9 votes
Posted 11 June 2015 - 08:19 PM
***UK POSTERS***
Do you know of any good e liquids sold from a UK shop online??
Canavape is apparently a solid product; 100mg for £21. I've heard from a poster on here from the US you can get 300mg for $10-20, from my research their doesn't seem to be a much better deal than 100mg for 20 odd in the UK... or is there?
cheerss
Edited by YimYam, 11 June 2015 - 08:26 PM.
Posted 15 June 2015 - 01:40 AM
I have to come back at my experience with smoking CBD. CBD isn't actually an antipsychotic, it's more like a truth-serum for me. I went full psychotic a month/couple weeks ago, I didn't realize it until I smoked some CBD, while under influence it hit me, I told myself I'm in a fucking psychosis, couple days later, BOOM, there was no turning back and my brain went into a full psychotic crash. I'm three weeks on antipsychotics again and I tried CBD again this past week, I realized something great but also sad, when I smoked the voices in my head did not increase or decrease so that's positive (though, because with CBD you dig more inside your head it takes 8-10 hours living withdrawn in myself, into my own world is a better way to say it).
However, I've been having a positive symptom where my heartbeat ticks differently when the other "person" takes "control" over my head (schizophrenia's definition is a "split-mind" for the ones that don't know). The great thing what happened to me was that the voices in my head and the voice that came from my heart when the other "person" took over were different from each other. It made me realize that the voices in my head are by far not true at all but the voice that came from my "heart" was great, it wasn't directly talking to me but it gave me hints/guidance on how to handle my feelings/the situation I am in (I rather not go into detail because it's too personal). The following day I followed this "CBD-truth-serum-heartbeat-guidance" (new word :P ) and took action solely on my own feelings and what the other person's "heart" guided me towards and it really cleared a lot of things with the personal issue I am in, which in turn brought me faster back to reality and the voices in my head shut-up faster if I didn't do what I did. This (maybe one time) experience also made me so creative I'm somewhat in awe from myself. However, even though this symptom also belongs to a positive symptom it's also sad because, in the end, it's part of a disease and I rather not take this with me for the rest of my life, it'll make living daily impossible, unless I want to be a really creative mad-man (artist) thinking I am still living in the Renaissance period.
Before I forget, I also noticed another "great" thing while under influence of CBD, when I thought about and/or when the other "person" was present I felt the other "persons" energy pushing against my head while writing psychotic stuff about that "person". This symptom was impossible to detect without smoking CBD, now that I know that it is a part of the psychosis it gave me more insight, which is great for my recovery.
Edited by YoungSchizo, 15 June 2015 - 02:16 AM.
Posted 15 June 2015 - 08:37 PM
trying to generate interest in a group buy of URB-597 (check out redan's recent post titled "potential new groundbreaking treatment for schizophrenia" or something similar). An FAAH Inhibitor, it works like CBD and increases anandamide, and is really cheap for the dosage you need. supposedly obliterates anxiety. the supplier requires a minimum order of 50 Euros, i'd like to split an order with some people if interested. let me know.
Posted 29 June 2015 - 10:48 AM
I'm in a process of obtaining CBD but the prices are crazy. I'd need 600mg of CBD a day and that is currently impossible for me so I'm not sure where to get real CBD to have at least 50mg a day and even 50mg seems out of my financial reach so I'm not sure where to look. If anyone has any idea where to get and what to get I'd appreciate it.
Posted 29 June 2015 - 05:16 PM
trying to generate interest in a group buy of URB-597 (check out redan's recent post titled "potential new groundbreaking treatment for schizophrenia" or something similar). An FAAH Inhibitor, it works like CBD and increases anandamide, and is really cheap for the dosage you need. supposedly obliterates anxiety. the supplier requires a minimum order of 50 Euros, i'd like to split an order with some people if interested. let me know.
I´m personally sceptic about this one because in theory, CB1 receptor agonism is anxiolytic and so on
but in practical usage, it might not work.
Or otherway arround: why does an agonism with THC not work as well ?
Furthermore, I have the assumption that redan makes money with it, so You wouldnt have a neutral report.
(just an assumption, no accusation)
Googleing arround, You´ll get some natural and OTC results for FAAH inhibitors( though, I cant say for 100% that they will work):
CBD is one
Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide
http://www.ncbi.nlm....les/PMC1573017/
Inhibition of fatty acid amide hydrolase by kaempferol and related naturally occurring flavonoids
http://www.ncbi.nlm....les/PMC2538700/
AM404, also known as N-arachidonoylaminophenol , the metabolite of Paracetamol/Acetaminophen
https://en.wikipedia.org/wiki/AM404
Though Paracetamol is highly livertoxic in overdoses !
Dont screw too much arround with this, unless You want literary a new Liver
http://emedicine.med...820200-overview
In the case any of them above works as a FAAH, why would You need to buy a relative expensive research chemical ?
Therefore my assumption about redan
Edited by Flex, 29 June 2015 - 05:16 PM.
Posted 29 June 2015 - 09:01 PM
I would also really like to buy URD 597 and start experimenting it with myself, but I am not sure that long term inhibition of an enzyme that clearly has it's purpose might be the best solution for my problem. CBD is antagonist on CB1 and CB2 and it might be that by antagonizing these receptors, there is higher concentration of endogenuous cannabinoids in the system that do their own work without high distruption of FAAH. Or there is something other happening that makes CBD antipsychotic, as I need it fot this purpose. Trials are made with 600 mg and it worked, but with 150$ for a gram it's not possible for me yet to fully use it as a medicine. I'd like to know what's the effective antipsychotic dosage for CBD. I've searched the whole damn internet and didn't find any info on the dosage treshold. Everyone is saying CBD is great for this and that and noone is making a decent research on this. And it's not psychoactive, legal everywhere and there is no clear info about what it is exactly doing. Makes me to rethink whole world and science and rethink my own sanity and intelligence as I see that there is something rotten in this area and would like someone to shed light and life in this area...
Edited by insearchfor, 29 June 2015 - 09:02 PM.
