63 replies to this topic

[nowayout]

I was specifically referring to herbs that have anxiolytic effects.  I've tried everything from St. John's Wort, Lemon Balm, Green Tea...on and on...

 

I've also tripped "balls" off good ol' shrooms and gobbled enough Mau Hung to pop my eyeballs out of my head (metaphorically speaking, of course.)  Cannabis...sure...unfortunately, or maybe fortunately, it began to GIVE me anxiety attacks.

 

I don't think dopaminergics are in general anxiolytic.  Au contraire...

 

How about a drink, sipped slowly?  It's what pretty much everyone else uses as a social lubricant. 

Edited by nowayout, 12 May 2015 - 03:15 PM.

[OneScrewLoose]

ephedrine is a dopamine releasing agent? you get your facts from where exactly? ephedrine is more like what i felt on high dose raspberry ketones, norepinephrine influx, felt shaky and sea sick.

 

FFS you don't got to be a dick a about it:

 

http://www.ncbi.nlm....pubmed/16386715

I told you, it's a minor effect, and it's only in the substantia nigra.

BTW, ephedrine was discovered in the Ma Huang plant over 100 years ago. Scientists found ephedrine to be useful, and just as they had begun to synthesize opiates, they wanted to make a synthetic version of ephedrine. They managed to do so, and named that molecule amphetamine.

[normalizing]

 

ephedrine is a dopamine releasing agent? you get your facts from where exactly? ephedrine is more like what i felt on high dose raspberry ketones, norepinephrine influx, felt shaky and sea sick.

 

FFS you don't got to be a dick a about it:

 

http://www.ncbi.nlm....pubmed/16386715

I told you, it's a minor effect, and it's only in the substantia nigra.

BTW, ephedrine was discovered in the Ma Huang plant over 100 years ago. Scientists found ephedrine to be useful, and just as they had begun to synthesize opiates, they wanted to make a synthetic version of ephedrine. They managed to do so, and named that molecule amphetamine.

 

 

dunno about this. i hate and try to avoid norepineprine whatever possible. its like just the anxiety and fight or flight sense without the fucking euphoria straight dopamine brings. i like dopamine, norepinephrine is NOT DOPAMINE
 

I was specifically referring to herbs that have anxiolytic effects.  I've tried everything from St. John's Wort, Lemon Balm, Green Tea...on and on...

 

I've also tripped "balls" off good ol' shrooms and gobbled enough Mau Hung to pop my eyeballs out of my head (metaphorically speaking, of course.)  Cannabis...sure...unfortunately, or maybe fortunately, it began to GIVE me anxiety attacks.

 

But let's take the Coca plant example.  Chewing leaf with lime doesn't resemble snorting Peruvian Pink in any way (again, thankfully.)

 

thats what cannabis did to me too. first was super anxyolytic, now it causes panic attacks 15 years later. not sure what the fuck the mechanism is about but seems unfixable.

[OneScrewLoose]

 

 

ephedrine is a dopamine releasing agent? you get your facts from where exactly? ephedrine is more like what i felt on high dose raspberry ketones, norepinephrine influx, felt shaky and sea sick.

 

FFS you don't got to be a dick a about it:

 

http://www.ncbi.nlm....pubmed/16386715

I told you, it's a minor effect, and it's only in the substantia nigra.

BTW, ephedrine was discovered in the Ma Huang plant over 100 years ago. Scientists found ephedrine to be useful, and just as they had begun to synthesize opiates, they wanted to make a synthetic version of ephedrine. They managed to do so, and named that molecule amphetamine.

 

 

dunno about this. i hate and try to avoid norepineprine whatever possible. its like just the anxiety and fight or flight sense without the fucking euphoria straight dopamine brings. i like dopamine, norepinephrine is NOT DOPAMINE
 

I was specifically referring to herbs that have anxiolytic effects.  I've tried everything from St. John's Wort, Lemon Balm, Green Tea...on and on...

 

I've also tripped "balls" off good ol' shrooms and gobbled enough Mau Hung to pop my eyeballs out of my head (metaphorically speaking, of course.)  Cannabis...sure...unfortunately, or maybe fortunately, it began to GIVE me anxiety attacks.

 

But let's take the Coca plant example.  Chewing leaf with lime doesn't resemble snorting Peruvian Pink in any way (again, thankfully.)

 

thats what cannabis did to me too. first was super anxyolytic, now it causes panic attacks 15 years later. not sure what the fuck the mechanism is about but seems unfixable.

 

 

I wasn't suggesting you take it. I was just demonstrating that some things that some drugs do, like being a dopamine releasing agent, have no natural equivalent.

[nowayout]

thats what cannabis did to me too. first was super anxyolytic, now it causes panic attacks 15 years later. not sure what the fuck the mechanism is about but seems unfixable.

