Posted by Shawn. T. on August 3, 2003, at 16:15:19
In reply to The effects of illegal drugs..., posted by Rickson Gracie on August 3, 2003, at 7:50:31
I believe that understanding neuropharmacology is an important means toward developing a comprehension of the basis of human feelings, behaviors, and perceptual disorders. Choosing not to learn about illegal drugs simply because they're illegal would certainly be a waste of a valuable learning opportunity.
> -How does LSD give hallucinations and the mind altering effects?
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LSD produces these effects by acting as a partial agonist at serotonin 5-HT2A receptors. Atypical antipsychotics are known to block this receptor type. An agonist is a drug that activates a receptor; an antagonist blocks a receptor. A partial agonist differs from a full agonist because it interferes with the activity of full agonists; administrating a partial agonist before a full agonist will create a less potent activation of the receptor than administrating a full agonist by itself. Also, LSD is known to affect serotonin 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT1F, 5-HT2A, 5-HT2C, 5-HT5, 5-HT6, 5-HT7, dopamine D1 and D2, and alpha-1 and alpha-2 adrenergic receptors; the drug's precise effects and binding affinities at the majority of these receptors are not well known (see http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10510170&dopt=Abstract ). Essentially, all you need to know is that LSD exerts its hallucinogen effects at 5-HT2A receptors. "Magic mushrooms" that include psylocybin are also known to affect 5-HT2A receptors in addition to serotonin 5-HT1A receptors. I could go into the mechanism involved in 5-HT2A mediated hallucinations, but the details are rather complicated and not yet fully described.> -How does MDMA give intense feelings of love?
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I don't believe that anyone has conducted research on this topic, but some inferences can be made. MDMA is known to induce the release of and inhibit the reuptake of serotonin and to a less degree, dopamine. So the drug basically increases extracellular levels of serotonin and dopamine in the brain which induces a number of other effects. Researchers have found that the density of serotonin transporters are decreased in people that have recently fallen in love (see http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10405096&dopt=Abstract ). If a similar effect occurs in the brain, extracellular levels of serotonin would be expected to increase after people initially fall in love. So an increase of the activity of serotonin at its receptors probably plays a role in MDMA's effects on the feeling of love. I also believe that dopamine plays a role; drugs that are similar to MDMA that do not affect dopamine release do not affect feelings of love or empathy like MDMA does.How does serotonin influence feelings of love? My assumption is that this phenomenon involves the release of a neuropeptide called oxytocin and possibly a neuropeptide called vasopressin. MDMA has been shown to increase levels of these two neuropeptides in rats (see http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11834612&dopt=Abstract ). The attraction involved in feelings of love is likely to involve oxytocin, vasopressin, endogenous opioids, and a few other factors (see http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12834023&dopt=Abstract ). The receptors that serotonin acts at to induce oxytocin and vasopressin release (primarily 5-HT1A and 5-HT2A receptors) are desensitized after long-term treatment with SSRI's; also, SSRI's and TCA's don't affect dopamine release like MDMA does. I believe that dopamine has also been associated with oxytocin release.
> -How is the high from heroin established?
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Heroin exerts its effects primarily by acting as an agonist at mu opioid receptors. Unlike opioids such as morphine, hydrocodone (Vicodin), and oxycodone (Percocet), heroin also acts as an agonist at kappa and delta opioid receptors (although with less effectiveness than at mu receptors; see http://jpet.aspetjournals.org/cgi/content/full/288/2/438 ). The "rush" of heroin is due to the fact that it penetrates the blood brain barrier more effectively than drugs like morphine and hydrocodone. A key region of the brain involved in subjective feelings of euphoria is the shell of the nucleus accumbens. Opioids mediate the inhibition of neurons in this region of the brain (see http://jn.physiology.org/cgi/content/full/85/1/72 ); both direct and indirect effects are likely to be involved. Most drugs known to cause a euphoric "high" have been shown to inhibit medium spiny neurons in the shell of the nucleus accumbens.> -How does GHB affect the brain to produce euphoria?
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GHB is a substance that exists naturally in the brain, although at low concentrations. It exerts its effects primarily by acting at a GHB- specific receptor in the brain. Little is currently known about this receptor. Also, GHB is a weak partial agonist at GABA-B receptors; these are receptors that exert relatively slow acting inhibitory effects on neurons. The mechanism involved in GHB- induced euphoria has not yet been well described. GHB specific receptors have been shown to be located in the nucleus accumbens (see http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12850570&dopt=Abstract ). I would assume that these receptors could mediate the inhibition of neurons in this region.> -How does alcohol affect your mind to get you drunk?
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Alcohol's behavioral effects are primarily mediated by its positive modulation of GABA-A receptors; these are receptors called ligand- gated ion channels that exert relatively fast inhibitory effects on neurons. The disinhibition that you experience while drinking is due primarily to alcohol's effects on these receptors.
Alcohol also acts at a number of other ligand- and voltage- gated ion channels in the brain. These include glutamate NMDA receptors, glutamate non-NMDA receptors (to a lesser degree), serotonin 5-HT3 receptors, nicotonic acetylcholine receptors, and glycine receptors. I would say that the two key receptors involved in making you feel drunk are GABA-A and NMDA receptors; alcohol negatively modulates NMDA receptors.> I know cocaine is a dopamine agonist but that is all I know.
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Cocaine could be considered to act as a dopamine receptor agonist, but only in the sense that it indirectly induces the activation of dopamine receptors. Cocaine inhibits the reuptake of dopamine, norepinephrine, and serotonin into nerve terminals. It is most potent as a dopamine reuptake inhibitor and least potent as a serotonin reuptake inhibitor. The addictive and euphoric effects of cocaine are primarily due to its effects on dopamine.> How is it these drugs create such euphoric states,while some serotonin(ssri's) TCA'S and other psychiatric drugs do not give the same feelings as illegal substances?
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These drugs don't affect dopamine like most illegal substances do. The motivation involved in addictive behaviors involves what is known as the "mesolimbic pathway." Most illegal, addictive drugs induce an increase in dopamine release from the nerve terminals of neurons in the ventral tegmental area. Some of these terminals release dopamine into the nucleus accumbens; dopamine inhibits neurons in this region. Whether mediated by dopamine release or some other mechanism, the ultimate mediator of euphoria is the inhibition of medium spiny neurons in the shell of the nucleus accumbens. Many euphoric drugs induce this inhibition by mechanism(s) that don't involve dopamine release (although increased dopamine levels exert a synergistic effect). SSRI's and TCA's don't exhibit similar effects.I've created a page that lists the mechanism of action of several other drugs; it's located at http://www.neurotransmitter.net/drugmechanisms.html if you're interested in learning more.
Shawn
poster:Shawn. T.
thread:247730
URL: http://www.dr-bob.org/babble/20030802/msgs/247797.html