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OD Moderators: Keif’ Richards | negrogesic
Benzos GABAPentin and Benzodiazepine cross-tolerance/Dependance.
- Thread starter Thomas29
- Start date
Their mechanism overlaps
bdomihizayka
Bluelighter
I am actually curious about this too. When I was in rehab for heroin/ benzos, the doctors kept on trying to give me neurotin....and I insisted that it worked on gaba in some unknown way and would only prolong my withdrawal, but they insisted it wouldn;t...... but I know better ( skim through bluelight daily lol).... so what exactly is the truth here?
Cane2theLeft
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Gabapentin is a GABA analogue and as such has some utility in reducing certain kind of seizure activity but does not agonize GABAa like benzodiazepines do which produce a much more complete anticonvulsant effect.
Gabapentin can reduce certain aspects of the withdrawal from benzodiazepines but there is not cross-tolerance because of their different mechanisms of action (the former's being poorly understood but certainly different from the latter). If someone goes cold turkey from a large benzodiazepine habit, they could not simply take gabapentin and feel fine or avoid the risk of seizure and other withdrawal symptoms, it would merely mitigate them to some degree.
Claims about gabapentin being equivalent to X amount of benzodiazepines are likely from studies where they measured the amount of anxiolysis produced or recreational potential but that doesn't mean they work in exactly the same way. Without a link to where you read this though, thomas29, I can only speculate about the specific information you're referring to based on what I've seen in the past.
Gabapentin can reduce certain aspects of the withdrawal from benzodiazepines but there is not cross-tolerance because of their different mechanisms of action (the former's being poorly understood but certainly different from the latter). If someone goes cold turkey from a large benzodiazepine habit, they could not simply take gabapentin and feel fine or avoid the risk of seizure and other withdrawal symptoms, it would merely mitigate them to some degree.
Claims about gabapentin being equivalent to X amount of benzodiazepines are likely from studies where they measured the amount of anxiolysis produced or recreational potential but that doesn't mean they work in exactly the same way. Without a link to where you read this though, thomas29, I can only speculate about the specific information you're referring to based on what I've seen in the past.
It means that some of their neurochemical effects are the same
There would be cross-tolerance
http://www.drregpeart.org/neurontin.html
There would be cross-tolerance
http://www.drregpeart.org/neurontin.html
Cane2theLeft
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Benzodiazepines are positive allosteric modulators of the ionotropic GABAA receptor protein complex.
Gabapentin is a GABA analogue so it there is GABA activity as a result, it would reflect the above. Its activity is actually believed to be due to other mechanisms of action -
That link you provided cites no studies to support his claims and in fact, likely confirms what I said above that they have certain therapeutic effects in common but that does not mean their mechanism of action is the same. He throws out a claim of cross tolerance without backing that up whatsoever. Claiming an NSAID is equal in it's analgesic ability to X amount of an opioid does not mean that NSAIDs and opioids are cross tolerant.
All of the information you can find on the pharmacology of benzodiazepines and gabapentin demonstrate disparate mechanisms of action and this argues against claims that they would be cross tolerant. There is an undeniable intersection of their effects but that doesn't mean one drug can adequately substitute for another in an individual that is physically dependent.
There is some that is known about gabapentin's mechanism of action and there is some that is poorly understood. What IS known contradicts claims that there is true cross tolerance and you can't infer that there is cross tolerance simply based on the fact that one drug is an analogue of a neurotransmitter than another drug agonizes very specific receptor subunits of.
Benzodiazepines do not bind to the same receptor site on the protein complex as the endogenous ligand GABA (whose binding site is located between α- and β-subunits), but bind to distinct benzodiazepine binding sites situated at the interface between the α- and γ-subunits of α- and γ-subunit containing GABAA receptors[6][7]
http://en.wikipedia.org/wiki/GABAA_receptor
Gabapentin is a GABA analogue so it there is GABA activity as a result, it would reflect the above. Its activity is actually believed to be due to other mechanisms of action -
Gabapentin was initially synthesized to mimic the chemical structure of the neurotransmitter gamma-aminobutyric acid (GABA), but is not believed to act on the same brain receptors. ... Some of [gabapentin's] activity may involve interaction with voltage-gated calcium channels. Gabapentin binds to the α2δ subunit (1 and 2) and has been found to reduce calcium currents after chronic but not acute application via an effect on trafficking[43] of voltage-dependent calcium channels in the central nervous system.[44] Another possible mechanism of action, reported by Ben Barres and colleagues in Cell in 2009, is that gabapentin halts the formation of new synapses.[45]
http://en.wikipedia.org/wiki/Gabapentin#Pharmacology
That link you provided cites no studies to support his claims and in fact, likely confirms what I said above that they have certain therapeutic effects in common but that does not mean their mechanism of action is the same. He throws out a claim of cross tolerance without backing that up whatsoever. Claiming an NSAID is equal in it's analgesic ability to X amount of an opioid does not mean that NSAIDs and opioids are cross tolerant.
