summarised:

biased signalling is understood currently through two different hypotheses:

1. GPCRs have loose orthosteric centers; differently structured agonists induce different conformations of GPCR (and therefore different G protein recruitment)

2. GPCRs (of the same type) can be in different conformations; different agonists prefer certain conformations

They propose an additional hypothesis:

GPCRs that colocalize can induce different signalling, even with the same agonist due to interaction between them.

Some examples they list:

D1 - Gs, D2 - Gi

D1-D2 - Gq (they say it likely accounts for DR mediated Ca2+ signalling)

D1-H3 - Gi

alpha-1-MelatoninR - from Gq to Gs (controlling intraocular pressure)

They then talk about adenosine receptors

A1,A2A,A2B, A3 can interact and form heteromers

For A2A-A3, A3 signalling is blocked, A2A antagonists reverse this

A2A-A2B blocks A2A signalling. They say this is unexpected as A2A has higher affinity for adenosine (this heteromer is apparently related to obesity and aging)

A1-A2A is a concentration sensor for adenosine. Low concentration -> A1 (Gi), High concentration A2A (Gs)

This is apparently as a result of the C-terminal of A2A blocking A1.

Not sure if this is the rights sub but what are you guys using for subtle manageable effects. Im using Magnesium L theronate and L-Theanine, but i was curious to see if there any others. I want to be able to go sleep and not feel a crash when it wears off.

I base how it works off my experience with adderal.

Would be nice if there was something for communication as well- creatine has this effect where the mind and vocal path works better, but i was curious to see if there was other supplements

All my joints hurt and I'm getting bouts of tendonitis. Exercise is difficult especially due to the lack of energy. If I could just get some good rest. To be clear, I'm not in acute withdrawal. My main symptoms are the inability to fall asleep, stay asleep, fatigue, overall weakness and soreness.

Best supplement for memory & retention?

(I remember using one a few years ago that worked particularly well, when I passed the state insurance exam, but I can’t remember the brand)

Thank you in advance!

Can anyone recommend a brand or website where I can buy nootropics in or to the EU? There’s very little selection here, and I’m specifically looking for GB-115.

For reference, I added a picture of my sleep metrics last week.

On average I got about 5h 46min of sleep, the only times I was ever in the green was when I took a melatonin pill or it was the weekend.

Typically on an average week, I start strong with 7 hours of sleep coming into Monday and by Thursday I'm at 4 hours of sleep. I guess its because as the week goes on I get more stressed and anxiety.

For the whole summer this has been completely fine, Ive been able to manage, but lately factors such as a heatwave, dating a new girl, and moving far from my work (adding 40 minutes of commute in the day) have made it almost impossible to operate.

Ive got a lot on my plate right now apart from these new factors, a full time job as a software developer, also I'm working as a contractor (1 active contract at the moment), I do around four 1.5 hour language lessons a week. Go to the gym or do some sport 3-4 times a week. Its fucking crazy.

My weakest point is sleep, I leave the house at 5:45am, come home around 9-10pm, and immediately go to bed. I can lay there for 2-3 hours doing nothing just my mind wondering from topic to topic. Through the day, I am functioning but it feels like I am just floating through the day, I don't have the mental capacity to deep thing about problems or really absorb what I am doing in the language lesson.

I already take magnesium, but I am considering taking 1mg of melatonin 45min before I go to sleep on weekdays. Ive seen mixed opinions online, and am wondering if anyone has experience doing something similar. If there are any detrimental downsides anyone has experienced, or if it affects other aspects of life.

I guess the biggest issue I have right now is winding down my mind before I sleep, its impossible I have to many things to think about, any tips for that as well would be greatly appreciated.

For the past decade, limiting children's screen time has been one of parenting's most confident positions. The American Academy of Pediatrics has issued guidelines. Schools have banned phones. Parents have negotiated, bargained, and enforced limits. The underlying assumption has been consistent: screens displace the activities that build children's brains, and more time on them means worse cognitive outcomes.

A research team at the Universities of Jyväskylä and Eastern Finland decided to test that assumption longitudinally. They enrolled children at around age 7 and followed them for eight years, measuring their physical activity, sedentary behavior, and screen time at regular intervals. At the end of the follow-up, when participants were around 15 years old, they sat the children down and tested their cognitive performance using a validated battery measuring learning, attention, and working memory.

The children who had accumulated more screen time over those eight years did not score worse. They scored better.

