I recently wrote this esay for a colledge course tell me what you guys think...i got a A Dissocative Anesthetics: Classification, Pharmacology And dangers associated with use Introduction: Dissociative Anesthetics are a certain class of drugs which are NMDA‘N-Methyl-D-Aspartate’ antagonists. The effects of the drugs actions will be detailed later, though theses hypothesized explanations later are not considered medical fact. There are thousands of reports on the effects and research papers on the classification, pharmacology and toxicology of NMDA blockers but we do not have a perfect model of action of how theses drugs work., we have a complete medical theory so to speak but it does not point to Medical fact. Unlike our judicial system that can make determinations based on circumstantial evidence as long as un-biased people ‘jurors’ are convinced. Medical Science needs a smoking gun, and a witness to see the actions take place. In summery I will try and piece together this theory that certain drugs act primarily as NMDA antagonists. dextromethorphan hydrobromide Chemical Formula: C18H25NO Molecular Weight: 271.40 (Racemethorphan) Melting Point: 122-124° DEA Schedule: OTC Antidote: Unknown Common route of administration: Gastrointestinal, Oral Classification: Dissociative; Psychedelic; Cough Suppressant Effects and notes: DXM is usually found in OTC cough preparations 300mgs is a common dose. It produces euphoria dissociation of mind from body and dream like states. The effects are nothing like most serotonin psychedelics but the effects can take you to the same places so to speak but by different routes. Visual perception remains unaltered until a higher dose is achieved where the user may experience blurred vision. Pupil dilation, aural hallucinations, decreased sexual function, confusion and disorientation is also noted from most user reports. Most user report strange effects while walking this is commonly referred to as the “robo walk” where a user will feel like there legs are doing the walking while there minds are just experiencing the movement. Also noted is discordination, reduced agility. Some of the negative effects are upset stomach, vomiting, dizziness; body itching, diarrhea and tachycardia. The drug is most commonly used by underage users looking for a cheep constantly available high. There have been many hospitalization of user who have taken DXM in cold and cough preparation with other toxic ingredients in it like Chlorphenarimine Maleate which is toxic in the doses which are needed to induce a Dissociative state from the DXM. The future of this drug use may lead to FDA regulation in the future due to more frequent hospitalization from the drug. This is a good model of action of Dissociative drugs and is commonly used as the basis for current NMDA receptor study. The dosage is commonly oral and con be tightly controlled a there is reports of dosages over 2000mg’s so the TI is high enough for safe study in controlled conditions or recreational use, Though the user who reported this dose required hospitalization and had noted he had health related problems months after. PCP: Name: Phencyclidine Chemical name: (1-(1-phenylcyclohexyl)-piperidine) Molecular weight: 243.38 DEA Schedule: I United States Patent No.: 3,097,136 Antidote: Unknown Classification: Dissociative; Psychedelic Common rote of administration: Smoked, Snorted and Eaten in pill form Common names: Angel dust, wet, sherm, water & Sherman Hemsley. Embalming Fluid Effects and notes: PCP was once used as a medical anesthetic for IV. use and was marketed under the trade name Sernylan. Because of emergence effects of the drug its use was discontinued and it became widely popular drug of use during the 60’s and was subsequently put under DEA scheduling as a Schedule 1 Chemical which has high potential for abuse and no excepted medical use. During the 60’s-70’s it had a reputation for inducing ‘Bad Trips’ and was not widely used, since the 80’s there has been widespread resurgence of the drug, it is easily clandestinely manufactured diluted and sold at street level in vials a vial of 300ml usually sells for $20 since we can not correctly identify potency of the level the pure crystalline form is diluted at doses are usually rough estimates. The drug is commonly dipped in Cigarettes, or joints then smoked, because of the rapid onset of the drug by route of administration some users may feel overwhelmed by the high and become manic, anxious or Psychosis. In recent years there was a media slam of PCP saying it caused users to get super human strength and to basically go crazy, the experience is usually described as Feeling as one is a Dwarf or is of Super human stature and height the rush the drug produces when smoked intensives theses effects, if the user may panic this could result in the user believing they can do things ordinarily not possible, and the factor that the sympathetic nervous system might be activated once the user feels the rush the addition of adrenaline intensifies this feeling. The other subjective effects can be referenced in the category of DXM the main difference is route of administration, higher affinity for the receptors possibly and dosage. There have been reports of people