Posted 30 June 2015 - 06:34 PM
I would also really like to buy URD 597 and start experimenting it with myself, but I am not sure that long term inhibition of an enzyme that clearly has it's purpose might be the best solution for my problem. CBD is antagonist on CB1 and CB2 and it might be that by antagonizing these receptors, there is higher concentration of endogenuous cannabinoids in the system that do their own work without high distruption of FAAH. Or there is something other happening that makes CBD antipsychotic, as I need it fot this purpose. Trials are made with 600 mg and it worked, but with 150$ for a gram it's not possible for me yet to fully use it as a medicine. I'd like to know what's the effective antipsychotic dosage for CBD. I've searched the whole damn internet and didn't find any info on the dosage treshold. Everyone is saying CBD is great for this and that and noone is making a decent research on this. And it's not psychoactive, legal everywhere and there is no clear info about what it is exactly doing. Makes me to rethink whole world and science and rethink my own sanity and intelligence as I see that there is something rotten in this area and would like someone to shed light and life in this area...
Just to chime in. Most of the positive effects of CBD are thought to be through FAAH inhibition for SZ. But, like I said earlier in another thread once you inhibit FAAH and elevate anandamide levels constantly, abrupt cessation can trigger a psychotic break; but, so would taking risperidone or olanzapine do the same or similar. So, if you're confident that FAAH inhibitors can treat SZ through DA modulation and GABA promoter ability, then keep on taking it. I wish the public knew more about some of these RC's as they can be literally a cure for some through judicious use.
Posted 30 June 2015 - 08:28 PM
I would also really like to buy URD 597 and start experimenting it with myself, but I am not sure that long term inhibition of an enzyme that clearly has it's purpose might be the best solution for my problem. CBD is antagonist on CB1 and CB2 and it might be that by antagonizing these receptors
CBD is actually a weak agonist at CB1 but antagonizing THC at, afaik, CB2 and also at the GPR55 (CB3 so to say)
Posted 30 June 2015 - 10:30 PM
I would also really like to buy URD 597 and start experimenting it with myself, but I am not sure that long term inhibition of an enzyme that clearly has it's purpose might be the best solution for my problem. CBD is antagonist on CB1 and CB2 and it might be that by antagonizing these receptors, there is higher concentration of endogenuous cannabinoids in the system that do their own work without high distruption of FAAH. Or there is something other happening that makes CBD antipsychotic, as I need it fot this purpose. Trials are made with 600 mg and it worked, but with 150$ for a gram it's not possible for me yet to fully use it as a medicine. I'd like to know what's the effective antipsychotic dosage for CBD. I've searched the whole damn internet and didn't find any info on the dosage treshold. Everyone is saying CBD is great for this and that and noone is making a decent research on this. And it's not psychoactive, legal everywhere and there is no clear info about what it is exactly doing. Makes me to rethink whole world and science and rethink my own sanity and intelligence as I see that there is something rotten in this area and would like someone to shed light and life in this area...
Just to chime in. Most of the positive effects of CBD are thought to be through FAAH inhibition for SZ. But, like I said earlier in another thread once you inhibit FAAH and elevate anandamide levels constantly, abrupt cessation can trigger a psychotic break; but, so would taking risperidone or olanzapine do the same or similar. So, if you're confident that FAAH inhibitors can treat SZ through DA modulation and GABA promoter ability, then keep on taking it. I wish the public knew more about some of these RC's as they can be literally a cure for some through judicious use.
can you point to any studies proving abrupt cessation of an FAAH inhibitor can induce a psychotic break, or are you just judging from your personal experience you posted about before? the reason i am asking is because i am wondering what other factors may have contributed to your 'break' when you quit URB 597 abruptly. i'd like to try it, and i haven't read anything saying that abrupt cessation can be harmful yet.
also redan, you were taking high dosages as well from what i've gathered, maybe that had something to do with it?
Posted 30 June 2015 - 11:42 PM
I would also really like to buy URD 597 and start experimenting it with myself, but I am not sure that long term inhibition of an enzyme that clearly has it's purpose might be the best solution for my problem. CBD is antagonist on CB1 and CB2 and it might be that by antagonizing these receptors, there is higher concentration of endogenuous cannabinoids in the system that do their own work without high distruption of FAAH. Or there is something other happening that makes CBD antipsychotic, as I need it fot this purpose. Trials are made with 600 mg and it worked, but with 150$ for a gram it's not possible for me yet to fully use it as a medicine. I'd like to know what's the effective antipsychotic dosage for CBD. I've searched the whole damn internet and didn't find any info on the dosage treshold. Everyone is saying CBD is great for this and that and noone is making a decent research on this. And it's not psychoactive, legal everywhere and there is no clear info about what it is exactly doing. Makes me to rethink whole world and science and rethink my own sanity and intelligence as I see that there is something rotten in this area and would like someone to shed light and life in this area...
Just to chime in. Most of the positive effects of CBD are thought to be through FAAH inhibition for SZ. But, like I said earlier in another thread once you inhibit FAAH and elevate anandamide levels constantly, abrupt cessation can trigger a psychotic break; but, so would taking risperidone or olanzapine do the same or similar. So, if you're confident that FAAH inhibitors can treat SZ through DA modulation and GABA promoter ability, then keep on taking it. I wish the public knew more about some of these RC's as they can be literally a cure for some through judicious use.
can you point to any studies proving abrupt cessation of an FAAH inhibitor can induce a psychotic break, or are you just judging from your personal experience you posted about before? the reason i am asking is because i am wondering what other factors may have contributed to your 'break' when you quit URB 597 abruptly. i'd like to try it, and i haven't read anything saying that abrupt cessation can be harmful yet.
also redan, you were taking high dosages as well from what i've gathered, maybe that had something to do with it?
I was taking it in the 5-8mg dose range. Effective doses via HED is 3mg per the studies done on FAAH inhibition levels on mice. I stopped taking it after I got back home for 2-3 days. I can't really say what was the contributing factor as I would sleep in excess of 18h for a couple of days. During that time I stopped taking URB-597 and when I went for a drive I noticed some perceptual disturbances similar to a high dose of THC. I was also taking a product I bought from etsy that contained high levels of CBD. I can't rule out if there was any THC in the product since it was so refined to the point of looking like some black tar. I suppose that the culmination of excess sleep, the CBD from etsy, and the lack of FAAH inhibition and possibly oversensitized CB1 receptors through could have triggered the perceptual disturbances I experienced. All in all I think FAAH inhibition for prolonged periods of time is not a bad thing per say; but, abrupt cessation can cause an increased risk of feeling "high" or just strange due to compensatory effects on CB1 and CB2 receptors....