All of the information you can find on the pharmacology of benzodiazepines and gabapentin demonstrate disparate mechanisms of action and this argues against claims that they would be cross tolerant. There is an undeniable intersection of their effects but that doesn't mean one drug can adequately substitute for another in an individual that is physically dependent.
There is some that is known about gabapentin's mechanism of action and there is some that is poorly understood. What IS known contradicts claims that there is true cross tolerance and you can't infer that there is cross tolerance simply based on the fact that one drug is an analogue of a neurotransmitter than another drug agonizes very specific receptor subunits of.
The link I provided is personal writing from a certified doctor with two very prestigious titles, both in specific relation to tranquilizers. I think your implicit claim of appeal to authority is out of the question.
But a NSAID doesn't almost completely eliminate opiate withdrawal, while gabapentin does benzodiazepine withdrawal, not to mention they both treat seizures, anxiety, social anxiety, tremors, restless legs, seizures, PTSD, and alcohol withdrawal, while basically the only thing in common that the two you mentioned treat is pain; your comparison isn't realistic. I can provide more sources if need be.
http://www.tandfonline.com/doi/abs/10.1080/08897070309511541 http://onlinelibrary.wiley.com/doi/...sCustomisedMessage=&userIsAuthenticated=false
http://books.google.com/books?id=j6...a=X&ei=fFZnUfy_O8Pi4APf1YHAAQ&ved=0CFMQ6AEwAg (a statement asserting that it works for "sedative-hypnotic withdrawal").
But a NSAID doesn't almost completely eliminate opiate withdrawal, while gabapentin does benzodiazepine withdrawal, not to mention they both treat seizures, anxiety, social anxiety, tremors, restless legs, seizures, PTSD, and alcohol withdrawal, while basically the only thing in common that the two you mentioned treat is pain; your comparison isn't realistic. I can provide more sources if need be.
http://www.tandfonline.com/doi/abs/10.1080/08897070309511541 http://onlinelibrary.wiley.com/doi/...sCustomisedMessage=&userIsAuthenticated=false
http://books.google.com/books?id=j6...a=X&ei=fFZnUfy_O8Pi4APf1YHAAQ&ved=0CFMQ6AEwAg (a statement asserting that it works for "sedative-hypnotic withdrawal").
Cane2theLeft
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Clonidine is used for opioid withdrawal, that doesn't make it cross-tolerant with opioids. I never denied it would mitigate symptoms of benzodiazepine withdrawal, I quibbled with claims of cross-tolerance and if you have any sources beside the word of a single person, say a study or something, I would certainly be interested.
You're ignoring that all of the documentation about their respective pharmacodynamics points to them having quite disparate mechanisms of action. They have undeniably similar effects in certain regards and similar indications but that does not mean that they function exactly the same and are completely interchangeable for someone who is physically dependent.
Gabapentin simply is not a GABAA agonist ergo they are not cross-tolerant.
You're ignoring that all of the documentation about their respective pharmacodynamics points to them having quite disparate mechanisms of action. They have undeniably similar effects in certain regards and similar indications but that does not mean that they function exactly the same and are completely interchangeable for someone who is physically dependent.
Gabapentin simply is not a GABAA agonist ergo they are not cross-tolerant.
Toz
Bluelighter
I took gabapentin when in withdrawals from benzos. It did nothing to provide relief.
I took benzos when in withdrawal from gabapentin. It did nothing to provide relief.
The 2 addictions are not in any way related. Gabapentin isn't even proven to work at all on GABA receptors from what I understand.
I took benzos when in withdrawal from gabapentin. It did nothing to provide relief.
The 2 addictions are not in any way related. Gabapentin isn't even proven to work at all on GABA receptors from what I understand.
Clonidine, however, doesn't almost fully eliminate opiate withdrawal. I gave another source, actually, since you don't trust a doctor with aforementioned credentials.
Mind sourcing "all the documentation"?
I never stated that they function exactly the same, only that they're cross-tolerant.
Mind sourcing "all the documentation"?
I never stated that they function exactly the same, only that they're cross-tolerant.
Cane2theLeft
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here you go 
It's not difficult to look around and see how they are not cross-tolerant. It appears like you cherry-picked and only looked for information to support your preconceived notion. And even then, all you came up with were ONE SINGLE DOCTOR making a claim not supported by any studies and a couple obscure references that don't even claim cross-tolerance. This alone should tell you something!
