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  1. Current high dose baclofen patient (140mg a day), who experienced great success (alcohol free, very little anxiety) for the first 7+ months, and then foolishly experimented with another GABAb agonist (phenibut) after losing a portion of my baclofen prescription. Though I was able to stop the other GABAb agonist by substituting it with baclofen, the dose I'd been at was no longer as effective. I titrated my baclofen use down to zero (with the aid of gabapentin to combat some of the anxiety I was experiencing), but only performed a baclofen drug holiday of 24 hours before resuming. In doing so, I increased my dose very rapidly, as I was not experiencing somnolence at doses of 80mg a day, and increased to 140 the next day. I am now suffering as baclofen is no longer as effective (battling extremely increased anxiety, vivid dreams and "electric shocks" in hands, but still alcohol free - in essence, it seems that I lost my "switch." My plan is to titrate my baclofen dose back down to zero to take more of an extended break, with the hope that resuming treatment will be effective after a hiatus. There are also a few supplements that I'm interested in exploring during my future break from baclofen, and I will share my results. Looking for support and information regarding others who have experienced tolerance issues with baclofen, and have perhaps found ways to overcome them. Currently experimenting, myself, and will be happy to share my findings/experience with the community. Much gratitude and warm wishes to all =)
  2. [Disclaimer: I have some background in pharmacology, but I am not a medical doctor.] Hey everyone! What follows is information regarding the mechanism of action of baclofen as well as similar substances, their effect on anxiety, and my thoughts/implications. [I've decided to add elements of my personal story and current situation in the hopes that others can learn from my insights as well as my mistakes.] Baclofen's mechanism of action involves agonism of the GABAb receptor, as well as slight inhibition/attenuation of voltage-dependent calcium channels (VDCC). Some studies suggest that it is the agonism of the GABAb receptor that causes the attenuation of the VDCC as a downstream effect, but further research is required. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2230969/) It is this combined action that is the mechanism by which baclofen's effects (lack of interest in drinking, reduction of anxiety) is achieved. How so? Well, it is well known that one of the mechanisms of alcohol's temporary reduction in anxiety is due to its agonism of the GABAa receptor. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574824/) Another study has shown that application of a GABAb antagonist (the opposite of an agonist) increased the GABAa's sensitivity to alcohol. (http://jpet.aspetjournals.org/content/312/3/1082) So, while this is some deductive reasoning on my part, it seems to stand to reason that one effect of a GABAb agonist such as baclofen is that it might decrease the pleasure/effectiveness of alcohol by decreasing the sensitivity of the GABAa receptor to its effects. Furthermore, it has been shown that GABAb agonism has positive effects in the mediation of depression and anxiety. (https://www.ncbi.nlm.nih.gov/pubmed/18195453) I believe that it is by these mechanisms - reduction of sensitivity of the GABAa receptor to ethanol's effects (speculative, but this could contribute to the "switch" that many who keep drinking up to a point report), and the positive effects GABAb agonism has on anxiety and depression (fact!), that many lose interest in drinking following the administration of high dose baclofen. As I stated, however, another one of baclofen's effects is its attenuation of voltage-dependent calcium channels (VDCC). VDCC attenuation has also been implicated in the reduction of anxiety. This has been shown by studies on lavender (product such as Calm Aid/Silexan, for example: https://www.ncbi.nlm.nih.gov/pubmed/29073181), as well as Neurontin (gabapentin), a well known medication that is prescribed off-label for anxiety that's primary mechanism of action is thought to be its attenuation of VDCC (with some kind of relation to GABAb, no less). (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1176314/). And so, there is strong evidence to suggest that GABAb agonism as well as attenuation of VDCC is what accounts for baclofen's effects. Another substance that has similar effects to baclofen is phenibut. Like baclofen, phenibut also selectively agonizes the GABAb receptor and attenuates the VDCC, but with reverse strength: baclofen is a stronger agonist of the GABAb receptor than phenibut, but phenibut attenuates the VDCC more strongly than baclofen. The actions of phenibut (r-phenibut, in the study), baclofen, and gabapentin in terms of their binding affinity/activity at the GABAb and VDCC were measured in this study: shttp://www.sciencedirect.com/science/article/pii/S009130571530037X Below is a table from that study that represents their findings: The measures of the binding affinity at the α2–δ subunit of voltage-dependent calcium channels are shown in comparison to GBP (gabapentin), as gabapentin exerted the strongest effects there of the substances tested (in this case the lower the number, the stronger the binding affinity, and the inverse relation of binding affinity of phenibut and baclofen at the VDCC and GABAb receptor are evident). Now, that is the groundwork from which I will now make some claims, as well as tell a little bit of my personal story. The first is that "anxiety," writ large, originates within the brain. The specific neurological/psychological underpinnings that "cause" anxiety, or make some more anxious in some