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Low dose alprazolam is energizing and motivating?

Mafioso

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Anecdotal warning:
I've decided to consult with a psychiatrist finally, after years of holding the typical self-medicating taboo against doctors, some for good reason, albeit. I've been diagnosed with PTSD, and wake up with adrenal fatigue, feeling like I just had to fight off an attacker in my sleep. It was a reality of my childhood, and one that I believe is rooted in my subconscious. Being that it was directed toward my from my father, the one that is supposed to protect normally, I believe my trust issues and not so much social anxiety as interpersonal anxiety stems from here, and other similar events. Also, I've dealt with suicidal ideation since 8-9 yrs old, and depression was basically my accepted norm until my 20's. I'm pretty sure I have a mild antisocial personality disorder(undiagnosed), or at least it seems likely to me.

My personal history aside, I have always found benzos, in general, to be extremely euphoric at low and uncommon dosages, and even numbly euphoric in a drunken kind of way at higher doses. Much of the euphoria quickly fades with tolerance, and leaves me feeling numb, and physically drained and exhausted. I suppose this would likely be explained by GABA receptor down-regulation(?) and the following rebound anxiety. Probably glutamate up regulation, as well as other factors contribute here.



Anyways:
My question comes mostly from the fact that when I use sparingly and in low doses, before any tolerance has built, I feel energized and empowered to accomplish things I would normally shy away from or feel very uncomfortable doing. Is that(potentially) caused by the loss/decrease in inhibition caused by the GABA agonism? What causes me to feel become more motivated and productive at low doses, imo, more so than stimulants as I'm not chasing the dopamine. I know there isn't a clear answer here, any the obvious answer is that my anxiety disorder progresses to antisocial/depressive tendendencies(so it seems to me at least). But if someone with a better understanding can give me their rough idea of what is happening on a neurological level, I'd be extremely interested and grateful.

Like with opioids, low I assume low doses are stimulating due to the dopamine agonism. However, it may not be intuitive. It's known that cannabis is found to be the most anxiolytic/stress relieving among individuals who use chronically, implying that much of the relief is actually relief from the cannabis withdrawal(largely endocannabinoid system shock I believe). Also, similarly, once dependent, I experience a fatigue as I go into withdrawal(which seems counterintuitive as I thought there'd be excessive glutamate), and the fatigue is lifted with a dose of the drug of addiction, even though they are sedatives.
 

sekio

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Gabaergics reduce inhibition in lower doses, this is seen with alcohol all the time.

It's not smart to self medicate with BZDs unless you want to get a serious dependency to them. If you're not careful you will end up unable to socialize at all without them
 

AlphaMethylPhenyl

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Alcohol is much, much more "dirty" than benzos, but it's mainly a GABAergic.

Xanax isn't as sedating as other benzos, which I guess they say is a result if it not being an alpha1 ligand. It targets mostly alpha2 and alpha3, creating anxiolysis without much sedation. It also has a separate antidepressant function (but this function isn't likely to be sustainable).

I take the same daily dose of benzos, but try to only take them to socialize when I absolutely must. Otherwise, they are to relax at night time.
 

Captain.Heroin

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I'm very sorry to hear about your struggles and issues. I also have PTSD and hope you reach some inner peace.

Alcohol is much, much more "dirty" than benzos, but it's mainly a GABAergic.

Xanax isn't as sedating as other benzos, which I guess they say is a result if it not being an alpha1 ligand. It targets mostly alpha2 and alpha3, creating anxiolysis without much sedation. It also has a separate antidepressant function (but this function isn't likely to be sustainable).

I take the same daily dose of benzos, but try to only take them to socialize when I absolutely must. Otherwise, they are to relax at night time.
Alprazolam is highly sedating to me.
 

