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Potentiating benzodiazepines in anxiety treatment

benzodiazepines benzos potentiation anxiety

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#1 Galaxyshock

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Posted 25 May 2023 - 10:26 AM


I take 0,5 - 1 mg of Lorazepam (a benzodiazepine) for anxiety most days. Been on this dosing for a few years and I still find Lorazepam helps with general anxiety though the effect at this point is quite subtle. I can take days off without clear withdrawal effects but I often feel a bit uncomfortable.

 

I wonder if there's something that would synergize or poteantiate the anxiolytic effects of Lorazepam. Maybe even so that I could cut it down to 1/4 mg and/or take more off-days. I've been taking GABAergic herbs like Gotu Kola and Ashwagandha but the effects are very subtle, still somewhat helpful though. I'm thinking perhaps a GABA re-uptake inhibitor like Tiagabine could work well by increasing GABA levels?

 

What about NMDA-antagonists, they supposably help prevent tolerance but could they even reverse benzo tolerance? I'm not sure what NMDA-antagonists are available, maybe Agmatine or DXM?

 

Feel free to share your ideas or experiences with benzodiazepines as sustainable anxiety treatment - is there such a thing or should I look for something else to manage anxiety?

 



#2 gamesguru

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Posted 30 May 2023 - 06:58 PM

No personal experience with benzos, speaking purely from a theoretical and
observational perspective.

I've not seen someone take them for over a decade with good results.

Even if you can get down to 0.25 mg and stay there for a few years, that is a
huge step in the right direction.
Benzos can have severe deleterious effects on the mind and were never intended
as long-term treatments.

Magnesium would probably be a good choice. I just obtained a bulk shipment of
Mg L-threonate. I'm not taking it every day, but my stress is not very severe.
PM me, I can send a pack.

Benzodiazepine/GABA(A) receptors are involved in magnesium-induced
anxiolytic-like behavior in mice
https://pubmed.ncbi....h.gov/18799816/
 

  while combined treatment with the non-effective doses of magnesium (10 mg/kg) and benzodiazepines (diazepam (0.5 mg/kg) or chlordiazepoxide (2 mg/kg)) produced synergistic interaction (increased time in open arms and number of open arm entries) in this test. The obtained data indicate that benzodiazepine receptors are involved in the anxiolytic-like effects of magnesium.


Kava could be used occasionally to round out difficult days, but should not be
combined (or used) on a continued basis.

From #5 on this list,
https://supplements....-increase-gaba/
 

5) Lemon Balm (Melissa officinalis)

  Lemon balm is traditionally consumed as a tea and is known for its calming properties. It has a complex pharmacological profile with many psychoactive organic chemicals, ranging from polyphenols to terpenes [96].

  Lemon balm has antioxidant properties, with rosmarinic acid as its most potent psychoactive compound [97].

  Rosmarinic acid increases GABA levels by indirectly inhibiting the enzyme (4-aminobutyrate transaminase) that converts GABA to L-glutamate [98].

  This enzyme is a popular target for treating anxiety and epilepsy-related neurological disorders [99].

  Lemon balm can be taken in its extract form. In 3 studies (18, 20, and 20 participants), between 300 – 1,000 mg of lemon balm extract reduced anxiety, insomnia, stress, and alertness, meanwhile improving memory, mood, and mental processing [100, 101, 102].

  Its calming properties also improved sleep quality in 20 volunteers who suffered from sleep disturbances and anxiety disorders [103].

  Lemon balm also relieved heart palpitations in a 55-participants of a human study (DB-RCT) [104].

  Lemon balm is well tolerated. No studies have yet reported serious side effects, tolerance, or dependence associated with lemon balm supplementation. In rats, chronic intake of lemon balm showed consistent calming properties without reported tolerance or side effects [105].


Ashwagandha I didn't find particularly useful. Gives me estrogen vibes, tho not
as strongly as red ginseng.
Gotu kola, will have to revisit. But it didn't feel like the tonic for me.

Memantine may be a superior NMDA antagonist, but glutamate plays a lesser role
here, and memantine is actually more useful for adderall tolerance in ADHD.