situations, or experience different kinds of anxiety, involve a complex picture of an individual's brain, genetics, experiences, psychology, substances/medications taken, and the interplay between. For some of us who grew up and experienced social anxiety in certain contexts, alcohol provided the right kind of relief in those situations - I fall into that category. For me personally, years of achieving relief in social situations gradually (over years) spilled into me drinking more and more, and I became an alcoholic. I actually experienced a period of time whereby I stopped drinking for about 2.5 years, and suffered from terrible post-acute withdrawal syndrome (PAWS). Why was this? Although this is something of an oversimplification (and going back to how everything stems from the brain), evidence suggests that a big part was that my years of alcoholism had down regulated my GABAa receptors (the same ones that benzodiazepines attach to/agonize), making them less able to provide an effective inhibitory response to stress/anxiety on their own (without the presence of alcohol/other GABAa agonists). (https://www.ncbi.nlm.nih.gov/books/NBK98172/) In my case, towards the end of my second year of abstinence, things actually did begin to improve at a fairly consistent and noticeable rate. I began to feel like my old self, in a sense, and could handle social situations/life in general far better than I had in the earlier stages of recovery. Unfortunately, however, that eventually lead to me thinking that I could try my hand at drinking again, and disaster and alcoholic patterns began to resurface full force about a year into my reintroduction. Eventually, after many attempts to stop (and during an abstinent period) I found baclofen approximately 8 months ago, and my life improved dramatically, with all of the benefits users report throughout this forum and beyond. Throughout my use of baclofen, I noticed a few interesting things after taking other substances. The first deals with benzodiazepines. There were a couple occasions in which I took small doses of benzodiazepines during my baclofen treatment with very little negative effect. However, there was one occasion in which I took multiple doses for a short time (I believe a day and a half, perhaps two days at most), and experienced very noticeable rebound anxiety for a period of about 4-5 days after. During that time, I had attempted to increase my baclofen dosage (my usual dose is 140mg/day) in order to offset that anxiety to no avail. I believe that the explanation for this is simple: benzodiazepines agonize GABAa receptors, while baclofen agonizes GABAb. The anxiety that I was experiencing was due to the lack of agonism at a receptor that baclofen simply doesn't hit, and thereby had little effect in mitigating. I bring up this example to again suggest that not all "anxiety" is the same, PARTICULARLY when it results from the use of other substances/medications. I also think this is why some of us who have used benzodiazepines extensively in the past fail to receive as much of an anxiolytic effect from baclofen - it is simply a different receptor, and the GABAa receptor must have time to upregulate on its own (away from any GABAa agonists) before anxiety stemming from that source will dissipate. This next bit of my story is admittedly uncomfortable for me to express because it describes a situation that I am currently dealing with, and it brings me a great deal of distress. My hope, however, is that it helps anyone else from falling in to what has happened to me, or helps to provide some insight into what others (anyone now or in the future) might experience. Awhile back I lost a portion of my baclofen prescription, and after some research on the internet (at this time, I was still unaware of how more baclofen could be procured through online pharmacies/sympathetic and wonderful souls on forums), found that phenibut would seemingly be able to serve much of the same purpose of baclofen given their incredibly similar molecular structure and mechanisms of action. I was, however, unaware of a key and aforementioned difference between them: while both agonize the GABAb receptor, phenibut also attenuates the VDCC much more strongly than baclofen. After a period in which I was combining a lower dose of baclofen (40mg-60mg) with phenibut to great success, I decided that enough was enough after I was able to get a refill of baclofen. The transition from lower dose baclofen with phenibut to my regular dose of baclofen, however, was crushing, as I was overwhelmed with intense anxiety that even higher doses of baclofen were unable to address. More internet research allowed me to find that many users of phenibut had successfully combat the anxiety of withdrawals with gabapentin, and I indeed felt immediate relief upon taking some that I'd had on hand from a leftover prescription. What I now know, but was unaware of at the time, is that my anxiety was due to my brain having grown accustomed to the level of VDCC attenuation provided by phenibut. When that was removed, massive, crippling anxiety followed until I was able to attenuate the VDCC yet again with gabapentin (making up for the difference in attenuation that baclofen lacked). However, I am now in a seemingly very dire situation. I recently began to try stopping gabapentin altogether, and moved from a dose of 1800mg/day (relatively high, that I'd been on for six weeks) to 900mg/day. In fact, the day after, I tried to eliminate gabapentin completely. Obviously, this was silly on my part, but I had no idea of what was to come. After experiencing rising anxiety in the days following my discontinuation, I eventually experienced the onset of delirium (visual signs, similar to what I had experienced during alcohol withdrawal) on the