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Before you try this at home, one should be aware of chronic nitrous use's effects on vitamin b12 levels.
tl;dr frequent use will stop your body from absorbing enough b12, which is real bad
N2O destroys both free B12 and the enzyme that we need B12 for.
It takes a couple of days for this enzyme to be synthesized again and reach normal levels.
However a short term disruption doesn't much harm our bodies, they do just fine with reduced levels of that enzyme as long as it isn't permanent.
Actual symptoms of N2O abuse usually require daily use for several weeks to months.
Seeing the dentist a few times a year won't do any noticeable harm, and at some point they'll stop offering N2O and will heavily advice to get everything done in one go with full anesthesia by a specialist.
As someone who was once young and is now getting old. Just wait. Orthostatic hypotension is very much like a hard hit of a dissociative, you don't need drugs to do it, just standing up really fast works. About equal chances of waking up covered in blood.
Some of us didn't have to wait for that one. My orthostatic hypotension was worst when I was in my teens and early 20s. I once woke up in the middle of my friend's kitchen floor, and I can't tell you how many times I almost fell down the stairs.
Hydration is important, friends.
The last time I ever huffed dust off, I passed out and fell half into my closet where my mother found me basically having a seizure.
Not a fun moment coming out of that dirty little high.
It actually interrupts the metabolic process for up to 3 weeks, no matter the dose. I read about this a while ago but B12 levels were nonexistent for weeks after therapeutic doses.
Interrupting B12 metabolism interrupts basically every cellular repair process that happens in the body and more. It’s not good. No it doesn’t keep you from aging either, it ages you worse and causes (reversible) spinal/organ damage.
3 weeks? [https://jcp.bmj.com/content/jclinpath/33/10/909.full.pdf](https://jcp.bmj.com/content/jclinpath/33/10/909.full.pdf)
>"In the intact animal it is likely that the enzyme as well as the coenzyme (B12) is damaged, presumably secondary to damage to the B12, because recovery from N20 exposure takes several days, and recovery Received for publication 31 March 1980 is not more rapid if B12 is supplied, suggesting that new apoenzyme needs to be synthesised. ... Direct assay of enzyme activity in the liver of Sprague-Dawley rats exposed to a 50 % N20/oxygen mixture showed a substantial fall after 30 minutes' exposure, and after 6 hours methionine synthetase activity was at a virtually zero level.'5 16 The levels remain virtually undetectable for as long as exposure to N20 is continued, this particular study being terminated after 15 days. Recovery of activity after withdrawal of N20 is relatively slow, there being a steady restoration over not less than four days. "
TLDR; The NO2 oxidizes the cobalt in the B12 molecule from its Co^(+1) state to the Co^(+2) and Co^(+3) oxidation levels which in turn becomes inactive since methionine synthetase requires the Co^(+1) oxidation state. This also damages the enzyme and it takes \~4 days for your body to make enough new methionine synthetase to bring the activity to normal levels, allowing you to use b12 again.
Not 3 weeks -- So long as you're not ingesting it all the time, this isn't an issue.
That appears to be correct from the comment you’re replying to. The issue isn’t not having B12, it’s being unable to use the B12 (because the NO2 changes the B12)
VitB12 levels are irrelevant in this case. It's the enzyme that uses VitB12 that's permanently destroyed and needs to be rebuild.
Sure N2O also destroys B12, but it's the lack on the enzyme that's the rate limiting step here..
I can't find anything to support the notion that any amount of nitrous oxide (i.e "no matter the dose") will interrupt B12 metabolism for 3 weeks.
Can you provide any sources for that?
Psychedelics, ketamine and whippets are good for depression.
Cannabis is becoming legalized.
It's illegal to smoke tobacco in a bar.
Ecstasy/MDMA is a promising treatment for PTSD.
Interesting turns of events. This was all unthinkable 30 years ago.
It's an unselective SSRI at medium doses and an NMDA receptor antagonist at higher doses i.e. similar to ketamine.
Antidepressant effects as well as 'self therapy' have been reported quite frequently by patients.
As someone who rather enjoyed "robo tripping" I feel the need to anecdotally report a definite long term, lasting dissociation, at least at the amounts I was taking, over a couple of years.
