valec

gonzales v raich is probably one of the more absurd examples of this

you don't know how to read papers then. first read the abstract. then the conclusion/discussion. then the methodology to see if the study was conducted reasonably. papers are made to be read by scientists -- dumbing them down to be understandable by layman would waste time for little gain. that is the job of science communicators and journalists -- and even these often do a pretty poor job of it.

your link is for PTSD, not depression. no studies have come out so far showing MDMA has any effectiveness in depression. the proposed mechanism for PTSD involves serotonin release leading to heightened extinction of fear memory in the hippocampus and amygdala. no reason to believe necessarily this will help with depression.

That's not what your comment said at all though.

>Neurotoxicity

unclear. on the onehand, unpublished studies in gorillas show no lesions. on the other, retroactive studies of heavy polydrug abusers show lesions. not super high-quality evidence either way. there's also rat studies showing lesions, but rats are unusually sensitive to neurotoxicity from dissociatives. they get similar lesions from nitrous oxide while humans get no such thing. honestly the potential bladder toxicity is more concerning imo.

>relapse rate

still much better success rates than SSRIs.

not saying ketamine is perfect --- would be better to have a purpose-built drug, and a lot of the clinics are kind of scummy and charge exorbitant prices. but this + non-psychedelic 5ht2a plastinogens are the most promising things to come out of depression research in the past 45 years.

this is not true at all. the dissociative effects only last a few hours. the clinical benefit is because ketamine stimulates neurogenesis in the mPFC and hippocampus, restoring plasticity lost in depressed patients.

don't make unsubstantiated leaps :-)

another technique sometimes used is using Transcranial Magnetic Stimulation to create temporary "virtual lesions" to study how knocking out a particular region affects task peformance

different ligands can bind to the same receptor in different ways and cause different signaling cascades. look up "biased agonism"

>Unrelated but another neurotransmitter fun fact: Serotonin is responsible for your feeling of self-confidence

this is so oversimplified as to be completely meaningless

i think you are very mistaken.

cocaine and amphetamines both enact their effects primarily by drastically raising dopamine levels in the brain (in particular the striatum in the case of the euphoria they cause). neither of them directly target acetylcholine to any capacity.

the main difference between cocaine and amphetamines is that amphetamines are dopamine/norepinephrine(/serotonin depending on the specific amphetamine) releasers, while cocaine is a dopamine/norepinephrine/serotonin reuptake inhibitor.

releasers make their way inside the presynaptic neuron either through DAT/NET/SERT or by diffusing directly across the membrane, where they then enter monamine vesicles through VMAT2 and collapse the pH gradient causing monoamines to spill into the cytosol, where it is then transported out of the cell by DAT (and sert and net for serotonin and norepinephrine). it is unclear the exact mechanism that amphetamine causes DAT/NET/SERT reversal. anyways end result is norepinephrine and dopamine spill into the synaptic cleft.

cocaine, as a SNDRI, simply blocks DAT/NET/SERT from removing their respective monoamines from the synaptic cleft/transporting them back into the pre-synaptic neuron.

IGF-1 is generally bad for longevity. Exercise is beneficial in spite of spiking IGF-1, not because of

you literally can't be high all the time on psychedelics (at least tryptamine-derived psychedelics) because of how quickly a complete tolerance to their effect forms at the 5ht2a receptors

how would you propose setting up a double-blind trial for a psychedelic?

i think it corresponds most exactly with the desensitization of dendritic autoreceptors

>While not to encourage being antisocial, chess also has very good computer programs to play against

even better, with the likes of Lichess and Chess.com there is near instant placement into matches with a similarly skilled human

I may be unusual in this regard but I don't think I can remember a single time that I have fallen asleep "by accident." I've never been able to fall asleep in class, or reading a book, or watching a movie or just lazing about the couch late at night. Is this something most people have to worry about?