 

 

Probably just different strains.  Cannabis is not a drug, it is a very variable combination of various drugs, the main ones being THC and CBD. 

 

Low THC strains tend to be anxiolytic.

High THC strains tend to be more pcychedelic, which can be either calming or anxiogenic depending on your state of mind and environment.  

 

Street weed nowadays is much higher THC than in the past, which could explain the difference in your experience.

Edited by nowayout, 13 May 2015 - 02:55 PM.

[normalizing]

nowayout, so maybe i need high CBD weed for relaxation and stress relief?

[nowayout]

nowayout, so maybe i need high CBD weed for relaxation and stress relief?

 

Yes, that is what they recommend, but you won't know unless you get it from a dispensary. 
 

[Flex]

 

 

ephedrine is a dopamine releasing agent? you get your facts from where exactly? ephedrine is more like what i felt on high dose raspberry ketones, norepinephrine influx, felt shaky and sea sick.

 

FFS you don't got to be a dick a about it:

 

http://www.ncbi.nlm....pubmed/16386715

I told you, it's a minor effect, and it's only in the substantia nigra.

BTW, ephedrine was discovered in the Ma Huang plant over 100 years ago. Scientists found ephedrine to be useful, and just as they had begun to synthesize opiates, they wanted to make a synthetic version of ephedrine. They managed to do so, and named that molecule amphetamine.

 

 

dunno about this. i hate and try to avoid norepineprine whatever possible. its like just the anxiety and fight or flight sense without the fucking euphoria straight dopamine brings. i like dopamine, norepinephrine is NOT DOPAMINE
 

 

thats what cannabis did to me too. first was super anxyolytic, now it causes panic attacks 15 years later. not sure what the fuck the mechanism is about but seems unfixable.

 

 

I believe that I´ve posted this somewhere on longecity:

one of the anxiogenic effects of THC, an overdrive of Glutamate in the Amygdala through desensitaion of CB1 receptors and therefore an extended signalling of glutamate.

 

Dont want to be rude but please search the references for Your self or just dont believe this.

I understand any scepticism but It takes sometimes too long to find the sources.

 

[Flex]

 

 

 

 

FFS you don't got to be a dick a about it:

 

http://www.ncbi.nlm....pubmed/16386715

I told you, it's a minor effect, and it's only in the substantia nigra.

BTW, ephedrine was discovered in the Ma Huang plant over 100 years ago. Scientists found ephedrine to be useful, and just as they had begun to synthesize opiates, they wanted to make a synthetic version of ephedrine. They managed to do so, and named that molecule amphetamine.

 

 

dunno about this. i hate and try to avoid norepineprine whatever possible. its like just the anxiety and fight or flight sense without the fucking euphoria straight dopamine brings. i like dopamine, norepinephrine is NOT DOPAMINE
 

 

thats what cannabis did to me too. first was super anxyolytic, now it causes panic attacks 15 years later. not sure what the fuck the mechanism is about but seems unfixable.

 

 

I believe that I´ve posted this somewhere on longecity:

one of the anxiogenic effects of THC, an overdrive of Glutamate in the Amygdala through desensitaion of CB1 receptors and therefore an extended signalling of glutamate.

 

Dont want to be rude but please search the references for Your self or just dont believe this.

I understand any scepticism but It takes sometimes too long to find the sources.

 

Edit: or due to the decrease of Gaba signalling by THC:

Finally, the researchers found that stimulating either of these brain cell pathways had opposing behavioral consequences. The glutamate neurons provoked an aversive, avoidance behavioral response and promoted anxiety-like behavior in the mice. In contrast, when Stuber’s team activated the GABAergic pathway projections from the BNST into the VTA, the animals showed reward-associated behaviors and less anxiety. They preferred that stimulation and would spend more time in the area of the cage where they had received it.

 

http://news.unchealt...2013/march/bnst

 

 

There aren't really that many strong herbs that can directly help with social anxiety, unfortunately. However, there are quite a few that can help with focus. This can be a foundation for your meditation, which itself can go a long way for your social anxiety.

 

Sigh.. Yes it looks also to me that this is true but its here and there reported that Cannabis makes one speechless like for some longterm smokers and/or guys who smoked in the adolescence.

at least for the latter ones (I´m one of them.....) I can only assume the reason behind:

 

Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity

http://www.pnas.org/.../E3149.full.pdf

 

This is not that related but the blunted dopamine firing could decrease the affect

Edited by Flex, 15 May 2015 - 05:01 PM.

[normalizing]

 

 

 

ephedrine is a dopamine releasing agent? you get your facts from where exactly? ephedrine is more like what i felt on high dose raspberry ketones, norepinephrine influx, felt shaky and sea sick.