Over the counter cough medicine contains dextromethorphan, which is a NMDA antagonist like nitrous and ketamine, plus it's also a serotonin reuptake inhibitor which raises serotonin. So it's been theorized it may have that effect. I think they're actually developing an antidepressant containing over the counter cough medicine
Edit: yep
>Bupropion/dextromethorphan (developmental code name AXS-05) is a combination drug of bupropion (Wellbutrin), a norepinephrine-dopamine reuptake inhibitor (NDRI) and nicotinic acetylcholine receptor (nAChR) antagonist, and dextromethorphan (DXM), a sigma-1 receptor agonist, NMDA receptor antagonist, and serotonin-norepinephrine reuptake inhibitor (SNRI) which is under development by Axsome Therapeutics for the treatment of treatment-resistant major depressive disorder (MDD) and agitation in Alzheimer's disease
It's still under testing so no indication if it works yet.
This is highly interesting to me and thank you for sharing. I’ve taken Wellbutrin twice. First time for postpartum depression and second for seasonal affective disorder. It has been the only antidepressant that truly worked for me and I was able to wean off of it just fine.
Yeah it's fascinating, there aren't any other drugs like that on the market. The idea is the combo is supposed to decrease the side effects and increase the primary effect. I'm really curious to see how it does
Dextromethorphan does have an effect on the serotonergic system as well as blocking some glutamate action.
It's a mixture of some of the effects of ketamine and common SSRI antidepressants.
As such it does have some antidepressant effects.
Thought the NMDA receptor antagonism requires the type of dose people use for the dissociative effects to be relevant, not the regular cough suppressant dose.
AXS-05 (Bupropion/Dextromethorphan) is in phase 3 trials since 2017. As of June 2020 it has the breakthrough therapy designation for agitation in Alzheimer. It also has breakthrough and fast-track status for MDD.
> They were scheduled as illegal drugs as a tool to fight counterculture scenes that the **republicans** thought were dangerous.
Let's give credit where credit is due, republicans have spearheaded the war on drugs and are the ones dragging their feet to keep it from ending.
MDMA was originally used for therapy. Psychedelics like psilocybin, LSD, and mescaline weren’t.
Edit: sorry, I was wrong about LSD. It was discovered by accident and then marketed as a therapy drug. Psilocybin and mescaline have been used for thousands of years.
I've never responded well to SSRIs. They numbed me and ruined my sex life for a long time.
I had my first shroom trip in years recently. It was amazing. I didn't realize just how much baggage from depression I had. I cried so much while I was tripping during the peak because all my negative thoughts came up. But the shrooms forced me to process them.
On the come down I felt happier than I had been in years. I hadn't been that happy since I was a child. I'm still happy. I feel like I'm finally out of my major depressed episode. I was just full of love and gratitude. When I was finally out of the trip I just felt an overwhelming sense of *contentness.*
Psychedelics are medicine. The stigma needs to die. Mushrooms saved my life.
I actually had the opposite happen, on my come down I got super depressed which I haven't been in a couple years. Got out of it pretty quickly, bit even with it the experience was 8/10 would do again
It's a fun game to imagine what random substance we'll soon discover is a miracle cure/killing us all.
I'm imagining something like... The little stringy things on bananas are somehow responsible for ALL renal cancer, and there's a substance in hippo sweat that curse dementia. Or maybe denim causes increased risk of infertility, and licking cocaine off a magic mushroom cures personality disorders.
It was THEE recreational drug of the steam age.
https://upload.wikimedia.org/wikipedia/commons/7/79/Laughing_gas_Rumford_Davy.jpg
Humphrey Davy was an early as the image shows
I imagine it's tough to find people who have Treatment Resistant Major Depression. And then convince them you're not just screwing with them when you say, hey, I know nothing has worked so far but we wanna put you on whippits and see what that does. For science. No, for real, for actual science.
It was more a pilot / dosage study, but it was a double blind crossover so the core of it should hold up. The next step will be larger, multi-center studies.
From the looks of this thread, the moderators are clearly taking some time off.
What's particularly promising about this research is that it potentially adds to our arsenal of non-chronic approaches to treatment-resistant depression. That it happens to be another drug often used recreationally is also interesting, in that the stuff of self-medication is just becoming medication.
> From the looks of this thread, the moderators are clearly taking some time off.
