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 entiformatie
EvolutionaryMovements
Registered: 03/06/03
Posts: 1,043
Loc: miami, florida
Last seen: 7 months, 18 days
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depends... how much you willin to pay?
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/opinion
.sean
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entiformatie
EvolutionaryMovements
Registered: 03/06/03
Posts: 1,043
Loc: miami, florida
Last seen: 7 months, 18 days
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 Re: How Hallucinogenic Drugs Work  [Re: entiformatie]
#3577885 - 01/04/05 01:06 AM (4 years, 5 months ago) |
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pffft, just kiddin. maybe a couple people could take on that at once?
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/opinion
.sean
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Annom
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Registered: 12/22/02
Posts: 5,469
Loc: the Netherlands
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Re: How Hallucinogenic Drugs Work [Re: entiformatie]
#3578060 - 01/04/05 01:49 AM (4 years, 5 months ago) |
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We should do that! 
How Hallucinogenic Drugs Work
Barry L. Jacobs (1987, "How Hallucinogenic Drugs Work", American Scientist vol. 75:386-392)
The site of action for hallucinogenic drugs such as LSD has now been identified. They act in the brain at a specific receptor subtype for the chemical neurotransmitter serotonin. My primary purpose here is to summarize the recent data which have led to this conclusion. This article is an update of an article which appeared in American Scientist in 1979 and which should be consulted for detailed background information (1).
Hallucinogenic drugs have been revered in many societies for their use in religious rites or as medicinal agents. Their use in modern Western societies has been much more controversial. On the one hand, they are considered to be dangerous drugs: the Federal Bureau of Narcotics and Dangerous Drugs has placed them in Schedule I, the most restrictive class. The general public has also had a negative attitude towards them, in part because of their association with the antiwar and counter cultural movement of the 1960s. On the positive side, hallucinogenic drugs are considered by some to be a liberating vehicle for exploration of the hidden recesses of the mind (Fig. 1).
Scientists have been interested in this drug group for several reasons. Because they produce profound changes in perception and affect, hallucinogenic drugs might provide some insight into these basic psychological processes. Similarly, some consider them to be of particular interest form a mental health perspective since they are psychotomimetic ? that is, their effects mimic certain aspects of the major psychoses. Finally, because these impressive effects are often produced by minute quantities (microgram amounts in the case of LSD), hallucinogenic drugs are of particular interest to those who study the brain; their potency implies that the drugs act with specificity at particular sites within the brain.
Edited by Annom (01/04/05 06:19 AM)
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Annom
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Re: How Hallucinogenic Drugs Work [Re: Annom]
#3578375 - 01/04/05 06:11 AM (4 years, 5 months ago) |
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Although a large number of drugs may be considered psychoactive (i.e., influencing psychological processes such as perception, emotion, memory and attention), only a small group are generally identified as hallucinogenic: LSD (lysergic acid diethylamide), 2,5-dimethoxy-4-methylamphetamine (DOM), N,N-dimethyltryptamine (DMT), Psilocin, mescaline, and their congeners.
The grouping of these drugs is not arbitrary or simply for the sake of convenience. They can be considered members of the same drug class for two important reasons. First, they elicit a common set of effects (2): sensory-perceptual (distorted time sense; altered sensations of colours, sounds, and shapes, ultimately developing into complex, often multimodal hallucinations; and synesthesia, or mixing of senses); psychic (dreamlike feelings; depersonalisation; and rapid and often profound alternations of affects such as depression or elation); and somatic (dizziness, tingling skin, weakness, tremor, nausea, and increased reflexes). Second, and perhaps more important, these drugs display cross-tolerance ? that is, a decrease efficacy of one drug taken shortly after another drug (e.g., 3, 4). Thus, if a person has a full-blown hallucinatory experience following ingestion of LSD, the normal hallucinatory response to mescaline of DOM taken the next day will be dramatically blunted or abolished. Therefore, even though it may be argued, and perhaps correctly so, that drugs such as marijuana and phencyclidine (PCP, or ?angel dust?) should also be classified as hallucinogenic, they do not belong to the class of LSD-like drugs since they show no evidence of cross-tolerance with them.