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#3 Daniel Cooper

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Posted 30 May 2023 - 07:45 PM

I agree with gamesguru, long term use of benzodiazepines even in moderate doses rarely turns out well. Except for a few specific seizure disorders, I don't think benzos should be prescribed long term at all.

 

On the other hand, the natural alternatives seem like very "weak sauce" in addressing any significant anxiety issues.

 

The bare truth as I see it is there aren't really any good pharmaceutical alternatives to address most significant anxiety disorders.  SSRIs work minimally if at all for depression and off label for anxiety they are even less effective. Antipsychotics in my opinion are too risky and come with too many side effects, and they mostly don't work for anxiety either. 

 

Maybe something like vagal nerve stimulation or stellate ganglion blocks have something to offer - I really can't say as I don't know that much about them.

 

Given the dearth of effective pharmaceutical options you're left with CBT, medication, and physical exercise. They help some but not all. 

 

Humans are just not evolved to live in the modern world we find ourselves in unfortunately. 


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#4 Galaxyshock

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Posted 31 May 2023 - 07:51 AM

I guess I'm lucky that I've never gotten in trouble with benzodiazepines despite taking them daily for longer time periods. I was on Diazepam for a couple of years and quit cold turkey without issues. Though Diazepam lost its anxiolytic effect whereas Lorazepam I still find somewhat effective. But yeah I've heard benzos can cause issues like memory problems so maybe it's time to try something else.

 

I'll get some Magnesium and Lemon Balm, thanks for the tip. I took Lemon Balm few years ago and it was actually quite pleasant anxiolytic herb.

 

I've been lazy when it comes to exercise. I take daily walks but maybe I should get back into resistance training. I've usually felt more satisfied and content with life when doing regular strength training.



#5 gamesguru

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Posted 31 May 2023 - 03:03 PM

Maybe you will be able to quit pretty easily then, who knows.

Lemon balm and magnolia I've not gotten around to trying (apart from the rosmarinic acid extract by LEF, which I found more stimulating than calming). But magnolia was one of the ones Science Guy identified way back as not causing rapid tolerance (i.e. receptor down-regulation). Magnesium was the other. I've not gotten into a phase where I take magnesium consistently twice a day, but I do take medium doses 5-6 times a week to round out periods of stress and before important interviews or social activities to promote a sense of calm and presence. And it has served me well there, and I've never had an issue with tolerance. Sometimes I find it a bit too sedating, and I like to face life head on, which is maybe why I don't take it multiple times a day. Bacopa has also been good. But I'm taking only 80-100 mg of synapsa a few nights a week (I did a loading phase years ago).

I've been lazy with work outs too. As I've slipped into adult life, it's increasingly become a chore. I've however upgraded my bicycle twice and purchased packs and a trailer for it, with the effect that today I often peddle it to the super market and am carbon neutral 4 or 5 days out of the week. I've made a couple friends who work out, have been going with my dad, and even if we are doing different workouts, just walking in together or agreeing to meet to do one exercise together can be enough to motivate me to the gym. I have a yoga mat and meditation pillows at home, which remain underutilized but are great on the few occasions I do use them. Cooking from scratch is another area I'm looking to improve and do more of, as I struggle with the unpalatability of restaurant food and the lack of nourishment.

SSRIs were also mentioned. There's definitely a connection between depression & anxiety. One relatively well tested and well-praised compound used off-label for depression is selegiline. Interestingly, recent evidence suggests MAO-B is more closely linked with GABA than dopamine. So normalizing GABA levels may be a long-term benefit of selegiline treatment.
 

Blocking GABA synthesis also restores the impaired synaptic plasticity in the FSL prefrontal cortex, providing a new antidepressant mechanism of Selegiline.


And from another study,
 

... MAO-B, but not MAO-A, was responsible for astrocytic GABA-mediated tonic inhibitory currents in the rat striatum. We conclude that, in contrast to the traditional belief, MAO-A and MAO-B have profoundly different roles: MAO-A regulates dopamine levels, whereas MAO-B controls tonic GABA levels.