third night. Gabapentin withdrawal induced delirium has been recorded in medical literature (a meta-analysis with PubMed ID numbers of other cases can be found here: http://journal.pulmccm.org/article/gabapentin-withdrawal-causing-adrenergic-toxidrome/). I immediately took another 300mg dose of gabapentin, fell into fractured (a couple hours at a time) sleep, and when I awoke took another 300mg dose of gabapentin. As it began to take effect, I experienced growing numbness along the right hand side of my body, literally in real time. In the days that followed, I (perhaps foolishly) enacted a start-stop relationship with gabapentin, thinking that I could just take an ever smaller dose every third day or so to prevent the onset of delirium. I never made it that far as the anxiety rising within me between each dose was simply too great. I began taking gabapentin again at a dose of 300mg twice daily, and am now in the process of tapering down (currently at 200mg twice daily). However, with each successive dose of gabapentin, I am experiencing more and more symptoms of neuropathy/numbness in areas throughout my body, as well as deterioration of vision and increased tinnitus. I am not entirely sure by what mechanism this is happening, but as gabapentin's primary indication is for the treatment of neuropathic pain, I can only assume that I am experiencing these effects as a result of its actions (attenuation of the VDCC) in combination with high dose baclofen. Now, I am aware that I have a unique history, had been using a relatively high dose of gabapentin in combination with my usual 140mg/day of baclofen, and did not initially think to taper it down in a conscientious or safe manner. I am by no means trying to insinuate that it is dangerous to use gabapentin in combination with baclofen, but I feel it necessary to share my experience in the possibility that there is a yet unstudied/unknown danger, perhaps at higher doses and for longer periods of time. At the very least, it stands to reason that one who is using gabapentin in combination with baclofen for an extended period might suffer from some anxiety after stopping gabapentin, similar to how some users of gabapentin report withdrawal/increased anxiety upon stopping (and because baclofen alone will not account for the increased attenuation of the VDCC that gabapentin provides). In the study I linked up above (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1176314/), the authors write that "It is concluded that GBP selectively activates presynaptic GABAB heteroreceptors, but not GABAB autoreceptors." It is above my pay grade to know exactly what that means, but it does certainly suggest that gabapentin has some activity with some GABAb receptors. In fact, another study found that gabapentin does potentiate (increase) some of the effects of baclofen by some mechanism: https://www.ncbi.nlm.nih.gov/pubmed/14704478. So, there is clearly some level of interaction between the two. I am worried that perhaps my use of high dose baclofen along with relatively high dose gabapentin (honestly, probably higher than I needed to simply combat the phenibut withdrawal) perhaps elevated the effects of the "dose" of baclofen I've been taking to something akin to higher than 140mg, and I am now in some state of constant, sub-acute withdrawal that is causing CNS dysfunction (and could also account for the onset of my delirium being more akin to baclofen withdrawal, rather than gabapentin withdrawal). This is pure speculation, but I thought I'd share it, nonetheless. And so, my current game plan is to continue to take 400mg/day in divided doses today and tomorrow, and then drop down to perhaps 100mg TID for a period of a few days before tapering back down to zero, and hoping as much as possible that (a) the CNS symptoms I'm experiencing progress at a slow enough rate that they are "tolerable," despite how ridiculously scary this entire enterprise is, and (b) that I do not begin to experience delirium again after stopping completely. If I do indeed begin to experience delirium again, I fear I will have no choice but to take gabapentin again, and then resort to potentially dangerous and blind measures, such as trying to stop gabapentin again while increasing my dose of baclofen to something higher than 140mg. I should say that there was a day (without the use of gabapentin) that I was able to increase from 140mg to 240mg, the only side effects being incredibly vivid dreams [Side note: A study here https://www.ncbi.nlm.nih.gov/pubmed/28347366 concluded that "in the absence of norepinephrine activity (as in REM sleep), cholinergic activity is unable to yield long-term synaptic changes, such as those implicated in memory retention, which would partly explain the well-known difficulty of recalling oneiric activity." Another study found that baclofen increases norepinephrine turnover (https://www.ncbi.nlm.nih.gov/pubmed/2873522), essentially the amount of its activity in the brain, which seems to explain why many people report vivid dreams that they remember at higher doses of baclofen ]. And so, if the onset of my delirium was in fact due to gabapentin having made my brain accustomed to a "higher" dose of baclofen by potentiating my regular dose, perhaps increasing baclofen alone will account for that deficit, and I will then be able to titrate down. This is of course incredibly scary, as I simply DO NOT KNOW exactly why I am experiencing all of these symptoms, and will not know more until I basically continue to run this crazy and frightening experiment on myself. My first course of action is to continue with what I am doing, CNS dysfunction notwithstanding, to see if tapering down my gabapentin at this rate allows me to stop it entirely without the onset of delirium. One absolute moral