 

FFS you don't got to be a dick a about it:

 

http://www.ncbi.nlm....pubmed/16386715

I told you, it's a minor effect, and it's only in the substantia nigra.

BTW, ephedrine was discovered in the Ma Huang plant over 100 years ago. Scientists found ephedrine to be useful, and just as they had begun to synthesize opiates, they wanted to make a synthetic version of ephedrine. They managed to do so, and named that molecule amphetamine.

 

 

dunno about this. i hate and try to avoid norepineprine whatever possible. its like just the anxiety and fight or flight sense without the fucking euphoria straight dopamine brings. i like dopamine, norepinephrine is NOT DOPAMINE
 

 

thats what cannabis did to me too. first was super anxyolytic, now it causes panic attacks 15 years later. not sure what the fuck the mechanism is about but seems unfixable.

 

 

I believe that I´ve posted this somewhere on longecity:

one of the anxiogenic effects of THC, an overdrive of Glutamate in the Amygdala through desensitaion of CB1 receptors and therefore an extended signalling of glutamate.

 

Dont want to be rude but please search the references for Your self or just dont believe this.

I understand any scepticism but It takes sometimes too long to find the sources.

 

 

 

an overdrive of glutamate! that must be it i believe. because, ive become so used to drinking alcohol with marijuana that marijuana by itself was causing me severe anxiety which explains it, regular alcohol consumption distrupts glutamate system and adding assault to injury by smoking marijuana alone is a sure problem. now my question is this, if marijuana does bring on glutamate influx, you believe it can be neurotoxic? especially when you have been drinking regularly and suddenly stopped too.
 

[Flex]

Sry cant say. I could imagine that when consuming both for a longer time and then cold turkey, You´ll elevate Glutamate even more.

Cannabis does inhibit gaba on it self, so the dimmishing effect to glutamate transmission is also weakened.

 

Better look for the source to check the claims,

Anyway here is it:

 

Cannabis Targets Receptors in the Amygdala Linked to Anxiety

https://www.psycholo...-linked-anxiety

 

 

Seems that one part of the amygdala (baso lateral) causes anxiolysis but the other anxiogenesis.

Lateral Paracapsular GABAergic Synapses in the Basolateral Amygdala Contribute to the Anxiolytic Effects of |[beta]|3 Adrenoceptor Activation

http://www.bionity.c...activation.html

 

Activation of 5-HT1A receptors in the rat basolateral amygdala induces both anxiolytic and antipanic-like effects.

http://www.ncbi.nlm....pubmed/23499701

 

BNST is connected with the amygdala and its also quiet implicated into anxiety.

If I´m not mistaken, it causes anxiety by deactivating the Amygdala.

 

The Bed Nucleus of the Stria Terminalis Mediates Inter-individual Variations in Anxiety and Fear

In fact, BNST-lesioned rats behaved like sham rats with high discriminative abilities in that they exhibited low contextual fear and a nonanxious phenotype in the EPM. Overall, this suggests that inter-individual variations in fear generalization and anxiety phenotype are determined by BNST influences on the amygdala and/or its targets.

http://www.jneurosci...9/33/10357.full

 

Mechanisms in the Bed Nucleus of the Stria Terminalis Involved in Control of Autonomic and Neuroendocrine Functions: A Review

The BNST receives dense serotoninergic innervation from caudal regions of the dorsal raphe nucleus [142, 143]. Moreover, BNST neurons express a variety of serotonin receptors, and 5-HT1A receptors is one the most prevalent receptor subtypes expressed [144]. In this way, serotonin elicits inhibitory responses, evoking membrane hyper-polarization, in the majority of BNST neurons by activation of postsynaptic 5-HT1A receptors [145, 146]. Interestingly, all effects following CBD microinjection into the BNST were inhibited after local pretreatment with a 5-HT1A antagonist [132, 133, 135]. Therefore, activation of local 5-HT1A seems to be a key mechanism involved in CBD action in the BNST.

http://www.ncbi.nlm....les/PMC3637669/

 

Btw: You could look into Zembrin which is a SSRI but doesnt cause perresisten sexual side effects

Acute Effects of Sceletium tortuosum (Zembrin), a Dual 5-HT Reuptake and PDE4 Inhibitor, in the Human Amygdala and its Connection to the Hypothalamus

http://www.nature.co...pp2013183a.html

 

Zembrin is a relative strong/weak inhibitor of CB1 receptors

http://www.longecity...na/#entry722001

 

CRF/CRH decreases endocanabinoids but I gues CRF elevation is not a good idea

 

Corticotropin-releasing hormone drives anandamide hydrolysis in the amygdala to promote anxiety.

http://www.ncbi.nlm....pubmed/25740517

Edited by Flex, 16 May 2015 - 01:38 PM.