There are other non-benzodiazapine pharmaceuticals: busperione (5-HT1A agonist), propranolol (beta blocker). But these are probably no more effective in the long-term than benzos, and may even be less safe physically on the organs.

 

The GABA receptors are complicated themselves. The benzodiazapine site is NOT the only allosteric modulation site.
 

These allosteric sites are the targets of various other drugs, including the benzodiazepines, nonbenzodiazepines, neuroactive steroids, barbiturates, alcohol (ethanol),[5] inhaled anaesthetics, kavalactones, cicutoxin, and picrotoxin, among others.[6]

 


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#6 Galaxyshock

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Posted 31 May 2023 - 04:17 PM

I used to find Bacopa beneficial but the last time I tried it, it made me sleep over 12 hours a night. I can't remember the dose I took, maybe it was too much.

 

I forgot to mention that I'm on Duloxetine 120 mg (SNRI) which was prescribed to relieve anxiety and dark moods during wintertime. Well it did seem to decrease the depressive feelings but did nothing for anxiety. I haven't experienced any side effects from it. It may be a bit wierd how these medications don't affect me much. I've heard people getting months or even years of withdrawal symptoms from benzos and persistent side effects from SSRIs / SNRIs. I would like to try Selegiline but I believe it's only approved for Parkinson's treatment in Finland.

 

I did consider Buspirone at some point but I heard it's not that effective in practice and you have to take it three times a day. I looked a bit into Tiagabine (GABA re-uptake inhibitor) and it seems to have similar side effects as benzos like memory impairment and somnolence so perhaps it's not any better anxiety med.

 

Pregabalin is sometimes prescribed for anxiety but I guess it has similar dependency issue as benzos? But perhaps I could only take it only for couple of weeks to help withdraw from Lorazepam and then come off?

 

 



#7 Mind

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Posted 31 May 2023 - 05:41 PM

I have heard nothing but awful experiences regarding benzos. This forum is littered with cautionary tales about benzos. I have several acquaintances who are still suffering after quitting them. And the kicker is, there really isn't much rigorous evidence that they help with any mental disorders.


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#8 Galaxyshock

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Posted 31 May 2023 - 06:02 PM

I have heard nothing but awful experiences regarding benzos. This forum is littered with cautionary tales about benzos. I have several acquaintances who are still suffering after quitting them. And the kicker is, there really isn't much rigorous evidence that they help with any mental disorders.

 

Yeah I guess my view on benzos is somewhat naive, simply because I've personally not had bad experiences with them. And I have to say that I've tried a ton things for anxiety during the past 10+ years and Lorazepam is one of the most effective on that list. But it is possible that if I keep taking it at some point I reach a threshold and can no longer withdraw painlessly. So I'm starting to dislike the idea of taking it anymore. Thanks for the warnings fellas.



#9 YoungSchizo

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Posted 31 May 2023 - 06:23 PM

I've seen the Xanax serie on Netflix a few months ago, some, like me love benzo's and they're lifesavers therefore I will never quit. I'm on Clonazepam 13 years and it still works like a charm and since I'm not planning to quit I will take them for the rest of my life.

 

Not that I'm planning to quit but I'm interested in Brexanolone aka Allopregnenolone, it also works on GABA, gotta love Gabaergics or hate them.

 

Btw Pregabalin is non comparable with benzo's it has a some sort of same effect like a benzo but it's not the same as a benzo.


Edited by YoungSchizo, 31 May 2023 - 06:39 PM.

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#10 Galaxyshock

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Posted 31 May 2023 - 07:01 PM

I've seen the Xanax serie on Netflix a few months ago, some, like me love benzo's and they're lifesavers therefore I will never quit. I'm on Clonazepam 13 years and it still works like a charm and since I'm not planning to quit I will take them for the rest of my life.

 

Not that I'm planning to quit but I'm interested in Brexanolone aka Allopregnenolone, it also works on GABA, gotta love Gabaergics or hate them.

 

Btw Pregabalin is non comparable with benzo's it has a some sort of same effect like a benzo but it's not the same as a benzo.

