47 replies to this topic

[kurdishfella]

 

CRHR1 and CNR1

It says I have these and they are contains Risk Alleles / Potentially bad gene. My question is what does this do? I know its part of the endocannabinoid system. Is the CNR1 gene same thing as the rs1049353 (TT) SNP? Both description says Low amounts of CB1 receptors. But then what is the CRHR1 responsible for? It says Contains Risk Alleles for that gene. Does it cause low levels of anandamide and  2-AG ?

Edited by farshad, 04 March 2018 - 02:07 PM.

[gamesguru]

CRHR1 is known to diminished the cortisol response.  in response to stress, do you feel more anxious or depressed?  do you bite your nails or fidget when you otherwise have no reason for  tension?  cortisol, glutamate, and dopamine are where i would pay more attention.

 

but i wouldn't look into this cannabinoid business too much.  rs1049353 is more associated with obesity than schizophrenia.  and genetic variants and their phenotypes are often highly geographically dependent, so even making a sound conclusion about the Japenese says very little about you.  this applies especially to neurotransmitter systems which have not received the same extent in academic research over the decades

 

receptors and substrates are like volume and pressure in a sealed environment.  if one goes up, the other goes down.  presynaptic receptors contribute to this feed-back loop and identifying the original cause becomes tricky.

[kurdishfella]

but these SNPS/genes is all I can go by I got nothing else. 

 

 I will try and Increase CB1 activation/receptors with THC/CBD OIL + Block  CRHR1  with Astressin-B which is a CHR (not just CRHR1) antagonist you can find it pretty easy but its topical so hopefully it works. But I wanna find a specific CRHR1 Antagonist if anyone knows of any to get OTC let me know.

 

and see if that will do it.

 

 

I will also try and increase CRHR2 if my Anxiety is still there.

 

My only Problem is this Constant anxiety I have 24/7.  And I dont have schizophrenia not even close.

 

[kurdishfella]

CRHR1 promotes anxiety in part by reducing cannabinoids in our amygdala. This happens when CRHR1 activation increases FAAH in the amygdala, which causes a reduction in the endocannabinoid anandamide (AEA) ®( thats why I wanna block this )


& anyone know of any CRHR2 Agonists

 

Whats the difference between 2-Arachidonoylglycerol (2-AG) and 2-Arachidonyl glyceryl ether (2-AGE)?

 

Also what are some Anandamide and 2-AG agonists? and FAAH inhibitors??

Edited by farshad, 04 March 2018 - 10:00 PM.

[kurdishfella]

so my best bet would be a FAAH inhibitor since 2-ag and anandamide are not orally bioavailiable. FAAH breaks down the two so blocking it will result in an increase in the two. I will try CBD oil apparantyl it inhibits FAAH.

Edited by farshad, 04 March 2018 - 10:19 PM.

[kurdishfella]

Anandamide (partial CB1 agonist) and 2-AG (full CB1 agonist).
are there any ways to increase those Besides inhibiting FAAH? wat r some potent faah inhibtors btw? Kaempferol ?? does faah breakdown 2-ag or just anandamide?


also can someone confirm THC increases cb1 but cbd blocks cb1 and increases cb2. is this right? bcus I keep reading different things by different people.

Edited by farshad, 05 March 2018 - 03:25 AM.

[kurdishfella]

http://www.longecity...ogical-anxiety/

CRHR1 gene together with few CB1 receptor and activation which I have. from the study= The researchers concluded that long-term dysregulation of CRF-FAAH mechanisms in the amygdala keeps anandamide from doing its job. Without anandamide to balance out the system, the brain is primed to react to stress.

WTF! Look ! Its my exacht problem and my SNPS/genes MATCH UP! See......

Low levels of CB1 together with an mutation in Crhr1 = impossible to handle stress and this study says so, and thats what my problem is. anxiety 24/7.





btw Pterostilbene inhibits FAAH?

Edited by farshad, 05 March 2018 - 04:37 AM.

[kurdishfella]

hmm these seem to be the most popular synthetic FAAH inhibitors

BIA 10-2474

JNJ-42165279

LY-2183240

MK-4409

PF-3845 

PF-04457845

URB597

 

anyone know how to get any of these?

[kurdishfella]

Anyone know what CRHR1-IT1 (CRHR1 intronic transcript 1) & MGC57346-CRHR1 gene is? I have risk alles with these but theres no description about them.

