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Benzos GABAA agonists, why so pleasant?

N

Neuroprotection

Bluelighter
Joined
Apr 18, 2015
Messages
1,082
hi everyone. through reading countless drug experiences over the years, I’ve noticed that sedative-hypnotics acting on the GABAA receptor, most commonly benzodiazepines today, have a very high likability rating. of course, other addictive drug classes like stimulants and opioids are very popular but a number of people strongly dislike them. just to clarify, I’m talking about their immediate pleasurable effect because most people who hate drugs do so because of addiction and long-term negative side-effects.
I’ve never tried any of these drug classes myself, so I can’t speak from experience. basically, I want to know if my observation is correct in that the overwhelming majority of people given a benzodiazepine like drug Will really enjoy it.

Also, I’m wondering if much of the rewarding affects of benzodiazepines actually comes from GABAA receptor potentiation simultaneously slowing down multiple brain regions, thus decreasing the general sense of awareness/consciousness which could be interpreted as a pleasant sensation.
Of course, we have to consider that most GABAAergic sedative-hypnotics provoke significant dopamine release, but so do many other drugs.
 
Most GABA-a positive allosteric modulators like benzos and other classes are rather boring on its own. They are a useful tool when mixed with other classes of drugs but dont bear much recreational value on its own imo.
 
Neuroprotection said:
hi everyone. through reading countless drug experiences over the years, I’ve noticed that sedative-hypnotics acting on the GABAA receptor, most commonly benzodiazepines today, have a very high likability rating. of course, other addictive drug classes like stimulants and opioids are very popular but a number of people strongly dislike them. just to clarify, I’m talking about their immediate pleasurable effect because most people who hate drugs do so because of addiction and long-term negative side-effects.
I’ve never tried any of these drug classes myself, so I can’t speak from experience. basically, I want to know if my observation is correct in that the overwhelming majority of people given a benzodiazepine like drug Will really enjoy it.

Also, I’m wondering if much of the rewarding affects of benzodiazepines actually comes from GABAA receptor potentiation simultaneously slowing down multiple brain regions, thus decreasing the general sense of awareness/consciousness which could be interpreted as a pleasant sensation.
Of course, we have to consider that most GABAAergic sedative-hypnotics provoke significant dopamine release, but so do many other drugs.
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What you say gets more and more correct cuz how stressful world is.
It ain't true that many people dislike opiods. I think among poly-drug users you're more likely to find someone disliking stimulants or finding them appropriate only once in a blue moon. With opiods, people find them a lot more dangerous, rightly or not, that depends on each individual.

Benzos are used in a same way as booze I would say. In a whole range of addiction and recreational use if that makes sense. So daily functional or not addicts, recreational binge or not users, borderline addicts, low dose, high dose users, solo or social...you get the picture. And I've seen most of those examples. With both booze and benzos or combo of both. Like opiods they are both wonderful and damaging. Better skipped if you have a good life and don't want to risk loosing it. TO ALL THE YOUNG PEOPLE READING THIS - STICK TO WEED & PSYCHEDELICS

Even dissos get very risky. Stims as much or more or less depending on both certian stimulant and you liking. Meth and crack are usually more addictive than dissos for most people. But definitely stay the fuck away from opiods and benzos. ESPECIALLY IF YOU THINK THEY AIN'T THAT SPECIAL AND YOU FIND IT EASY TO STOP IT EVEN AFTER X DAYS!
Those who fall in love right away usually understand why those drugs are the doom of so many people. But some buy the crap some preach (like I did) that you can use opiods for once a week forever and not get hooked. While truth is that if you start that shit treat it like MDMA should be treated for max safety and MAYBE you wont get hooked that way. So a few times a year, not a lot of redoses etc Still understand that you'll need a good bit of LUCK even that way.
 
VERY IMPORTANT NOTE - I've met both people who handle their benzos very well and people who handle their opiates very well but I'm yet to find a person who can handle both without a problem. Even those who handle one of those two well often first fucked up badly first with one or other, or both. Trust old hippies on this one. And ffs even plain amphetamine can fall into dangerous abusable drug category, benzos and opiates become that way easier.

Love you all old and new friends!
 
SpiralusSancti said:
VERY IMPORTANT NOTE - I've met both people who handle their benzos very well and people who handle their opiates very well but I'm yet to find a person who can handle both without a problem. Even those who handle one of those two well often first fucked up badly first with one or other, or both. Trust old hippies on this one. And ffs even plain amphetamine can fall into dangerous abusable drug category, benzos and opiates become that way easier.