 

Have you at any point had to increase the dose of Clonazepam? Rest of you life huh, that might be a long time, remember we're on a forum where people are aiming to live forever  ;)

 

It seems to me that for most people benzos are only good for short term when necessary, but some of us can take them longer, even several years without major issues. But of course one can't possibly know what exactly they are doing to your brain when it comes to memory etc. so the risks are still there. I haven't looked much into neurosteroids but there's indeed potential.

 

Yeah I know Pregabalin has different mechanism of action, but it might be effective for anxiety management in a sort of transition period where I come off using Lorazepam regularly.



#11 Galaxyshock

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Posted 31 May 2023 - 07:30 PM

Of course if I simply return to being anxious most of the time when off Lorazepam, well maybe it's worth the risk taking it long-term. I feel like I've exhausted a lot of options when it comes to anxiety treatment, and if there's a med that works I kinda feel like sticking to it at this point.

 

Humans are just not evolved to live in the modern world we find ourselves in unfortunately. 

 

Indeed, all we can do is try to adapt. But it's hard with the war in Europe and all.



#12 YoungSchizo

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Posted 31 May 2023 - 07:50 PM

Have you at any point had to increase the dose of Clonazepam? Rest of you life huh, that might be a long time, remember we're on a forum where people are aiming to live forever  ;)

 

 

 

No not really, I'm balancing the dose, usually I have enough with 1mg a day but when I'm having symptoms I increase to 2mg but usually only 1mg does the trick, 2mg as needed.

 

I rather stay on Clonazepam the rest of my life even if it shortens my lifespan than have such debilitating symptoms wanting to die. 

 

Pregabalin has indeed strong anti anxiety effects which effects are similar to benzo's, you can try that and see if it helps


Edited by YoungSchizo, 31 May 2023 - 08:00 PM.


#13 Daniel Cooper

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Posted 31 May 2023 - 08:04 PM

Some people seem to be able to go long periods of time and get decent anxiety mitigation on a stable dose of benzos. Weirdly, some will go a long time (maybe even a decade) and find that they suddenly have to start escalating the dose to maintain the effect.

 

As far as other reasons people take benzos - insomnia for instance - those effects seem to wane pretty quickly and if you want to maintain the effect you're on the dose escalation treadmill. 

 

The bigger problem is that there are at least a couple of studies that say long term use of benzodiazepines seem to predispose people to develop dementia later in life.

 

Unfortunately, I know a lot more about benzos than I wish I did. I was prescribed benzos and later z-drugs for chronic insomnia for a number of years. I've been off them for 6 years now and still have lingering issues that seem to be the result of my use and discontinuation of these drugs.  I personally know a number of people who have had long term devastating effects from these things. If I had a time machine I'd go back and never have taken them.

 

If you can find some other way to address your anxiety issues other than benzos I think you'd be wise to do so.

 

 

 

 



#14 Galaxyshock

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Posted 31 May 2023 - 08:23 PM

 

 

 rather stay on Clonazepam the rest of my life even if it shortens my lifespan than have such debilitating symptoms wanting to die. 

 

Indeed sometimes we have to resort to treatments that might be harmful but improve life quality so the benefits outweight the negatives. Living to 120 as anxious mess doesn't sound very appealing. I originally started this topic for ideas to potentiate benzos, I'm still wondering if for example perhaps a combination of Tiagabine and a low-dose benzodiazepine would be more effective and safe than only taking the benzo at higher dose.

 

Maybe some day they come up with a neurosteroid or some kind of modulator that hits the GABA system just the right way without the downside of benzos, but for now we'll just have to go with what we have?

 

 

Some people seem to be able to go long periods of time and get decent anxiety mitigation on a stable dose of benzos. Weirdly, some will go a long time (maybe even a decade) and find that they suddenly have to start escalating the dose to maintain the effect.

 

As far as other reasons people take benzos - insomnia for instance - those effects seem to wane pretty quickly and if you want to maintain the effect you're on the dose escalation treadmill. 

 

The bigger problem is that there are at least a couple of studies that say long term use of benzodiazepines seem to predispose people to develop dementia later in life.

