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Table of Contents

1. Physical Effects

   • Sedation
   • Spontaneous Bodily Sensations
   • Changes in Felt Bodily Form & Gravity
   • Physical Euphoria
   • Perception of Bodily Lightness
   • Motor Control Loss
   • Increased Blood Pressure
   • Dehydration
   • Tactile Suppression
   • Pain Relief
   • Optical Sliding
   • Dizziness
   • Increased Salivation
   • Nausea
   • Gustatory Hallucination
   • Difficulty Urinating
   • Decreased Libido
   • Orgasm Suppression
   • Physical Autonomy

2. Visual Effects

   • Suppression
   • Double Vision
   • Pattern Recognition Suppression
   • Acuity Suppression
   • Frame Rate Suppression
   • Distortions
   • Perspective Distortion
   • Environmental Cubism
   • Environmental Orbism
   • Scenery Slicing
   • Geometry
   • Hallucinatory States

3. Cognitive Effects

   • Analysis Suppression
   • Anxiety Suppression
   • Cognitive Euphoria
   • Compulsive Redosing
   • Conceptual Thinking
   • Déjà vu
   • Delusion
   • Depersonalization & Derealization
   • Depression Reduction
   • Disinhibition
   • Dream Potentiation
   • Ego Inflation
   • Focus Suppression
   • Immersion Enhancement
   • Increased Music Appreciation
   • Introspection
   • Memory Suppression
   • Mania
   • Psychosis
   • Spatial Disorientation
   • Suggestibility Enhancement
   • Thought Deceleration
   • Time Distortion
   • Addiction Suppression

4. Auditory Effects

5. Disconnective Effects

6. Multi-sensory Effects

7. Transpersonal Effects

8. Experience Reports

9. Research

10. Toxicity and Harm Potential

    • Bladder Damage
    • Harm Reduction
    • Antibiotic Properties
    • Cognitive Effects
    • Urinary Tract Effects
    • Neurotoxicity
    • Dependence and Abuse Potential
    • Permatolerance
    • Overdose
    • Intravenous Use Caution
    • Dangerous Interactions

11. Legal Status

Ketamine: A Comprehensive Overview

Introduction to Ketamine

Ketamine, also known by various street names such as Ket, K, Special K, vitamin K, and Kitty, belongs to the classical dissociative substances of the arylcyclohexylamine class. It stands out as one of the most prominent and prototypical members of dissociatives, a diverse group that includes PCP, methoxetamine, DXM, and nitrous oxide. While its mechanism of action isn't entirely understood, it is believed to involve the blocking of the NMDA glutamate receptor.

Historical Background and Development

Originally developed by Parke-Davis Laboratories in 1963, ketamine was initially aimed to replace the surgical anesthetic phencyclidine (PCP). Over time, it found extensive use in both human and veterinary medicine, particularly in surgical and intensive care settings. However, its significance has further burgeoned due to recent clinical research findings, indicating its potential to rapidly alleviate treatment-resistant depression and suicidal ideation.

Recreational Use and Cultural Significance

Recreational utilization of ketamine was first observed among medicinal chemists in the United States in 1967. Subsequently, its popularity surged in Europe during the 1990s, where it became notorious as an adulterant in ecstasy tablets. Presently, it is deeply ingrained in popular culture, often associated with nightclub and rave scenes.

Pharmacological Effects

Ketamine induces a range of subjective effects including motor control loss, pain relief, internal hallucinations, memory suppression, conceptual thinking, immersion enhancement, euphoria, and depersonalization/dissociation. Its effects bear similarity to those of PCP and DXM but with a shorter duration and rapid onset. Ketamine is distinguished for its tendency to produce relatively "pure" dissociation, minimizing stimulation and mania compared to PCP or MXE.

Dose-Dependent Effects

The effects of ketamine exhibit high dependency on dosage. At lower doses, users typically experience alcohol-like disinhibition and relaxation. Conversely, higher doses can induce a hallucinogenic trance-like state, commonly referred to as a "k-hole," characterized by an "out-of-body" or "near-death" experience.

