Opioids and Benzodiazepines

[splenda]

Why do people always think that benzodiazepines, GABAergic drugs, "potentiate" opioids?

If I recall correctly, one of the opioid's pleasure response is via GABA ANTAGONISM to release dopamine in the VTA. Yet, combining a benzodiazepine, which is a GABA agonist, with opioids, gives some people a "higher" feeling.

Why is this? Alright, thanks!

Interesting review:

The elevated plus-maze test was used to determine if the opiate antagonist naloxone could potentiate the anxiolytic-like effects of the benzodiazepine diazepam, the barbiturate pentobarbital, the propanediol carbamate meprobamate and the partial benzodiazepine receptor agonist [R]-1-[(10-chloro-4-oxo-3-phenyl-4H-benzo[a]quinolizin-1-yl) carbonyl]-2-pyrrolidine-methanol (Ro19-8022) in the rat. A subeffective dose of each of these compounds was combined with naloxone, 10 mg/kg. Naloxone had no effect by itself, but potentiated all drugs except Ro19-8022. The proportion of entries on the open arm increased while the total number of arms entries was not modified. These results coincide with and extend data previously obtained in the mouse. One possible explanation for naloxone's effect could be that it blocks opioid inhibition of GABAergic (gamma-aminobutyric acid) neurons thereby enhancing the effects of benzodiazepines. Another possibility is that naloxone blocks opioid effects on adenosinergic systems.

http://www.ncbi.nlm.nih.gov/entrez/..._uids=10771294&query_hl=1&itool=pubmed_DocSum

 

[BilZ0r]

Very good questions.

People think benzos potentiate opioids, because they do. That is to say, if you're hanging out for a hit of opioids, and you don't have enough, mixing what you've got with benzos (even with antihistamines) helps if come on stronger.

Yeah, the idea often cited is that opioids cause disinhibition of VTA/SNC dopaminergic neurons, via presynaptic inhibition, and cause dopamine release.

Things get more complicated still when you try and consider all the data; and the system as a whole.

The evidence goes GABA(A) receptors play a relatively small role in regulating tonic DA release. GABA(B) is where it is at. Indeed, direct GABA(A) agonists in the dopaminergic cell body regions can actually facilitate tonic DA release [1, 2].

It probably means that opioids increase DA output via inhibiting GABA(B) activity.

Most papers show that Benzos on the other hand decrease DA release.

 

[5-HT2]

^^^Benzos could also potentiate the non-catecholaminergic reward pathways triggered by opiates in addition to potentiating dopamine release at the proper (probably barely sedative) doses.

 

[BilZ0r]

^ Come again, what's this non-catecholaminergic reward pathway?

 

[5-HT2]

OK, maybe I shouldn't have termed them "reward" pathways, but it seems pretty clear that not all the psychoactive effects of opiates are mediated by catecholamines, and that opiates probably act indirectly to stimulate catecholaminergic neurons via multiple routes.

 

[splenda]

OK, maybe I shouldn't have termed them "reward" pathways, but it seems pretty clear that not all the psychoactive effects of opiates are mediated by catecholamines, and that opiates probably act indirectly to stimulate catecholaminergic neurons via multiple routes.

Such as?

In this vein I also wonder if taking GABAergics with opioids would reduce reinforcement.

 

[benzofan]

Very good questions.

People think benzos potentiate opioids, because they do.

WRONG it is not so easy

 

[Mudeltakappa]

A completely non-technical answer: increased sedation and feelings of intoxication and thus there's a subjective perception of being "more high."

 

[atara]

I seriously doubt dopamine plays a major role in opioid euphoria. Dopamine antagonists, to my knowledge, do not inhibit the euphoric or addictive properties of opioids.

Here's a horrible (though well-cited!) website, and the relevant quote:

Although dopamine excitation likely increases the rewarding effect of opioids, it appears that reinforcement is not contingent upon dopamine activation. A key study found that heroine self-administration continues after disruption of DA innervation in NA, which suggests that rewarding effects of opiates are only partially contingent on DA release in the NA (Koob and Bloom, 1988). The finding is consistent with the discovery that animals will self-administer opioids in the NA (Olds, 1982), which suggests that opioid activity in the NA has a rewarding effect independent of neurons from the VTA.

http://www.macalester.edu/psychology/whathap/UBNRP/Dopamine/opioids.html

Also, alcohol, at least, is known to increase the activity of endogenous opioids. This may be general for GABA-A agonists:

http://www.ncbi.nlm.nih.gov/pubmed/9000113

 

[mandrake]

I find that benzos make an opiod high cleaner which is illogical, I know. I'd POd 15mg of hydro and railed 15mg of oxy and got a somewhat drained, speedy and dirty high. Added 1mg Lorzazepam, 0.5mg of xanax and 7.5mg of versed into the mix. Now I got a totally other feeling. Idential to IV Dilaudid. Really clean. Really nice taste in the mouth. Laidback smooth energy and a glow from the top of my spine down to tips of my toes.

 

[negrogesic]

Certain opioids, especially the semi-synthetic thebaine derivatives (codones, morphones) can have anxiogenic properties, so the benzo can have a synergism of sorts......

The answer to this question is simple. The effects of concomitant administration of opioids-benzos result in "additive" CNS depression. Benzos do not significantly alter an opioids tolerance or metabolism etc........

 

[Deleted member 137730]

I seriously doubt dopamine plays a major role in opioid euphoria. Dopamine antagonists, to my knowledge, do not inhibit the euphoric or addictive properties of opioids.

Here's a horrible (though well-cited!) website, and the relevant quote:


http://www.macalester.edu/psychology/whathap/UBNRP/Dopamine/opioids.html

Also, alcohol, at least, is known to increase the activity of endogenous opioids. This may be general for GABA-A agonists:

http://www.ncbi.nlm.nih.gov/pubmed/9000113

This doesnt mention the VTA which is critical for opiate reward and the role that glutamate plays in opiate reward.

Logically and from experience i find benzos to mess up a good opiate euphoria. It just adds to the nod and sedation. Total waste IMO.