Love you all old and new friends!
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Thank you so much for that reply, Love the experience/anecdotes and personal perspective you brought to the topic. your point about the high anxiety modern lifestyle making hypnotics more reinforcing seems very true and I certainly agree with that.
Also, your advice to stay away from benzos and opioids is very valuable. I’m not going to try those drugs, but I could certainly see how I would become very addicted to them if I did. my general preference would be for a more functional mood lifting compound, perhaps a mild dopaminergic stimulant like Selegiline, bupropion or nomifensine. i’m also interested in trying a few things you’ve suggested to me in previous posts, such as chamomile, passionflower and blue Lotus. i’m thinking of starting some or all of these once I quit caffeine. what really caught my attention with these things is that they generally tend to work with the body in a subtle yet potent manner. for example, from what I’ve heard, I assume that benzos and perhaps opioids simply shut down The emotional centres of the brain, temporarily masking anxiety. Meanwhile, herbs probably have no noticeable effects on immediate anxiety, but they should boost stress resilience, helping one to push through A difficult experience rather than breaking under the pressure.
Perhaps once I’ve completely quit caffeine, I will use milder herbal supplements on a regular basis and leave stronger things like nicotine for occasional use.
 
I guess they carry very little potential for dysphoric side-effects, so few people really dislike the sensation

However it's also a rather boring effect and few people really like benzos, it's a drug of desperation not pleasure
 
Neuroprotection said:
I’ve never tried any of these drug classes myself, so I can’t speak from experience. basically, I want to know if my observation is correct in that the overwhelming majority of people given a benzodiazepine like drug Will really enjoy it.
Click to expand...
Not sure why but if someone (me) does not have anxiety or is not experiencing anxiety and takes a benzo not much happens. Lately I have needed to take on occasion as a tool for anxiety. When a benzo takes away anxiety it feels great. I had to go to a medical physical a few weeks ago and those always give me anxiety. A tiny bit of a benzo got rid of that and made me feel normal. However any other time I have tried to take a benzo "just to chill" not much happens except sleep. I mean it sounds enticing to "chill on the couch" with a benzo and watch movies. My issue is I can not get absorbed into the movie like I do with THC and I fall asleep. There is a thin line between the movie and my attention that makes the movie boring. Then can't remember what I watched. That goes against what is recreational for me. Most of the time when I need a benzo I am thankful the next day after it wears off.

But what I have learned from BL is that if a person has a lot of anxiety a benzo will calm them and make them feel better. If a person does not have anxiety and takes it not much happens (except amnesia for me) i would never take a benzo and go to a concert or show. It would rob the event of any sparkle and snappiness. So in that aspect they are not recreational. But a person on his way to a doctor who is shaking would feel much better after a benzo. (pyrazolam is awesome for that but still a bit strong for me unless I keep it under 1 mg).

Now gabapentinoids are different. I would for sure go to a concert on pregabalin or gabapentin. I can get absorbed in an expanded way. But they are totally different drugs. Sometimes compared but yeah, different drugs and methods of action. Maybe someday we will know why calcium channel blockers cause stimulation as well as sedation and minor visuals. I don't think medicine knows a damn thing yet but that does not stop them from prescribing them.
 
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JackARoe said:
Not sure why but if someone (me) does not have anxiety or is not experiencing anxiety and takes a benzo not much happens. Lately I have needed to take on occasion as a tool for anxiety. When a benzo takes away anxiety it feels great. I had to go to a medical physical a few weeks ago and those always give me anxiety. A tiny bit of a benzo got rid of that and made me feel normal. However any other time I have tried to take a benzo "just to chill" not much happens except sleep. I mean it sounds enticing to "chill on the couch" with a benzo and watch movies. My issue is I can not get absorbed into the movie like I do with THC and I fall asleep. There is a thin line between the movie and my attention that makes the movie boring. Then can't remember what I watched. That goes against what is recreational for me. Most of the time when I need a benzo I am thankful the next day after it wears off.

But what I have learned from BL is that if a person has a lot of anxiety a benzo will calm them and make them feel better. If a person does not have anxiety and takes it not much happens (except amnesia for me) i would never take a benzo and go to a concert or show. It would rob the event of any sparkle and snappiness. So in that aspect they are not recreational. But a person on his way to a doctor who is shaking would feel much better after a benzo. (pyrazolam is awesome for that but still a bit strong for me unless I keep it under 1 mg).

Now gabapentinoids are different. I would for sure go to a concert on pregabalin or gabapentin. I can get absorbed in an expanded way. But they are totally different drugs. Sometimes compared but yeah, different drugs and methods of action. Maybe someday we will know why calcium channel blockers cause stimulation as well as sedation and minor visuals. I don't think medicine knows a damn thing yet but that does not stop them from prescribing them.
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To be honest, your experience definitely makes sense, especially if taking a benzodiazepine orally at reasonable doses. if you don’t have anxiety, there’s probably not much contrast before and after taking the drug, So you won’t really feel anything special.
 
Does anyone have any experience with neurosteroids? They have unique binding sites on GABAA receptors and possess the range of pharmacological/ psychoactive effects associated with this GABAA receptor enhancing action. however, neurosteroids might be more rewarding and less prone to tolerance development than traditional GABAergics. i’d love to hear all your opinions on this.
 