Posted 01 July 2015 - 08:26 PM
So I found a supplier that can provide pure crystal CBD for a price od 150$ per gram. That's insane. As I was researching for CBD what it does, it antagonizes CB1 and CB2 with some FAAH inhibition with some interaction with GPR55 and antioxidative properties. My guess is that what it does it antagonizes with adequate Ki affinity so there are no sideefects like with Rimonabant that is CB1 antagonist. So I think that CBD actually is a perfect natural drug that somehow regulates cannabinoid system in the body that is clearly connected to every other system including DA, GABA, GLU, serotonergic etc. CB2 has receptors in immune system so it works even there and I guess it is great antinflamatory agent and it normalizes probably every function in the human body. Andanamide has very quick reuptake and if you disrupt this process strongly it might not be the best option for me. I wish there is more info on CBD and companies that can provide it to people with reasonable prices. Hope it will happen soon.
Posted 16 August 2015 - 12:36 PM
Steve_86
I can't provide you with info on that, but even GABA is prohibited in your country, so it would be well worth the trouble to find out. I suggest you call Australian Customs, or perhaps there is a governmental website? CBD and THC share a precursor, but they are quite different subtances, so I'm not sure it's an analog. Then again, CBD is schedule II in Canada, whilst the US has to import hemp from Canada IIRC. So it's all twisted and politicians are idiots is the common conclusion. Make some calls.. Then again, I was told by a customs officer I can't import any medication, and later I found on the website it was legal to do so for private use. Remember to double check
Australia has the highest degree of Dark & Evil laws ive ever seen for a country. These laws are of course worse than committing child-molestation, since the prohibition of things that help mental illness leads to the perpetuation of far, far more suffering than that of a child abuse victim, or of being branded with hot-irons.
Since Legislators, or hopefully most of them, wouldnt like branding people with hot irons or raping children, you would think they even more so wouldnt like prohibiting people from using things to reduce intense pain, suffering & destruction.
But it seems to me that with most people, they do not care if they destroy other people's lives. So long as it is not their own lives or family's lives that are destroyed, it is then ok to destroy other people's lives. These sick demonic-creatures are beyond all possible explanation. I imagine that David Chalmers' thought experiment about philosophical zombies isnt just a thought experiment. He should reconsider his belief that they do not exist. seems to me most people are organic portals & philosophical zombies. Otherwise, alternatively, they do have a sentient consciousness but are just completely retarded & saturated with darkness, evil & sociopathy. One of the two is obviously the case, either non-sentient, or somehow sentient and this evil at the same time, which the latter is very difficult to imagine.
Its a shame there is no such thing as instant Karma that i can see. If so that would make all evil people suffer from their own evil reflected back to them. Evil sociopaths suffering from their own evil reflected back to them is one of my biggest dreams and fantasies, Ive become a bit obsessed with that concept, after being exposed to nothing but retarded evil & harm-doers, since birth. Gosh I wish their was instant Karma or a way to very strongly induce it on people, so that they suffer from the same harm they do to others.
I might be interested in cannabidiol due to its binding profile. Its said to be an Allosteric Modulator of Mu & Delta, but doesnt even say if its a positive or negative modulator, and at what affinity and intrinsic activity. We can never get the full data on hardly anything. CBD also is an agonist at 5-HT-1a
Speaking of binding profiles, and 5-HT-1a ; this is off topic, but did you know that cyproheptadine is an antagonist of many receptors, but is highly selective for 5-HT2a? It has lower unfavorable antagonist activity at 5-HT1a compared to any other 5-HT2a antagonist. Furthermore it has the lowest affinity for dopamine of any 2a antagonist
This begs the question; if Psychitrists keep wanting to give people 5-HT-2a targeted antagonists for bipolar and anxieties ; why the FUCK are they choosing the ones that are far less selective than cypro is, ones that also hit 1a hard and hit dopamine hard, ones like seroquel, hydroxyzine, trazadone and more. Are doctors just completely retarded and unaware of cyproheptadine's binding profile ?? go look at its wikipedia entry, theres no 5-HT-2a antagonist like this, yet its never used. Its like everything psychiatrists do is sub-par, wrong, incorrect, stupid and evil.
I know people find these posts very uncomfortable, and some people even have Stockholm Syndrome where they defend their evil over-seers who perform Tyrannical PsyOps Disinfo & Policies.... but I am not a crazy person who has been taking megadoses of notropics that made me insane. I have always wrote like this, long before any nootropics or alternative treatments I am merely stating the objective and verified truth that all 196 nations on Earth are Authoritarian-Collectivist Tyrannies and set laws that cause more suffering than child-rape. They evil back their laws with death & torture .. the Torture of arrest and imprisonment to any company personnel who sell treatments, and that arrest is then backed by deadly force with automatic weapons.
So if you stop an think about it a moment, essentially, people are being tortured by being denied medicines that helped them, and if anyone tries to provide these medicines, they will be met with deadly force and have their bodies pumped full of lead with automatic weapons, unless they surrender to being arrested and imprisoned to be tortured. Does that make any sense, or is that completely and utterly schizoprenic and saturated with darkness & demonic evil?
All those who prohibited the Human Right of Health-Freedom & ban medications under threat of deadly force: Suffer from your own evil reversed back to you, and metaphorically burn in hell.
-Synostic Truther / Saffron (Most Hardcore & Powerful Direct-Truth Forum Poster in the World; World-Class Abolitionist-Transhumanist Philosopher, Ethics Speaker, Evil Exposer, And hater of all transhumanism except for Abolitionist-Centered Transhumanism)
Edited by Saffron, 16 August 2015 - 01:06 PM.
Posted 16 August 2015 - 12:59 PM
So I found a supplier that can provide pure crystal CBD for a price od 150$ per gram. That's insane. As I was researching for CBD what it does, it antagonizes CB1 and CB2 with some FAAH inhibition with some interaction with GPR55 and antioxidative properties. My guess is that what it does it antagonizes with adequate Ki affinity so there are no sideefects like with Rimonabant that is CB1 antagonist. So I think that CBD actually is a perfect natural drug that somehow regulates cannabinoid system in the body that is clearly connected to every other system including DA, GABA, GLU, serotonergic etc. CB2 has receptors in immune system so it works even there and I guess it is great antinflamatory agent and it normalizes probably every function in the human body. Andanamide has very quick reuptake and if you disrupt this process strongly it might not be the best option for me. I wish there is more info on CBD and companies that can provide it to people with reasonable prices. Hope it will happen soon.