I think calling it a caffeine "addiction" is a bit misleading. Dependence is a more accurate word.

what are your thoughts on wellbutrin and isopropyphenidate? (not combined haha)

I'd be curious about the effectiveness of atypical stimulants such as bromantane in treating ADHD. Unlike methylphenidate or amphetamine, they don't directly inhibit reuptake or induce reverse transport of dopamine but instead upregulates transcription of enzymes responsible for the production of dopamine in the CNS. Or even weak but selective DRIs like modafinil.

i'm sorry but if my only concerns as a shorter man were not reaching things on the shelf my life would be immensely better

>while US States are administrative districts of a single sovereign nation

this is false. under a unitary government system that would be true but the US runs under a federalist system. states and the federal government are considered sovereign---at least as far as domestic issues go---and maintain a clear separation of powers. federal government is involved with national and intra-state issues while the states are involved with police and making regulations for their citizens. the federal government, can't, for example dissolve a state government like China could dissolve a province's government.

the A-10 is actually the perfect "fighter mafia" plane aside from its weight.

the fighter mafia basically wanted more maneuverability, cheaper planes and CAS than interdiction bombing. A-10 is all of those except light.

they were vehemently opposed to optimizing planes for beyond visual range (BVR) combat like by improving sensors or stealth because they considered it "a fantasy."

problem is missiles fired 100 miles away don't care what you consider fantastical.

the A-10 is actually a giant hunk of junk outside of COIN operations. it has no stealth, it's slow and its gun is useless against modern armor. against terrorists in flipflops with AKs it can be useful but that's only because they don't have any sort of AA. even stingers are a huge problem. and in an uncontested airspace you may as well bring in a plane with even more firepower and loiter time like an ac-130.

so basically the a-10 in this day and age is a solution in search of a problem. it's big, slow, heavy and would be shot out of the sky in a peer confrontation before you could even blink. its gun is useless against modern tanks and an f-35 can carry a similar amount of munitions.

honestly the reddit r/fitness faq is pretty good. if you don't mind reading a lot the strongerbyscience guides on squatting, deadlifting and benching are very high quality.

in terms of programming: starting strength is ok for beginners but don't stay glued to it for too long. once you start stalling move on to an intermediate program like the texas method, any of the SBS programs, 5/3/1 bbb, or some sort of ppl.

also, while starting strength is fine for beginners (the low volume isn't a problem as in beginners few gains are made the first month due to poor physiological recovery capacity, and beginners respond to basically any volume), mark rippetoe is a stubborn dogmatist who has never broken any records or coached anyone who's broken any records. take a lot of things he says with a grain of salt.

the most important things are: push yourself in the gym, increase weights or reps regularly (or more generally difficulty so you keep adapting to higher demands/build muscle), eat at a slight surplus, and sleep at least 7 hours, preferably 9 if it's possible.

> i personally do not want to live in a society in which services that use to be available to readily available are no more cause huge chunks of people aren't working/govt is paying them to do nothing.

what it seems like you're saying here is that creating a permanent class of mindless worker-drones being forced to work two $9-an-hour jobs is ok as long as you can get a burger for $4.

Sure on the coast but the Great Lakes-adjacent region should fare pretty well, or at least better than everywhere else.

Siberia recently suffered some of the worst wildfires on the entire planet haha. I think probably the safest would be East Canada as they're cold enough but not as tree-like.

hacker news only cares about free speech when it can be used to dunk on "the left"

glyphosate is safe. on it's own it's not carcinogenic. however, the supporting ingredients and solvents are very carcinogenic.

...or to look at your dick from above then closer up

no, it's not. best estimates (admittedly poor) put the incidence around 1/50,000 for frequent users.

considering the potential mental health uses and the extremely low toxicity (i'm not sure anybody has ever overdosed on lsd) banning psychedelics would be a huge mistake.

and > They can turn functioning people into permanently non-functioning ones. It is an incredibly dangerous drug. applies to legal drugs too. alcohol for example. or painkillers or benzos.

steroids only harm the user though. cheats ruin the game for everyone.