[OneScrewLoose]

normalizing, are you willing to try pharmaceuticals in your approach as well, or does it all have to be supplements/OTC? Do you feel there is a difference between something like Piracetam, Rhodiola, and Celexa?

[normalizing]

onescrewloose im not one of those "natural" junkies who obsess with "organic" and crap. i can go for anything really. very open minded.

and to describe the three you mentioned, piracetam had very minor effect few times but then nothing. rhodiola made me feel fucking weird, i hated it, it was like dosing on yohimbine. and celexa, pure crap. typical SSRI where i feel too dull but not really in much of possitive.

[OneScrewLoose]

I would actually avoid the DAT inhibitors and Dopamine releasing agents, and go for a non-stimulant way of increasing dopamine (it fascinates me to know end how different methods of increasing dopamine change whether it's a stimulant properties).

2.5mg of selegiline might be a good start. It can easily be bought on alldaychemist.com. So you get a lot of the benefits of a DRI/DRA without the resulting stim and norepiephrine feeling.

The primary mechanism THC seems to work by, in addition to many others, such as what's been discussed, is that it reduces GABA output. This lowers sensory gating, and increase the amount off sensory input a person can receive past the thalamus. This is what accounts for the insightful/creative aspects of weed. But in a lot of people, this can be nerve-wracking. Search my threads for info I've posted on CBD. It's a legal,, non-psychoactive cannabinoid that is an inverse agonist at CB2. Since it does the opposite of an agonist, it can actually increase GABA output. I've seen the effects of this vary a lot with people's actual experiences. It goes from feeling nothing at all from it, to near instant relaxation. I've never seen it actually make someone feel worse though, like THC can.

 

How do you feel about the selegiline? Do a good amount of research before getting it though. Even though it doesn't inhibit MAO-A (@ 10mg and below at least), inhibiting MAO-B is still quite a potent thing. 2.5mg is rather low though, so I wouldn't worry too much there. I take it indefinitely at 1mg/day, as there's a good deal of research showing that MAO-BIs can greatly lower the risk of dopaminergic diseases like Parkinson's and Alzheimer's. If that changes, then I'll switch, but the evidence seems pretty solid. Even tobacco, despite all its harm, has shown to reduce the risk of Parkinson's:

http://www.ncbi.nlm....pubmed/24240736

This has been attributed to Tobacco's natural MAO-BI (which also greatly increases the addictive potential of nicotine, without which it's not nearly as addictive). I'd look into it.

[nowayout]

Like other psychedelics, THC can have opposite effects depending on the environment in which you take it, your expectations, and who, if anybody, you are with.

You can go into self reinforcing loops, so if you expect to be anxious, THC can magnify it. But it can also be very, very relaxing to have a cuddle, a massage, listen to music, or have sex on it in a safe space.

Also, while it may be hard to get to sleep when high, this relaxation can last for days afterward, so I don't buy the GABA depletion hypothesis, at least not for once weekly use.

Edited by nowayout, 19 May 2015 - 04:33 PM.

[OneScrewLoose]

Like other psychedelics, THC can have opposite effects depending on the environment in which you take it, your expectations, and who, if anybody, you are with.

You can go into self reinforcing loops, so if you expect to be anxious, THC can magnify it. But it can also be very, very relaxing to have a cuddle, a massage, listen to music, or have sex on it in a safe space.

Also, while it may be hard to get to sleep when high, this relaxation can last for days afterward, so I don't buy the GABA depletion hypothesis, at least not for once weekly use.

This isn't consider a hypothesis. This is considered a known and understood mechanism:

 

http://www.ncbi.nlm....les/PMC2882293/
http://www.ncbi.nlm....pubmed/22133429
http://jpet.aspetjou.../316/2/608.long

From the last study:

 

The present results unequivocally show that the principal effect of cannabinoids on GABAergic neurotransmission in the globus pallidus is inhibition of neurotransmission—GABA uptake was not significantly changed.

[normalizing]

onescewloose, whats your reason for suggesting use of selegiline so intesively? from my experience, moclobemide was more potent, but even then, those are just overated designer drugs.

[OneScrewLoose]

Because you seem to get positive effects with dopamine, but the negative aspects have to do with stimulation. This would avoid that. 2.5mg hardly qualifies as intensively. Moclobemide works on MAO-A, Selegiline on MAO-B. So the effects will be different.

[nowayout]

 

Like other psychedelics, THC can have opposite effects depending on the environment in which you take it, your expectations, and who, if anybody, you are with.

You can go into self reinforcing loops, so if you expect to be anxious, THC can magnify it. But it can also be very, very relaxing to have a cuddle, a massage, listen to music, or have sex on it in a safe space.

Also, while it may be hard to get to sleep when high, this relaxation can last for days afterward, so I don't buy the GABA depletion hypothesis, at least not for once weekly use.