[gamesguru]

 

but these SNPS/genes is all I can go by I got nothing else. 

 

 I will try and Increase CB1 activation/receptors with THC/CBD OIL + Block  CRHR1  with Astressin-B which is a CHR (not just CRHR1) antagonist you can find it pretty easy but its topical so hopefully it works. But I wanna find a specific CRHR1 Antagonist if anyone knows of any to get OTC let me know.

 

and see if that will do it.

 

 

I will also try and increase CRHR2 if my Anxiety is still there.

 

My only Problem is this Constant anxiety I have 24/7.  And I dont have schizophrenia not even close.

 

 

All you have to go by are some lab results?  What about just your feelings, the nuts and bolts of your experiences, what others tell you about yourself?  If all you're relying on is genetic tests, you're limiting yourself.  The year is 2018 not 2818

 

You can't just see the words 'stress' and 'cannabinoid' and start connecting dots like some game.  "Risk" alleles with scant research do not make good scapegoats.

 

concerning the CRHR1 and cortisol, i would just go the route of grapefruit.  have had good results on 2 a day.  i know you wouldn't know, but that's where i was going with that.  but they are really helpful for the depressive or self-injurious responses to stress.  Not saying that's you, but seems like it could be

 

now schizophrenia.  it takes on different forms.  not all sufferers are griping at leather straps with snakes writhing down their back.  you've just admitted to anxiety, now what about some other features of the negative schizophrenic?  a one who somehow functions on the edge of insanity

 

long hair or an unkempt appearance, withdrawal and depressive ideation, exhibition or displayal of a flat or limited range of emotions (flat face monotone speech), subtle cognitive impairments especially of the social sphere, unusual or superstitious interpretation of events, as well as general suspiciousness and paranoia of others, and how did i forget the excessive persistent social anxiety which derives moreso from paranoid apprehension than negative self-assessment.  You'll notice there's nothing about voices or angels rising out of your skin, because those features aren't prominent here.

 

Having settled on anxiety, you need only satisfy three additional symptoms to meet diagnosis and embark on your road to recovery

[kurdishfella]

so CRF1 and CRF2  are receptors of the CRH hormone ( Corticotropin-releasing hormone ) . 

 

I know blocking the CRF1 decreases anxiety, But what about CRF2? Does increasing it or blocking it decrease anxiety?

[Galaxyshock]

You go from one neurotransmitter to another and wonder if it does this or that. Well I can tell you it probably does a bit of both. No one neurochemical, receptor or brain function is there simply to only do you harm. You had good respone to Olanzapine so why not take that in the lowest effective dose.

[xEva]

SNP>
 
rs1049353 linked to the gene CNR1. Your genotype is TT, which is observed in 3% of all individuals reported.

• The T allele may cause lower CB1 receptor numbers and less CB1 activation, although this has not been experimentally confirmed (R).
• With this variation, the receptors also don't become significantly less sensitive when activated (R)

rs7766029 CC 18%
 
rs806377 CC 26%

 

 
Hello farshad!   I happen to have the same snps, and even worse: for rs806377 the ancestral allele is C, which is what you have, but I got TT there (in addition to the same TT and CC in the first two snps you mention). 
 
I too was prone to anxiety, and what worked for me was lotsa sport and 'healthy lifestyle' (right food and sleep). And yes, magnesium is very good too.

 

I say "was" not because I do not suffer from anxiety anymore, but, I think some of those 'receptors' have simply burned out and what I get now under stress is, instead of becoming all wound up and active, my heart racing as if I want to jump out of my skin, I become 'paralyzed' -- meaning, I can't do a thing and outwardly look as if I could not care less. Internally, I'm sort of calm too, mentally resigned to 'die here and now' -- sorta 'what does it matter then?' attitude.  
 
The things that made it worse are too much coffee and cigs, lack of sleep and bad quality ecstacy.
 
But! what I have discovered recently is that amantadine (which I take only occasionally), surprisingly, makes me feel super-calm. Unprecedented calm. The calm I like and have never experienced before. This is surprising, because, according to Wiki, here is what most people should experience:

 

 CNS side effects include nervousness, anxiety, agitation, insomnia, difficulty in concentrating,

 

on me it has the exact opposite effect. I'm so amazed by this discrepancy that I'm about to ask the forum here what it may mean. I happened to notice your thread before posting and it opened with the list of the same snps as I have. 

