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02-02-2007, 03:03 AM
Opiates (heroin, morphine, etc.)

The human body naturally produces its own opiate-like substances and uses them as neurotransmitters. These substances include endorphins, enkephalins, and dynorphin, often collectively known as endogenous opioids. Endogenous opioids modulate our reactions to painful stimuli. They also regulate vital functions such as hunger and thirst and are involved in mood control, immune response, and other processes.

The reason that opiates such as heroin (http://www.heroin.org)and morphine affect us so powerfully is that these exogenous substances bind to the same receptors as our endogenous opioids. There are three kinds of receptors widely distributed throughout the brain: mu, delta, and kappa receptors.

These receptors, through second messengers, influence the likelihood that ion channels will open, which in certain cases reduces the excitability of neurons. This reduced excitability is the likely source of the euphoric effect of opiates and appears to be mediated by the mu and delta receptors.

This euphoric effect also appears to involve another mechanism in which the GABA-inhibitory interneurons of the ventral tegmental area come into play. By attaching to their mu receptors, exogenous opioids reduce the amount of GABA released (see animation). Normally, GABA reduces the amount of dopamine released in the nucleus accumbens. By inhibiting this inhibitor, the opiates ultimately increase the amount of dopamine produced and the amount of pleasure felt.

Chronic consumption of opiates inhibits the production of cAMP, but this inhibition is offset in the long run by other cAMP production mechanisms. When no opiates are available, this increased cAMP production capacity comes to the fore and results in neural hyperactivity and the sensation of craving the drug.

exjunky
10-21-2007, 11:11 PM
I always wondered how a "weak opiate" like subutex prevents a person from getting high from "strong opiates" like heroin. I would think that heroin is such a powerful drug that it would overpower anything weaker. The source of my confusion is that I didn't understand how the opiates molecules stimulate the receptors.

You can imagine opiods as a key, and your receptors as a lock. It's not a perfect metaphor but for us laypeople it's good enough. However the stimulation to the receptor doesn't happen when the opiod first encounters the receptor, it happens when it breaks away from the receptor. Some opiates fit the receptors very well, and occupy the receptor site for hours. Others only bind to the receptor for a few seconds then break off again.

Therefore the full-on opiates make a "loose fit" ... binding to a receptor weakly, then very quicky it breaks away, only to find another receptor to stimulate. Because this happens so quickly and in rapid succession, it creates the "high" as well as CNS depression.

The drugs which fit your receptors nearly perfectly are the opiate blockers like nalaxone (Narcan™) or buprenephrine (Subutex/Suboxone). These cling to your receptors so that other opoids like heroin can't find any receptors to bind to.

llewyn
01-14-2008, 09:03 PM
So how does withdrawal from heroin work? Does this occur when the opiate leaves the receptor site? When would withdrawal be complete (that is, would it happen when all molecules of the opiate had been cleared)?