Abuse Potential and Health Risks

Ketamine carries a moderate to high potential for abuse. Chronic use, particularly at high doses with repeated administration, is associated with compulsive redosing and psychological dependence. Despite limited research on the health risks of chronic or heavy ketamine use, emerging evidence suggests its link to bladder dysfunction and potential cognitive and memory impairments.

Conclusion and Harm Reduction Practices

Given the potential risks associated with ketamine use, it is highly recommended to adopt harm reduction practices when engaging with this substance.

Dosage and Bioavailability of Ketamine

Bioavailability

Ketamine boasts a bioavailability of approximately 45%. This means that when administered through various routes such as oral, intranasal, intravenous, or intramuscular, roughly 45% of the drug enters systemic circulation to exert its effects.

Dosage Ranges

• Threshold: The minimum dosage required to elicit noticeable effects of ketamine is around 5 mg.

• Light: Light dosages typically range between 10 to 30 mg, resulting in mild effects that may include altered perception and subtle dissociation.

• Common: Common doses fall within the range of 30 to 75 mg. At this level, users typically experience moderate dissociation, along with other subjective effects such as euphoria and altered sensory perception.

• Strong: Strong doses range from 75 to 150 mg. These doses induce profound dissociative effects, potentially leading to the infamous "k-hole" experience characterized by intense dissociation and hallucinations.

• Heavy: Heavy doses surpass 150 mg and can lead to extremely intense dissociative experiences, often accompanied by complete detachment from reality and profound alterations in consciousness.

It's crucial to note that individual responses to ketamine can vary significantly based on factors such as tolerance, body weight, metabolism, and overall health. Therefore, it's advisable to start with lower doses and gradually increase dosage under controlled circumstances, ensuring safety and minimizing potential risks.

History and Culture of Ketamine

Synthesis and Medical Development

Ketamine was first synthesized by the American scientist Calvin Stevens at Parke Davis Laboratories. Its creation stemmed from the need for a new anesthetic to replace PCP, which was unsuitable for human use due to its severe hallucinogenic effects upon recovery of consciousness. Initially patented in Belgium in 1963, ketamine found its first application as a veterinary anesthetic. Subsequently, after Parke-Davis patented it for both human and animal use in 1966, it became available by prescription in 1969 in the form of ketamine hydrochloride, marketed under the name Ketalar. The United States Food and Drug Administration approved its human consumption in 1970. Its favorable sympathomimetic properties and wide safety margin led to its administration as a field anesthetic to soldiers during the Vietnam War.

Recognition and Cultural Significance

Ketamine's significance is underscored by its inclusion on the World Health Organization’s "Essential Drugs List," denoting it as one of the safest and most effective drugs essential for a modern healthcare system.

Common Names and Street Terminology

Ketamine is known by various names in both medical and recreational circles. Common street names include "Special K," "K," "Kit Kat," "kitty," "horse/dog/cat tranquilizer" (referring to its veterinary use), "Cat Valium," and "Jet."

Chemical Composition and Enantiomers

Chemically, ketamine, or (RS)-2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone, belongs to the arylcyclohexylamine class of synthetic organic compounds. It consists of a cyclohexane ring bound to an aromatic ring with an amine group. Ketamine is a racemic mixture comprising equal amounts of two enantiomers: esketamine and arketamine. Esketamine exhibits greater potency as an NMDA receptor antagonist and dissociative hallucinogen compared to arketamine.

Pharmacological Action

Ketamine functions as a non-competitive NMDA receptor antagonist, disrupting the passage of electrical signals between neurons in the brain and spinal column. This blockade leads to dissociative effects, including loss of sensation and movement, culminating in the "K-hole" state. Additionally, ketamine interacts with μ-opioid receptors, sigma receptors, muscarinic receptors, serotonin receptors, and voltage-gated calcium channels, exerting various pharmacological effects.

Research and Psychoplastogen

Ketamine is identified as a psychoplastogen, capable of promoting rapid and sustained neuroplasticity, which may underlie its therapeutic effects.

Subjective Effects

At higher doses, ketamine induces significant cognitive impairment and alterations, often resulting in the loss of symbolic reasoning, communication, and fine motor abilities. Users may also experience an antidepressant afterglow lasting days or weeks.