Not only is evidence of cross-tolerence important for grouping drugs, but it provides presumptive evidence for a common biological site of action and encourages the strategy of searching for a single site in the brain shared by all of the drugs in the class. From a strictly molecular point of view, it is not obvious that this should be the case, since the various drugs are structurally dissimilar (fig. 2): LSD is an ergot derivative; mescaline and DOM are phenylethylamines; and Psilocin and DMT are indoleamines. However, as we shall see,
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 mjshroomer
Sage
Registered: 07/21/99
Posts: 13,774
Loc: gone with my shrooms
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You can if you have the time.
mj
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Annom
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Registered: 12/22/02
Posts: 5,469
Loc: the Netherlands
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Re: How Hallucinogenic Drugs Work [Re: Annom]
#3610994 - 01/11/05 12:41 AM (4 years, 5 months ago) |
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evidence from basic biological studies does indeed support a common site of action for all of them.
Before proceeding, it will be helpful to trace briefly the events which permit brain cells (neurons) to influence each other. Most neurons in the mammalian brain communicate chemically, as shown diagrammatically in figure 3. Chemicals (neurotransmitters) are released from the axon terminals of one neuron and cross a small gap (synapse) between neurons to forum a chemical bond with a protein receptor produces either excitation or inhibition of the target neuron. If all the inputs to the target neuron summate to produce a sufficient level of excitation at the cell body, the neuron fires or discharges an action potential which propagates down tot the axon, repeating the cycle of release of neurotransmitter into the synaptic gap.
A surprisingly large number of substances are thought to mediate chemical neurotransmission in the brain (somewhere between 20 and 50), and additional ones are still being discovered. Many of them are relatively simple molecules, either amino acids or derivatives of amino acids, while others are more complex peptides. A major breakthrough took place in the 1960?s, when, using an anatomical method called fluorescence histochemistry, a group of Swedish investigators mapped the location of neurons in the brain that utilize norepeniphrine, dopamine, and serotonin for chemical neurotransmission (5,6).
Specification of the location of the cell bodies, axon pathways, and terminals of each of these groups of neurons permitted maps based on neurochemical identify to be drawn. No only did this facilitate the development of more meaningful ?wiring diagrams? of the brain, but it attorded scientists the opportunity to study and manipulate particular groups of neurons. The neurons that we shall be examining in detail, those containing serotonin (5-hydroxytryptamine, or 5-HT), have their cell bodies (the point where an action potential is initiated) in a primitive part of the brain called the brainstem (Fig. 4)), which is known to control many basic physiological processes such as respiration and functioning of the cardiovascular system. From this site of origin, the axons of serotonergic neurons project to virtually all portions of the brain, including the most recently evolved neocortex.
One complication of this simple picture of chemical neurotransmission that is of special relevance to our story is the fact that each neurotransmitter can act at more than one type of receptor. It is assumed that these receptor subtypes exist for the purpose of diversifying the cellular effects of any given neurotransmitter. Thus, serotonin acts as 5-HT1A, 5HT1B, possibly 5-HT1C, and 5-HT2 receptor subtypes in the brain (Fig. 5). Because the protein molecules, which constitute receptor sites, have slightly different conformations for each subtype, drugs can be developed to stimulate (or block) a particular receptor subtype. This preferential action presumably does not occur under normal physiological conditions, since the endogenous neurotransmitter is active at all the receptor subtypes
Edited by Annom (01/11/05 12:48 AM)
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Annom
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Posts: 5,469
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Re: How Hallucinogenic Drugs Work [Re: Annom]
#3611031 - 01/11/05 12:50 AM (4 years, 5 months ago) |
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Please help me and put this:
into text!
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redgreenvines
irregular verb
Registered: 04/08/04
Posts: 11,641
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Re: How Hallucinogenic Drugs Work [Re: Annom]
#3616735 - 01/12/05 04:43 AM (4 years, 5 months ago) |
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"Much of the research on hallucinogenic drugs has focussed on brain serotonin. there are two major reasons for this. First it was discovered early on that many of the major hallucinogens had a molecular structure similar to that of serotonin. Second, animal studies examining brain neurochemistry following adnimistration of hallucinogens invariably reported changes in serotonin.