This isn't consider a hypothesis. This is considered a known and understood mechanism:

 

http://www.ncbi.nlm....les/PMC2882293/
http://www.ncbi.nlm....pubmed/22133429
http://jpet.aspetjou.../316/2/608.long

From the last study:

 

 

 

The present results unequivocally show that the principal effect of cannabinoids on GABAergic neurotransmission in the globus pallidus is inhibition of neurotransmission—GABA uptake was not significantly changed.

 

 

The studies you quote are acute effects in mouse brain slices in vitro, which don't unequivocally show anything or establish any known or understood mechanism even in live mice, never mind humans (whose brains often work differently, even opposite, to those of mice).   

 

Also, the three cases of acute effects, aftereffects of acute use, and effects of chronic use are often (even most of the time) quite different (e.g., aftereffects or effects of chronic use can be opposite to acute effects, or see the various mutually inconsistent hypotheses for why SSRIs need chronic use for efficacy, which have been studied much longer and more deeply than THC and none of which have been confirmed even today).   Not to mention dose-response curves, which can also be quite complex, e.g., you can have opposite effects at different doses of the same medication.

Edited by nowayout, 20 May 2015 - 02:22 PM.

[Flex]

 

How do you feel about the selegiline? Do a good amount of research before getting it though. Even though it doesn't inhibit MAO-A (@ 10mg and below at least), inhibiting MAO-B is still quite a potent thing. 2.5mg is rather low though, so I wouldn't worry too much there. I take it indefinitely at 1mg/day, as there's a good deal of research showing that MAO-BIs can greatly lower the risk of dopaminergic diseases like Parkinson's and Alzheimer's. If that changes, then I'll switch, but the evidence seems pretty solid. Even tobacco, despite all its harm, has shown to reduce the risk of Parkinson's:

http://www.ncbi.nlm....pubmed/24240736

This has been attributed to Tobacco's natural MAO-BI (which also greatly increases the addictive potential of nicotine, without which it's not nearly as addictive). I'd look into it.

 

Found recently this:

Effect of repeated treatment with high doses of selegiline on behaviour, striatal dopaminergic transmission and tyrosine hydroxylase mRNA levels.

http://www.ncbi.nlm....ubmed/11862330/

 

..The dopamine metabolite DOPAC was reduced by more than 50% after acute administration of selegiline and even more so on day 8 by the same dose, after repeated administration. The basal concentrations of dopamine (before challenge with selegiline) were not altered by the repeated administration, whereas the basal concentrations of DOPAC were decreased by more than 80% by the repeated administration of selegiline, suggesting a decrease in dopamine turnover.

 

..Acute administration did not have any influence on TH mRNA levels, whereas chronic treatment significantly reduced TH mRNA levels in substantia nigra and ventral tegmental area. In conclusion, repeated administration of selegiline leads to behavioural sensitization independent of altered dopamine levels. In addition, it leads to a decrease, probably due to a down-regulation, of dopamine turnover and tyrosine hydroxylase.

 

Cant say anything whether is a longterm thing or not, just wanted to mention.

[OneScrewLoose]

 

 

How do you feel about the selegiline? Do a good amount of research before getting it though. Even though it doesn't inhibit MAO-A (@ 10mg and below at least), inhibiting MAO-B is still quite a potent thing. 2.5mg is rather low though, so I wouldn't worry too much there. I take it indefinitely at 1mg/day, as there's a good deal of research showing that MAO-BIs can greatly lower the risk of dopaminergic diseases like Parkinson's and Alzheimer's. If that changes, then I'll switch, but the evidence seems pretty solid. Even tobacco, despite all its harm, has shown to reduce the risk of Parkinson's:

http://www.ncbi.nlm....pubmed/24240736

This has been attributed to Tobacco's natural MAO-BI (which also greatly increases the addictive potential of nicotine, without which it's not nearly as addictive). I'd look into it.

 

Found recently this:

Effect of repeated treatment with high doses of selegiline on behaviour, striatal dopaminergic transmission and tyrosine hydroxylase mRNA levels.

http://www.ncbi.nlm....ubmed/11862330/

 

..The dopamine metabolite DOPAC was reduced by more than 50% after acute administration of selegiline and even more so on day 8 by the same dose, after repeated administration. The basal concentrations of dopamine (before challenge with selegiline) were not altered by the repeated administration, whereas the basal concentrations of DOPAC were decreased by more than 80% by the repeated administration of selegiline, suggesting a decrease in dopamine turnover.

 

..Acute administration did not have any influence on TH mRNA levels, whereas chronic treatment significantly reduced TH mRNA levels in substantia nigra and ventral tegmental area. In conclusion, repeated administration of selegiline leads to behavioural sensitization independent of altered dopamine levels. In addition, it leads to a decrease, probably due to a down-regulation, of dopamine turnover and tyrosine hydroxylase.

