View source for Talk:Dissociatives

[[File:Dissociatives w - glutamate.png|370px|thumbnail|A diagrammatic comparison of the structures of [[glutamate]] and various popular dissociatives.]]
'''Dissociatives''' (also known as '''dissociative anesthetics''') refer to a class of [[hallucinogen]] which distort sensory perceptions (mainly of sight and sound) to produce feelings of disconnection, detachment, and dissociation from the environment and self. This is done by reducing or blocking signals to the conscious mind from other parts of the brain.<ref name="Tamminga CA, Tanimoto K, Kuo S, Chase TN, Contreras PC, Rice KC, Jackson AE, O'Donohue TL.">PCP-induced alterations in cerebral glucose utilization in rat brain: blockade by metaphit, a PCP-receptor-acylating agent.| http://www.ncbi.nlm.nih.gov/pubmed/2850626</ref>

Although many classes of [[psychoactive substances]] are capable of such action, dissociatives are unique in that they do so in such a way that they produce hallucinogenic effects, which generally include sensory deprivation, dissociation, hallucinations, and dream-like states or trances.<ref name="Snyder.">Snyder, Solomon H. (1980). "[[Phencyclidine]]". Nature 285 (5764): 355–6. | http://www.nature.com/nature/journal/v285/n5764/abs/285355a0.html</ref> Some dissociatives, which are non-selective in action and affect the [[dopamine]]<ref name="Giannini">Giannini, A. James; Nageotte, Catherine; Loiselle, Robert H.; Malone, Donald A.; Price, William A. (1984). "Comparison of Chlorpromazine, Haloperidol and Pimozide in the Treatment of Phencyclidine Psychosis: Da-2 Receptor Specificity". Clinical Toxicology 22 (6): 573–9. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/6725621</ref> and/or [[opioid]]<ref name="Giannini2">Giannini, A. James; Underwood, Ned A.; Condon, Maggie (2000). "Acute Ketamine Intoxication Treated by Haloperidol". American Journal of Therapeutics 7 (6): 389–91. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/11304647</ref> systems, may also be capable of inducing euphoria.

==Mechanism of action==
{{Further|NMDA receptor antagonist}}
NMDA [[receptor]]s within the brain exist to allow for the transfer of electrical signals between [[neuron|neurons]] in the brain and in the spinal column. For electrical signals to pass, the NMDA receptor must be open. To remain open, the neurotransmitters known as [[glutamate]] and [[glycine]] must bind to the NMDA receptor. An NMDA receptor that has glycine and glutamate bound to it and has an open ion channel is called "activated." 

Dissociatives are classed as NMDA receptor [[antagonist]]s. This means they bind to the receptor, but do not activate it and block other neurotransmitters from doing so. The result is a dose dependent decrease in the passing of electrical signals across the brain and an overall disconnection of neurons. This leads onto states of disconnection between conscious parts of the brain and its sensory organs as well as out-of-body experiences and accompanying hallucinations.



==Subjective effects==
{{Preamble/SubjectiveEffects}}

<div class="flex-panel">
    <div class="flex-column">
		<div class="panel radius">
			<h3 class="panel-header">Visual effects [[File:Eye.svg|x20px|right|link=]]</h3>

			<ul class="featured-table">
				<li class="featured list-item">
<h4 class="media-heading">Suppressions</h4>
*[[Double vision]]
*[[Pattern recognition suppression]]
*[[Optical sliding]]
*[[Visual acuity suppression]]
*[[Frame rate suppression]]
				</li>

				<li class="featured list-item">
<h4 class="media-heading">Distortions</h4>
*[[Perspective distortions|Perspective distortions]]
*[[Environmental cubism|Environmental cubism]]
*[[Environmental orbism|Environmental orbism]]
*[[Scenery slicing|Scenery slicing]]
				</li>