mistaking actual Embalming fluid or formaldehyde which is a potent toxin, formaldehyde is metabolized into formic acid in the body which is even more toxic. Formaldehyde is one of the precursor chemicals in the manufacturing process along with other chemicals such as cyanide, since most people who make it are not experienced chemists this might explain the adverse reactions and subsequent hospitalizations associated with PCP use. Ketamine: Name: Ketamine Chemical name: (±)-2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone Molecular weight: 237.73 DEA Schedule: III MELTING POINT: 262-263° C (Hydrochloride) LD50: 224±4 mg/kg (adult mice) LD50: 229±5 mg/kg (rats) Classification: Dissociative; Psychedelic Common rote of administration: Snorted, IM. Injection Common names: Vitamin k, K, Special K, Molecular weight: 237.73 Chemical Formula: 13H16ClNO Antidote: Unknown Effects and notes: The subjective effects are very similar to DXM and PCP now the difference again is basic Pharmacokinetics Ketamine is commonly insufflated (snorted) this brings on affects faster then DXM but slower then PCP. This drug is Synthetic and most if not all street doses are stolen from Vetenarins, it comes from the manufactures in a liquid solution for IV use it is then heated slowly and dried to its Powdered form it is most frequently used at Dance parties commonly referred to as raves doses are sold by bump (a small amount usually the end of a key) roughly 10-50mg’s or by larger amounts sold by the gram for roughly $100 or more. The effects are commonly referred to as entering the “K Hole” which is a feeling of dissociation of being and subjectively experiencing stimuli as if not completely there. MK-801: Dizocilpine Chemical name: (+)-5-methyl-10,11-dihydroxy-5h-dibenzo (a,d)cyclohepten-5, 10-imine</span> DEA Schedule: Not Controlled, Research Chemical Classification: Dissociative; Psychedelic, Anticonvulsant Effects and notes: I have limited knowledge of this particular drug and its specific actions the pharmacology and research of this drug is stated later in the Toxicology selection. I could not find any user reports of this drug. This drug is commercially available to buy online for research purposes but im sure anyone with a credit card could get there hands on it, this seems to be the most Potent weight per strength NMDA blocker there is. This drug was originally studied as a drug that could prevent all neurological damage related to strokes at was perceived as a miracle drug until it was found it created damage to the Areas of the brain Dissociatives act upon, this may complete the Dissociatives theory of the mechanism of action, to sum up my theory with the blockade of NMDA. Important areas of the brain related to speech, and comprehension are turned off and do not receive stimuli that would normally pass through the NMDA receptors, so during a stroke theses areas are left undamaged, but to achieve this the person must under go a Anesthetic dose of the drug to turn off the activation of theses parts of the brain, but there is Certain toxicity at this dose referred to later. N2O: Name: Nitrous Oxide Chemical name: Dinitrogen monoxide Chemical Formula:N2O Molecular weight: 44.01 Melting Point: - 90.81° C Boiling Point: - 88.46° C Solubility: Slightly Water Soluble CAS #: 10024-97-2 DEA Schedule: Un-Scheduled, OTC Classification: Dissociative Anesthetic Gas Other names: Nitrous, Hippy Crack, Laughing Gas Effects and notes: could not found awhole lot of information as to why I belive N20 to be a dissocative anesthetic, Erowid even has it listed as one on its pages, I once stumbled upon recent research that came from FAU that it was but I could not find this article to reference it, I found plenty of medical journal references to it being a dissocitive but no decent pharamacolgical evidence. It should also be noted N20 use depletes vitamin b-12. N2o is commonly sold at head shops and is in the form of cartrages that can be open, There contents are usaly put into ballons and inhaled, Comercail grade N20 is avalible OTC but is only supposed to be sold to Dentists but theses large blue tanks are commonly found at rave partys. NOS which is commonly used to super cool engines to increase proformance is not to be used recreationaly as there are additives wich make it flammable. N2O is a true Gas even though its inhaled the high it produces is nothing like inhaling or ‘Huffing’ Solvents its not a hydrocarbon like gasoline either. That’s why its belived to be in a totally different category, User reports all mimic a short duration high that resembles most dissocitive anesthetics. Other NMDA Blockers: APV (also called AP5</span>) is a selective NMDA receptor (NMDAR) antagonist that competitively inhibits the active site of NMDAR. Its chemical name is 2-amino-5-phosphonovalerate. Riluzole: is a drug used to treat amyotrophic lateral sclerosis. Riluzole has several actions: Sodium channel blockade High-voltage calcium channel blockade N-methyl-D-aspartate (NMDA)/glutamate receptor blockade Riluzole preferentially blocks TTX-S sodium channels, which are associated with damaged neurons. This reduces influx of calcium ions and indirectly prevents stimulation of glutamate receptors. Together with direct