 

Unfortunately, I know a lot more about benzos than I wish I did. I was prescribed benzos and later z-drugs for chronic insomnia for a number of years. I've been off them for 6 years now and still have lingering issues that seem to be the result of my use and discontinuation of these drugs.  I personally know a number of people who have had long term devastating effects from these things. If I had a time machine I'd go back and never have taken them.

 

If you can find some other way to address your anxiety issues other than benzos I think you'd be wise to do so.

 

Sorry to hear these drugs have caused lasting issues. There are sites like benzobuddies that are full of stories where people experience bad withdrawals. I have decided to try manage my anxiety without Lorazepam. I can always go back to it if other methods fail I guess.



#15 Daniel Cooper

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Posted 31 May 2023 - 08:29 PM

 

Sorry to hear these drugs have caused lasting issues. There are sites like benzobuddies that are full of stories where people experience bad withdrawals. I have decided to try manage my anxiety without Lorazepam. I can always go back to it if other methods fail I guess.

 

If I were going to stay on benzos long term, I'd start looking at research for strategies to mitigate the tolerance effects.

 

This is going from memory, but I think there's a paper out there that says that taking BPC-157 concurrently with benzodiazepines can reduce or eliminate tolerance. Of course, now you're taking a peptide forever so you have consider that.

 

I think there is a similar paper on taking agmantine with benzos having a similar tolerance reducing effect.  You might want to look that one up.


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#16 gamesguru

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Posted 31 May 2023 - 08:30 PM

Yes, lower dose. Bacopa at larger doses has a strong hypnagogic effect and can cause drowsiness and thyroid interactions. Lately, redditors have suggested lower doses (50-100 mg instead of 200-300 mg for 55% synapsa). I've found synapsa (full-spectrum) in particular has less of the sedating effects, especially at low doses, but i still think nighttime is best for bacopa. After the loading phase long ago, I've used it only a few times a week or month, but have still had benefits and consider it indispensable. I think a lot of people get turned away by the soporific qualities.

 

Synapsa is a 25:1 extract meaning that 25 kg of Bacopa monnieri is used to produce 1 kg of Synapsa and it is standardized to 55% +/- 5% Bacosides. It also looks like the extract was designed to preserve all of its natural components, while achieving the highest concentration of Bacosides possible.

 

I would avoid pregabalin or phenibut or anything that's not a clear improvement. Otherwise you could end trading one drug for another.

 

Being on an SNRI is complicates treatment, and makes me leery of trying anything stronger than magnesium tbh.

 

I would try to find magnesium. Either threonate or glycinate ideally, but any is better than none.

 

Adaptogens have never worked for me, but maybe add one of your choosing. Astragalus extract every couple days has been nice, it's one of the few that for me hasn't caused any obvious anxiety (ginseng/ginkgo) or lethargy (ashwagandha).

 

If you have access to affordable talk therapy, you can bring up these challenges in that setting and have them challenge & hold you accountable to a schedule and specific process for making the change.

 

You can try to gradually taper off and quit and if you do find it difficult, to re-initiate at a lower dose (0.25 mg daily, in the afternoon/evening).

 

Try to find doctors which align to your thinking and aren't just trying to push some product.


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#17 Galaxyshock

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Posted 01 June 2023 - 08:00 AM

Daniel Cooper, on 31 May 2023 - 11:29 PM, said:snapback.png

I think there is a similar paper on taking agmantine with benzos having a similar tolerance reducing effect.  You might want to look that one up.

 

I'll look into Agmatine, I think it's anxiolytic and antidepressive itself and mostly harmless supplement.

 

 

gamesguru, on 31 May 2023 - 11:30 PM, said:snapback.png

I would avoid pregabalin or phenibut or anything that's not a clear improvement. Otherwise you could end trading one drug for another.

 

Definitely not touching Phenibut ever again. I simply can't use it properly. Pregabalin should be less problematic, especially if I can get it prescribed for only maximum of one month or so. You're right I don't want to end dependent on another drug - the feeling of being dependent on something can worsen anxiety itself.

 

 

gamesguru, on 31 May 2023 - 11:30 PM, said:snapback.png

Adaptogens have never worked for me, but maybe add one of your choosing. Astragalus extract every couple days has been nice, it's one of the few that for me hasn't caused any obvious anxiety (ginseng/ginkgo) or lethargy (ashwagandha).