It is not surprising that much of the brain and a number of its neurotransmitters react to the administration of these powerful drugs. Howerver, the only reliable and consistent change common to all LSD-like hallucinogens is seen in brain serotonin, manifesting itself as changes in synthesis, release, catabolism, or receptor action.
It is well known that he hallucinatory experience is a varied and complex one - in fact, this is one of the hallmarks of hallucinations. Therefore, it may appear naive to speak of these effects being mediated by a single specific neurotransmitter system. However, we are talking about the primary (or initiating) site of action of hallucinogenic drugs. Once a drug acts upon the brain and many of its constituent neurochemical systems.
thus the brain serotonin system acts as a trigger for a multitude of changes whose elaboration generates the hallucinatory experience"
my take:
serotonin is an alternate neurotransmitter in the brain.BUT WHAT DOES IT DO???
well it facilitates sub threashold multiaxxon transmission to cell bodies largely in midbrain structures. Normally you expect One Shot transmission from one neuron to affect only one other neuron, but many neurons running from the cortex to the basal ganglia have branched axxons and emit sub threashold amounts of neurotransmitter to each cell conntacted. serotonin in the region allows these minor chemical triggers to elicit a full response by the receiving cell.
when it is sucked out of a region or blocked in action it inhibits the lesser potentiated circuits (i.e. the weaker subthreashold transmissions do not succeed to trigger).
the whole brain system runs darker and only the most trained circuits when serotonin is depleated or blocked (hence SSRI's help with depression and obsession)
I gave the rest of my theory above about normal brain function, but I will repeat that any substance that increases the persistence of a moment's neural resonance beyond it's natural duration will establish a condition of layered moments (frame stacking) or being subject to psychedellic enhanced life. Increasing the serotonin is a great way to increase the connections and the feedback or echo-ing of associations and primary signals in a moment in the brain.
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~ ~ ~ ~ ~ ~ ~ ~
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Annom
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Registered: 12/22/02
Posts: 5,469
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Re: How Hallucinogenic Drugs Work [Re: redgreenvines]
#3618307 - 01/12/05 01:47 PM (4 years, 5 months ago) |
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Great! Thanks!
I'll do some more if I have some time....
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Anno
Experimenter
Registered: 06/17/99
Posts: 24,020
Loc: my room
Last seen: 6 days, 17 hours
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Re: How Hallucinogenic Drugs Work [Re: Annom]
#3630372 - 01/15/05 07:59 AM (4 years, 5 months ago) |
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Pages 6+8:
Research on the role of serotonin in the action of hallucinogenic drugs has gone through three distinct phases, The first phase was initiated in the mid-1950s. It was based on the then recently discovered fact that the LSD molecule was structurally similar to that of serotonin. Investigators correctly reasoned that this might imply that l.SD's effects were mediated by an action on the neurotransmission of serotonin in the brain. Unfortunately, the level of technical expertise in the field of brain research was so primitive at that time that this hypothesis had to be tested on peripheral tissue (i.e., outside the brain), Two different groups of scientist reported that LSD exerted a powerful blockade of serotonin's biological action (8, 9). This hypothesis was quickly challenged, however, by studies employing brom-LSD a close structural analogue of LSD with a single bromine atom attached to it (10). Brom-LSD was less potent as LSD in blocking the action of serotonin in the periphery, but it did not cause hallucinogenic activity in humans We now know that the action of a drug at one site in the body does not necessarily generalize to the drug's action at another site, especially when one site is in the brain and the other is not.
In the second phase, the action of hallucinogenic drugs on the brain was examined directly. This work was begun by Daniel Freed man at Yale University in the 1960s. In his neurochemical studies he reported that the administration of hallucinogenic drugs to animals increased the level of brain serotonin and decreased the level of serotonin's metabolic by-products (11). This pattern of results implied that neurons utilizing serotonin for neurotransmission were being turned off or inhibited by the drugs. Technical advances in the mid-1960s permitted the direct testing of this hypothesis. As mentioned above, a group of Swedish investigators had mapped the location of the cell bodies, axons and terminals of several neurotransmitter systems in the brain, including serotonin. With this information in hand, the next logical step was to insert a recording microelectrode into the brain- stem areas where serotonin neurons are most densely aggregated and to administer a hallucinogenic drug. When George Aghajanian at Yale University did this in anesthetized rats, he found that the characteristically slow (1 or 2 action potentials/second) and highly regular pattern of electrical activity of these neurons was dramatically suppressed by injections of LSD(12). This supported the theory that I so and related hallucinogens acted by directly suppressing the activity of serotonin neurons themselves?the so-called presynaptic hypothesis.