glutamate receptor blockade, the effect of the neurotransmitter glutamate on motor neurons is greatly reduced. Addiction Potential: From one viewpoint, of course, anything can be addictive television, chocolate, masturbation, etc. So in that sense, yes, Dissociative Anesthetics can be addictive. Somewhat more relevant are the degree to which Dissociative Anesthetics are addictive, and how such addiction manifests itself. The quick answer is, Dissociative Anesthetics can be addictive if you use too much, too often. The traditional distinction made with respect to addiction is between physical addiction and psychological addiction. As examples, alcohol is physically addictive, whereas marijuana is psychologically addictive. Unfortunately this distinction has its problems not the least of which is that since the brain is a physical construct, any addiction is in some sense "physical." As physical addiction is a somewhat strange concept at best, I prefer to use the concrete ideas of tolerance and serious withdrawal symptoms. Tolerance is a process by which the body and brain adjust to a drug so that the dosage must be increased to achieve the same effect (some drugs, such as nitrous oxide, exhibit reverse tolerance, becoming more potent the more often they are used). Serious” withdrawal symptoms are somewhat less clear, unfortunately. Note that it is possible to become tolerant to a drug without being psychologically addicted; in fact, some people lose the desire to use a drug when tolerance takes away its more interesting effects. There is considerable evidence based on personal reports that tolerance to DXM more interesting Dissociative effects builds quickly. This is a result of up regulation or sensitization of NMDA receptors, as well as possible changes in other receptors and systems indirectly affected by DXM. Cross-tolerance exists between DXM, PCP and Ketamine, naturally. Usually it takes several doses before tolerance is noticeable, although a few people have noted tolerance after just one dose. Larger doses will lead to quicker tolerance. Once tolerance has built, it takes at least three weeks before receptors will reregulate to normal levels. To avoid this problem, it is probably best to dose only once a week at most. Also, some people believe that receptors which are upregulated (or downregulated) for long periods of time may tend to stay that way. Psychological addiction to Dissociative Anesthetics has been noted a few times, and can theoretically lead to physical addiction. Generally, though, dissociatives aren't considered particularly habit-forming, since they tend to have such "heavy" effects. Low-dose DXM might be an exception due to its moderate to strong stimulant effect. Most people who use Dissociative Anesthetics have noticed little or no addiction, and only mild tolerance. A few unfortunate people have developed problems with Dissociative Anesthetics. Prolonged, heavy use of Dissociative Anesthetics seems to induce dysphoria, anxiety, and/or depression in some people; as the dosage is increased, the problem gets worse. Unfortunately, at this point, there may be withdrawal problems. Pharmacology: The drugs of discussion are commonly referred to as Dissociativeanesthetics but are not used recreationally at the anesthetic level, though some of the pharmaceutical drugs are. To make the subject less complicated I won’t try and correct labeling of any drug that might fall into either category, all though theses drugs will cause anesthesia at some dose defined level. It is believed that the anesthesia that theses drugs produce is by separating neural connections between certain parts of the brain. The parts of the brain that are believed to be most affected are the posterior cingulate and retrosplenial cortex. Current Nueropharmacology does not demonstrate exactly how theses areas of the brain work; it is believed that the posterior cingulate cortex is the posterior (rear) part of the cingulate cortex, a section of the cerebral cortex interconnected with the limbic areas. The front part of the cingulate cortex is called, appropriately enough, the anterior cingulate cortex like most areas of the brain; the boundaries of the cingulate cortex are somewhat indistinct. There are differences between the posterior and anterior cingulate cortex (beyond the obvious one of location); notably, the anterior cingulate cortex has fewer pyramidal neurons than the posterior cingulate, and in the anterior cingulate these neurons have more complex connections. This entire area may relay information between the hippocampus (and other limbic systems) and other areas of the brain. There is a lot of disconnected research that points towards possible purposes for the posterior cingulate cortex. It may be one of the components of verbal and auditory memory, multisensory perception, visuospatial cognition and/or evaluation of emotional behavior. The right hemisphere posterior cingulate is activated in comprehension of metaphors, and the left in associative learning. Story comprehension seems to use the posterior cingulate. In late Alzheimer's disease the posterior cingulate may be subject to atrophy. It is activated during anxiety and in OCD (Obsessive-Compulsive Disorder), and may be