of the story is to never use phenibut if already taking baclofen - @Jetsman32, I understand you were using phenibut prior to your use of baclofen, so I suspect that you'd be in nothing like the same boat as me, though I'm wondering if perhaps you found that baclofen did not do as much to alleviate your anxiety as you had hoped? Though gabapentin might theoretically offer some reprieve in that regard, I'd humbly warn against being inclined to take high doses of it for long periods of time until more is known about the interplay between it and baclofen, and to TAPER down if you elect to use it. Again, this is all PURE theoretical reasoning, and so I AM NOT trying to tell anyone what to do or to raise any kind of undue alarm. As for my situation, I will report back here when I can, and am happy to answer any questions for as long as I can. Though I am absolutely scared of what fate will befall me (that I've brought upon myself), I am not depressed, just merely disappointed. I love life, and all that there is to it. I wish all of you all the best, and truly hope that no situation such as mine is ever experienced by anyone, ever. Warmly, TR P.S. On another, unrelated note, I am incredibly interested in finding accounts of people who have successfully tapered off of high dose baclofen completely after being on it for a stretch. I'd like to know what the experience of life was like after coming off of it completely, namely as to whether there were any symptoms of discontinuation (anxiety, mood changes, etc.). This is because I am wondering if, like benzodiazepines, there would be any symptoms of post-acute withdrawal due to GABAb downregulation after coming off of a high dose of a GABAb agonist like baclofen for some time. I also wonder whether GABAb downregulation accounts for why many who titrate down need to go up higher to (or possibly don't ever) find their "switch" (thanks, @Baclofenman). The only other GABAb agonist that I can find that some people have taken regularly for long periods is GBL/GHB, however I am unable to find any accounts online of anyone actually stopping and recovering after long periods of use. In any case, that is a discussion/topic for another time, as at present, I obviously have far bigger things to deal with. Also, thanks to @Felina, @Molly78, and again @Baclofenman for getting back to me when I initially posted an albeit incomplete introduction, and before I realized just how serious of a situation I was in. ------------------------- @Admin1, @Admin2 @baclofenresearch - I just want to bring this post to your attention, as it includes much research as well as my personal plight.
  3. Jetsman32

    First day on Baclofen

    Hi All, Hope everyone is doing well. Yesterday my order of Baclofen finally came in the mail! I was so excited to get it and decided to start it today. So, I've now been clear of alcohol for 9 days straight - which I'm pretty proud of. Anyway, during this time I've still been dosing phenibut daily- usually around 3-4 grams to maintain my sanity (this is a fairly high dose). On top of that I take a ton of herbs like passion flower, l-theanine and Valerian. I also use aniracetam- a nootropic for mood improvement and klonopin (although I've hardly touched it over the last week). I read a lot of places that phenibut and baclofen have a very similar chemical composition but didn't want to risk having them on the same day (couldn't find any info on the web about combining the two)- that is why I waited until today to start. I was really scared of a bad reaction. So instead, I stopped phenibut cold turkey and started today on the baclofen. I'm starting my dosage at 30mg per day (10mg X3 times per day). I know it is recommended to start a bit slower but I did some research and figured that the phenibut tolerance I've built up would make it necessary to avoid some really bad withdrawal symptoms associated with Phenibut. So far I've dosed twice today. Initial side effects are mild naseau and some slight tingling in my left arm. Other than that it's been fine. I should also add that I was prescribed a 6 day treatment of prednisone (oral steroid) for my back which I started today as well so the side effects could be coming from that. I've still been using my other stuff today. Had 2 servings of aniracetam and l-theanine but have still avoided the klonopin. My anxiety is definitely there today- i can tell i'm not on phenibut for sure but it is almost manageable. Anyway, I took my first 10mg this morning at 7am, my second at 1:00pm and will take my 3rd at 7:00pm. In reading through these pages I saw that peeing the bed is a possible side effect as well as bad dreams so I'm making sure my final dose is well before bed (11:00pm). Anyone else had these side effects? My one huge fear is that I'm not going to be able to sleep tonight. Phenibut has a really long half life and allowed me to get to bed and fall asleep quickly. I'm worried the withdrawals are going to have me up all night once the last dose of baclofen wears off. I stopped and picked up some melatonin though and if it comes to it, I will take the Klonopin just to get some rest (I fly out to Boston tomorrow for a business trip). My plan is to still titrate slowly. I will use 30mg for 3 days then move up to 40mg for 3 days and so on. I've even created a dosage calendar for myself so I can hold myself accountable. I've also met some awesome people on here that have been very supportive so I think this plan will work. Three big questions 1) Does that sound like a good plan- if not- be honest! 2) Any suggestions for withdrawals and getting to bed? 3) Am I mixing any herbs with baclofen that could lead to a bad reaction? Really hoping the baclofen works for me. Thanks everyone!
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