Disclaimer: The subjective effects listed are sourced from anecdotal user reports and should be approached with caution. Higher doses increase the likelihood of experiencing the full spectrum of effects, which may include addiction, severe injury, or death.

Physical Effects of Ketamine

Sedation

Ketamine exhibits a moderate sedating effect, discouraging physical activity and potentially rendering the user immobile at higher doses.

Spontaneous Bodily Sensations

Users commonly report experiencing a sharp, pleasurable tingling sensation, referred to as the "ketamine body high." This sensation is often location-specific to the hands, feet, and head, leading to feelings of out-of-body experiences or disconnection between the mind and body. Physical euphoria may accompany these sensations.

Changes in Felt Bodily Form & Gravity

Ketamine profoundly alters the user's perception of their bodily form, particularly at higher doses where individuals may feel entirely disconnected from their body and the earth.

Physical Euphoria

While some users may experience physical euphoria, it is less pronounced and reliable compared to substances like opiates or MDMA.

Perception of Bodily Lightness

Ketamine can induce a sensation of weightlessness, with users feeling as if their body is floating and effortlessly movable, particularly at lower doses.

Motor Control Loss

Loss of gross and fine motor control, balance, and coordination is common, especially at higher doses. Users are advised to remain seated during the onset to prevent injury from falls.

Increased Blood Pressure

Higher doses of ketamine have been associated with increased blood pressure.

Dehydration

Dehydration may occur, particularly in hot, high-activity settings such as dance floors.

Tactile Suppression

Ketamine can suppress the sense of touch, leading to feelings of numbness in the extremities.

Pain Relief

Ketamine provides significant pain relief, suppressing most physical sensations.

Optical Sliding

Users may experience eye wiggling or shaking, known as nystagmus, particularly at higher doses.

Dizziness

Some users report feelings of dizziness while under the influence of ketamine.

Increased Salivation

Nausea

Nausea may occur, especially at higher doses and near the peak of the experience.

Gustatory Hallucination

Difficulty Urinating

Decreased Libido

Ketamine tends to strongly decrease libido, making sexual activity unappealing and difficult to perform, coinciding with tactile suppression and orgasm suppression.

Orgasm Suppression

Ketamine inhibits orgasms and normal sexual arousal responses at moderate to high doses.

Physical Autonomy

Relatively uncommon, but some users may experience a feeling of their body performing gestures and movements outside of their control.

Visual Effects of Ketamine

Suppression

Ketamine suppresses various visual functions, including double vision, pattern recognition, and acuity.

Distortions

Visual distortions such as perspective distortion, environmental cubism, and environmental orbism may occur.

Scenery Slicing

Geometry

Ketamine induces brightly colored geometric patterns, although less complex than those experienced with other dissociatives or psychedelics.

Hallucinatory States

Higher doses of ketamine may produce hallucinatory states, including machinescapes, internal and external hallucinations, and autonomous entities.

Cognitive Effects of Ketamine

Analysis Suppression

Ketamine impairs normal or logical thinking, while enhancing creative or non-linear thinking.

Anxiety Suppression

Cognitive Euphoria

Compulsive Redosing

Conceptual Thinking

Ketamine stimulates artistic or creative faculties, often leading to dream-like mental spaces and new insights.

Déjà Vu

Delusion

Depersonalization & Derealization

Depression Reduction

Disinhibition

Dream Potentiation

Ego Inflation

Focus Suppression

Immersion Enhancement

Increased Music Appreciation

Introspection

Memory Suppression

Ketamine strongly suppresses short and long-term memory during the experience.

Amnesia

Personal Bias Suppression

Mania

Psychosis

Spatial Disorientation

Suggestibility Enhancement

Thought Deceleration

Time Distortion

Addiction Suppression

Auditory Effects of Ketamine

Auditory Suppression

Auditory Distortion

Auditory Hallucinations

Disconnective Effects of Ketamine

Ketamine is known for its disconnective effects, including cognitive, physical, and visual disconnection.

Multi-Sensory Effects of Ketamine

Synaesthesia

Transpersonal Effects of Ketamine

Transpersonal effects, such as existential self-realization and spirituality enhancement, may occur but are less consistent than with psychedelics and entactogens.