				<li class="featured list-item">
<h4 class="media-heading">[[Geometry]]</h4>
In comparison to other classes of [[hallucinogen]], this effect is significantly less complex and intricate with a limited range of effects. It does not extend beyond level 4 and is variable within most of its [[Geometry#Variations|variations]] but is exclusively simplistic in complexity, unstructured in organization, dimly lit in lighting, slow in movement and immersive in depth.
				</li>

				<li class="featured list-item">
<h4 class="media-heading">Hallucinatory states</h4>
*[[Perspective alterations]]
*[[Autonomous entities]]
*[[Scenarios and plots]]
*[[Settings, sceneries, and landscapes]]
*[[Shadow people]]
<h5 class="media-heading" style="font-weight: bold;">[[External hallucinations]]</h5>
In comparison to other classes of [[hallucinogen]], this effect can occur at heavy dosages, but is extremely infrequent in comparison to the same effect found within [[deliriant]]s. <p>It can be comprehensively described through its [[Visual_effects:_Internal_hallucinations#Variations|variations]] as delirious in believability, autonomous in controllability and solid in appearance.</p><p> The most common theme for this effect to follow is one of experiencing and talking to friends around oneself when they are not actually present.</p>
<h5 class="media-heading" style="font-weight: bold;">[[Internal hallucinations]]</h5>
In comparison to other classes of [[hallucinogen]], this effect can occur at heavy dosages but is considerably less common than the same effect found within [[psychedelic]]s and [[deliriant]]s. <p>It can be comprehensively described through its [[Visual_effects:_Internal_hallucinations#Variations|variations]] as delirious in believability, fixed in style, equal in new experiences and memory replays in content, autonomous in controllability and solid in appearance.</p>
				</li>
			</ul>
		</div>
	</div>
    <div class="flex-column">
    	<div class="panel radius">
    		<h3 class="panel-header">Disconnective effects [[File:Chain-broken.svg|x20px|right|link=]]</h3>

    		<ul class="featured-table">
				<li class="featured list-item">
*[[Consciousness disconnection]]
*[[Detachment plateaus]]
*[[Tactile disconnection]]
*[[Visual disconnection]]
**[[Visual_disconnection#Holes.2C_spaces_and_voids|Holes, spaces and voids]]
***[[Visual_disconnection#Structures|Structures]]
				</li>
			</ul>
		</div>

		<div class="panel radius">
			<h3 class="panel-header">[[Cognitive effects]] [[File:User.svg|x20px|right|link=]]</h3>

			<ul class="featured-table">
				<li class="featured list-item">
*[[Amnesia]]
*[[Conceptual thinking]]
*[[Déjà vu]]
*[[Depersonalization]]
*[[Derealization]]
*[[Dream potentiation]]
*[[Increased music appreciation]]
*[[Information processing suppression]]
*[[Introspection]]
*[[Memory suppression]]
**[[Ego death]]
*[[Personal bias suppression]]
*[[Subconscious communication]]
*[[Thought connectivity]]
*[[Thought deceleration]]
*[[Thought loops]]
*[[Time distortion]]
*[[Unity and interconnectedness]]
				</li>
			</ul>
		</div>
	</div>

	<div class="flex-column">
		<div class="panel radius">
			<h3 class="panel-header">Physical effects [[File:Child.svg|x20px|right|link=]]</h3>

			<ul class="featured-table">
				<li class="featured list-item">
*[[Physical autonomy|Physical autonomy]]
*[[Tactile suppression|Tactile suppression]]
*[[Pain relief]]
*[[Orgasm suppression]]
				</li>
			</ul>
		</div>

		<div class="panel radius">
			<h3 class="panel-header">Auditory effects [[File:Volume-up.svg|x20px|right|link=]]</h3>

			<ul class="featured-table">
				<li class="featured list-item">
*[[Auditory distortion]]
*[[Auditory hallucinations]]
*[[Auditory suppression]]
				</li>
			</ul>
		</div>

		<div class="panel radius">
			<h3 class="panel-header">Multisensory effects [[File:Cogs.svg|x20px|right|link=]]</h3>