Mafioso

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Thanks for the support about my struggles. But back to the science...
Gabaergics reduce inhibition in lower doses, this is seen with alcohol all the time.
They would reduce at high doses, as well, as seen with alcohol and similar.
Xanax isn't as sedating as other benzos, which I guess they say is a result if it not being an alpha1 ligand. It targets mostly alpha2 and alpha3, creating anxiolysis without much sedation. It also has a separate antidepressant function (but this function isn't likely to be sustainable).
This is fascinating, thank you. Do you know of any benzos that are less anxiolytic while being more sedating, and the difference in mechanism behind that... by chance?

Also, I'm very curious about the antidepressant function. I'm sure Seiko is partially right, in that any anxiolytic would be perceived as "energetic" in the treatment of anxious depression, or social anxiety and similar, as situations that might normally be considered frightening and uncomfortable will then be perceived as exciting, adventurous, and comforting even. Similar to the way conquering any fear is invigorating.

However, I'm of the notion that something greater is at play, because it isn't just a general lack of inhibition(although at higher doses it does become so), at lower doses I find myself more motivated to do things specifically for others, as well to do things in general, to open up about personal issues and concern myself with others, and general increased empathy. This is generally followed the next day by the opposite, a sort of hyde and jeckle, where my empathy is gone and even find myself imaging ways I'd commit suicide. This again can, in part, be explained by a lack of inhibition, but it seems similar to MDMA rise and fall. And the unsustainable antidepressant effects seem like maybe some sort of agonism?
 
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Captain.Heroin

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I was under the impression the subunit association to effects was overstated... but don't remember where I read it. Oh dear.
 

AlphaMethylPhenyl

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This is fascinating, thank you. Do you know of any benzos that are less anxiolytic while being more sedating, and the difference in mechanism behind that... by chance?

Also, I'm very curious about the antidepressant function. I'm sure Seiko is partially right, in that any anxiolytic would be perceived as "energetic" in the treatment of anxious depression, or social anxiety and similar, as situations that might normally be considered frightening and uncomfortable will then be perceived as exciting, adventurous, and comforting even. Similar to the way conquering any fear is invigorating.

However, I'm of the notion that something greater is at play, because it isn't just a general lack of inhibition(although at higher doses it does become so), at lower doses I find myself more motivated to do things specifically for others, as well to do things in general, to open up about personal issues and concern myself with others, and general increased empathy. This is generally followed the next day by the opposite, a sort of hyde and jeckle, where my empathy is gone and even find myself imaging ways I'd commit suicide. This again can, in part, be explained by a lack of inhibition, but it seems similar to MDMA rise and fall. And the unsustainable antidepressant effects seem like maybe some sort of agonism?
Honestly the "non-benzodiazepines" work mostly on the alpha1 subunit, like ambien and lunesta. As for benzos, halcion and temazapam are pretty highly selected for alpha1. alpha1 allosteric binding is most associated with the sopoforic effect. More of inhibitory anions enter the postsynaptic cell because the ion channel is open longer via the benzo, or opens at a higher rate. In any case, yeah...

I don't know much about that mechanism behind that mechanism of xanax, just that it's probably dopaminergic. But less anxiety itself in someone with an otherwise terrible anxiety disorder would also lead to a reduction in depression, secondarily.

It's a bad thing to get dependent on without a doctor saying it's the right thing to do. More so, that suicidality makes me think you should have no business taking it...

I'll look into the xanax antidepressant mechainsm.

edit: explained that mechanism very roughly so if anyone wants me to elaborate I can.
 
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som3dankbudz

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Anecdotal warning:
I've decided to consult with a psychiatrist finally, after years of holding the typical self-medicating taboo against doctors, some for good reason, albeit. I've been diagnosed with PTSD, and wake up with adrenal fatigue, feeling like I just had to fight off an attacker in my sleep. It was a reality of my childhood, and one that I believe is rooted in my subconscious. Being that it was directed toward my from my father, the one that is supposed to protect normally, I believe my trust issues and not so much social anxiety as interpersonal anxiety stems from here, and other similar events. Also, I've dealt with suicidal ideation since 8-9 yrs old, and depression was basically my accepted norm until my 20's. I'm pretty sure I have a mild antisocial personality disorder(undiagnosed), or at least it seems likely to me.

