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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.
 
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
 
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.
 
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.
 
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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I was under the impression the subunit association to effects was overstated... but don't remember where I read it. Oh dear.
 
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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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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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'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
 
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
 
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.
 
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.
 
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.
 
@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 interjected...
 
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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.
 
Well thank you for remembering. Im surprised im still alive.
 
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. ?
 
There are 2 main types of receptors that are relevant to psychopharmacology (I am leaving out steroid receptors and receptor tyrosine kinase for simplicity): ligand gated ion channels, and g protein coupled receptors.

A ligand gated ion channel such as the AMPA receptor or the GABA a receptor will simply open up when an agonist binds, and allow an influx of ions into the cell. Depending on the charge gradient of the ions the cell will be either depolarized (and fire an action potential) or become hyper polarized and need more excitation to fire an action potential. Ion channels are mediators of fast signaling because they primarily either induce action potentials (and often synaptic release of neurotransmitters onto the next cell), or they inhibit them all in a short time scale.

G protein coupled receptors are receptors that are coupled to G proteins : ) When one is activated the G protein is released from the receptor and interacts with second messenger proteins and ion channels. A common second messenger is cyclic AMP (cAMP) which is produced from ATP by the enzyme adenylate cycles. cAMP activates a variety of enzymes and proteins that generally increase the excitability of cells. Different g proteins have different functions, and the receptors are classified based on function. Gs coupled receptors when activated will turn on adenylate cyclase, and Gi receptors will inhibit its activity. These can both be occurring at the same time, and the level of activity of adenylyl cyclase is regulated that way (this is actually a super common concept in a lot of signaling mechanisms in life, reciprocal effects will feed into systems simultaneously to better tune it.) Anyway, GPCRs regulate signalling in a slower fashion than fast ion channels, and can be viewed kind of like changing volume knobs and other parameters of the signal, where ion channels are more directly the signal itself (this is pretty crude, but kind of how I think of it usually).

The opioid disinhibiting GABA thing I'll be even more cursory on. When analyzing a circuit, you should think of the neurons as simple functions that can multiply a thing by 1 or -1. Each neuron adds another function, so a circuit with one inhibitory neuron (represented by -1) and one excitatory neuron (represented by 1) could be summed up by a function that multiplies the input by -1. A circuit with 2 inhibitory neurons would be like multiplying -1 × -1, so it would equal 1 and have excitatory nature (you would be inhibiting inhibitions).

In the case of the vta dopamine signalling, the mu opioid receptor is Gi coupled, but the G protein also opens an inhibitory ion channel causing fast inhibitory transmission. This directly synapses onto GABA A neurons which are inhibitory ion channels, which inhibit dopamine neurons. The sum effect of activating VTA mu opioid receptors is therefore potentiation of dopamine signaling.

Looking at neurotransmitters on a global level is akin to looking at a malfunctioning computer and saying that there is probably a problem with the resistors. That could be very well true, but it doesn't mean a lot, other than reflecting the most common phenotype that resistors give the global circuit.
 
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