			<ul class="featured-table">
				<li class="featured list-item">
*[[Machinescapes]]
				</li>
			</ul>
		</div>
	</div>
</div>

==Pharmacological classes==

<div class="flex-panel">
    <div class="flex-column">
		<div class="panel radius">
			<h3 class="panel-header">[[Arylcyclohexylamine|Arylcyclohexylamines]]</h3>

			<ul class="featured-table">
				<li class="featured list-item">
* [[2-Fluorodeschloroketamine]] (''2-FDCK'')
* [[3-MeO-PCMo]]
* [[3-MeO-PCP]]
* [[3-MeO-PCE]]
* [[4-MeO-PCP]]
* [[DCK]]
* [[Ketamine]]
* [[Methoxetamine]] (''MXE'')
* [[Methoxyketamine]]
* [[O-PCE]]
* [[Phencyclidine]] (''PCP'')
				</li>
			</ul>
		</div>
	</div>

    <div class="flex-column">
		<div class="panel radius">
			<h3 class="panel-header">[[Morphinan]]s</h3>

			<ul class="featured-table">
				<li class="featured list-item">
* [[Dextromethorphan]] (''DXM'')
* [[Dextrorphan]] (''DXO'')
				</li>
			</ul>
		</div>

		<div class="panel radius">
			<h3 class="panel-header">[[Diarylethylamine]]s</h3>

			<ul class="featured-table">
				<li class="featured list-item">
* [[Diphenidine]]
* [[Methoxphenidine]] (''MXP'')
* [[Ephenidine]]
				</li>
			</ul>
		</div>
	</div>



		<div class="panel radius">
			<h3 class="panel-header">[[Conantokins Peptides| Conantokins Peptides]]</h3>

			<ul class="featured-table">
				<li class="featured list-item">
* [[Conantokin-G]] (Con-G'')
* [[Conantokin-T ]](Con-T'')
* [[Conantokin-R ]](Con-R'')
* [[Conantokin-L ]](Con-L'')
* [[Conantokin-P ]](Con-Pr1, Con-Pr2 and Con-Pr3'')
* [[Conantokin-Rl-A]](Con-Rl-A'')
* [[Conantokin-Br]](Con-Br'')

				</li>
			</ul>
		</div>
	</div>

    <div class="flex-column">
		<div class="panel radius">
			<h3 class="panel-header">Others</h3>

			<ul class="featured-table">
				<li class="featured list-item">
* [[Ibogaine]]
* [[Myristicin]]
* [[Nitrous oxide]]
* [[Xenon]]
* [[Memantine]]
* [[Salvinorin A]]
				</li>
			</ul>
		</div>
	</div>
</div>

==Toxicity and harm potential==
{{toxicity}}
[[File:harmchart.png|thumb|right|300px|This radar plot shows relative physical harm, social harm, and dependence of ketamine.<ref>Development of a rational scale to assess the harm of drugs of potential misuse (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0140673607604644</ref>]]
===Ketamine===
Fatal ketamine overdoses are particularly rare, but not completely unheard of. However, the [[Toxicity::exact toxic dosage is unknown]]. 

The first large-scale, longitudinal study of ketamine users found that frequent ketamine users (at least 4 days/week, averaging 20 days/month) had increased depression and impaired memory by several measures, including verbal, short-term memory and visual memory. However, infrequent (1–4 days/month, averaging 3.25 days/month) ketamine users and former ketamine users were not found to differ from controls in memory, attention and psychological well-being tests. This suggests the infrequent use of ketamine does not cause cognitive deficits and that any deficits that might occur may be reversible when ketamine use is discontinued. However, abstinent, frequent, and infrequent users all scored higher than controls on a test of delusional symptoms.<ref>"Addiction Users Study : Consequences of chronic ketamine self-administration upon neurocognitive function and psychological wellbeing: a 1-year longitudinal study - http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2009.02761.x/abstract</ref>