 

I've had good experiences with adaptogens. Reishi is the most calming one, I think I'll buy some dual-extract.

 

 

I didn't take any Lorazepam yesterday and felt quite fine except had some anxiety before going to bed. But I wonder if the possible withdrawals come with a delay.

 

Hmm I'm having trouble with quoting posts lol, hopefully this reply doesn't look like a mess.



#18 gamesguru

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Posted 01 June 2023 - 09:51 PM

I didn't take any Lorazepam yesterday and felt quite fine except had some anxiety before going to bed. But I wonder if the possible withdrawals come with a delay.

 

Yeah, may take a few days. I'm not sure. With cannabis the withdrawal i know sets in quickly (2-18 hours).

 

You might get lucky. If it does start to creep up on you, it's a shame Kava isn't allowed in Finland.. because you could slide right into that.

 

If you look at the original study i posted on magnesium, by co-administering it they achieve the same effects with a lesser dose of benzo. Which is precisely the potentiation mechanism you're looking for (in a safe and widely available form). You could lower your benzo dose to the lower end of the therapeutic window, and it would probably make it easier to quit altogether if you wanted to.


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#19 Galaxyshock

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Posted 02 June 2023 - 08:23 AM

Yeah, may take a few days. I'm not sure. With cannabis the withdrawal i know sets in quickly (2-18 hours).

 

You might get lucky. If it does start to creep up on you, it's a shame Kava isn't allowed in Finland.. because you could slide right into that.

 

If you look at the original study i posted on magnesium, by co-administering it they achieve the same effects with a lesser dose of benzo. Which is precisely the potentiation mechanism you're looking for (in a safe and widely available form). You could lower your benzo dose to the lower end of the therapeutic window, and it would probably make it easier to quit altogether if you wanted to.

 

According to wikipedia the elimination half-life of Lorazepam is 10–20 hours. It's day 3 now so it should be out of my system? So far I haven't felt anything major but if I start to feel too uncomfortable I'll try the 0,25mg dose.

 

Yeah I wish Kava was allowed here. I did manage to order it before from iHerb and BulkSupplements but the last time I ordered it couple years ago it did not get through the customs. Luckily I did not get any fees, I simply did not declare it so they sent the package back. I know one vendor within EU which seems to sell good quality Kava extract but I've yet to try ordering some.

 

Indeed Magnesium is something I do want to supplement. Magnesium Citrate is the only cheap form sold here which I believe has somewhat good bioavailability?

 

I have some bulk Theanine too which should be completely safe to supplement.

 

I am pretty sure I'll be able to withdraw from Lorazepam quite painlessly. But the challenge is to manage anxiety without resorting to these problematic tranquilizers in the future.



#20 gamesguru

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Posted 02 June 2023 - 01:15 PM

According to wikipedia the elimination half-life of Lorazepam is 10–20 hours. It's day 3 now so it should be out of my system? So far I haven't felt anything major but if I start to feel too uncomfortable I'll try the 0,25mg dose.

 

Indeed Magnesium is something I do want to supplement. Magnesium Citrate is the only cheap form sold here which I believe has somewhat good bioavailability?

 

I have some bulk Theanine too which should be completely safe to supplement.

 

I am pretty sure I'll be able to withdraw from Lorazepam quite painlessly. But the challenge is to manage anxiety without resorting to these problematic tranquilizers in the future.

 

 

Yes, but the pharmacokinetics of a steady state are vastly different from those of a single acute dose.

The drug concentration in the steady state grows to a factor of sometimes 10 or 50 of the initial dose being taken. It's related to the ratio of time between the dosing interval and the half-life. The more frequent the doses, the less time the body has to metabolize the drug, and the more of it will build up in your system.  If this were to happen with lorazepam to the point of 16 mg concentration, it would require 7 half-life periods (3+ days) to return to the 0.25 mg threshold level. So I would say by day 4-7 you should feel the withdrawal if you are going to feel it at all. This is also a simplistic model which doesn't account for enzyme down-regulation and other factors which may additionally delay the response time.