They bind more heavily to extrasynaptic GABAa receptors because of the incorporation of delta subunits rather than gamma at the synaptic receptors. Benzos binds at synaptic receptors preferentially for this same reason

Another fun fact is that benzos also activate a receptor in glia which upregulates the production of several endogenous neurosteroids which act on GABAa and NMDA receptors
 
I was never particularly interested about benzodiazepines before I developed serious anxiety and executive dysfunction. Even tho I liked opiates, alcohol and amphetamines.

Now I like them even more than alcohol in some sense because they are less dirty and confusing.

Anyway, how do GABA-B-agonists work out? I am no sure but I have understood they are good muscle relaxants, 'aight? And alcohol works as one, more so than as a GABA-A-agonist? How about barbiturates? GHB? does it have any direct activity other than in GHB-receptor? Baclofen and phenibut are GABA-B-active at least.

I definitely can not separate elements from chaos reliably, but my gut feeling is that GABA-B-agonists are the recreational stuff.
 
Pissed_and_messed said:
I was never particularly interested about benzodiazepines before I developed serious anxiety and executive dysfunction. Even tho I liked opiates, alcohol and amphetamines.

Now I like them even more than alcohol in some sense because they are less dirty and confusing.

Anyway, how do GABA-B-agonists work out? I am no sure but I have understood they are good muscle relaxants, 'aight? And alcohol works as one, more so than as a GABA-A-agonist? How about barbiturates? GHB? does it have any direct activity other than in GHB-receptor? Baclofen and phenibut are GABA-B-active at least.

I definitely can not separate elements from chaos reliably, but my gut feeling is that GABA-B-agonists are the recreational stuff.
Click to expand...


Neuropharmacology is complex and seemingly full of contradictions/paradoxes. in regards to alcohol, yes, it has an extremely dirty pharmacology as it targets many proteins and ion channels. nevertheless, the main intoxicating effects of benzodiazepines and low-dose alcohol are due to GABAA agonism. barbiturates are extremely powerful GABAA receptor potentiators making them far stronger and far more dangerous than benzodiazepines or alcohol, especially in overdose.
Regarding GABAB activation, this is the mechanism of the antispasmodic and mild sedative Baclofen. GHB also activates GABAB, but simultaneous activation of the unrelated excitatory GHb receptor May be required for the drugs recreational effects.
Therefore, based on my very limited knowledge, I would suggest that GABAA receptor activators have greater potential for recreational use than highly selective GABAB agonists.
 
For me lower anxiety in general and relaxation ability.
generally no hangover with doses.
gabapentioids as well just don't get around to that too often lately.
cannot explain it
Be well,
j
 
does anyone know how neurosteroids fit into The mechanism of the recently named post finasteride syndrome. I understand how finasteride and other 5Alpha reductase inhibitors can acutely induce symptoms of anhedonia, depression, anxiety, sexual dysfunction, insomnia and general despair. these occur because such drugs prevent the synthesis of neurosteroids, thus excessively increasing neuronal excitability and producing negative changes in the nucleus accumbens which lead to a wide range of emotional dysregulation. however, shouldn’t the removal of such drugs Restore synthesis of neurosteroids with the possibility of the brain being even more sensitive to such steroids?
For some reason, the negative symptoms of 5Alpha reductase inhibitors can persist in some patients years after the drugs were stopped. I thought of a few possibilities guided by the limited research available but I would love feedback or suggestions from anyone else here.
1 Neurosteroid synthesis might not return to normal after discontinuation of 5Alpha reductase inhibitor is discontinued, though I think this is very unlikely.
2 perhaps a sufficiently long period of decreased neurosteroid availability could produce neuroplastic changes e.g. too much LTP in the anxiety/stress systems of the brain. The anhedonia and depression aspects could be due to a dramatic increase in dynorphin synthesis/release, something which is linked to The onset of major depression after chronic stress or trauma.
3 this is purely theoretical, but perhaps A very specific amount of neurosteroids is needed for optimum well-being. Though I’m not particularly convinced of this one, it may be that stopping 5Alpha Reductase inhibitors could lead to a paradoxical overproduction of neurosteroids, GABAA receptor supersensitivity or a combination of both. however, I would expect this to produce more sedation, memory impairment and possibly a sense of weakness, rather than severe anxiety.
 
I don't think you can cover all benzos in one fell swoop. There are so many variations...seems like the particular drug's half-life plays one crucial role. The anxiolytics with the shorter half-lives like alprazolam, lorazepam, etizolam seem to have the most addiction potential. Someone who is naturally more "high-strung" or prone to anxiety find these medications -very- reinforcing & very soothing. Benzos with longer half-lives like Clonazolam and Pyrozalam have a lot less overt intoxication and work more "under the radar" to ease symptoms, enough where you can go about your normal life. Also different benzos are geared for the relief of certain symptoms rather than others....a) ease anxiety, b) to ease insomnia, c) for muscle relaxation, and d) for sedation/hypnotic. I don't know the pharmacology and why some work relatively better in one area rather than another but there are -so- many benzo formulations out there either legit RX or research chemical that there is likely one that fits your own unique brain chemistry perfectly, like hand in glove.
 
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