 

Cant say anything whether is a longterm thing or not, just wanted to mention.

 

 

It's obvious that other mechanisms of producing/maintaining dopamine are going to be reduced when taking something that increases it. This is the natural homeostatic response, and happens with virtually all medications. It only becomes an issue if that response goes below the initial levels of the neurotransmitter, in this case dopamine. Although TH may be reduced, Selegiline will increases overall dopamine. He could also take EGCG as a COMT inhibitor to maintain dopamine levels.

Also, the dose used in that study is insanely high. 10mg/kg daily, which comes to 1.6mg/kg daily for humans. If you are 70kg, that's a daily dose of 112mg. That should kill just about everyone taking that dose.

[OneScrewLoose]

 

 

Like other psychedelics, THC can have opposite effects depending on the environment in which you take it, your expectations, and who, if anybody, you are with.

You can go into self reinforcing loops, so if you expect to be anxious, THC can magnify it. But it can also be very, very relaxing to have a cuddle, a massage, listen to music, or have sex on it in a safe space.

Also, while it may be hard to get to sleep when high, this relaxation can last for days afterward, so I don't buy the GABA depletion hypothesis, at least not for once weekly use.

This isn't consider a hypothesis. This is considered a known and understood mechanism:

 

http://www.ncbi.nlm....les/PMC2882293/
http://www.ncbi.nlm....pubmed/22133429
http://jpet.aspetjou.../316/2/608.long

From the last study:

 

 

 

The present results unequivocally show that the principal effect of cannabinoids on GABAergic neurotransmission in the globus pallidus is inhibition of neurotransmission—GABA uptake was not significantly changed.

 

 

The studies you quote are acute effects in mouse brain slices in vitro, which don't unequivocally show anything or establish any known or understood mechanism even in live mice, never mind humans (whose brains often work differently, even opposite, to those of mice).   

 

Also, the three cases of acute effects, aftereffects of acute use, and effects of chronic use are often (even most of the time) quite different (e.g., aftereffects or effects of chronic use can be opposite to acute effects, or see the various mutually inconsistent hypotheses for why SSRIs need chronic use for efficacy, which have been studied much longer and more deeply than THC and none of which have been confirmed even today).   Not to mention dose-response curves, which can also be quite complex, e.g., you can have opposite effects at different doses of the same medication.

 

This is the last response I'm having in this argument. GABA disruption is a known and accepted mechanism in humans:

http://www.ncbi.nlm....les/PMC2864503/

 

This study specifically talks about effects in humans. Scroll down to the section that focuses on GABA. There are plenty of links to other studies there.

You can believe what you want, for whatever reasons you have. But this is accepted. It's how weed increases sensory richness that many experience when they smoke it. And like I said, this lowered GABA can cause anxiety for a lot of people, which is why I don't use it.

[normalizing]

Because you seem to get positive effects with dopamine, but the negative aspects have to do with stimulation. This would avoid that. 2.5mg hardly qualifies as intensively. Moclobemide works on MAO-A, Selegiline on MAO-B. So the effects will be different.

 

i have used both back to back, selegiline is much a MAO B as MAO A depending on dosage. Moclobemide is actually MAO B and it felt similar to selegiline for me, except, greater potency. highly underrated.
 

[OneScrewLoose]

 

Because you seem to get positive effects with dopamine, but the negative aspects have to do with stimulation. This would avoid that. 2.5mg hardly qualifies as intensively. Moclobemide works on MAO-A, Selegiline on MAO-B. So the effects will be different.

 

i have used both back to back, selegiline is much a MAO B as MAO A depending on dosage. Moclobemide is actually MAO B and it felt similar to selegiline for me, except, greater potency. highly underrated.
 

 

 

Not quite. First of all, Selegiline only begins to inhibit MAO-A above 10mgs. I've never seen a dose that high used consistently, either anecdotally or in a paper, due to the side effects of simply increasing MAO-B that much.

 

Moclobemide is part of a class of drugs that are called RIMAs, or Reversible Inhibitors of Monoamine Oxidase A. It doesn't effect B:

http://www.ncbi.nlm..../pubmed/8259692

 

How much of each were you on when you were taking both, and how often did you take them?

[nowayout]

 

 

 

Like other psychedelics, THC can have opposite effects depending on the environment in which you take it, your expectations, and who, if anybody, you are with.

You can go into self reinforcing loops, so if you expect to be anxious, THC can magnify it. But it can also be very, very relaxing to have a cuddle, a massage, listen to music, or have sex on it in a safe space.

Also, while it may be hard to get to sleep when high, this relaxation can last for days afterward, so I don't buy the GABA depletion hypothesis, at least not for once weekly use.