Since you keep skirting most of what I bring up I will be more direct -
Benzodiazepines are well established to work through GABAA agonism. Can you find any source that gabapentin does this?
For drugs to be cross-tolerant, they need to have the same mechanism of action. GABA analogues and -diazepines do not.
It's not difficult to look around and see how they are not cross-tolerant. It appears like you cherry-picked and only looked for information to support your preconceived notion. And even then, all you came up with were ONE SINGLE DOCTOR making a claim not supported by any studies and a couple obscure references that don't even claim cross-tolerance. This alone should tell you something!
Since you keep skirting most of what I bring up I will be more direct -
Benzodiazepines are well established to work through GABAA agonism. Can you find any source that gabapentin does this?
For drugs to be cross-tolerant, they need to have the same mechanism of action. GABA analogues and -diazepines do not.
I really don't understand you. Clearly, since anecdotes concur, they treat the same illnesses with precisely the same effects, and they both increase extracellular levels of GABA, and reduce the release of various monoamines, they will be somewhat cross-tolerant. Your source, if anything, proves my point.
And you still won't admit how credible this person is who I cite, which is why I cited another source, which you continue to ignore.
Two substances don't have to have an identical mechanism to be cross-tolerant.
And you still won't admit how credible this person is who I cite, which is why I cited another source, which you continue to ignore.
Two substances don't have to have an identical mechanism to be cross-tolerant.
Cane2theLeft
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I think the fundamental reason we don't seem to be able to agree is that what you and I are using as criteria for cross-tolerance is rather different. It's really impossible to have a discussion when the definition of key terms are not agreed upon.
As I understand it, very basically, cross-tolerance is the ability of one drug to substitute for another when someone is physically dependent on it or when someone has a tolerance to a substance they have not used through extensive use of another substance.
Gabapentin potentially produces some of its effects due to GABA activity but at best, this is background to several other mechanisms of action and a relatively insignificant component of why it produces the effects that it does. Gabapentin is a very poor anticonvulsant and only indicated for such in very specific circumstances AND only when used in conjunction with another, superior, anticonvulsant. On it's own, it can not prevent or stop serious grand-mal seizures and for this reason, it doesn't meet the criteria for cross-tolerance as I understand it and have been using it.
I don't take any individual's word on a subject as gospel when, if their claim were true, there would be a plethora of other sources from other mouths, studies, etc. to cite to support that claim. There isn't an amount of credential that would change that for me and it's just how I operate. I'm a naturally skeptical person and prefer to have a rather substantial amount of evidence to believe something and when this topic first came up, I did the same google searches you did because I wanted to make sure there was no new information that might contradict what I had previously learned and I found none of that conclusive or convincing.
As I've mentioned previously, I certainly don't deny that they produce *similar* effects in many regards, but I find it dangerous to put out there that they are cross-tolerant because someone seriously dependent on benzodiazepines could read such, try to substitute their benzos with gabapentin and seize or worse. That's not a risk I am willing to take and why I have pursued this to the degree that I have.
If I am incorrect in the specificity of what is required to call something cross-tolerant, than I apologize but at very least, I think my understanding mirrors what many, at least around here, would view the term as meaning and hence the claim could prove dangerous for some people if they put it into use with that understanding.
I am certainly not trying to attack you personally and I hope none of the above has come off that way. I appreciate the respective, professional discussion we've been having this and I certainly still have a great deal of respect for you as an individual based on probably hundreds of your posts (if not more) that I've read over the years. I also hope this clarifies my position a bit better.
As I understand it, very basically, cross-tolerance is the ability of one drug to substitute for another when someone is physically dependent on it or when someone has a tolerance to a substance they have not used through extensive use of another substance.
Gabapentin potentially produces some of its effects due to GABA activity but at best, this is background to several other mechanisms of action and a relatively insignificant component of why it produces the effects that it does. Gabapentin is a very poor anticonvulsant and only indicated for such in very specific circumstances AND only when used in conjunction with another, superior, anticonvulsant. On it's own, it can not prevent or stop serious grand-mal seizures and for this reason, it doesn't meet the criteria for cross-tolerance as I understand it and have been using it.
I don't take any individual's word on a subject as gospel when, if their claim were true, there would be a plethora of other sources from other mouths, studies, etc. to cite to support that claim. There isn't an amount of credential that would change that for me and it's just how I operate. I'm a naturally skeptical person and prefer to have a rather substantial amount of evidence to believe something and when this topic first came up, I did the same google searches you did because I wanted to make sure there was no new information that might contradict what I had previously learned and I found none of that conclusive or convincing.