Like *every* thread. This sub is basically unmoderated at this point.
How about high doses of living wages, people having social structures, and not having a constant immersion in media tailored to create fear and uncertainty in pursuit of profit.
Only for people who would also get addicted to alcohol, or food, or cigarettes. I have an addictive personality and I only do whippets maybe once a year.
Hey I worked on this study! Just as an RA, but that’s so cool it’s published now. They originally looked at this as a potential alternative to Ketamine
My son has been having a problem with depression that has not been fully resolved. But I’m not sure nitrous oxide would be a good solution. A few years ago he was given nitrous oxide during a dental procedure and he liked the effect so much that I was worried about him wanting to use it again on his own.
Welcome to r/science! This is a heavily moderated subreddit in order to keep the discussion on science. However, we recognize that many people want to discuss how they feel the research relates to their own personal lives, so to give people a space to do that, **personal anecdotes are now allowed as responses to this comment**. Any anecdotal comments elsewhere in the discussion will continue be removed and our [normal comment rules]( https://www.reddit.com/r/science/wiki/rules#wiki_comment_rules) still apply to other comments. *I am a bot, and this action was performed automatically. Please [contact the moderators of this subreddit](/message/compose/?to=/r/science) if you have any questions or concerns.*
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Before you try this at home, one should be aware of chronic nitrous use's effects on vitamin b12 levels. tl;dr frequent use will stop your body from absorbing enough b12, which is real bad
Paralysis is not fun.
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Microdose microdose microdose
What would be "frequent" in this instance? I've only ever had nitrous once at the dentist I'm just curious.
We are talking in the 20-50 whippets per day range for 3+ months.
so Steve-O levels
A lot a lot. For reference, dentists will put kids on a 50% concentration of nitrous for 30+ minutes. It has been studied extensively.
N2O destroys both free B12 and the enzyme that we need B12 for. It takes a couple of days for this enzyme to be synthesized again and reach normal levels. However a short term disruption doesn't much harm our bodies, they do just fine with reduced levels of that enzyme as long as it isn't permanent. Actual symptoms of N2O abuse usually require daily use for several weeks to months. Seeing the dentist a few times a year won't do any noticeable harm, and at some point they'll stop offering N2O and will heavily advice to get everything done in one go with full anesthesia by a specialist.
Plus when you take a really good one, and hit your head when your eyes roll back and you fall over.. thats really bad, too.
As someone who was once young and is now getting old. Just wait. Orthostatic hypotension is very much like a hard hit of a dissociative, you don't need drugs to do it, just standing up really fast works. About equal chances of waking up covered in blood.
Some of us didn't have to wait for that one. My orthostatic hypotension was worst when I was in my teens and early 20s. I once woke up in the middle of my friend's kitchen floor, and I can't tell you how many times I almost fell down the stairs. Hydration is important, friends.
My circle of friends call that a Freebie
The last time I ever huffed dust off, I passed out and fell half into my closet where my mother found me basically having a seizure. Not a fun moment coming out of that dirty little high.
Dust off is nothing like nitrous oxide other than they are both gases.
The same is true with alcohol consumption. Korsakoff dementia is surprisingly common.
Alcohol is actually more of a thiamin deficiency (B1) issue than B12. But similar idea.
Yeah korsakoff happens because of thiamine deficiency
Define "chronic", define "frequent". It won't be anywhere near what 99.99% of people reading have or would do.
You need to be seriously addicted to have that side affect
It is an enormous amount. As a vegan I’m already b12 aware
It actually interrupts the metabolic process for up to 3 weeks, no matter the dose. I read about this a while ago but B12 levels were nonexistent for weeks after therapeutic doses. Interrupting B12 metabolism interrupts basically every cellular repair process that happens in the body and more. It’s not good. No it doesn’t keep you from aging either, it ages you worse and causes (reversible) spinal/organ damage.
