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Sanction

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Sanction last won the day on October 2

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About Sanction

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    Externalizated Symbol for Ras' Death Anxiety

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  1. I think this topic is done, but my 2 cents -- in matters of law, the outcome is often uncorrelated with the effort expended.
  2. You guys are as romantic as a gas station urinal
  3. So I see this scenario. GF meets up with them, but Sam and JB are standing, arms crossed, behind GF, staring at the accomplice. GF sits down and courteously says "Rocko, check the boxes". JB says "Sure boss." Sam keeps staring and says "Boss, you want for me to do what we done to the last guy?" GF says "Ah, such unpleasantness. No. At least... not yet." Sam looks unhappy, spits some chewing tobacco at the floor and continues staring. "No, we're just going to have a nice little chat about recompense for any missing property, isn't that right Mr. __?"...
  4. My stance with pets now is that to adopt and love them is to simultaneously suffer and grieve their loss. Come to think of it, to some degree I also apply that to my relationships with humans and life itself.
  5. Ah, I'm so sorry you've lost your canine companion. Pets can be more dear to us than people are sometimes.
  6. Rather than brushing up on the subtleties of Epistemology in the Philosophy of Science (which should be a compulsory course, especially for nutritionists), I'm going to have a burger and see if I die.
  7. There are challenges to the methodology and conclusions https://www.hsph.harvard.edu/nutritionsource/2019/09/30/flawed-guidelines-red-processed-meat/#qa Here's a sample excerpt, criticizing the procedure for evaluating outcomes: "If the same procedure were used to evaluate the evidence for other dietary (such as low consumption of fruits and vegetables, high consumption of sugary beverages), lifestyle (such as physical inactivity and inadequate sleep), and environmental (such as passive smoking and air pollution) factors, none of the current recommendations on these factors would be supported by high- or even moderate-quality evidence. "
  8. "... rats that were given THC had higher levels of activated ERK, showed more anxiety behaviours ... ...another interesting finding was that CBD alone had no effect on the ERK pathway. "However, by co-administering CBD and THC, we completely reversed the direction of the change on a molecular level. CBD was also able to reverse the anxiety-like behaviour and addictive-like behaviour caused by the THC." https://www.eurekalert.org/pub_releases/2019-09/uowo-csr093019.php
  9. newfags can't triforce ▲ ▲ ▲
  10. Frequently. I also conclude that i'm not as smart as I used to be.
  11. BTW, it took 2 years for my bite to feel more normal. For the longest time my jaws would not meet to make a firm contact on my molars. Looking back, you guys gave me amazing advice and support. Thanks! 🥰🍕
  12. I decided to post the full text of this reddit entry since it might not exist there forever. Strychnine: my experiences. High Risk (Warning: this is one of those cases I would recommend to ‘not try at home’. My goal here is to report an experience and spread information.) I few years ago when I was in college, I decided to mess around with strychnine, which is undoubtedly the most risky substance I’ve ever purposefully ingested. I know this was foolish, but there is a very real nootropic/physical/sexual value to this compound. First, I will describe my experiences, and second I will explain the rationale that led me to experiment with a known toxin.. I read about some old 20th century folk taking strychnine for athletic enhancement, aphrodisiac, and sensory enhancing properties. Naturally, as a biochem college student not afraid of strong drugs, I felt the pull of the desire to self experiment. After some initial cursory research (see below) I decided to try it. Strychnine is found in Nux vomica. You can get nux vomica seeds from a few Indian websites if you look around. I first ground up some Nux Vomica seeds in a coffee grinder (these seeds are incredibly hard), and then weighed 100mg of powdered seed, which is roughly equivalent to 4mg of strychnine given that approximately 1.5-5% of the seed is alkaloid and 35-50% of the alkaloid content is strychnine. (**note LD50= 1-2mg/kg, so a gram of the seed would be bad news) I got ready for a run, and then took the nux vomica. My field of vision expanded noticeably. Every object seemed more sharply defined, with deeper shadow variations and color vividness. I also felt like I could zoom in on far off objects. This was like going from 360p to 720p. I became acutely aware of the cooling tactile sensation of the wind in the humid air, and exactly where the sun was hitting me. Sounds also became ‘easier’ to process, I could swear I could hear the beating of a bird’s wings above me. Also, the smell of that pizzeria across the street was particularly noticeable. It felt slightly overwhelming, this enhanced influx, and soon my spinal stiffness began to kick in. This is not a drug for ameliorating anxieties. I have dabbled with meditation before, and this whole experience reminded me of getting into that lovely sensory meditative pocket of deep self awareness where the world seems to slow down for you to drink it in. I began to feel jumpy, and really needed to move. So I started my run. Flying through the streets and woods was a different experience. I moved easily and everything felt bright and