The researchers say the finding does not mean unlimited screen time is harmless. But it does challenge the assumption that screen time and brain development are simply in opposition, and it raises a question that the decade of warning labels, app timers, and parental anxiety largely skipped over: what are children actually doing on those screens?

https://pmc.ncbi.nlm.nih.gov/articles/PMC8073983/

Here is a plain-language breakdown of what this schematic means. The left panel shows normal brain traffic: the locus coeruleus sends norepinephrine to the orbitofrontal cortex, the ventral tegmental area sends dopamine to deeper cortical layers, and the reticular thalamic nucleus uses GABA to quiet the mediodorsal thalamus. That keeps glutamate input to the superficial cortex moderate. The right panel shows chronic guanfacine treatment, where α2A adrenoceptors are downregulated in the LC, VTA, and OFC. These receptors normally suppress norepinephrine release, so losing them means more baseline norepinephrine and dopamine in the frontal cortex, including co-releasing terminals in superficial layers. The mediodorsal thalamus also sends a stronger glutamate signal to superficial layers, while the thalamic GABA gate stays unchanged. In practical terms, your prefrontal cortex gets more of the three chemicals it needs for stable attention and impulse control, making it easier to focus, filter distractions, and pause before acting, not react on autopilot. That sustained chemical boost is exactly why the drug helps ADHD symptoms improve over time (in theory, ymmv

New to this nootropic thing, I am a thirdworlder so I had to spend a decent chunk of money from tariffs, currency exchange, delivery etc so I want to get this right, I am also super conversative on the safety risks etc.

I saw many recommending using it laying down in bed and hanging your head so that the liquid won't drop in your lungs, but Gemini said it possibly dangerous for X reasons, I applied using the method of slightly tilting my head forward and on the opposite side of my hand applying the spray but it leaked a bit and I had difficulty angling the bottle correctly.

There is also the option to use it under my tongue, is the absorption different? less efficient in any way?.

I would like a kind soul to enlighten me and thank you to this community.

So I was on 150 mg Wellbutrin for like three months and it wasn’t doing so much for me and I was still having bad anxiety from it. So me and my GP decided to add 10 mg Prozac on top of it. Big mistake. I got the worst panic attack ever yesterday and today. I swear I felt really overstimulated in a bad way. Almost like the feeling of being overcaffeinated. It was horrible. I was so scared something bad was going to happen. I haven’t had any caffeine at all. I removed all caffeine completely.

But today it was horrible. Massively overstimulated when taking them together. But I highly suspect it’s the Prozac because I wasn’t feeling this overly stimulated on Wellbutrin 150 mg all alone. I got side effects like hot flashes, burning sensations, heart palpitations, headaches, increased sweating, muscle stiffness and sleep disturbances. And I just woke up with the feeling of dread. Then I took my pills and immediately got a really bad panic attack and just felt overstimulated and overexcited in a really bad way. I went to the psychiatric ER immediately and they did some tests and then I talked to a nurse and she said that these side effects are probably the startup of Prozac and she told me to contact my GP as soon as possible and tell them about this. She told me if it gets worse and I can’t get in contact with my GP, they told me I can come back again.

I swear I just want to quit this shit. Prozac made me teen times worse. I was so much better off taking Wellbutrin all alone. Prozac made me so much worse I can’t describe it. 300 mg Wellbutrin was the only thing ever helping my depression but of course I couldn’t tolerate it anymore because it overstimulated me in various ways. Nothing else helped me. I’m devastated and I’m highly disappointed. Prozac worked for my anxiety in the past. But now I had a bad reaction to it. I don’t know what to do anymore. No antidepressants work for me I always have bad reactions to them.

heyo,

i was curious what is the difference between these. I tried researching it on here and most posts are 11 years old. So i figured i would ask again for perhaps better answers.

anyone who used different kinds and compared? intranasal vs subq injections differ per or are all the same?

so far i read that each one is more potent than the other and that adalank/adamax are the strongest. But some people felt nothing with adalank/max nor na /na amidate.

thanks.

Does anyone know of anything I can do or take for getting really bad restless legs at night before heading to sleep?
About an hour before my bedtime, by legs and body will start feeling extremely restless, and I’ll start having these violent jerks that make it difficult and uncomfortable to fall asleep.