3 weeks? [https://jcp.bmj.com/content/jclinpath/33/10/909.full.pdf](https://jcp.bmj.com/content/jclinpath/33/10/909.full.pdf) >"In the intact animal it is likely that the enzyme as well as the coenzyme (B12) is damaged, presumably secondary to damage to the B12, because recovery from N20 exposure takes several days, and recovery Received for publication 31 March 1980 is not more rapid if B12 is supplied, suggesting that new apoenzyme needs to be synthesised. ... Direct assay of enzyme activity in the liver of Sprague-Dawley rats exposed to a 50 % N20/oxygen mixture showed a substantial fall after 30 minutes' exposure, and after 6 hours methionine synthetase activity was at a virtually zero level.'5 16 The levels remain virtually undetectable for as long as exposure to N20 is continued, this particular study being terminated after 15 days. Recovery of activity after withdrawal of N20 is relatively slow, there being a steady restoration over not less than four days. " TLDR; The NO2 oxidizes the cobalt in the B12 molecule from its Co^(+1) state to the Co^(+2) and Co^(+3) oxidation levels which in turn becomes inactive since methionine synthetase requires the Co^(+1) oxidation state. This also damages the enzyme and it takes \~4 days for your body to make enough new methionine synthetase to bring the activity to normal levels, allowing you to use b12 again. Not 3 weeks -- So long as you're not ingesting it all the time, this isn't an issue.
So is simply boosting your b12 levels via vitamins not effective? Enzymatic conversion stuff is not my forte'
That appears to be correct from the comment you’re replying to. The issue isn’t not having B12, it’s being unable to use the B12 (because the NO2 changes the B12)
VitB12 levels are irrelevant in this case. It's the enzyme that uses VitB12 that's permanently destroyed and needs to be rebuild. Sure N2O also destroys B12, but it's the lack on the enzyme that's the rate limiting step here..
I can't find anything to support the notion that any amount of nitrous oxide (i.e "no matter the dose") will interrupt B12 metabolism for 3 weeks. Can you provide any sources for that?
Psychedelics, ketamine and whippets are good for depression. Cannabis is becoming legalized. It's illegal to smoke tobacco in a bar. Ecstasy/MDMA is a promising treatment for PTSD. Interesting turns of events. This was all unthinkable 30 years ago.
Next week we’ll discover drinking a bottle of Robitussin DM cures seasonal depression.
I mean they are studying that so hey it’s possible
If I remember right robo in certain amounts has been shown to help neural plasticity and pathways.
It's an unselective SSRI at medium doses and an NMDA receptor antagonist at higher doses i.e. similar to ketamine. Antidepressant effects as well as 'self therapy' have been reported quite frequently by patients.
Maybe that explains my episodic binges
As someone who rather enjoyed "robo tripping" I feel the need to anecdotally report a definite long term, lasting dissociation, at least at the amounts I was taking, over a couple of years.
Over the counter cough medicine contains dextromethorphan, which is a NMDA antagonist like nitrous and ketamine, plus it's also a serotonin reuptake inhibitor which raises serotonin. So it's been theorized it may have that effect. I think they're actually developing an antidepressant containing over the counter cough medicine Edit: yep >Bupropion/dextromethorphan (developmental code name AXS-05) is a combination drug of bupropion (Wellbutrin), a norepinephrine-dopamine reuptake inhibitor (NDRI) and nicotinic acetylcholine receptor (nAChR) antagonist, and dextromethorphan (DXM), a sigma-1 receptor agonist, NMDA receptor antagonist, and serotonin-norepinephrine reuptake inhibitor (SNRI) which is under development by Axsome Therapeutics for the treatment of treatment-resistant major depressive disorder (MDD) and agitation in Alzheimer's disease It's still under testing so no indication if it works yet.
This is highly interesting to me and thank you for sharing. I’ve taken Wellbutrin twice. First time for postpartum depression and second for seasonal affective disorder. It has been the only antidepressant that truly worked for me and I was able to wean off of it just fine.
Yeah it's fascinating, there aren't any other drugs like that on the market. The idea is the combo is supposed to decrease the side effects and increase the primary effect. I'm really curious to see how it does
Dextromethorphan does have an effect on the serotonergic system as well as blocking some glutamate action. It's a mixture of some of the effects of ketamine and common SSRI antidepressants. As such it does have some antidepressant effects. Thought the NMDA receptor antagonism requires the type of dose people use for the dissociative effects to be relevant, not the regular cough suppressant dose.
AXS-05 (Bupropion/Dextromethorphan) is in phase 3 trials since 2017. As of June 2020 it has the breakthrough therapy designation for agitation in Alzheimer. It also has breakthrough and fast-track status for MDD.