?Not only is evidence of cross-tolerance important for grouping drugs, but it encourages the strategy of searching for a single site of action in the brain?
Page 7:
Figure 2. Although hallucinogenic drugs are grouped together by their tendency to elicit common psychic, somatic, and sensory-perceptual effects and by their display of cross-tolerance, they differ in molecular structure. Representatives of the three major classes are LSD (lysergic acid diethylamide), an ergot derivative; mescaline and DOM (2,5-dimethoxy-4-methylamphetamine), which are phenylethylamines; and psilocin and DMT (N,N-dimethyltryptamine), which are indoleamines.
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Anno
Experimenter
Registered: 06/17/99
Posts: 24,020
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Re: How Hallucinogenic Drugs Work [Re: Anno]
#3630380 - 01/15/05 08:08 AM (4 years, 5 months ago) |
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Page 9
Although the hypothesis is attractively parsimonious, there are a number of experimental findings at variance with it. For example, our studies of serotonin neurons in awake, freely moving cats have found that the behavioral effects of LSD (e.g., limb flicking, grooming, head shakes, investigatory and play behavior, and constant eye movements) greatly outlast the suppression of neuronal activity produced by the drug. Furthermore, animals given repeated doses of LSD ultimately develop tolerance, displaying little or no behavioral response, yet the magnitude of the concomitant suppression of serotonin neuronal activity is undiminished (13). Finally, and perhaps most importantly, some of the major hallucinogens, such as mescaline and dom, produce robust behavioral effects in spite of a failure to suppress significantly serotonin neuronal activity (14).
Behavioral pharmacology studies by James Appel at the University of South Carolina also question the pre-synaptic hypothesis. If the hallucinogenic drugs act by suppressing the activity of brain serotonin neurons, then prior destruction of these neurons (or depletion of serotonin from its axon terminal storage sites) should make the drugs behaviorally inactive, because the system is already maximally suppressed. To the contrary, such manipulations if anything enhance, rather than diminish, the behavioral effects of lsd and related hallucinogens in animals (15-77). Similar results have also been reported in studies on humans {18, 19). These enhanced effects in animals and humans are probably attributable to a proliferation of serotonin receptor sites on the target neurons to which serotonin neurons project. This phenomenon, which often follows neuronal destruction or neurotransmitter depletion, is called "de-
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Annom
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Re: How Hallucinogenic Drugs Work [Re: Anno]
#3630389 - 01/15/05 08:22 AM (4 years, 5 months ago) |
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Thanks!!! I'm putting everything together in a word document.
Page 9:
Although the hypothesis is attractively parsimonious, there are a number of experimental findings at variance with it. For example, our studies of serotonin neurons in awake, freely moving cats have found that the behavioral effects of LSD (e.g., limb flicking, grooming, head shakes, investigatory and play behavior, and constant eye movements) greatly outlast the suppression of neuronal activity produced by the drug. Furthermore, animals given repeated doses of LSD ultimately develop tolerance, displaying little or no behavioral response, yet the magnitude of the concomitant suppression of serotonin neuronal activity is undiminished (13). Finally, and perhaps most importantly, some of the major hallucinogens, such as mescaline and DOM, produce robust behavioral effects in spite of failure to suppress significantly serotonin neuronal activity (14).
Behavioral pharmacology studies by James Appel at the University of South Carolina also question the presynaptic hypothesis. If the hallucinogenic drugs act by suppressing the activity of brain serotonin neurons, then prior destruction of these neurons (or depletion of serotonin from its axon terminal storage sites) should make the drugs behaviorally inactive, because the system is already maximally suppressed. To the contrary, such manipulations if anything enhance, rather than diminish, the behavioral effects of LSD and related hallucinogens in animals (15-17). Similar results have also been reported in studies on humans (18, 19). These enhanced effects in animals and humans are probably attributable to a proliferation of serotonin receptor sites on the target neurons to which serotonin neurons project. This phenomenon, which often follows neuronal destruction or neurotransmitter depletion, is called ?denervation supersensitivity,? and the increase in the number of receptor sites appears to be a compensatory response to the decreased input. In this way, synaptic homeostasis is maintained.