As I've mentioned previously, I certainly don't deny that they produce *similar* effects in many regards, but I find it dangerous to put out there that they are cross-tolerant because someone seriously dependent on benzodiazepines could read such, try to substitute their benzos with gabapentin and seize or worse. That's not a risk I am willing to take and why I have pursued this to the degree that I have.
If I am incorrect in the specificity of what is required to call something cross-tolerant, than I apologize but at very least, I think my understanding mirrors what many, at least around here, would view the term as meaning and hence the claim could prove dangerous for some people if they put it into use with that understanding.
I am certainly not trying to attack you personally and I hope none of the above has come off that way. I appreciate the respective, professional discussion we've been having this and I certainly still have a great deal of respect for you as an individual based on probably hundreds of your posts (if not more) that I've read over the years. I also hope this clarifies my position a bit better.
Ok after consulting one of the highest minds on bluelight I accede that they aren't largely cross-tolerant but I still think they are slightly so.
No personal attacks too, that's what keeps argument logical. I'm sorry if what I said could have been construed as such.
I've read your posts and doubtless (reflected in your position) you are qualified and intelligent.
Just wondering, what degree are you pursuing?
No personal attacks too, that's what keeps argument logical. I'm sorry if what I said could have been construed as such.
I've read your posts and doubtless (reflected in your position) you are qualified and intelligent.
Just wondering, what degree are you pursuing?
Cane2theLeft
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I'll PM you
fairnymph
Ex-Bluelighter
Not cross-tolerant at all IME. Alternating between gabapentin and clonazepam would help prevent dependence and tolerance. It's a good method to get the most out of both.
I'll PM you
No pm ><
Others may want to hear, like me.
I would think you're trying to be a pharmacist no?
Cane2theLeft
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^ ha.
I was initially hesitant to share this information publicly, but I do think it's fair to share what informs a lot of what I say on here and the background I'm coming from. Also, the interest is rather flattering (and baffling to me).
I am not interested at all in becoming a pharmacist. I will say that I've taken some pharmacology courses and that I finished the courses for a program in addiction counseling but moved out of state before sitting for the certification exam and since addiction counseling credentialing is governed individually state-by-state, my education didn't transfer.
My previous plan was to do the quick certification program to get working in the field while I further pursued education in psychology. I've considered medical school and while I haven't completely ruled it out, I think I will probably pursue graduate-level education in psychology. My passion revolves around personality analysis (especially Millon's and Oldham's theories as well as the more clinically-utilized Five Factor Model and Keirsey and MBTI to a lesser extent). My goal down the road is applying personality theory to addiction treatment to create more personalized treatment plans for individuals rather than the one-sized-fits-all approaches currently in use.
The new edition of the DSM (5) coming out shortly is transitioning to using a dimensional approach to diagnosing personality disorders for the first time. Although some clinicians have been arguing for decades (Millon and Oldham primarily) that personality disorders are extreme variants of normal personalities, the diagnostic approach has been that they are unique disorders separate from healthy personalities. With the field transitioning to factor analysis as a means of understanding personality disorders, I hope to work with using this approach to further understanding and treatment of addictions.
I was initially hesitant to share this information publicly, but I do think it's fair to share what informs a lot of what I say on here and the background I'm coming from. Also, the interest is rather flattering (and baffling to me
).I am not interested at all in becoming a pharmacist. I will say that I've taken some pharmacology courses and that I finished the courses for a program in addiction counseling but moved out of state before sitting for the certification exam and since addiction counseling credentialing is governed individually state-by-state, my education didn't transfer.
My previous plan was to do the quick certification program to get working in the field while I further pursued education in psychology. I've considered medical school and while I haven't completely ruled it out, I think I will probably pursue graduate-level education in psychology. My passion revolves around personality analysis (especially Millon's and Oldham's theories as well as the more clinically-utilized Five Factor Model and Keirsey and MBTI to a lesser extent). My goal down the road is applying personality theory to addiction treatment to create more personalized treatment plans for individuals rather than the one-sized-fits-all approaches currently in use.
The new edition of the DSM (5) coming out shortly is transitioning to using a dimensional approach to diagnosing personality disorders for the first time. Although some clinicians have been arguing for decades (Millon and Oldham primarily) that personality disorders are extreme variants of normal personalities, the diagnostic approach has been that they are unique disorders separate from healthy personalities. With the field transitioning to factor analysis as a means of understanding personality disorders, I hope to work with using this approach to further understanding and treatment of addictions.