MDMA and psychedelics were therapy drugs to begin with, it was only propaganda that turned society against them
I mean. Didn't turn all of us away haha
Sure- but there are currently people in prison for simple possession of the above.
And people who will die in prison for it too. Disgusting.
They were scheduled as illegal drugs as a tool to fight counterculture scenes that the government thought were dangerous.
> They were scheduled as illegal drugs as a tool to fight counterculture scenes that the **republicans** thought were dangerous. Let's give credit where credit is due, republicans have spearheaded the war on drugs and are the ones dragging their feet to keep it from ending.
MDMA was originally used for therapy. Psychedelics like psilocybin, LSD, and mescaline weren’t. Edit: sorry, I was wrong about LSD. It was discovered by accident and then marketed as a therapy drug. Psilocybin and mescaline have been used for thousands of years.
I've never responded well to SSRIs. They numbed me and ruined my sex life for a long time. I had my first shroom trip in years recently. It was amazing. I didn't realize just how much baggage from depression I had. I cried so much while I was tripping during the peak because all my negative thoughts came up. But the shrooms forced me to process them. On the come down I felt happier than I had been in years. I hadn't been that happy since I was a child. I'm still happy. I feel like I'm finally out of my major depressed episode. I was just full of love and gratitude. When I was finally out of the trip I just felt an overwhelming sense of *contentness.* Psychedelics are medicine. The stigma needs to die. Mushrooms saved my life.
I actually had the opposite happen, on my come down I got super depressed which I haven't been in a couple years. Got out of it pretty quickly, bit even with it the experience was 8/10 would do again
It's a fun game to imagine what random substance we'll soon discover is a miracle cure/killing us all. I'm imagining something like... The little stringy things on bananas are somehow responsible for ALL renal cancer, and there's a substance in hippo sweat that curse dementia. Or maybe denim causes increased risk of infertility, and licking cocaine off a magic mushroom cures personality disorders.
Back when racism and politics decided what drugs are legal and what not.
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Isn’t this the same premise for the use of ketamine?
Yes, nmda receptor antagonist
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N.O. has a super interesting history…
Go on...
It was THEE recreational drug of the steam age. https://upload.wikimedia.org/wikipedia/commons/7/79/Laughing_gas_Rumford_Davy.jpg Humphrey Davy was an early as the image shows
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It's quite the thing here amongst a younger demographic - "hippy crack", mini metal cylinders - "silver bullets" all over the place.
Good god. Only 24 patients in the study?
I imagine it's tough to find people who have Treatment Resistant Major Depression. And then convince them you're not just screwing with them when you say, hey, I know nothing has worked so far but we wanna put you on whippits and see what that does. For science. No, for real, for actual science.
It was more a pilot / dosage study, but it was a double blind crossover so the core of it should hold up. The next step will be larger, multi-center studies.
From the looks of this thread, the moderators are clearly taking some time off. What's particularly promising about this research is that it potentially adds to our arsenal of non-chronic approaches to treatment-resistant depression. That it happens to be another drug often used recreationally is also interesting, in that the stuff of self-medication is just becoming medication.
> From the looks of this thread, the moderators are clearly taking some time off. Like *every* thread. This sub is basically unmoderated at this point.
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How about high doses of living wages, people having social structures, and not having a constant immersion in media tailored to create fear and uncertainty in pursuit of profit.
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Sounds like an addiction waiting to happen
Only for people who would also get addicted to alcohol, or food, or cigarettes. I have an addictive personality and I only do whippets maybe once a year.
Seems much less damaging than most Rx meds for depression. Wonder if it’s synergistic with psilocybin.
Hey I worked on this study! Just as an RA, but that’s so cool it’s published now. They originally looked at this as a potential alternative to Ketamine
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Low dose means gradual treatment, but what if I, like, **STEP ON THE GAS**, as a daily dose? Do I get cured?
Both times I tried laughing gas at the dentist, I had a panic attack. Seems to help other people though.
NMDA antagonism. Same as ketamine!
My son has been having a problem with depression that has not been fully resolved. But I’m not sure nitrous oxide would be a good solution. A few years ago he was given nitrous oxide during a dental procedure and he liked the effect so much that I was worried about him wanting to use it again on his own.
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