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Thread: Do CNS depressants potentiate each other or just synergize with each other?

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    Do CNS depressants potentiate each other or just synergize with each other? 
    #1
    Bluelighter Swimmingdancer's Avatar
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    What I mean is, when you take 2 CNS depressants together, for example opioids + benzos, or benzos + alcohol, etc, do they actually potentiate each other in a way that is more than just additively? Like, say, would taking benzos with alcohol be stronger than taking just a larger dose of benzos? Sorry if this is discussed somewhere, I couldn't find any concrete info anywhere.

    EDIT: It may be that I didn't fully understand the difference between potentiation, synergism and additive - see below.
    Last edited by Swimmingdancer; 11-08-2012 at 02:28.
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    #2
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    this may be of some interest to you SD

    Potentiation

    Potentiation occurs when two drugs are taken together and one of them intensifies the action of the other. This could be expressed by a +b= B. As an example, Phenergan(R), an antihistamine, when given with a painkilling narcotic such as Demerol(R) intensifies its effect, there by cutting down on the amount of the narcotic needed.

    Synergism
    Synergism is similar to potentiation. If two drugs are taken together that are similar in action, such as barbiturates and alcohol, which are both depressants, an effect exaggerated out of proportion to that of each drug taken separately at the given dose may occur. This could be expressed by 1+1= 5. An example might be a person taking a dose of alcohol and a dose of a barbiturate. Normally, taken alone, neither substance would cause serious harm, but if taken together, the combination could cause coma or death.
    (source)
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    #3
    It is more than additive effect for benzos and alcohol, for example. They potentiate each other's effects, as well as synergize. Benzos increase the firing rate of GABA (the frequency of activity), and alcohol (and barbs) allow the channel to stay open for longer than it normally would allowing more GABAergism (the potential duration of activity). That is a rough description of how I THINK it works with benzos and alcohol (and barbs). So, the benzo will increase the firing rate, while the channel is left open longer due to the alcohol. I COULD be mistaken as to how exactly they work, but it is something along those lines. The effect is not a 1 + 1 deal, though - that is certain. When I had no tolerance, 0.5 mg alprazolam would make me feel relaxed and a little "buzzy" if I was out and about in public, and a strong drink (just one) would cause me to get a typical buzz one gets with alcohol but a bit stronger, but when I took those two together at those doses I was literally forced asleep - sleeping all day, I think? I couldn't think straight - and was just totally trashed. Once I took 2.5 mg alprazolam with no tolerance, and while I had a good deal of amnesia and general benzo-effects, I was able to stay up and watch TV, sleep well, and be relaxed through the next day. Benzos + alcohol, when I had no tolerance, was some serious sedation. Not so much now that I am benzo-dependent for almost 2 years now on 4 mg clonazepam a day and a mg + of alprazolam a day, too, but it still doesn't take much alcohol to get me lit, though I can tolerate larger amounts.
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    Bluelighter Swimmingdancer's Avatar
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    Potentiation
    Potentiation occurs when two drugs are taken together and one of them intensifies the action of the other. This could be expressed by a +b= B. As an example, Phenergan(R), an antihistamine, when given with a painkilling narcotic such as Demerol(R) intensifies its effect, there by cutting down on the amount of the narcotic needed.

    Synergism
    Synergism is similar to potentiation. If two drugs are taken together that are similar in action, such as barbiturates and alcohol, which are both depressants, an effect exaggerated out of proportion to that of each drug taken separately at the given dose may occur. This could be expressed by 1+1= 5. An example might be a person taking a dose of alcohol and a dose of a barbiturate. Normally, taken alone, neither substance would cause serious harm, but if taken together, the combination could cause coma or death.
    Oh, interesting, thanks tricomb. So perhaps my understanding of "synergism" is off. I kept hearing people say for 2 drugs to have a synergistic effect meant that they share some of the same effects, so you simply had the effects of one drug added to the other, like 1 + 1 = 2. Like say you took 1 aspirin and 1 APAP it would be similar to taking 2 aspirin or 2 APAP. But when people talked about drugs like CNS depressants synergizing with each other, it seemed to be in my experience stronger than just an additive effect. So the source you quoted seems to concur with that, and that synergy really means that the effect is out of proportion from the cumulative effects of taking each drug separately. So basically the difference between potentiation and synergy is that with potentiation the effects of one of the drugs are made stronger, whereas with synergy the effects of both drugs are made stronger, correct? And additive means a different thing, just that one drug is added to another (so in a case where 2 drugs are both analgesics there would be a greater effect simply because you are taking more analgesic), is that correct?

    So potentiation could be expressed as a + b = B (or a + b = a + bx2)
    synergism could be expressed as 1 + 1 = 5
    additive could be expressed as 1 = 1 = 2


    Alex00 - I'm not entirely sure whether or not that's exactly how it works, but it does definitely seem like more than a 1 + 1 = 2 effect to me too. I was interested for all drugs as well, just using benzos + alcohol as an example. I think my problem is that a lot of people don't know the actual definition of terms like synergistic and I was just going by how others had explained it to me..
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    #5
    Bluelighter Znegative's Avatar
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    Yeah the way I thought of it, as far as CNS depressants go, unless they are working at the same receptor site (GABA, Opiate receptors) than they are just synergizing the effects of each other-though this is not always the case (diphenhydramine actually does potentiate opiates).
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    #6
    Bluelighter Swimmingdancer's Avatar
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    Thanks, I think the problem was that people have different ideas about what "synergize" means, like some people say it means just an additive effect. But I think the source tricomb posted that defines synergism as more than an additive effect and actually making both drugs stronger makes more sense to me and seems in line with my experience with taking CNS depressants together. For example, taking heroin and benzos together seemed way stronger than if I took double the dose of the heroin or double the dose of the benzo.
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    For example, I would say general anesthesia, like fentanyl+midazolam is synergistic, both independently produce strong CNS depressant effects and work together to keep the patient out of pain, and unaware of what's going on.

    Taking heroin and benzos together would be way stronger than a double dose of either alone, that's why I don't recommend people mix the two unless they can safely take each drug in excess. For simplicities sake, someone who wants to take 1mg xanax with 1 bag of IV heroin. I wouldn't recommend anyone mix them unless they can handle 10mg xanax on it's own or 10 bags of heroin on it's own, due to the exponential CNS depression when mixed.
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    It seems that potentiation is kind of like centrifugal force (in reality this is just straightline velocity and force requires acceleration, think F=m a, but it feels like a force is pulling in that direction. ) in that it's an entity that doesn't actually exist, but it makes explaining certain behavior easier.
    Why I say this is, there is actually no interaction of say opioids and first gen antihistamines such as diphenhydramine, but the added sedation makes it feel like the already existing sedation from the opioid is stronger while the pain-reducing effects stay the same. So we say it potentiates or makes the opioid stronger when in reality it just feels stronger because they both cause sedation.

    Where synergism is actually acting on the same receptor types or subtypes or releasing the same neurotransmitters (think cocaine+opioid) producing most of the same effects, therefore it may seem like the effects are amplified across the spectrum, since they have all of the same effects. More of the 1+1=3 idea.

    It's hard to quantify effects of drugs unless a predetermined set of parameters are defined.
    Last edited by scottd420; 11-08-2012 at 16:37.
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    Quote Originally Posted by scottd420 View Post
    It's hard to quantify effects of drugs unless a predetermined set of parameters are defined.
    Agreed.
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    #10
    does alcohol potentiate cocaine or synergize with it to form coacythelene? (sp. I know I suck at sp.)
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