Sure, yes, I too hope that will happen soon, And I also hope that dark sociopathic creatures from hell do not ban it and then point assault rifles at anyone who has it to get them thrown into prison to be tortured, because they had it to reduce their pain, suffering & PTSD destruction
- Saffron (Most Powerful Direct-Truth Forum Poster in the World)
Posted 18 August 2015 - 01:46 PM
So I tried couple of drops of CBD oil maybe half an hour ago thanks to a longecity member who sent me a free sample. You know who you are and my biggest thanks for such a pleasant surprise!
I calculated the dosage and it might be around 17mg of CBD in my first dosage.
And it is not placebo. I can surely feel the stuff in my system.
I feel that is is now absorbed through my mouth and I feel it's cannabinergic effect.
The taste of oil had typical cannabis aroma with that typical spicy zesty taste not sure how to describe it.
Anyone who tried cannabis oil orally know what the taste is like, but this product had milder flavour.
What I can report about this CBD oil is that I definately feel it's physical effects.
Kind of "stoned without being stoned" feeling.
There is a kind of heavyness behind my eyeballs and physical relaxation comparable to the feeling you have when your cannabis high ends.
You know the moment when you're not stoned anymore, but still there are lingering effects that you can feel after the major stoned effects have stopped. That kind of feeling.
I was "slightly elevated and energetic" this morning and after ingestion of this oil things changed.
Now I'm suddenly feeling lazy, but still functional. I know I can do whatever I want, but I'm feeling like listening to music and relaxing.
I had stiff neck and couldn't turn my head to the right and now I'm feeling that I'm not feeling pain anymore and I can turn my head normally.
What I can surely say is that there is noticeable sedative effect, not like benzo/GABA sedation but cannabinergic sedation, very specific type you can get only from cannabinoids. Sedation that makes you more "naturally" sedated... Lazy and stronger physical feel.
This cannabinoid has some putative properties, not sure how to put this putative effect into words.
I think it would be good to use CBD oil in the times you want to relax, after work, in the evening or when having any kind of nerve pain.
This is potent substance.
Will report more after further experiementation with CBD. 
Posted 13 September 2015 - 03:45 PM
I'm interested in your results;
We have ordered from CW Botannicals (very reputable) for my 12 year old who suffers from epilepsy (absence seizures).
I would try it myself for anxiety, however since it can show up on a urinalysis (the kind where they test for all cannibinoids), I can't risk it. But I sure hope it helps my little girl, She has terrible problems sleeping and gets bad headaches all the time.
Since it's legal by federal law (it's made from the Charlotte's web strain, which is industrial hemp and the oil is classified as a food supplement, correct me if I'm wrong) and out state legalized it, I should be ok using it for my daughter (.75 mg twice a day). A friend whose child also has absence seizures started their child on it, and after just getting a 24 hour eeg he is verified seizure free.
Posted 16 September 2015 - 08:18 AM
GW Pharma released some early results from their CBD clinical trials yesterday:
http://www.gwpharm.c...izophrenia.aspx
Posted 20 September 2015 - 06:57 AM
Anxiogenic-like effects of chronic cannabidiol administration in rats.
Several pre-clinical and human-based studies have shown that acutely administered cannabidiol (CBD) can produce anxiolytic-like effects
The present study investigated the effects of chronic administration of CBD on rat behaviour and on the expression of brain proteins.
Male Lister-hooded rats (150-200 g, n = 8 per group) received daily injections of CBD (10 mg/kg, i.p.) for 14 days. The rats were subjected to two behavioural tests: locomotor activity and conditioned emotional response (CER). The expression of brain-derived neurotrophic factor (BDNF), its receptor tyrosine kinase B (Trk B), extracellular signal-regulated kinases (ERK1/2) and phospho-ERK1/2 and the transcription factor cyclic AMP response element binding protein activation (CREB) and phospho-CREB were determined in brain regions such as the frontal cortex and hippocampus using Western immunoblotting.
CBD significantly increased the time spent freezing in the CER test with no effect on locomotor activity. CBD significantly reduced BDNF expression in the hippocampus and frontal cortex with no change in the striatum. In addition, CBD significantly reduced TrkB expression in the hippocampus with a strong trend towards reduction in the striatum but had no effect in the frontal cortex. In the hippocampus, CBD had no effect on ERK1/2 or phospho-ERK2, but in the frontal cortex, CBD significantly reduced phospho-ERK1/2 expression without affecting total ERK. Chronic administration of CBD produced an anxiogenic-like effect in clear opposition to the acute anxiolytic profile previously reported. In addition, CBD decreased the expression of proteins that have been shown to be enhanced by chronic treatment with antidepressant/anxiolytic drugs.
Cannabidiol is a negative allosteric modulator of the type 1 cannabinoid receptor.
Cannabidiol has been reported to act as an antagonist of cannabinoid agonists at type 1 cannabinoid receptors (CB1 ). We hypothesized that cannabidiol can inhibit cannabinoid agonist activity through negative allosteric modulation of CB1 .
CB1 internalization, arrestin2 recruitment, and PLCβ3 and ERK1/2 phosphorylation, were quantified in HEK 293A cells heterologously expressing CB1 and in the STHdhQ7/Q7 cell model of striatal neurons endogenously expressing CB1 . Cells were treated with 2-arachidonylglycerol or Δ9 -tetrahydrocannabinol alone and in combination with different concentrations of cannabidiol.
Cannabidiol reduced the efficacy and potency of 2-arachidonylglycerol and Δ9 -tetrahydrocannabinol on PLCβ3- and ERK1/2-dependent signaling in cells heterologously (HEK 293A) or endogenously (STHdhQ7/Q7 ) expressing CB1 . By reducing arrestin2 recruitment to CB1 , cannabidiol treatment prevented CB1 internalization. The allosteric activity of cannabidiol depended upon polar residues being present at positions 98 and 107 in the extracellular amino-terminus.