Regarding the magnesium citrate I'm not able to give a clear affirmation. Because while everything in common experience seems to dictate the fact that magnesium once absorbed in the gut is all equal, everything in the literature seems to contradict that and ascribe a kind of specialty to the activity of threonate in the brain [ https://pubmed.ncbi....h.gov/36558392/ ] [ https://pubmed.ncbi....h.gov/32857294/ ]. The magnesium salt or magnesium acid chelate may not be dissociated in the gut? I haven't found information regarding the chemistry behind this. But in that case, differences in chemical properties of the amino acid complexes (chiefly lipophilicity) could result in vastly different propensities to cross the blood-brain-barrier and therefore delivering more to the brain (where it is then presumably finally dissociated) and explaining the apparent bias in academic research.

Theanine is similar to picamilon for me, in that both are relaxing yes, but in a strange way and were never elevated to lifelong status. I prefer to obtain my theanine from ceremonial grade tea. And I found magnesium works better than picamilon or valerian or virtually anything else I've tried for anxiety (kava, exercise and a few other things already mentioned here have also worked).

Yes. I'm not sure if benzos are actually addictive, but the age you started could also affect the degree of plasticity, making you more vulnerable to relapsing under stress in the future.



#21 Galaxyshock

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Posted 02 June 2023 - 01:52 PM

Yes, but the pharmacokinetics of a steady state are vastly different from those of a single acute dose.

The drug concentration in the steady state grows to a factor of sometimes 10 or 50 of the initial dose being taken. It's related to the ratio of time between the dosing interval and the half-life. The more frequent the doses, the less time the body has to metabolize the drug, and the more of it will build up in your system.  If this were to happen with lorazepam to the point of 16 mg concentration, it would require 7 half-life periods (3+ days) to return to the 0.25 mg threshold level. So I would say by day 4-7 you should feel the withdrawal if you are going to feel it at all. This is also a simplistic model which doesn't account for enzyme down-regulation and other factors which may additionally delay the response time.

 

Thanks for clearing that up. I'll watch out the following days if I start feeling withdrawal symptoms. If I have to reinstate I'll try if 0,25mg dose is enough and stay on that for a while until I get my supplements. I'm not sure if Lorazepam has metabolites that are active - that would delay things too.

 

 

 

Theanine is similar to picamilon for me, in that both are relaxing yes, but in a strange way and were never elevated to lifelong status. I prefer to obtain my theanine from ceremonial grade tea.

 

To me Theanine doesn't feel strange, I like the relaxed state it produces. But I've only been taking it at night time at somewhat high dose of 600 mg. Perhaps I could mix 300 mg in my morning coffee and see if suits me during day-time too.



#22 gamesguru

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Posted 02 June 2023 - 09:39 PM

As far as the magnesium citrate question from before. It is pretty bio-available, but I'm not sure it reaches the brain. You could test large doses. If you don't get a mild sedative effect, it's likely not working as well as threonate could.

 

Thanks for clearing that up. I'll watch out the following days if I start feeling withdrawal symptoms. If I have to reinstate I'll try if 0,25mg dose is enough and stay on that for a while until I get my supplements. I'm not sure if Lorazepam has metabolites that are active - that would delay things too.

 

To me Theanine doesn't feel strange, I like the relaxed state it produces. But I've only been taking it at night time at somewhat high dose of 600 mg. Perhaps I could mix 300 mg in my morning coffee and see if suits me during day-time too.

 

Yes, that's true. I forgot. A lot of compounds have metabolites that build up and have effects, sometimes more so than the original compound itself.

iirc the EU concluded even the Japanese are unlikely to naturally be exposed to amounts of theanine exceeding 50-100 mg daily. So it does make the larger doses seem unnatural. And even before I was aware of this information, my own experience with theanine powder in excess was day dreamy, nauseous, and hollow. Even the taste was slightly sweet, in a way that seemed artificial.

 

I suspect to use theanine on an ongoing basis, it needs to be 50-100 mg tops.