overactive in bipolar disorder; it is deactivated during phobic fear. It has been suggested that the cingulate cortex in general may be involved in evaluating (posterior) and acting on (anterior) one's own behavior and spatial orientation. To put it simply, the job of the posterior cingulate cortex might be to evaluate and consider where you are and what you're doing. Since Dissociatives tend to interfere with the ability to evaluate one's own behavior, it may be that the posterior cingulate is a part of a self-evaluation system. There was considerably less information published on the retrosplenial cortex. One paper found that it was activated during the encoding of novel situations. Another suggests that the circuitry between the retrosplenial cortex and hippocampus is an important path by which the hippocampus affects learning, memory, and emotional behavior. Numerous papers suggest it has a role in visual processing (interestingly, some Dissociative users report problems getting their eyes to track right after heavy binges). My totally unfounded hunch is that the retrosplenial cortex may be involved in converting the two-dimensional data that appears on the retina into a three-dimensional space, and the "third person perspective" some get on Dissociative may be related to retrosplenial cortex disruption. In summary theses areas of the brain are used when we evaluate ourselves and what we are experiencing in relation to our minds, without trying to get metaphysical… theses areas of the brain translate certain neural/sensory input into normal understanding to be later stored in memory. The effects are dose and route of administration dependant, a small dose may cause a slight weird feeling of being away, above or inside oneself where moderate dose brings a Dissocative Stupor where objects take on strange meaning, like perceiving a tree as being something not inanimate but as a symbol of life, death, birth or any other sort of possibly that the blockade of the receptor effect has the user trying to piece together. Higher does cause Very strange effects like perceiving yourself in the third person or a Out Of Body experience the stronger the blockade the greater the areas defined show to be effected. Anesthetic dose produce unconsciousness via this mechanism this is where the Toxic effects come into play. PCP was once used as a human anesthetic. Dissociatives are not frequently used as anesthetics in humans because of what are known as "emergence effects", various odd affects that can happen when people come out of anesthesia. All anesthetics can produce these effects, but with the dissociatives it is much more common and much more severe. Dissociative anaesthetics (ketamine and tiletamine) are used in veterinary practice, since animals don't often complain about out-of-body experiences. Due to lack of knowledge and papers publish on theses theories the Pharmacokinetics are well beyond my grasp of trying to piece together or explaining. Though NMDA receptors seem to be the primary site of action most dissocitave anesthetics inhibit GABA and increase dopamine production there is also a noted bloackage of acetylcholine receptors that results in antichlorigenic affects at high doses. Antichlorigenic blockage or poisoning results in Delirium which maybe another factor or the high theses drugs produce, It should be noted this blockage happens at near anesthetic doses in lab animals and cannot be confirmed in humans. Neurotoxicty: There seems to be a heavily debated toxicity of all Dissociative anesthetics known as NMDA Antagonist Neutotoxicity or Olney’s Lesions (after the name of the man who discovered it). Though there are thousands of user reports of related damage of use of theses drugs, and the fact that the damage reported seems to correlate with the area of the brain theses drugs effect. It is important to note that Olney’s Lesions have only been viewed and observed in lab animals at the anesthetic level, doses most user do not use at, but 1 anesthetic dose of Ketamine or DXM might be just as bad as 12 high level stupor inducing doses of the same drug. When NMDA antagonists were first studied they seemed like a dream come true: here were drugs which could block from part to all of the damage from strokes, head injury, hypoxia, polio, and a variety of other conditions. However, it seems that nature never gives something for nothing, and here too there was another side to the coin. The dream ended when Olney et al. demonstrated that animals given high doses of Dizocilpine (MK-801), a new Dissociative used in research, showed curious vacuoles (essentially, tiny holes) in their brains. Specifically, the vacuoles showed up in the posterior cingulate cortex and retrosplenial. Further research showed that other indicators of damage were present, such as proliferation of microglia, secretion of a protein called HSP70 (Heat-Shock Protein 70). Since then, Onley's lesions, also known as NMDA Antagonist Neurotoxicity or NAN, have been discovered with Ketamine, PCP, and dextrorphan (the metabolite of DXM), as well as a bunch of dissociative drugs you won't find outside of a research lab. PCP causes additional damage to the cerebellum and other areas, by the way. For a long time, nobody