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Annom
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Registered: 12/22/02
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Re: How Hallucinogenic Drugs Work [Re: Anno]
#3630393 - 01/15/05 08:25 AM (4 years, 5 months ago) |
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  I just wasted some time 
edit: or you wasted some time 
edit2: compromise, WE wasted some time 
Edited by Annom (01/15/05 08:36 AM)
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Annom
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Re: How Hallucinogenic Drugs Work [Re: Annom]
#3630419 - 01/15/05 08:50 AM (4 years, 5 months ago) |
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page 13:
Drugs, independent of their structure, exert their critical action at a 5-HT2 receptor site (36). They took a series of 22 drugs whose potency to elicit hallucinations in humans was known. The drugs were drawn from the three different structural groups of hallucinogenic drugs: ergot, phenyl ethylamine, and indoleamines. Employing radioactively labelled compounds =, they examined the affinity of these drugs for binding to 5-HT2 receptor sites in brain tissue taken from rat cerebral cortex. They found that the correlation coefficient of human hallucinogenic potency and affinity for binding was nearly perfect. This strongly supports the hypothesis that the strength of a drug?s action at the 5-HT2 receptor site predicts its potency in evoking hallucinations in humans.
A critical experiment remains to be carried out as the ultimate test of the hypothesis. Will pre-treatment of human subjects with drugs that are highly specific antagonists of serotonin?s action at the 5-HT2 site block, or markedly attenuate, the hallucinogenic effects of LSD, mescaline, DOM, Psilocin, and DMT? We may have to wait a long time for an answer to this question because of federal restrictions on such experiments.
Serotonin and the brain
Data from a variety of different sources lead to the conclusion that hallucinogenic drugs exert their critical action at a specific serotonin receptor subtype, 5-HT2. (Depending on the particular brain area, the action may
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Anno
Experimenter
Registered: 06/17/99
Posts: 24,020
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Re: How Hallucinogenic Drugs Work [Re: Annom]
#3630465 - 01/15/05 09:30 AM (4 years, 5 months ago) |
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How are you doing the translation, manually?
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Annom
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Re: How Hallucinogenic Drugs Work [Re: Anno]
#3630473 - 01/15/05 09:34 AM (4 years, 5 months ago) |
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Yes. Do you have a program for that? I couldn't find a good one.
I type pretty fast: 300hits/min.
This is what I get if I use HP scan software(I need to print and scan it, stupid program and loss of quality):
~either exGt,)?):rv or mhib,tOf'/, ) ThJsd~ notprecjude , .
the()ther ~ the a(tion()t n,11tucjnogenic dru~s! In fact# structural
ble fQr vanati(ms in the effect$ pr~
d..A:.i.Ib" t'h' c c
uCcu y t em"
A major rttm4jnlng issue is how thjs triQ;
genng .';.,'. "';0', C:' :.,Q".r:i.,,'~
actionof rect1ptors evokes '
h'c.J "".'t(, "
ht'i
st e ex~nente we tt;;Aenn{yas a nalc U(.inat1on \; al t:' th,lnge5 th{\ p~'ychic. and somat1C lft.main.'i j\s (urther
p'ro;gessis m1de inetucidattn~ the ,~ ,.,c."".".:~~. , ", , ,.c p c
"euraJ substrates (,t( emQtiQn, ~rception, a"d other
l'rtU.Dsses Wil wiii ~tter underst,tnd huw a ,han
g;e irt rc~'..',.- " -c'c.
etc.....
Edited by Annom (01/15/05 09:42 AM)
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delta9
Active Ingredient
Registered: 10/28/04
Posts: 5,238
Loc: California
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Re: How Hallucinogenic Drugs Work [Re: Annom]
#3630504 - 01/15/05 09:48 AM (4 years, 5 months ago) |
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Quote:
Annom said:
Thanks!!! I'm putting everything together in a word document.