This isn't consider a hypothesis. This is considered a known and understood mechanism:

 

http://www.ncbi.nlm....les/PMC2882293/
http://www.ncbi.nlm....pubmed/22133429
http://jpet.aspetjou.../316/2/608.long

From the last study:

 

 

 

The present results unequivocally show that the principal effect of cannabinoids on GABAergic neurotransmission in the globus pallidus is inhibition of neurotransmission—GABA uptake was not significantly changed.

 

 

The studies you quote are acute effects in mouse brain slices in vitro, which don't unequivocally show anything or establish any known or understood mechanism even in live mice, never mind humans (whose brains often work differently, even opposite, to those of mice).   

 

Also, the three cases of acute effects, aftereffects of acute use, and effects of chronic use are often (even most of the time) quite different (e.g., aftereffects or effects of chronic use can be opposite to acute effects, or see the various mutually inconsistent hypotheses for why SSRIs need chronic use for efficacy, which have been studied much longer and more deeply than THC and none of which have been confirmed even today).   Not to mention dose-response curves, which can also be quite complex, e.g., you can have opposite effects at different doses of the same medication.

 

This is the last response I'm having in this argument. GABA disruption is a known and accepted mechanism in humans:

http://www.ncbi.nlm....les/PMC2864503/

 

This study specifically talks about effects in humans. Scroll down to the section that focuses on GABA. There are plenty of links to other studies there.

You can believe what you want, for whatever reasons you have. But this is accepted. It's how weed increases sensory richness that many experience when they smoke it. And like I said, this lowered GABA can cause anxiety for a lot of people, which is why I don't use it.

 

 

Sorry, but It is not "accepted." Far from it.  From the study you quoted above:

 

 

The mechanisms by which cannabinoids produce transient psychotic symptoms, while unclear may involve dopamine, GABA, and glutamate neurotransmission.  The mechanisms by which exposure to cannabinoids increase the risk for developing a psychotic disorder are unknown.

 

 

However, recent studies suggest that the loss of CB₁R from GABAergic neurons does not have any significant effect on any of the major effects of cannabinoids [158].

 

 

The effects of cannabinoids on increasing DA, reducing GABA, and reducing glutamatergic neurotransmission may contribute to their capacity to induce transient positive, negative, and cognitive symptoms, but the precise mechanism remains unclear.

 

So at most there may be some GABA-related effect (amongst a plethora of other confounding effects on a host of other neurotransmitters also mentioned in the article), but it is far from settled science.  Let's not pretend that it is. 

Edited by nowayout, 21 May 2015 - 02:45 PM.

[triffid113]

Holy Basil ( tulsi ) raises dopamine, seratonin, and lowers cortisol in 72 hours ( faster than Zoloft). Works quite well, even as a tea.

[OneScrewLoose]

 

 

 

 

Like other psychedelics, THC can have opposite effects depending on the environment in which you take it, your expectations, and who, if anybody, you are with.

You can go into self reinforcing loops, so if you expect to be anxious, THC can magnify it. But it can also be very, very relaxing to have a cuddle, a massage, listen to music, or have sex on it in a safe space.

Also, while it may be hard to get to sleep when high, this relaxation can last for days afterward, so I don't buy the GABA depletion hypothesis, at least not for once weekly use.

This isn't consider a hypothesis. This is considered a known and understood mechanism:

 

http://www.ncbi.nlm....les/PMC2882293/
http://www.ncbi.nlm....pubmed/22133429
http://jpet.aspetjou.../316/2/608.long

From the last study:

 

 

 

The present results unequivocally show that the principal effect of cannabinoids on GABAergic neurotransmission in the globus pallidus is inhibition of neurotransmission—GABA uptake was not significantly changed.

 

 

The studies you quote are acute effects in mouse brain slices in vitro, which don't unequivocally show anything or establish any known or understood mechanism even in live mice, never mind humans (whose brains often work differently, even opposite, to those of mice).   

 

Also, the three cases of acute effects, aftereffects of acute use, and effects of chronic use are often (even most of the time) quite different (e.g., aftereffects or effects of chronic use can be opposite to acute effects, or see the various mutually inconsistent hypotheses for why SSRIs need chronic use for efficacy, which have been studied much longer and more deeply than THC and none of which have been confirmed even today).   Not to mention dose-response curves, which can also be quite complex, e.g., you can have opposite effects at different doses of the same medication.

 

This is the last response I'm having in this argument. GABA disruption is a known and accepted mechanism in humans:

http://www.ncbi.nlm....les/PMC2864503/

 

This study specifically talks about effects in humans. Scroll down to the section that focuses on GABA. There are plenty of links to other studies there.