My personal history aside, I have always found benzos, in general, to be extremely euphoric at low and uncommon dosages, and even numbly euphoric in a drunken kind of way at higher doses. Much of the euphoria quickly fades with tolerance, and leaves me feeling numb, and physically drained and exhausted. I suppose this would likely be explained by GABA receptor down-regulation(?) and the following rebound anxiety. Probably glutamate up regulation, as well as other factors contribute here.



Anyways:
My question comes mostly from the fact that when I use sparingly and in low doses, before any tolerance has built, I feel energized and empowered to accomplish things I would normally shy away from or feel very uncomfortable doing. Is that(potentially) caused by the loss/decrease in inhibition caused by the GABA agonism? What causes me to feel become more motivated and productive at low doses, imo, more so than stimulants as I'm not chasing the dopamine. I know there isn't a clear answer here, any the obvious answer is that my anxiety disorder progresses to antisocial/depressive tendendencies(so it seems to me at least). But if someone with a better understanding can give me their rough idea of what is happening on a neurological level, I'd be extremely interested and grateful.

Like with opioids, low I assume low doses are stimulating due to the dopamine agonism. However, it may not be intuitive. It's known that cannabis is found to be the most anxiolytic/stress relieving among individuals who use chronically, implying that much of the relief is actually relief from the cannabis withdrawal(largely endocannabinoid system shock I believe). Also, similarly, once dependent, I experience a fatigue as I go into withdrawal(which seems counterintuitive as I thought there'd be excessive glutamate), and the fatigue is lifted with a dose of the drug of addiction, even though they are sedatives.
I don't know about glutamate up regulation; gaba b is what regulates glutamate directly(correct me if I'm wrong). I know what you meant though. Of course benzo's and z-drugs(esp z drugs IMO); regulate glutamate somewhat indirectly, and to a large extent for not having a direct mechanism to regulate glutamate. Antagonists of Gaba a1 specifically; have a large impact on glutamate regulation(z-drugs). More than benzos at least. It's been theorized by me, or possibly read that zolpidem tartrate has an effect that is somewhat "downstream" on nmda(if there's any info on the truth of this matter please do respond). I believe having some influx on nmda; something resembling nmda antagonism. Therefore regulating glutamate to say the least in a very selective manor. Most likely there is some down regulation of glutamate in theory? Due to gaba a up regulation, and maybe not directly but there is most likely more of a struggle to regulate glutamate after gaba a up regulation occurs. Gaba b once again has more responsibilities as far as regulating glutamate; and not to mention gaba itself. I just thought I'd add that my two cents on that one. Although; I think your stimulation from low dose alprazolam is mostly due to relief because of monoamine regulation that does not normally occur.
 

Nicomorphinist

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I am inclined to think that it is part of the GABA agonism continuum -- I think this because when I was taking pregabalin to supercharge my opioids analgesia wise it made me feel like Jesus' son on six hits of E in the morning and 12 lines of Bolivian Marching Powder at night . . . all until one day I get this rash on my arm that makes it look like a coelacanth. . . .

Plus, I blew up until I looked like Hermann Göring -- it was awful. For some reason, the first 110 kilos came back off in a little under 10 months and the last 25 in the next four . . . I kept telling the doctors that I was searching high and low for ways to take off the weight but I had copious quantities of blood taken every month and a couple of procedures where they snaked cameras up both ends to assure us all that some kind of oncologic process or TB or something was not contributing as well . . . . I know that Göring loved morphine, dihydrocodeine, and oxycodone too, but in the prior 20 years I actually declined slightly from my weight at the age of 18 and was in the 5 Gramme Club for morphine hydrochloride 24-hour equivalent three times for a total of nine years . . .

People also get stimulated in that fashion by low to moderate doses of alcohol -- as one climbs from baseline to over 500 mg/dl, the effects of alcohol seem to go like caffeine, E, nitrazepam. dextropropoxyphene, nitrzepam + bromodiphenhydramine, meprobamate,, methaqualone + diphenhydramine, Seconal + atropine, flunitrazepam, phencyclidine, and then, in the end, and in lots of cases above 500 mg/dl, syrup of ipecac + succinylcholine + curare. Not good.

