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  • BDD Moderators: Keif’ Richards | negrogesic

Misc Is there a Gabapentinoid and Benzodiazapine cross-tolerence?

E

evo4ever

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Hey all.

Currently I've got a high tolerence to Benzos. I take 20mg of Clonazepam every 3-4 days (long-life). A few days ago I took 500mg of Pregabalin and it done absolutely nothing to me, no after effects the next day either.

Any thoughts?
 
Jekyl Anhydride said:
Gabapentenoids affect GABA through a downstream process involving VDCC's, etc. and not directly at the GABA-A site like an agonist/ positive allosteric modulator. So in actuality there's no cross tolerance. Although seeing as they both affect GABA I could see the massive dose of Clonazepam completely nullifying any effect from gabapentin/ Pregabalin since it has a much weaker effect on GABA vs Benzos.
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So in theory is pretty useless combining Pregabalin with Clonazepam?
 
Gabapentinoids have a very different psychological effect IMO. Benzos are well dubbed as "tranquilizers" as they can in the sense make you quite tranquil. Gabapentin and the like have a very different quality that I would say is hard to pinpoint, but more akin to the feeling of drunkenness if taken at a high dosage. Also slightly stimulating in another sense.
 
Cheers for the replies guys, i agree with chicken hoagie that it can make u feel as if ur intoxicated by alcohol. I took 700mg last night and it certainly effected me this time lol. I took it with Promethazine as well 200mg of it, maybe that played a role too.
 
There shouldn't be any cross-tolerance as they do not affect any of the same receptors. Though gabapentinoids are thought to affect GABA production downstream, which means they would not produce tolerance to GABAergic drugs that directly affect GABA receptors like benzos do. But it's possible that benzos, in desensitizing the receptors, might be able to cause gabapentinoids to be less effective as the downstream GABA production would have less impact. However that's far from all that gabapentinoids are doing. I'm speculating a little bit, but gabapentinoids do not directly affect any GABA receptors. The two drugs work through different systems.
 
Shadowmeister said:
There shouldn't be any cross-tolerance as they do not affect any of the same receptors. Though gabapentinoids are thought to affect GABA production downstream, which means they would not produce tolerance to GABAergic drugs that directly affect GABA receptors like benzos do. But it's possible that benzos, in desensitizing the receptors, might be able to cause gabapentinoids to be less effective as the downstream GABA production would have less impact. However that's far from all that gabapentinoids are doing. I'm speculating a little bit, but gabapentinoids do not directly affect any GABA receptors. The two drugs work through different systems.
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So if I took if took a benzo then an hour later I took Pregabalin it would be less effective?
 
No that's not what I'm saying. I think it's more likely that if you were dependent on benzos, so your receptors were less sensitive to GABA, it might be less effective in general whenever you took it, but again, I'm not sure. Being high on a benzo and then taking pregabalin should increase the strength of pregabalin, since it would be two drugs acting in two different systems at the same time. You would be more high than with either by itself. Even if your GABA receptors are downregulated and desensitized, the fact that took a benzo will move those more towards normal.
 
Imagine taking Alprazolam, Pentobarbital, and Pregabalin at the same time. If you had a benzo tolerance do u think that would kill u?
 
gabapentin doesn't actually have any effect on GABA levels or GABA receptors, as wiki puts it:
There is currently no evidence that the effects of gabapentin are mediated by any mechanism other than inhibition of α2δ-containing VDCCs.
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Nice cool, thanks for that. I've read opinions in both directions on whether it has downstream GABA modulation effects or not.
 
evo4ever said:
Currently I've got a high tolerence to Benzos. I take 20mg of Clonazepam every 3-4 days (long-life). A few days ago I took 500mg of Pregabalin and it done absolutely nothing to me, no after effects the next day either.

Any thoughts?
Click to expand...
Benzos are GABA receptor positive allosteric modulators, when pregabalin is gabapentinoid, but they are both sharing the same mechanism of action - modulation of GABA neurotransmission, so they both belongs to "GABAergic modulators". According to this, cross-tolerance between those two drugs does exists.
 
Actually see sekio's post above, they have not been found to have any effect on GABA levels, their effects are entirely mediated though inhibition of α2δ-containing VDCCs. The reason the term "gabapentinoid" has "gaba" in it is because structurally they are very close to GABA. But their mechanism of action is different.

evo4ever said:
Is Pentobarbital banned in western countries? If so is it legal anywhere else?
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I believe it is but we don't do legal questions, I'm sure if you google it you can find it easily though.
 
Well Gabapentinoids act on the Voltage-dependent calcium channel subunit alpha-2/delta-1- equipped Voltage-gated calcium channel. So Gabapentinoids like lyrica, pregabalin, phenibut, and the recently approved mirogabalin, which is similarly to lyrica, but with significantly higher potency. Now this effect, can cause Anxiolytic, sedating, lowering of blood pressure, calmness, effects acting similar to how benzos work on the GABAA receptor. Benzodiazepines are in definitively stronger than gabpentinoids, but regardless, they would be useful, and better than not having Gabapenintoids while in benzo withdrawal. -MystickChemistrick33
 
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From personal experience and from what friends of mine have reported is that yes there is indeed a cross tolerance.
 
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