 

So, I'd say, try amantadine. It could help. It works for me from just one 100 mg capsule and in half an hour it has unmistakable calming effect that lasts through the rest of the day.

 

 

PS

I don't swallow it but let it dissolve on the top of my tongue -- I sorta like its bitterness and, as with selegiline, which I also take occasionally, I noticed that having it dissolve 'into the pallet', has a different, better, effect than when dissolving it under the tongue. I think this may be because there are ancient receptors on the roof of the mouth, which go directly into the brain -- supposedly, that's how wild mammals 'sniff' or 'taste' pheromones (with the opened mouth, if you noticed) -- for what it's worth

Edited by xEva, 10 March 2018 - 01:53 AM.

[kurdishfella]

@xEva 

 

Have you done the 23AndMe thing? If so upload your 23andme Data to SelfDecode Site which can tell you different SNPS/genes you have and its free.  

  Search for the ´´CRHR1´´ gene on SelfDeCode and see if you have that too. Probably not but its worth a look. Look for the red / yellow marked genes .That gene also supposedly lowers the levels of Cannabinoid receptor 1 , as do the SNPs you mentioned.

 

Have you tried Marijuana? Maybe that could be another option for your anxiety if you somehow cant get amantadine  anymore.  I know its legal in some states in USA. Marijuana is a CB1 agonist which mean it activates the CB1 receptors which according to the SNPs should help. I would suggest lowish dose (10mg) of Edible Marijuana if you do end up trying it.

 

 

Edited by farshad, 10 March 2018 - 03:41 PM.

[gamesguru]

But what about CRF2? Does increasing it or blocking it decrease anxiety?

 

who cares?  you'll never get your hands on any anyways son.  and did you read what i said about grapefruit and reflecting on experiences, or is your head as thick as your posts 

 

You go from one neurotransmitter to another and wonder if it does this or that. Well I can tell you it probably does a bit of both. No one neurochemical, receptor or brain function is there simply to only do you harm. You had good respone to Olanzapine so why not take that in the lowest effective dose.

He wants to figure things out for himself.  An answer is exactly what he wants, but a solution he can do without 

[kurdishfella]

 

But what about CRF2? Does increasing it or blocking it decrease anxiety?

 

who cares?  you'll never get your hands on any anyways son.  and did you read what i said about grapefruit and reflecting on experiences, or is your head as thick as your posts 

 

You go from one neurotransmitter to another and wonder if it does this or that. Well I can tell you it probably does a bit of both. No one neurochemical, receptor or brain function is there simply to only do you harm. You had good respone to Olanzapine so why not take that in the lowest effective dose.

He wants to figure things out for himself.  An answer is exactly what he wants, but a solution he can do without 

 

just go away man.

[xEva]

Thanks a lot farshad!  I will definitely follow your advice with SelfDecode -- oops maybe it was free when you signed up, but they want $59 now (or maybe it's just for us Americans -? we pay for all things med and pharma through the nose) 

 

re amantadine, I got it at allDayChemist and mj helps a lot

Thanks again

[Justin BoBustinBananaFanaF]

CBN is known for its neuroticizing, dysphoric, even derealizing effects.  THCV is known to inhibit short-term memory and promote anxiety.  when talking of the lesser cannabinoids, it is certainly not all "healing properties".  even medical cannabis has no quality control, it has been bred fairly randomly.  between batches, between strains, of what is measured, little is known.  pair that up with yourself, another relative unknown, and you have yourself a science experiment in the making!  i would only recommend cbd to someone already hooked on the bad stuff.  are you taking magnesium, have you grabbed the low-hanging fruit yet?

Can you cite a study for the derealizing effects of CBN? I suffer from derealization and it doesn't seem like CBN makes it worse (although CBD does in high enough doses especially if it isn't isolated). I'd be curious to know the mechanism as I don't remember it touching opioid receptors, perhaps its via a 5HT receptor? Knowing this would help keep the benefits (sleep/muscle relaxation) while minimizing the downsides.

While I agree that there are negative effects to CBD the same can be said for almost all compounds. CBD has been a major boon to me and I would've been much healthier if I tried it years ago. Rather than singling out supplements to avoid I'd recommend people understand their genetics/predispotions, how supplements work and experiment until they understand themselves and chemical pathways relatively well. There aren't too many people (including Doctors) who completely understand chemical pathways and people who don't do their homework won't get timely results.