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Ne0

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I've found that only higher doses of alprazolam will give some "energy" and makes mood better at least 2mg, but 0,5mg just takes of the anxiety. But anything over 3mg gives blackout very easily. High doses of benzos makes you say shit that you regret afterwards.
 

negrogesic

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I've found that only higher doses of alprazolam will give some "energy" and makes mood better at least 2mg, but 0,5mg just takes of the anxiety. But anything over 3mg gives blackout very easily. High doses of benzos makes you say shit that you regret afterwards.
I am perpetually haunted by the things ive said to people on benzos
 

AlphaMethylPhenyl

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If you can't sleep because of anxiety, alprazolam might have this ("secondary") hypnotic effect.

Another thing is that xanax seems to have an additional dopaminergic effect. I don't know much about it, but this might be a good reason for its experience as a mood-booster.

Edit: okay let's get the ball rolling:

-https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007139.pub2/abstract
-So now some alpha2-specific experimentation: https://www.sciencedirect.com/science/article/pii/S0166432810006819
 

PtahTek

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But less anxiety itself in someone with an otherwise terrible anxiety disorder would also lead to a reduction in depression, secondarily.
This is hitting the nail and driving it home.
I am perpetually haunted by the things ive said to people on benzos
Oh, god. Man, tell me about it; the shit i did on xanax and alcohol could be considered sociopathic, psychotic and outright fucking dumb. Glad i grew outta that stage/time.
 

ReneDescartes

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I am prescribed 1mg of Xanax to take first thing in the morning and another 1mg at noon. I use it because it really helps me with my procrastination issues. I think that when I have a big task ahead of me, the xanax helps me just do it and stay on track.

I even find myself doing household chores without even realizing that I'm doing them. It really just helps me initiate the task without thinking twice, and then once I'm doing it, I am able to finish it.

I don't have severe anxiety about any particular thing, but I have mild anxiety about almost everything. So if you are like me, I think that this might be a helpful medication for people that have similar issues.
 

negrogesic

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This is hitting the nail and driving it home.

Oh, god. Man, tell me about it; the shit i did on xanax and alcohol could be considered sociopathic, psychotic and outright fucking dumb. Glad i grew outta that stage/time.
I've got most people beat. Heavy benzo use resulted in my practicing medicine without a license, quite successfully I might add. Fortunately i stopped eventually and never had a legal problem, all while providing a high level of care. Its a long, interesting story.
 

negrogesic

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@sekio The story begins with a nearly fatal overdose of etaqualone. Family members found me nonresponsive and not breathing. Last thing i remember i put on a pore clarifying mud mask in preparation for a bath, and took a hit of etaqualone of foil.

4 days later i wake up in an ICU, intubated. Of course i start gagging from the tube down my throat and started pulling it out, before nurses ran over. "Did you do this to yourself? Were you trying to commit suicide" was the first thing they asked. Apparently i had done the whole clinically dead thing, but survived. Convinced i might have brain damage from having not been breathing for an unknown time, they did many tests. Was there for a week total. I had the strangest feeling for a few days, like part of me actually had died. As soon as i got home i went straight for my benzos stash.

Weeks later im in line at a hospital pharmacy. A loud mouth jewish man in front of me was arguing with the pharmacist about the pharmacological properties of some drug and its contraindications. I interject with my insights (they were both incorrect in a sense). "Are you a medical student?", then i say.... "yes I am, im actually an international medical graduate and finished medical school in Australia. I'm working now to get licensed here in my state" (this was of course a benzo and methylphenidate infused lie). We talk and talk, he is clearly impressed by me, and in the parking lot he gives me a briefcase full of medical files. He is a psychiatrist who also does QME's (qualified medical exams -- testimony for court). He is impressed with my knowledge of pharmacology and asked if I would be willing to work for him and help him on some of his cases. I agree. This is how it started. Eventually i would end up working at his practice, had my own office, patients, and started writing expert medical testimony.