alive. I beat my old records and ran a mile in under 6 mins. It was a bit of an overload. As I went on I felt slightly cramped and stiff. So I headed back to my dorm, drank some kava (the recommended antidote if diazepams are not available) , and proceeded to pump out 10 pages of thesis work because if I wasn’t moving, my mind was racing, speed reading became a breeze..maybe just from the new sensory experience. I then called the girl next door to come over, and proceeded to have some amazing sex. I was much harder than usual and much more sensitive to touch, could definitely see where the aphrodisiac rumors comes from. Only problem was my whole body was somewhat stiff. I sampled strychnine dozens of more times with no issues, and it became a member of my noots stack (taken at smaller doses (~1mg). However, I did have a negative experience when I accidently took about 200mg of seed powder. After taking the powder I headed off to the lab to go to work, and I started to feel very anxious as I walked over. In the lab I broke out in cold sweats, started shaking uncontrollably, and ran to the bathroom to vomit. I went home and drank some kava, and proceeded to calm down. That was a bit much and haven't felt the need to try again it since. Here is a sloppy summary of the research I gathered before trying strychnine: Strychnine induces generalized muscular convulsions at high doses (hence its use as a poison since ancient times), but how? Strychnine is a relatively bulky molecule compared to most other neurotransmitters (excluding peptides), it has a high binding affinity (Kd=2-12 nM), sticking to the extracellular domain of certain glycine receptor subunit residues, thus preventing the binding of other ligands with proximal targets. Strychnine induced inhibition of the glycine receptor prevents the normal inhibitory influx of chloride ions typically elicited by glycine agonism. This allows the neuron to ignore normal postsynaptic inhibitory regulations and keep firing away. Strychnine, being a competitive antagonist is displaced by glycine, b-alanine, and taurine and vice versa depending on the relative concentrations and affinities. Inhibition of an inhibitory neurotransmitter (glycine) leads to stimulation. Makes sense. After ingestion, strychnine is deposited into gastric tissue fairly quickly due to poor blood protein binding. Its XlogP (1.73) indicates it can cross the blood brain barrier, yet it is not very centrally active. This lipophilic nature leads to a broad systemic distribution. It is metabolized by CYP3A4. It begins to exert its effects 5 min- 1hour after ingestion. The title of neurotoxin does not necessarily imply it curb-stomps neurons on contact. But we don’t want excitotoxicity… or possible peripheral neuropathy. I think the key here is in the dose. Specifically, which receptors/neurons? The glycine receptor has five subunits, each of which are composed of four alpha subunit segments. The following information shows the subunits strychnine interacts with and their localization. Receptor subunit Distribution (**in rats and mice mostly) α2 Retina, Tenia tecta, piriform cortex, infralimbic cortex, layer VI cerebral cortex, hippocampus (CA1, CA2, CA4 and dentate gyrus), geniculate and supergeniculate nuclei, dorsal horn of spinal cord, neutrophils, macrophages, Neural stem progenitor cells. α10 Pituitary, Keratinocytes, cochlear, vestibular hair cells α1 Spinal cord, trigeminal nuclei, superior olive nucleus, nuclei of lateral lemniscus, vestibular nuclei, cuneate nucleus, gracile nucleus, hypoglossal nucleus, dorsal motor nucleus of vagus, superior colliculus, retina, sperm, spinal cord, hypothalamus, neural stem progenitor cells, cochlear nuclei, hippocampus, cerebellum, olfactory bulb α3 spinal cord, retina, cochlea, internal granule layer of olfactory bulb, hippocampus, hypothalmus. α9 pituitary, glad, keratinocytes, olfactory epithelia, dorsal root ganglion neurons Clearly the perceived sensory ‘enhancement’ stems from strychnine’s antagonism of glyR at the olfactory, retinal, and cochlear sites. The diverse distribution of the glycine receptors makes localized treatment difficult. So maybe treatment with general hyperpolarization inducing/inhibitory drugs would do the trick in mitigating toxic effects. For example: What happens when glyR is broken, as in a disease model? ..Hyperekplexia, a genetic disease characterized by pronounced tactile and acoustic sensitivity, is associated with malfunctioning glyR, and is treated with clonazepam ( a benzo).. Possible physiological effects due to muscarinic/nicotinic acetylcholine receptor interaction: Neutral allosteric modulation on M1 Positive allosteric modulation on M2→ increased heart rate Negative Allosteric modulation on M3 → vasoconstriction Positive allosteric modulation on M4→ decreased locomotion Negative Allosteric modulation on M5 → ? Strychnine is an interesting compound with a long history. I don't think it really has a place in common nootropic stacks, but there are effects that I would like to see targeted. If we could make a drug selective for the receptors responsible for the sensory and sexual enhancement, while leaving out the muscular targets, that would be AMAZING. Sources IUPHAR: http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=347 http://www.pnas.org/content/89/5/1765.full.pdf http://en.wikipedia.org/wiki/Hyperekplexia http://www.sciencedirect.com/science/article/pii/S1674638412600057
  13. Uh huh. By any chance are these big, used bathtowels for sale?
  14. You can still DL 2 or 3 of me without a sweat
  15. And a lot of fiber from other beings
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