• Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

  • N&PD Moderators: Skorpio

Real 'cross tolerance' between clonazepam/high potency benzodiazepines and opioids

K

Kdem

Bluelighter
Joined
Mar 14, 2015
Messages
334
So I was just doing some research, and I stumbled on a few things. And one can always question sources. Technically, this is not 'cross tolerance' in the most conventional sense.

http://www.biology-pages.info/D/Drugs.html

'Opioids depress nerve transmission in sensory pathways of the spinal cord and brain that signal pain. This explains why opioids are such effective pain killers.
Opioids also inhibit brain centers controlling coughing, breathing, and intestinal motility. Both morphine and codeine are used as pain killers, and codeine is also used in cough medicine. '

Clonazepam has also been administered to reduce suffering in palliative care.

The way I'm reading that, opiods act on the brain stem and in some fashion on the spinal cord.
All high potency benzodiazepines, especially clonazepam (lowest Ki value), act strongly on the braim stem. Clonazepam itself also acts in some fashion, directly or indirectly, on the spinal cord.

And in my case I was so 'lucky' to also have taken lorazepam for 2-3 months, both drugs were prescribed. I'll save everyone my personal misery and health problems. But everything got worse after I had been on the lorazepam and went back.
I've read stories stating that the combination of lorazepam plus opiates in particular is dangerous because of the potential for fatal respiratory depression.

Again, both types of drugs act strongly on the brain stem. I'm just not sure if that explains my opiate 'tolerance'. I know that SSRIS also act on the brain stem. I'm wondering if there are any other categories of drugs that also act on the brain stem ? From a practical point of view, I'm wondering what might help or harm.

And just when I believed I was at the end of my post, I noticed something else.

http://nawrot.psych.ndsu.nodak.edu/courses/465projects07/morphine/Page3WP.htm

'As a general concept, drugs affect certain areas of the brain more so than others. Specifically, opiates can affect four areas of the brain that cause people to act out of their norm: the brainstem, the cerebellum, the midbrain, and the cortex.'
The cerebellum, isn't that part of the motor cortex ?

https://www.drugs.com/ppa/clonazepam.html '



'The exact mechanism is unknown, but believed to be related to its ability to enhance the activity of GABA; suppresses the spike-and-wave discharge in absence seizures by depressing nerve transmission in the motor cortex.'

Also, 'cross tolerance' ?

Any particular implications ? I'm far from 'fine'.
 
BZDs do not effect opioidergic transmission, it's two wholly different receptor systems. GABA agonism and mu-opioid activation are both depressants but that doesn't mean tolerance to one will result in tolerance to the other.

Receptors of various sorts are scattered around the brain, just because you find them colocated in a certain area doen't mean dick all.

Studies in humans and animal models prove time and time again that tolerance to bzds and tolerance to opioids (as well as substitution trials, e.g. does a rat trained to like morphine accept benzos as a substitute (answer is no)) are two seperate things.
 
sekio,

I think that I've read that there can be some indirect interactions between GABA and opiates/endorphin (systems). Receptor systems interact, do they ? But that wasn't really my point.

The phrase about opiods that was used 'depress nerve transmission'. If you google for that phrase and 'clonazepam' you see phrases like (https://www.drugs.com/ppa/clonazepam.html) 'depressing nerve transmission in the motor cortex.' http://www.encyclopedia.com/medicine/drugs/pharmacology/clonazepam 'To do this, they block the effects of a specific chemical involved in the transmission of nerve impulses in the brain' . A different phrase is 'reduces the electrical activity' when its anticonvulsant effects are described.

'Studies in humans and animal models prove time and time again that tolerance to bzds and tolerance to opioids (as well as substitution trials, e.g. does a rat trained to like morphine accept benzos as a substitute (answer is no)) are two seperate things' I agree, different receptors. But clonazepam is a heavy dirty drug, after long term daily use and quite possibly other issues ('sensitization') ... I've read about the use of low dose naltrexone for benzodiazepine withdrawal ...
 
Clonazepam is not "dirty" pharmacologically speaking, it's actually quite selective for the GABA-A receptor. If you want "dirty" drugs look at the old antipsychotics a la Thorazine. Those hit just about every receptor and then a couple more.

Many drugs depress nerve transmission - barbiturates, cannabinoids, opioids, antipsychotics, sedatives, GHB, and so on. But different drugs act on different cells in different parts of the brain, this is why, for instance, blocking GABA activity causes seizures and yet blocking opioid activity doesn't. And though there may be similar effects between varying pathways, that doesn't mean that tolerance develops to all of them if you stimulate just one pathway. Most tolerance is not due to desensitization to the electrical stimualtion of nerves, it happens on the receptor level (eg. less GABA-A receptors present in response to overstimulation)

Naltrexone has been used for many withdrawal symptoms, I'vre heard of people attempting to use it for alcohol and cannabis dependency, but that doesn't mean it works, and even if it does work, maybe not the way you think it would go.
 
You must log in or register to reply here.
Top