Cannabidiol behaved as a non-competitive negative allosteric modulator of CB1 . Allosteric modulation, in conjunction with non-CB1 effects, may explain the in vivo effects of cannabidiol. Allosteric modulators of CB1 have the potential to treat central nervous system and peripheral disorders while avoiding the adverse effects associated with orthosteric agonism or antagonism of CB1 . This article is protected by copyright. All rights reserved.Potential anxiogenic effects of cannabinoid CB1 receptor antagonists/inverse agonists in rats: comparisons between AM4113, AM251, and the benzodiazepine inverse agonist FG-7142.
Cannabinoid CB1 inverse agonists suppress food-motivated behaviors, but may also induce psychiatric effects such as depression and anxiety. To evaluate behaviors potentially related to anxiety, the present experiments assessed the CB1 inverse agonist AM251 (2.0-8.0mg/kg), the CB1 antagonist AM4113 (3.0-12.0mg/kg), and the benzodiazepine inverse agonist FG-7142 (10.0-20.0mg/kg), using the open field test and the elevated plus maze. Although all three drugs affected open field behavior, these effects were largely due to actions on locomotion. In the elevated plus maze, FG-7142 and AM251 both produced anxiogenic effects. FG-7142 and AM251 also significantly increased c-Fos activity in the amygdala and nucleus accumbens shell. In contrast, AM4113 failed to affect performance in the plus maze, and did not induce c-Fos immunoreactivity. The weak effects of AM4113 are consistent with biochemical data showing that AM4113 induces little or no intrinsic cellular activity. This research may lead to the development of novel appetite suppressants with reduced anxiogenic effects.
Agonistic properties of cannabidiol at 5-HT1a receptors.
Cannabidiol (CBD) is a major, biologically active, but psycho-inactive component of cannabis. In this cell culture-based report, CBD is shown to displace the agonist, [3H]8-OH-DPAT from the cloned human 5-HT1a receptor in a concentration-dependent manner. In contrast, the major psychoactive component of cannabis, tetrahydrocannabinol (THC) does not displace agonist from the receptor in the same micromolar concentration range. In signal transduction studies, CBD acts as an agonist at the human 5-HT1a receptor as demonstrated in two related approaches. First, CBD increases [35S]GTPgammaS binding in this G protein coupled receptor system, as does the known agonist serotonin. Second, in this GPCR system, that is negatively coupled to cAMP production, both CBD and 5-HT decrease cAMP concentration at similar apparent levels of receptor occupancy, based upon displacement data. Preliminary comparative data is also presented from the cloned rat 5-HT2a receptor suggesting that CBD is active, but less so, relative to the human 5-HT1a receptor, in binding analyses. Overall, these studies demonstrate that CBD is a modest affinity agonist at the human 5-HT1a receptor. Additional work is required to compare CBD's potential at other serotonin receptors and in other species. Finally, the results indicate that cannabidiol may have interesting and useful potential beyond the realm of cannabinoid receptors.Decreased brain serotonin 5-HT1A receptor availability in medication-naive patients with major depressive disorder: an in-vivo imaging study using PET and [carbonyl-11C]WA Y-100635
Serotonin (5-HT) is involved in the pathophysiology of major depressive disorder (MDD). Among the numerous serotonergic receptors, the 5-HT1A receptor subtype is of interest because of its involvement in cognition, hippocampal neurogenesis, and mechanism of action of antidepressant drugs. Previous imaging studies have suggested altered availability of 5-HT1A receptors in MDD but prior antidepressant medication and chronicity of the illness may confound the interpretation. We examined 21 drug-naive primary-care patients with MDD using positron emission tomography (PET) imaging with [carbonyl-11C]WAY-100635, a radioligand for 5-HT1A receptors, along with 15 healthy control subjects. Binding to receptors was assessed both regionally and at voxel level with the binding potential (BP) that was estimated using arterial blood input. Compared with healthy controls, the BP of [carbonyl-11C]WAY-100635 was reduced in patients with MDD in most brain regions, ranging from −9% to −25%. Voxel-level analysis confirmed this finding by showing a widespread reduction of [carbonyl-11C]WAY-100635 BP. No statistically significant associations were observed between BP and total HAMD scores in the patients, but lower BP was associated with higher likelihood of insomnia. This study demonstrated a widespread reduction in the availability of serotonin 5-HT1A receptors in a relatively large sample of drug-naive primary-care patients with MDD, suggesting the involvement of this receptor subtype in the pathophysiology of the illness. Lack of correlation with overall severity of the illness may relate to a largely trait-like nature of this abnormality in depressive disorders.
The orphan receptor GPR55 is a novel cannabinoid receptor
The endocannabinoid system functions through two well characterized receptor systems, the CB1 and CB2 receptors. Work by a number of groups in recent years has provided evidence that the system is more complicated and additional receptor types should exist to explain ligand activity in a number of physiological processes.
Cells transfected with the human cDNA for GPR55 were tested for their ability to bind and to mediate GTPγS binding by cannabinoid ligands. Using an antibody and peptide blocking approach, the nature of the G-protein coupling was determined and further demonstrated by measuring activity of downstream signalling pathways.
We demonstrate that GPR55 binds to and is activated by the cannabinoid ligand CP55940. In addition endocannabinoids including anandamide and virodhamine activate GTPγS binding via GPR55 with nM potencies. Ligands such as cannabidiol and abnormal cannabidiol which exhibit no CB1or CB2 activity and are believed to function at a novel cannabinoid receptor, also showed activity at GPR55. GPR55 couples to Gα13 and can mediate activation of rhoA, cdc42 and rac1.
These data suggest that GPR55 is a novel cannabinoid receptor, and its ligand profile with respect to CB1 and CB2 described here will permit delineation of its physiological function(s).
... both anandamide and O1602 but not WIN55,212-2 treatment induced the activation of rhoA, cdc42 and rac1. This effect was blocked by the GPR55 antagonist, cannabidiol.Blockade of GPR55 in the dorsolateral striatum impairs performance of rats in a T-maze paradigm.