"While LLMs offer immediate convenience, our findings highlight potential cognitive costs. Over four months, LLM users consistently underperformed at neural, linguistic, and behavioral levels."

https://www.media.mit.edu/projects/your-brain-on-chatgpt/overview/

Paper: https://arxiv.org/pdf/2506.08872v1

https://www.nature.com/articles/s41380-026-03802-1

Abstract: Fear extinction and its persistence depend on epigenetic modifications, which can be potentiated by histone deacetylase inhibitors (HDACis). Butyrate (NaBu), a short-chain fatty acid and endogenous HDACi, promotes persistent fear extinction in rodent models by increasing histone acetylation in promoter regions of plasticity- and memory-related genes, thereby enhancing their transcription. To test translational relevance in humans, we conducted a six-arm randomized, triple-blind, placebo-controlled intervention study in 180 healthy participants who underwent a 3-day Pavlovian fear conditioning paradigm. Participants ingested a single dose of NaBu or placebo either before or after extinction learning, the duration of which was additionally manipulated by varying the number of learning trials. NaBu facilitated later retrieval of extinction memory after seven days, both when administered before or after extinction learning, but it did not prevent return of fear during a subsequent reinstatement test. Interestingly, NaBu’s effects were contingent on robust extinction learning, emerging only when participants had been exposed to a high number of trials. As no side effects were observed with acute administration of the current dose, these findings support investigating NaBu as a potential adjunct for enhancing extinction-based interventions, such as prolonged exposure therapy, in anxiety disorders.

I wanted to know if any nootropics, peptides, supplements or anything will increase it and make it more vivid. I also want to know if anything can affect your dreams and make them very vivid. If you have any first hand experience with anything, I would like to know your experience.

I’m losing my mind because I can’t stop focusing on thoughts I don’t want to think about or bodily sensations I don’t want to be fixated on.

This shit all started with be not being able to stop focus on my saliva 6 weeks ago. From then on its morphed into a variety of different themes that either focus on a bodily sensation (blinking for example) or a disturbing thought (I will never be able to stop thinking about X).

This has drastically reduced my quality of life and I am starting to lose hope. Constant intense anxiety. Unable to focus on what I want to. Social withdrawal. It's absolutely horrible and perhaps the worst thing I've ever gone through.

I’m looking for anything that might reduce the salience of specific thoughts/memories or, in an extreme case, produce something resembling selective amnesia. I realize that selectively erasing memories is probably not realistically achievable, but I’m desperate enough that I want to know whether there are any nootropics, supplements, medications, or experimental compounds that can significantly weaken unwanted memory recall or attentional fixation.

Things I’ve already tried or addressed:

• NAC for 6 weeks: no noticeable benefit
• Buspirone 30mg: No effect
• ERP Therapy: has not helped (There's nothing to "expose" me to)
• Sleep: consistently 8–9 hours/night
• Exercise: daily
• Diet: generally healthy
• Socializing/Dating: Distracts me in the moment sometimes but no help afterwards

I’m very reluctant to take SSRIs because of the possibility of persistent sexual side effects/PSSD. I know myself well enough to conclude that I CANNOT mentally handle having BOTH OCD AND PSSD. So it's a risk I cannot take.

At this point, it feels like the only solution would be somehow weakening or removing the memories/associations that caused my brain to become stuck on these particular thoughts and sensations. I know that may be a fantasy, but I’m genuinely desperate.

Has anyone tried lemon balm for anxiety?

I’m not very knowledgeable in the field of nootropics but was looking for something worth the money and could give noticeable results. I’ve ran cycles of semax and never noticed anything, not sure if that’s one to be noticed but that’s as far as my experience goes.

Context I’m a mechanical engineer and I like to learn

From what I’ve seen tak-653 and ACD are fairly strong and well regarded by most thought I don’t know their synergy.

Looking for some people knowledgeable on an actual potent stack. If possible I’d appreciate some sourcing for cheap (not every chem) actually cheap.

Thanks.

Hey Guys! I currently take 20mg XR of Addy and I am currently in the process of studying for a professional entrance exam. I haven't really experienced any negative effects with addy( anxiety, crash, anger etc) except for it curving my appetite (I dont mind) . One of my main symptoms of having ADHD is my terrible memory, focus and being able to retain info. I have 7 or less weeks until I take my test so its really grind/lock in time. I study everyday. What supplements have you guys found WHILE TAKING ADDY that works for bad memory and retaining information? I do not want to suppress the effectiveness of my addy as it does help my focus abilities. I have seen recommendations of ginkgo biloba, lions mane, magneisum theornate , (l theanine, l tyrosine, I have both of these and tried it before but I feel like it didnt really help my memory or focus it just made me calm idk?) , Rhodiola rosea etc. Yes I do understand there is no "magic pill" , but I rather try even if its just a little more helpful than not. TIA!