You can believe what you want, for whatever reasons you have. But this is accepted. It's how weed increases sensory richness that many experience when they smoke it. And like I said, this lowered GABA can cause anxiety for a lot of people, which is why I don't use it.

 

 

Sorry, but It is not "accepted." Far from it.  From the study you quoted above:

 

 

The mechanisms by which cannabinoids produce transient psychotic symptoms, while unclear may involve dopamine, GABA, and glutamate neurotransmission.  The mechanisms by which exposure to cannabinoids increase the risk for developing a psychotic disorder are unknown.

 

 

However, recent studies suggest that the loss of CB₁R from GABAergic neurons does not have any significant effect on any of the major effects of cannabinoids [158].

 

 

The effects of cannabinoids on increasing DA, reducing GABA, and reducing glutamatergic neurotransmission may contribute to their capacity to induce transient positive, negative, and cognitive symptoms, but the precise mechanism remains unclear.

 

So at most there may be some GABA-related effect (amongst a plethora of other confounding effects on a host of other neurotransmitters also mentioned in the article), but it is far from settled science.  Let's not pretend that it is. 

 

Dude...*sigh*. It says that which mechanism is the primary cause for developing a psychotic disorder are unknown. It does not say these mechanisms don't happen.

 

 

 

However, recent studies suggest that the loss of CB₁R from GABAergic neurons does not have any significant effect on any of the major effects of cannabinoids [158].

If I ask an honest question, can you give an honest answer? Did you actually read on of the study linked through '158'? Here's some of it:

 

 

 

Deletion of CB1 receptors in GABAergic neurons in GABA-CB1−/− mice, where endocannabinoid-mediated DSI in the hippocampus is abolished, does not alter the behavioral seizure response to KA. Considering that the endocannabinoid system controls a portion of GABA-ergic transmission in the hippocampus (Chevaleyre et al., 2006; Alger, 2002; Freund et al., 2003; Marsicano and Lutz, 2006; present results) and that GABAergic interneurons are intensely activated during KA-induced seizures (Ben-Ari and Cossart, 2000), this is a surprising result. The reasons of this lack of involvement of GABAergic interneurons in the CB1 receptor-dependent control of behavioral KA-induced seizures by the endocannabinoid system are not clear at the moment. However, a recent publication by Földy et al. (2006) showed that the CB1 receptor-dependent control of GABAergic transmission in the hippocampus is strictly regulated by the firing rate of the presynaptic GABAergic interneuron. CB1 agonist- and endocannabinoid-dependent reduction of GABAergic transmission is strongly reduced (Therefore it exists) when the firing rate of the presynaptic interneuron is above a certain threshold. Kainic acid, mainly through the activation of GluR5-containing KA receptors, directly and strongly increases the firing rate of GABAergic inter-neurons (Ben-Ari and Cossart, 2000). Therefore, it is possible that, in the presence of seizure-inducing doses of KA, GABAergic interneurons fire at frequencies that are sufficient to free them from the control of the endocannabinoid system (Földy et al., 2006).

So it clearly states that CB1 agonists cause a reduction of GABA-ergic transmission, but that the this might not be so strong when having a seizure induced by a very specific drug. On top of that, this doesn't even go into CB2 receptors.

Dude, this info is crystal clear. Can you at least tell me why you have such a personal investment in the notion that weed does not impede/reduce GABA-ergic transmission? If you want to increase GABA, get some CBD eJuice. it's an inverse agonist at CB2, thus having the opposite effect, and enhances GABA-ergic neurotransmission. I use it for my neuropathic symptoms.

Edited by OneScrewLoose, 22 May 2015 - 09:55 PM.

[John250]

Any updates on the two herbs mentioned in this thread?

Salvia Miltiorrhiza:
Thunbergia Laurifolia:

[Rocket]

I don't think dopaminergics are in general anxiolytic. Au contraire...

How about a drink, sipped slowly? It's what pretty much everyone else uses as a social lubricant.

Phenibut works just as well and you can't fail a police breath test and lose your drivers license.

[John250]

Correct me if I’m wrong but the best natural dopamine stack for restoration without the chance of depletion after cessation of use seems to be:
NALT
ALCAR
R-ALA(NA)
Taurine
Choline
Nicotine
Selenium
Vinpocetine
Ginkgo
Magnesium
Vitamin D
BenaGene
Gastrodin
Benfotiamine
NAC
Niagen
Glycine
Cordyceps
Lions Mane
Forskolin
DanShen
UMP
Holy Basil
Rhodiola Rosea
Eleuthero
Panax
Schizandra
Jiaogulan
Ashitaba
Neuravera(green oat)
Mucuna Pruriens
skullcap baicalensis
Palmitoylethanolamide
Theanine
Tributyrin
Rehmannia Glutinosa
Thunbergia Laurifolia

Edited by John250, 12 July 2018 - 05:00 AM.