the data of ketamine abuse in Hong Kong, in recent years, it has become more common among the teens. In Hong Kong, since 2005 it has become the commonest drug of abuse among persons aged 21 years or less; compared to the first three quarters of 2005, the number of ketamine abusers among teenagers has doubled in the first three quarters of 2008.  In 2008, ketamine abuse constituted 85% of all kinds of drug abuse among persons aged below 21 years, compared to 61% in 2005. Also, data collected by the Hospital Authority Hong Kong Poison Information Centre (HKPIC) showed that ketamine abusers represented 16% of all drug abusers attending accident and emergency departments in the period of 1 July 2005 to 31 December 2005, while the proportion rose to 40% in the period of 1 January 2008 to 30 June, indicating a steep increase of the number of ketamine abusers.  
Solutions?
The reason I decided to put a question mark after this sub topic is because there is no concrete evidence that the treatments I list below will 100% cure the patient. To overcome the psychological dependence on ketamine, the ultimate factor during the process will be the patient’s endurance and willpower. Without consistency to finish the whole course of treatment is no different to receiving no treatment. Just like antibiotics, you have to finish the whole course in order to fully recover from your illness.
We live in an inconsistent and contradictory society. On the bright side, we advise the society not to abuse drugs and say no to the people who sell or offer them to you; yet on the other hand, medical practitioners are encouraging us to take medicine that might cause similar effects and consequences as drugs like ketamine. While we tell young people that ketamine is illegal and dangerous for their health, we ignore to a large extent the bad effects that alcohol has on health, thus making it legal even if it has devastating effects on our body as well. The world has slowly turned into a place where benefits and money take hierarchy over the health of the public. There is an increase in frequent reports of making fake milk powder and eggs, as well as drug manufacturers such as the recent incident of Contergan taking the blame of causing Phocomelia in infants whose parents had taken the medicine. One of the main reasons that ketamine is still one of the most popular party drugs nowadays is due to the commercial income it brings when it comes to selling and buying. Drug dealing is happening around the globe every day, and what attracts people to do it is not the drug, but the money. Values have been overthrown by the nature of human kind, where selfishness topples conscience in the business world, no matter legal or illegal. Laws and regulations are developed over time to control the extent of these shameful behaviors, yet ultimately there is no thorough solution to this problem. Most societies are uncomfortable with people going off into trance and hallucinatory intoxications, and indeed setting up the laws against the usage and possession of drugs are to discourage people from falling into those in-built worlds of their own. But innate, neuropsychological changes in a person’s body cannot be controlled by legislation. Provided that they have the desire to take the drug, they will always be satisfied – by themselves.
Alcohol may no longer fulfill the need for teenagers to take off from reality into their virtual world of desires after they become fully exposed to it, and slowly they turn to seek stronger effects by trying out drugs like marijuana and ketamine. As they become satisfied with the effects given by the drugs, trying gradually becomes abusing. They start to develop unwise behavior as they reckon that the feeling is brought by the pills rather than from their own nervous systems getting into trouble when the pills no longer work so well. Their drug abuse becomes more frequent and compulsive, yet with less reward. This misconception is the first step to developing drug dependence, no matter whether the drug is marijuana or ketamine or if it produces physiological dependence or not. Dependence on the drug cannot be broken until the misconception is cleared. Drug abusers live on their own reasons to continue, and only those who realize that he/she has been using the drug merely as an excuse for having an experience that is superficial comes to see that the drugged state is not exactly the same with the experience he/she wants. Alternatively, they will start looking for ways that may fulfill the slight desire to lift up from reality, such as meditation and sleeping. If we look in closely to the successful examples of quitting drugs: Many drug abusers give up drugs for consciousness, but little gives up consciousness for drugs.
Conclusion
We see people travelling through time and going into the mind of others to retrieve thoughts and ideas in fiction and movies, and it is definitely something that I would love to do as well. Yet is it possible to live in dreams and neglect what’s really happening in the world we exist in? By altering the state of our consciousness, our brain is simply sending the wrong signal back to ourselves, putting us into a world of our own desires and fantasies. Ketamine can definitely achieve this, but after the short-lived dreams disappear, we will only fall deeper into the “K-hole” and become more dependent on the drug. We must be clear about the severe effects and consequences that ketamine brings to the individual and the society, and reiterate these problems to the public to prevent further abuse of it.
Psychoactive drugs will always be present as a part of our life. The society needs to recognize the problems caused by the misuse of ketamine and deal with them immediately in an open and realistic way. Drug abuse is now connected with other social problems as well, such as social deprivation or family issues. We actually do not know whether the people who abuse it really likes it, but all we need to know is how ketamine can vastly change a person’s life when you become addicted to it. From the medical research evidence shown, ketamine can really ruin your life when you are associated with it, yet why blame the drug when it is down to you to choose the reality or to stay in the dreams built by your own desires?