Please no.  Use an open format. 
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delta9
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Anno
Experimenter
Registered: 06/17/99
Posts: 24,020
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Re: How Hallucinogenic Drugs Work [Re: Annom]
#3630509 - 01/15/05 09:50 AM (4 years, 5 months ago) |
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I use AbbyFinereader.
P preprocess the images by resampling them to 300 dpi and scaling them up double the visible size they are now.
you can download a trial:
http://www.abbyy.com/download/?param=28844
Page 10
nervation supersensitivity," and the increase in the number of receptor sites appears to be a compensatory response to the decreased input. In this way, synaptic homeostasis is maintained.
Postsynaptic action of hallucinogens
If hallucinogenic drugs do not exert their important action directly on serotonin neurons, is there an alternative hypothesis which still preserves the concept of a serotonin-like effect? The answer is yes, and the data supporting it represent the third (and current) phase of research on serotonin and hallucinogenic drug action. The hypothesis proposes that LSD and related drugs act directly at receptor sites on serotonin target neurons; Serotonin is known to exert both excitatory and inhibitory actions at these sites. One of the most compelling aspects of the data which support this postsynaptic hypothesis is their convergent nature and the number of different laboratories which have contributed to them.
A simple behavioral study was one of the first things that suggested to us the importance of the postsynaptic actions of hallucinogenic drugs (20). We found that the administration of lsd to rats elicited a constellation of behavioral effects that had been shown in previous studies to be produced exclusively by the administration of serotonin or drugs that mimicked its action. Furthermore, the fact that ISO could also elicit this "serotonin syndrome" in animals whose brains were depleted of serotonin demonstrated that LSD acted direct-ly upon serotonin receptors, rather than indirectly through the release of axon terminal stores of serotonin. We also found that neurotoxin-induced destruction of serotonin axon terminals enhanced this behavioral response to lsd (denervation supersensitivity, once again attributable to a proliferation of postsynaptic serotonin receptors). An important extension and generalization of these studies demonstrated that both mescaline and pom also produced the serotonin syndrome (21).
Studies employing radioactively labeled compounds that bind to particular receptors with great specificity and high affinity also point to the importance of postsynaptic serotonin receptors in hallucinogenic drug action. With repeated administration, we found that LSD became less and less effective in eliciting the behavioral syndrome in rats (20. 22). This change was accompanied by a significant decrease in the number of serotonin binding sites available on postsynaptic neurons. The specificity of the effect is demonstrated by the fact that no change was found in the availability of receptors for dopamine, another brain neurotransmitter. Recently, these results have been confirmed and extended in an important way. Repeated administration of LSD to rats was found to decrease the availability of the 5-HT: receptor subtype. Binding at the 5-HT, subtypes was unchanged (23).
Additional evidence favoring the postsynaptic hy-(Hypothesis comes from studies employing monoamine oxidase inhibitors (maois), which are widely used to treat depression in humans. One of the changes that prolonged administration of these drugs produces is a decrease in the number of serotonin receptor binding sites in the brain (24). Irwin Lucki and Alan Frazer at the University of Pennsylvania found that when rats were treated for a number of days with maois and then given
?A surprisingly large number of substances are thought to mediate chemical neurotransmission in the brain (somewhere between 20 and 50), and additional ones are still being discovered?
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Anno
Experimenter
Registered: 06/17/99
Posts: 24,020
Loc: my room
Last seen: 6 days, 17 hours
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Re: How Hallucinogenic Drugs Work [Re: Annom]
#3630514 - 01/15/05 09:50 AM (4 years, 5 months ago) |
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>Use an open format.
How about HTML (not word html......)
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delta9
Active Ingredient
Registered: 10/28/04
Posts: 5,238
Loc: California
Last seen: 8 months, 8 days
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Re: How Hallucinogenic Drugs Work [Re: Anno]
#3630515 - 01/15/05 09:52 AM (4 years, 5 months ago) |
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Quote:
Anno said:
>Use an open format.
How about HTML (not word html......)
That'll do for me. most ANYTHING is better than the idiotic mangling word does to data.
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delta9
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