Toxicity and Harm Potential of Ketamine

Bladder Damage

Both ketamine and esketamine may increase the risk of bladder damage. Ketamine has been associated with severe cases of bladder and liver injury. Esketamine, a newer nasal spray formulation, has a purportedly better safety profile, but short-term clinical trials have shown an increase in adverse bladder events compared to placebo. It is important to note that any physiological damage from ketamine use can be acute and immediate, particularly at typical antidepressive doses.

Harm Reduction

Given ketamine's abuse potential and potential for harm, it is strongly advised to use harm reduction practices when consuming this substance.

Antibiotic Properties

There is some evidence suggesting that ketamine may have antibiotic properties at higher doses. However, the implications for normal human use are unclear and require further research.

Cognitive Effects

Frequent ketamine use has been linked to increased depression and impaired memory, particularly verbal and visual memory. However, infrequent use does not appear to cause cognitive deficits, and any deficits that do occur may be reversible upon discontinuation of use. It is important to note that ketamine users may score higher on tests of delusional symptoms compared to non-users.

Urinary Tract Effects

Ketamine dependence has been associated with irritative urinary tract symptoms, collectively referred to as "ketamine-induced ulcerative cystitis" or "ketamine-induced vesicopathy." These symptoms include urge incontinence, decreased bladder compliance, decreased bladder volume, and painful haematuria (blood in urine). The severity and onset of these symptoms vary depending on the extent and chronicity of ketamine use.

Neurotoxicity

Studies have shown that ketamine exposure at high concentrations can lead to significant loss of differentiated cells in GABAergic neurons and long-term alterations of dendritic arbor in differentiated neurons. Additionally, ketamine use in adolescent primates has been associated with decreased locomotor activity and indicators of increased cell death in the prefrontal cortex.

Dependence and Abuse Potential

Ketamine has moderate to high abuse potential and can lead to psychological dependence with chronic use. Tolerance to its effects develops with prolonged and repeated use, leading users to consume increasingly larger doses to achieve the same effects. Ketamine also presents cross-tolerance with other dissociatives.

Permatolerance

Chronic ketamine use may lead to a long-term or permanent form of tolerance known as "permatolerance," where users require substantially more of the substance to achieve dissociation effects compared to their first use. This poses additional risks considering ketamine's negative effects on the urinary tract.

Overdose

Fatal ketamine overdoses are rare but extremely high doses may result in damage to the brain and other organs.

Intravenous Use Caution

Intravenous use of ketamine administered too quickly can cause breathing depression for a short time.

Dangerous Interactions

Ketamine can interact dangerously with other substances, leading to severe health risks. Combining ketamine with alcohol, GHB/GBL, opioids, or benzodiazepines can increase the risk of unconsciousness, respiratory depression, and vomiting aspiration.

Legal Status

Ketamine's legal status varies by country. In some countries, it is classified as a controlled substance and illegal to possess or sell without proper authorization. In others, it is legal for medical and veterinary use but illegal for recreational purposes. Always ensure compliance with local laws and regulations regarding ketamine use and distribution.

FAQ (Frequently Asked Questions)

Is ketamine safe to use?

While ketamine can be used safely under medical supervision, recreational use carries risks, including physical and psychological harm.

Can ketamine cause bladder damage?

Yes, ketamine use has been associated with bladder damage, particularly in cases of chronic use.

What are the cognitive effects of ketamine?

Ketamine can impair memory and cognitive function, particularly with frequent or high-dose use. It may also induce delusions and psychosis in susceptible individuals.

Is ketamine addictive?

Yes, ketamine has moderate to high abuse potential and can lead to psychological dependence with chronic use.

How should ketamine be used safely?

It is important to use harm reduction practices when consuming ketamine, including starting with a low dose, avoiding mixing with other substances, and taking breaks to reduce tolerance and potential harm.

What are the legal implications of ketamine use?

Ketamine's legal status varies by country, but it is generally controlled or regulated due to its potential for abuse and harm. It is important to understand and comply with local laws and regulations regarding ketamine use and distribution.