Seeking literature re: the overdose risks of combining depressants

[ClarityPSY]

Hi everyone. I am just here to ask if any of you know of any scientific/academic primary literature (or textbooks) that speaks directly to the mechanisms involved in fatal depressant polysubstance-induced overdose. I know it is anecdotally well established that combining depressants like benzodiazepines with another GABAergic substance in high doses leads to an increased risk of severe respiratory, coma, and death in the worst cases, and is always advised against from a HR-POV.

However, a search of online databases like PubMed and GoogleScholar does not seem to yield much in the way of specific citations (or even many applicable case studies). The best I've managed to find is a discussion on the risks of combinining alcohol and benzodiazepines specifically. I could just be doing it wrong though. I would sincerely appreciate it if you could point out the right direction, either to specific papers, along with search engines, or keywords, so that I can continue this sort of research independently as well.

Cheers,

 

[Solipsis]

I think you're making it harder than it is?

afaik: Depressants like those act on inhibitory receptors like GABAa (among others of course) which when activated reduce the excitability of neurons. There are several kinds of GABAergic effects like direct agonism or allosteric effects that enhance the binding and activation of GABA ligands.

This effect can be additive (multiple inhibitory activity on neurons causing other neurons to fire less as well). So eventually this CNS depression can lead to such dangers as you mentioned: resp depression, coma, etc when the overall activity gets too low.

The main problem is that this synergy or additive effect can be unpredictable, there are many factors involved which determine how much of a certain depressant combination leads to such serious health risks. Some combinations involve competing depressants which doesn't really cause extreme synergy because they act so similarly and are basically 'in each other's way'. Other combinations though depress the CNS from different sides and this can be too much.

Depressants particularly affecting the autonomous nervous system are tricky to begin with as they are able to eventually affect things like respiration too much (e.g. many opioids). Others have limited effects on autonomous function and by themselves don't usually cause life or health threatening states.

I appreciate if you want the literature references on some of this but it would probably help if you would formulate more specific questions you have about these effects, especially if you want to apply what you learn to yourself and your use/abuse.