knew whether Olney's lesions applied to human beings or not, or at what dosage they applied. The amount of ketamine used to knock out a rat, for example, is obviously different than the amount used for humans; it's also not the same dosage in mg/kg (milligrams per kilogram) either. And different effects of drugs "scale" differently too. I've reviewed reports from many hundreds of users of Dissociative Anesthetics, some of whom have used it heavily and been clearly harmed. Second, more recent studies have shown that damage occurs to lab animals' brains even at lower doses (including ordinary anaesthetic doses of ketamine and dizocilpine). Third, reports of ketamine-related brain damage have started to show up. Finally, the type of impairment people are reporting coincides exactly with the areas of the brain damaged in lab animals. To sum up: these are the skills which damage to these areas might impair: Memory, especially language-related (e.g., finding words) Understanding metaphors Evaluating, and possibly controlling, your own behavior Multi-sensory thinking Learning in new situations Certain aspects of visual perception With increasing doses, damage spreads beyond the posterior cingulate and retrosplenial cortex into other areas of the brain including the hippocampus and olfactory areas. Damage to the olfactory tubercule would, obviously, impair one's sense of smell. Damage to the limbic system itself could have wide-ranging consequences including: Autobiographical memory Declarative memory (as opposed to remembering skills) Place-memory (learning and remembering your way around) Coupling of emotions to experience William E. White believes theses to be possible Pharmacological explanations of the damage. (The following is a exert from his research papers publish at Erowid.org) Dissociatives activate neurons in the posterior cingulate cortex (PC) and retrosplenial cortex (RC). These overactive neurons pass along their excitation to "downstream" areas such as the hippocampus and olfactory areas. There are two theories on why the PC and Research Chemical neurons get overexcited in the first place; either one, both, or neither could be true. One theory is that NMDA receptors are found on inhibitory GABA interneurons, and that when these receptors are blocked, these interneurons secrete less GABA, and thus excitatory pyramidal neurons that normally receive a lot of GABA inhibition are overexcited. The other theory is that the PC and Research Chemical are less affected by NMDA blockade than the hippocampus (and related areas), and that these formations serve as feedback to the hippocampus and surrounding networks. As these limbic networks are inhibited, the PC and Research Chemical increase their output to compensate, resulting in overactivity. The overactive cells begin to heat up, use up their energy supply generate toxic waste products, and/or let in too many calcium ions. Regardless of the mechanism, or whether the mechanism is none of the above, the overactivity seems to cause intracellular organelles (notably mitochondria and endoplasmic reticulum) to malfunction. The mitochondria probably lose their proton gradient and allow their innards to spill into the surrounding cell material, where they cause all sorts of trouble, possibly including forming free radicals which cause further damage to the cell. Another possibility is that the free radicals come first, and they cause damage to the mitochondria and other organelles. Mitochondrial damage can occur within 15 minutes of the drug dose, the endoplasmic reticulum is damaged 30 minutes, and in both cases gets worse as time progresses. The free radicals, basically, destroy everything in the cell like a rampant two-year-old on a spending spree through Toys-R-Us. The cell responds to this damage with a protein called HSP70. This "heat shock" protein is made and activated when something (such as overheating, thus the name "heat shock protein" or HSP) is causing a cell to malfunction so badly as to be in danger of self-destructing, and its job is to turn the cell off until repairs can be made. Hopefully, the cell will get a lot of rest (about 24 hours) until it goes back to normal. At this point the problem is still reversible and the brain cells have not been permanently damaged. If the cell continues to be overexcited, it eventually burns out completely as the increased temperature, disrupted ion gradient, hypoxia, calcium ions, free radicals, and/or buildup of waste products kill it. At this point, surrounding support cells called microglia are activated and come in and eat the cell (probably under the theory that if an infectious organism caused the cell death, it'd better be destroyed before the infection can spread).” Conclusion: Due to the fact that all the drugs described share all the similar properties we therefore should better define where Special K, DXM, PCP and possibly nitrous oxide fit in this Dissociative anesthetic category. The final word is not in yet on the chance that Olney’s Lesions happen in humans but the dangers are apparent from hundreds of people reporting damage that correlates exactly to the areas of the brain affected. Though most drugs can be used safely this one might not fall into this category.