To investigate the role of GPR55 receptors, which are expressed in human and rat striatum (a structure that regulates procedural memory), Wistar rats received five training sessions (10 trials/session, 1 session/day) to solve a T-maze paradigm. From these data, we constructed learning curves following pharmacological manipulation of GPR55. Five minutes before each session, animals received bilateral intradorsolateral striatum injections of noladin-ether (3.1 nmol/l; endogenous agonist of GPR55 and CB1 receptors), CID16020036 (5.6 nmol/l; GPR55 antagonist), AM251 (5.6 nmol/l; CB1 antagonist), or a combination of noladin-ether with each antagonist. Noladin-ether by itself induced no significant changes in the learning curve. Nevertheless, while simultaneously blocking CB1 receptors (with AM251), noladin-ether improved acquisition. In contrast, while simultaneously blocking GPR55 (with CID16020036), noladin-ether weakened acquisition. CID16020036 by itself impaired learning, whereas AM251 by itself reduced the efficiency in the task. There were no differences between groups in the latency to reach the arms from the starting point; thus, no motor coordination impairments interfered with this task. These results strongly suggest a role of GPR55 in procedural memory and constitute the first evidence indicating that this receptor regulates cognitive processes.
Cannabidiol is a allosteric modulator at mu- and delta-opioid receptors.
The mechanism of action of cannabidiol, one of the major constituents of cannabis, is not well understood but a noncompetitive interaction with mu opioid receptors has been suggested on the basis of saturation binding experiments. The aim of the present study was to examine whether cannabidiol is an allosteric modulator at this receptor, using kinetic binding studies, which are particularly sensitive for the measurement of allosteric interactions at G protein-coupled receptors. In addition, we studied whether such a mechanism also extends to the delta opioid receptor. For comparison, (-)-Delta9-tetrahydrocannabinol (THC; another major constituent of cannabis) and rimonabant (a cannabinoid CB1 receptor antagonist) were studied. In mu opioid receptor binding studies on rat cerebral cortex membrane homogenates, the agonist 3H-DAMGO bound to a homogeneous class of binding sites with a KD of 0.68+/-0.02 nM and a Bmax of 203+/-7 fmol/mg protein. The dissociation of 3H-DAMGO induced by naloxone 10 microM (half life time of 7+/-1 min) was accelerated by cannabidiol and THC (at 100 microM, each) by a factor of 12 and 2, respectively. The respective pEC50 values for a half-maximum elevation of the dissociation rate constant k(off) were 4.38 and 4.67; 3H-DAMGO dissociation was not affected by rimonabant 10 microM. In delta opioid receptor binding studies on rat cerebral cortex membrane homogenates, the antagonist 3H-naltrindole bound to a homogeneous class of binding sites with a KD of 0.24+/-0.02 nM and a Bmax of 352+/-22 fmol/mg protein. The dissociation of 3H-naltrindole induced by naltrindole 10 microM (half life time of 119+/-3 min) was accelerated by cannabidiol and THC (at 100 microM, each) by a factor of 2, each. The respective pEC50 values were 4.10 and 5.00; 3H-naltrindole dissociation was not affected by rimonabant 10 microM. The present study shows that cannabidiol is a NEGATIVE (see attached pdf) allosteric modulator at mu and delta opioid receptors. This property is shared by THC but not by rimonabant.
CANNABIDIOL IS A NEGATIVE ALLOSTERICMODULATOR AT THE μ OPIOID.pdf 123.72KB
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Posted 25 October 2015 - 10:57 PM
As someone thinking about giving CBD a try this thread is of interest to me. I'am a bit concerned that you get a very small amount for the money though, if a high dose is required for the anti-anxiety effect then I don't know how I could afford it. It's a shame the low THC / high CBD strains aren't scent-less otherwise it'd just be easier to grow high CBD strains. But I presume they smell just as strongly and it'd be hard for anyone to grow them without being detected or smoke them without having the weed smell about them.
It seems im developing a strong tolerance to cdb. Ive had no noticeable effect with my usual 15 drop dose the last 3 times i took them..
This sounds disappointing, although it sounds higher than the dose most of these companies recommend (two drops) so maybe tolerance built quicker?
Thanks for updating mastermind57
Well I suppose it needn't be continuously profound, but it could most definitely serve as an adjunct with other subtle anxiolytics. Perhaps combined with L-Theanine it could prove a useful regimen for some.
jerichodotm:
Curious to read about your experience as well.
n95: How's the synthesis coming along?
The synthesis isn't actually going at all at the moment. I'm currently in the process of gathering data on the potential long term benefits, which would justify entire venture.
i think it much more easier growing a high cbd specie (cannatonic, janita la lagrimosa, cb crew...) and then extracting CBD than synthesize it
It probably is, but it'll stink up your property and you'll get caught doing it.
Does anyone know for sure if this is legal in the UK?
JD
It is, there are UK suppliers, although most of them seem to import it from America. There are a few making it in the UK but they want payment by bank transfer which doesn't seem 100% legit somehow.
As promised here is my review.
I have been using the product twice per day for 4 days. I put about a half of the dropper on my tongue and try to keep it there for about 60 seconds before swallowing. At times, I think I might be less anxious then at other times I don't think it's doing anything.
Does CBD take time to build up and stark working unlike THC? If this is the case, I'll order a second bottle and give this a full 2 months rather than just 1 if nothing it noticeable.
if you bought it from dixie i can tell you that the dose you take are too low
That's what I'm worried about with the UK suppliers. They supply these tiny bottles or sprays of it and I just don't see how such low doses can be effective.
Saved that file for if I ever retrieve my cognition.
Thanks for sharing!
Regarding Dixie Botanicals: What was it? 2 months ago, maybe more now, that the website stated international shipment would be available soon?
Empty promises! Still only available in US and Canada.
Sadly, people are uninformed, and only want THC. Thus marketing CBD is marginally effective.
Too bad, would have been a nice idea, especially in Holland.
Any updates on effects people?
You can get it from UK suppliers, shipping will be faster and cheaper because it's in the EU and virtually next to Holland anyway. I just typed in "UK CBD" into google and got loads of results.
Sadly, people are uninformed, and only want THC. Thus marketing CBD is marginally effective.
Too bad, would have been a nice idea, especially in Holland.