My first write up was a wrongful death lawsuit where a man in the army died from apparently drug related cause, but the family felt that the army physician was at fault. I argued (on behalf of his family) that the base's physician treatments (high dose tramadol, for a patient known to abuse tramadol, co-prescribed with citalopram) resulted in his death (autopsy consistent with serotonin syndrome).

Aside form writing me "expert" testimony I began seeing his patients in his frequent and sporadic absences (he was bipolar and suffering from ocd -- he even had his license suspended due to a psychiatric hospitalization) as he was unreliable so i started seeing some of them. Then, I proposed the idea of integrating buprenorphine treatment into his practice because it was lucrative. I dealt with all the licensing, and even took the 8 hour online test for him to get the DEA waiver to allow its prescription...

The story goes on, maybe ill tell more later.

I really was a pretty decent psychiatrist and an excellent administrator. Ultimately, other psychiatrists started consulting with me for guidance in integrating buprenorphine treatment into their practices. I became a sort of expert on how to introduce a new revenue stream into ones practice by offering buprenorphine therapy. No one doubted me for a moment. I had few doubters (his female medical biller did doubt me howeve, and jokingly said she wanted to see my diploma, so I fired her and hired a replacement). (I also ran the office so I hired and fired all staff.)

This would have never happened without benzos and stimulants. I also believe that the recent temporary brain damage i experienced from being hypoxic for so long contributed to this significantly. Ultimately I quit because the other doctor was not treating the buprenorphine patients as they needed to be, so I pulled his DEA and SAMHSA waivers/license to provide buprenorphine services.

So, in short, i ODd on etaqualone, was clinically dead for a bit, and under the influence of benzos, started practicing psychiatry.
 
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Skorpio

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gaba b is what regulates glutamate directly
This feels wrong to me, do you have any papers that prove otherwise?

Gaba b is a gi coupled gpcr, which has some euphoric effects due to downstream disinhibition of dopamine circuits.

Also, I feel like a lot of Bl relies too heavily on global assessments of what neurotransmitters do; what matters a lot more is their actions at the circuit level. For example mu opioids are euphoric because they inhibit gaba neurons which inhibit dopamine neurons in the vta. It would be incorrect to say opioids are gaba antagonists at the global level, and I see this logical error type a lot here. (Also this is not even going into Gq coupled receptors, or different secondary messengers or secondary messengers that are restricted to parts of the cell via scaffold proteins).

Also, glad to see you posting Negrogesic. You were around bluelight when I joined like 8 years ago or so, and I remember your colourful descriptions of o-desmethyltramadol narcosis, or the mixture of gin and focalin fondly.
 

Mafioso

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This feels wrong to me, do you have any papers that prove otherwise?

Gaba b is a gi coupled gpcr, which has some euphoric effects due to downstream disinhibition of dopamine circuits.

Also, I feel like a lot of Bl relies too heavily on global assessments of what neurotransmitters do; what matters a lot more is their actions at the circuit level. For example mu opioids are euphoric because they inhibit gaba neurons which inhibit dopamine neurons in the vta. It would be incorrect to say opioids are gaba antagonists at the global level, and I see this logical error type a lot here. (Also this is not even going into Gq coupled receptors, or different secondary messengers or secondary messengers that are restricted to parts of the cell via scaffold proteins).

Also, glad to see you posting Negrogesic. You were around bluelight when I joined like 8 years ago or so, and I remember your colourful descriptions of o-desmethyltramadol narcosis, or the mixture of gin and focalin fondly.
can you explain what a "gi coupled gpcr" is/ means? This sounds really interesting, but I haven't the time to research it myself atm.

Also, would love to hear more about how mu opioids are euphoric as a result of inhibiting gaba neurons which inhibits dopamine neurons. I suppose I would be in the lump of BLers who rely too heavily on global assessments of what neurotransmitters do, as my understanding is fairly simplistic. This seems counterintuitive to me, but I also realize I have a lot to learn.

Thanks for all the replies everyone, some interesting stuff. keep it going. 👍
 
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