Short-term exposure of cultures of [[GABAergic]] [[neuron]]s to ketamine at high concentrations led to a significant loss of differentiated cells in one study, and non-cell death-inducing concentrations of ketamine (10 μg/ml) may still initiate long-term alterations of dendritic arbor in differentiated neurons. The same study also demonstrated chronic (>24 h) administration of ketamine at concentrations as low as 0.01 μg/ml can interfere with the maintenance of dendritic arbor architecture. These results raise the possibility that chronic exposure to low, subanesthetic concentrations of ketamine, while not affecting cell survival, could still impair neuronal morphology and thus might lead to dysfunctions of neural networks.<ref>Low concentrations of ketamine initiate dendritic atrophy of differentiated GABAergic neurons in culture (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0300483X07001138</ref>
<ref>Neuroprotective NMDA antagonists: the controversy over their potential for adverse effects on cortical neuronal morphology (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/7976530</ref>

More recent studies of ketamine-induced neurotoxicity have focused on primates in an attempt to use a more accurate model than rodents. One such study administered daily ketamine doses consistent with typical recreational doses (1&nbsp;mg/kg IV) to adolescent cynomolgus monkeys for varying periods of time. Decreased locomotor activity and indicators of increased cell death in the [[prefrontal cortex]] were detected in monkeys given daily injections for six months, but not those given daily injections for one month.<ref>Chronic ketamine exposure induces permanent impairment of brain functions in adolescent cynomolgus monkeys | http://onlinelibrary.wiley.com/doi/10.1111/adb.12004/abstract</ref>

Studies have shown that the serotonin systems affected by such serotonergic drugs are linked to the [[NMDA]]/[[glutamate]] systems.<ref> author=Arvanov V, Liang X, Russo A, Wang R |title=LSD and DOB: interaction with 5-HT2A receptors to inhibit NMDA receptor-mediated transmission in the rat prefrontal cortex | http://onlinelibrary.wiley.com/doi/10.1046/j.1460-9568.1999.00726.x/abstract</ref> Tests on rats indicate that 5-HT agonists like [[LSD]] and [[Psilocin#psilocybin|psilocybin]] can prevent neurotoxicity due to NMDA receptor antagonists.<ref>Farber N, Hanslick J, Kirby C, McWilliams L, Olney J | Serotonergic agents that activate 5HT<sub>2A</sub> receptors prevent NMDA antagonist neurotoxicity | http://www.nature.com/npp/journal/v18/n1/full/1395108a.html</ref>

===Urinary tract effects===
In general, dissociatives are considered to have harmful effects on the urinary tract of humans when used heavily and/or for extended periods of time for reasons that have yet to be fully understood.{{citation needed}}

For example, according to a recent systematic review, 110 documented reports of irritative urinary tract symptoms from ketamine dependence exist.<ref>Ketamine-induced vesicopathy: a literature review | http://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2010.02502.x/abstract</ref> Urinary tract symptoms have been collectively referred to as "ketamine-induced ulcerative cystitis" or "ketamine-induced vesicopathy" and they include urge incontinence, decreased bladder compliance, decreased bladder volume and painful haematuria (blood in urine).

The time of onset of lower urinary tract symptoms varies depending, in part, on the severity and chronicity of ketamine use; however, it is unclear whether the severity and chronicity of ketamine use corresponds linearly to the presentation of these symptoms. All reported cases where the user consumed greater than 5&nbsp;grams per day reported symptoms of the lower urinary tract.<ref> Ketamine use: a review | http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2011.03576.x/abstract</ref>

It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug.
===Tolerance and addiction potential===
Although there is a significant amount of variation within the NMDA receptor antagonist family, their chronic use is typically considered [[Addiction potential::moderately addictive with a high potential for abuse]] and are capable of causing psychological dependence among certain users. When addiction has developed, cravings and [[withdrawal effects]] may occur if a person suddenly stops their usage.

===Dangerous interactions===
{{DangerousInteractions/Intro}}
{{DangerousInteractions/Dissos}}

==See also==
*[[Responsible use]]
*[[Hallucinogens]]
*[[Psychedelics]]
*[[Deliriants]]

==References==
<references />