Any updates on effects people?
the reason behind this is that pothead are too scared that the government legalize CBD because it has almost all the benefits of cannabis without the psychoactivity of thc and permanently ban their lovely "therapeutic" THC ( and let's talk truth by therapeutic cannabis we all know that it's mean gettin high legally ) so their don't make effort to breed high CBD strains and continue to spread misinformation about cbd ex; CBD is inactive, cbd doesn't have therapeutic potential without THC, CBD is weak, CBD can't get extracted, cbd have limited therapeutic value etc...
they blame governments for spreading propaganda about cannabis yet they act exactly like them to protect their precious legal high..hum sorry i mean medicinal cannabis
it's pathetic
thankfully they are more and more people aware of it huge benefits and superiority over THC in treating the same illness
This irks me a bit too because THC itself can be harmful and most of these stoners pushing for Cannabis legalization "because it's medicinal" don't know the story behind it, that too much THC is damaging and it's actually the CBD that's good. All they want is legal Cannabis to get high from.
In my opinion high CBD cannabis should be legal, but how would we be able to differentiate which weed people were growing? So maybe legalization should be restricted not to growing plants, but just to shops selling certified high CBD / low THC strains and maybe some strains for recreational use with a moderate THC amount sold in a similar manner to alcohol.
But if it were sold in shops at a time when we're trying to get people to quit smoking it should probably be in e-liquid form only anyway. Maybe then it'd get more people who smoke tobacco and weed onto purely ecigs.
ive given it to my girlfriend to help her during her time of the month, it helped her immensely she became super relaxed and fell asleep. i do think its effective at reducing anxiety but more so because its sedating than anything else. i dont see it being very useful if you plan on being productive.. its a marijuana high without all the giggles.
It is supposed to be a good painkiller as well. But the productive part isn't good as I'd hoped to use it in daily life, but some people are saying that goes after a few days.
Back to experiences. I have been an avid user of Dixie's dew drops for 8 months. I take a half dropper of the 500mg formula twice a day.
It drives me crazy to hear people lazily describing CBD as "like pot but less so" or saying "you need to use half a bottle to achieve anything". It's true that many studies look at acute does measured in mg/kg. That doesn't mean it's required to achieve any effect. And as for the association with the effect of pot - that's probably just plain lazy and wishful thinking. In reality these users want to try CBD during times that are safe. They have no where to go, and nothing to do. So of course it's relaxing. They're probably listening to music and kicking back on their day off.
What I've found is that at low (half dropper) doses I am stimulated by CBD. If I take it before bed I won't be able to sleep well. If I take it in the morning I'm not mellow at all. I kick my morning in the ass then I take another half dropper at lunch to fuel more ass kicking after lunch. That said what I notice is that I am less sensitive to stimulus. Things that would exhaust me are less stressful. My heart doesn't race before answering a client phone call. The immensity of work before me isn't invading my sense of peace - instead I tap into the work I can do. I play the hand I'm dealt. I don't forget anything mind you, but I feel free not to worry about it.
I find communicating with other people to be much less irritating. Without CBD I often truncated my spoken thoughts because I don't enjoy talking or listening. I find the process is a bit overwhelming at times. Especially with people I don't know very well.
Now that I've said my schtick I'll confess that if you're not naturally on edge, anxious or irritable it might dull you a bit. But for me it takes me from hypersensitivity to regular sensitivity, and I love it. Worth every penny - it belongs right next to your multivitamin jar.
This is interesting that you say it stimulated you, sounds good to me since I want to function on it. When I did weed before (only a few times in my whole life though) I didn't really enjoy it that much. My friend told me it was a very strong strain. Every time the "spaceman" feeling and my stomach doing summersaults just felt too much and although I felt calm on it I didn't like going out when I'd had it because walking seemed to take forever and I got paranoid that I wasn't acted normal or that I had a stoner look on my face, plus I didn't feel entirely there. But when back in private it was relaxing I guess, if a bit much. Too much sedation, couldn't really think and didn't feel like talking much. Just agreed with whatever someone said without really listening.
I'm wondering which effects were influenced by THC or CBD. The paranoia about not being normal sounds like THC, the spaceman feeling THC and CBD, but the sedated, lazy, "dumb" feeling could be CBD?
I want to be anxiety free but I don't want to be a potato.
I don't think there is any significant amount of CBD in the Dew Drops, unless they've changed the formulation recently.
I've taken half a bottle with no more than a slightly woozy feeling. On the contrary, there is no mistaking the effect high-CBD dispensary weed has.
This is why the medical stuff should be legalised here.
I've read about and experienced a bunch of shadiness dealing with Dixie Botanicals. They're running a scam.
High CBD/low THC cannabis from a dispensary has a very definite effect on me. Immediate anxiolysis along with zoning out/depersonalization, followed by an antidepressant effect that develops over a couple of days.
Anti-depressant effect sounds nice, but what is depersonalization? On Phenibut at times I'd totally be able to be oblivious to the world around me and walk down the street and not even care or really even see anyone (obviously I could see they were there, but I didn't even care, check out their faces or even bother - I have social anxiety btw)
I found CBD very effective the first few times I tried, now I don't feel anything.
Maybe it's stopped working or you're just used to it? Does it still help with anxiety or not?
Posted 27 October 2015 - 11:39 PM
Posted 08 February 2016 - 05:02 PM
I am interested in trying CBD for my long term struggle with various anxiety issues such as social phobia. Can you pls recommend me some of the best CBD product especially for these severe anxiety problems (preferably from European Union ) ?
So far, I was thinking to place an order through this site :
http://www.naturalwo...-with-pipette?
Has anyone tried any products from them ? Can you recommend me their CBD oil for anxiety ?
Thanks !
Posted 07 March 2016 - 12:03 AM
Posted 05 August 2016 - 10:17 PM
trying to generate interest in a group buy of URB-597 (check out redan's recent post titled "potential new groundbreaking treatment for schizophrenia" or something similar). An FAAH Inhibitor, it works like CBD and increases anandamide, and is really cheap for the dosage you need. supposedly obliterates anxiety. the supplier requires a minimum order of 50 Euros, i'd like to split an order with some people if interested. let me know.
What supplier are you talking about? Has anyone ordered with success? How were the results? 50 euros is cheap, I see a few places that want $150 for 10 gm which is not bad. I could just go and order some, but that is a large supply. Maybe we could put together a group buy and get it cheaper and not have to order as much per person? That would depend on interest of course. If no one is interested in getting in I will order the 10gm myself. Ideally a buy of a kilo from china would save a lot of money but that would take loads of interest. I started a thread in the products forum.
People are interested in cbd, this naturally increases the cbd in your body and brings about the same result. If we can get the cbd people onboard this would take off for sure.
Posted 06 August 2016 - 12:59 AM
trying to generate interest in a group buy of URB-597 (check out redan's recent post titled "potential new groundbreaking treatment for schizophrenia" or something similar). An FAAH Inhibitor, it works like CBD and increases anandamide, and is really cheap for the dosage you need. supposedly obliterates anxiety. the supplier requires a minimum order of 50 Euros, i'd like to split an order with some people if interested. let me know.
What supplier are you talking about? Has anyone ordered with success? How were the results? 50 euros is cheap, I see a few places that want $150 for 10 gm which is not bad. I could just go and order some, but that is a large supply. Maybe we could put together a group buy and get it cheaper and not have to order as much per person? That would depend on interest of course. If no one is interested in getting in I will order the 10gm myself. Ideally a buy of a kilo from china would save a lot of money but that would take loads of interest. I started a thread in the products forum.
People are interested in cbd, this naturally increases the cbd in your body and brings about the same result. If we can get the cbd people onboard this would take off for sure.
Posted 06 August 2016 - 03:39 PM
Yes, that is the problem. There are a couple companies on the net promising to send it, $15 a gm is not bad but you have to order 10gm. Neither of those have any reviews on the net so no way of knowing if they are legit. I'm tempted to go ahead and order the 10gm but it could be bogus, might have little or none of the active ingredient, and I don't know how long it will keep. If I used an average of 5 mg per day 10gm will last 7 years or so. Assuming I didn't run into major tolerance issues, which apparently it does promote tolerance so you could not use it every day.
Surely someone has bought this stuff and it was the real thing? The only legit looking companies are asking extortionate prices which is normal for those companies. Ripping off the consumer is a way of business. $4 to $20 a mg is a ripoff in my book. That is as bad as cbd prices, and there are lots of ripoffs with that too.
A search brings up chinese companies which will sell it. From experience I know they want a large order, probably at least a kilo but it might be cheap. Then you take the risk of an adulterated substance, china itself is notorious for contamination, their own food supply is very often contaminated. Their standards are lax and seldom enforced. Thats why I'd like to hear from someone who has tried it and has a good source. This stuff has been known for years, surely there are some successes? The fact no one is speaking up suggests everyone got ripped off as you may have been yourself, nicklesprout.
Posted 17 August 2016 - 10:01 AM
I have to come back at my experience with smoking CBD. CBD isn't actually an antipsychotic, it's more like a truth-serum for me. I went full psychotic a month/couple weeks ago, I didn't realize it until I smoked some CBD, while under influence it hit me, I told myself I'm in a fucking psychosis, couple days later, BOOM, there was no turning back and my brain went into a full psychotic crash. I'm three weeks on antipsychotics again and I tried CBD again this past week, I realized something great but also sad, when I smoked the voices in my head did not increase or decrease so that's positive (though, because with CBD you dig more inside your head it takes 8-10 hours living withdrawn in myself, into my own world is a better way to say it).
However, I've been having a positive symptom where my heartbeat ticks differently when the other "person" takes "control" over my head (schizophrenia's definition is a "split-mind" for the ones that don't know). The great thing what happened to me was that the voices in my head and the voice that came from my heart when the other "person" took over were different from each other. It made me realize that the voices in my head are by far not true at all but the voice that came from my "heart" was great, it wasn't directly talking to me but it gave me hints/guidance on how to handle my feelings/the situation I am in (I rather not go into detail because it's too personal). The following day I followed this "CBD-truth-serum-heartbeat-guidance" (new word :P ) and took action solely on my own feelings and what the other person's "heart" guided me towards and it really cleared a lot of things with the personal issue I am in, which in turn brought me faster back to reality and the voices in my head shut-up faster if I didn't do what I did. This (maybe one time) experience also made me so creative I'm somewhat in awe from myself. However, even though this symptom also belongs to a positive symptom it's also sad because, in the end, it's part of a disease and I rather not take this with me for the rest of my life, it'll make living daily impossible, unless I want to be a really creative mad-man (artist) thinking I am still living in the Renaissance period.
Before I forget, I also noticed another "great" thing while under influence of CBD, when I thought about and/or when the other "person" was present I felt the other "persons" energy pushing against my head while writing psychotic stuff about that "person". This symptom was impossible to detect without smoking CBD, now that I know that it is a part of the psychosis it gave me more insight, which is great for my recovery.
No! CBD is not a truth serum. If you have medical issues then you should not play around with cannabis at all. There is not enough research onCBD and we don't know if it can help people with schizophrenia. There is not enough research on any specific strain.
https://www.reddit.c...mbat_psychosis/
As someone said it is a snakes oil industry. You might get filthy product or very dangerous synthetic cannibinoids which could trigger psychosis or mania.
https://www.reddit.c...il_contains_k2/
Don't order any tea or hemp from unknown vendors. It can actually be fake! Spice sellers are flooding the market with their shit.
http://www.ncbi.nlm....les/PMC4201992/
http://www.ncbi.nlm....les/PMC3470439/
People can be allergic to hemp, it could trigger skin rashes and flu like symptoms.
In layman's terms, common respiratory symptoms appear in the form of itchy, watery and/or red or swollen eyes, runny nose, wheezing, coughing, sneezing or nasal congestion, possibly combined with a mild case of hives or slightly itchy skin. Some of the more severe - yet widely unknown - symptoms include allergic rhinitis, allergic conjunctivitis, asthma, food allergies, eczema, drug eruptions, contact urticaria and, most worryingly, anaphylaxis. While allergy symptoms and hypersensitivity are troublesome and can affect everyday life, anaphylaxis can easily lead to death, as the throat swells and airways are closed off - exactly what happens when those with severe peanut or shellfish allergies come into contact with their triggers.
Although severe allergic reactions can be treated with corticosteroids, antihistamines and epinephrine, some sufferers are still unaware that their wonderful weed may be the cause of their discomfort. This, combined with the fact that marijuana is only legal in a few states, means that people are not receiving the necessary treatment because they have not yet figured out that their pot consumption or exposure is the problem. Thus, self-diagnoses may be critical to those who live in areas of the United States where personal Cannabis use is often not discussed in public, or at all, due to fear of Drug War penalties.
http://www.cannabis....ic-to-cannabisp
http://www.cbsnews.c...lem-study-says/
Edited by YOLF, 21 August 2016 - 06:53 PM.
typos
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