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#23 Galaxyshock

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Posted 03 June 2023 - 07:38 AM

Yes. I'm not sure if benzos are actually addictive,

 

Some people experience euphoria from certain benzos. Personally I haven't found them particularly recreational. In my case the possible addiction may be mostly psychological. I have this stubborn idea that my brain needs some amount of GABAergic boost in order to feel normal.

 

 

 

iirc the EU concluded even the Japanese are unlikely to naturally be exposed to amounts of theanine exceeding 50-100 mg daily. So it does make the larger doses seem unnatural. 

 

I see, my Theanine doses may be a bit excess then. I have this tendency to think more is better lol. 

 

Day 4 now, slept really well and feeling quite good. I'm starting to like the idea of not being on Lorazepam anymore.


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#24 YoungSchizo

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Posted 03 June 2023 - 09:20 AM

Some people experience euphoria from certain benzos. Personally I haven't found them particularly recreational. In my case the possible addiction may be mostly psychological. I have this stubborn idea that my brain needs some amount of GABAergic boost in order to feel normal.

 

 

 

 

For me it's the same, I have found benzo's never to be used recreational and/or addictive, I don't pop them to feel euphoria (I never felt euphoric on it), my brain just produces to less GABA therefore a benzo does the trick and gives my brain a boost of it.

 

In 2010 I admit myself to the hospital due to a crisis, that's the first time they gave me a benzo, after the first pill the (evil) voices stopped immediately, if it wasn't for benzo's I would be admitted for the rest of my life instead of just 2 weeks. 

 

I still have disrupted thoughts and/or paranoia that leads to severe anxiety, popping a benzo and in worse days an extra dose smoothes everything out and I'm symptom free and can function normally.

 

Back in the day I was on Zyprexa and it's a crap antipsychotic for me, it just zombified me and my emotions, after 2010 my first line of defense against (evil) voices was Clonazepam. Since 2015 I use Lurasidon, as an antipsychotic it's the best that has worked on me but I won't survive without a benzo cause we all know antipsychotic is chemical crap.


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#25 Galaxyshock

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Posted 03 June 2023 - 10:04 AM

For me it's the same, I have found benzo's never to be used recreational and/or addictive, I don't pop them to feel euphoria (I never felt euphoric on it), my brain just produces to less GABA therefore a benzo does the trick and gives my brain a boost of it.

 

In 2010 I admit myself to the hospital due to a crisis, that's the first time they gave me a benzo, after the first pill the (evil) voices stopped immediately, if it wasn't for benzo's I would be admitted for the rest of my life instead of just 2 weeks. 

 

I still have disrupted thoughts and/or paranoia that leads to severe anxiety, popping a benzo and in worse days an extra dose smoothes everything out and I'm symptom free and can function normally.

 

Back in the day I was on Zyprexa and it's a crap antipsychotic for me, it just zombified me and my emotions, after 2010 my first line of defense against (evil) voices was Clonazepam. Since 2015 I use Lurasidon, as an antipsychotic it's the best that has worked on me but I won't survive without a benzo cause we all know antipsychotic is chemical crap.

 

If Clonazepam does work so well for psychotic and anxiety symptoms then yeah I understand very well that you want to keep taking it. Hopefully tolerance doesn't creep up at some point - it seems unlikely since you've been on Clonazepam for a very long time without the need to up the dose. But perhaps having some withdrawal protocol in mind in case Clonazepam stops working is still advisable?

 

I guess we are still very much in state of psychiatry where different medications are really trial-and-error. Therefore when you finally find a medication that works for you, it's understandable to not want to go off, even if there are risks.

 

In my case I've also had the thought that Lorazepam is lesser evil than drinking alcohol for my anxiety or something.


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#26 YoungSchizo

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Posted 03 June 2023 - 10:19 AM

If Clonazepam does work so well for psychotic and anxiety symptoms then yeah I understand very well that you want to keep taking it. Hopefully tolerance doesn't creep up at some point - it seems unlikely since you've been on Clonazepam for a very long time without the need to up the dose. But perhaps having some withdrawal protocol in mind in case Clonazepam stops working is still advisable?

 

I guess we are still very much in state of psychiatry where different medications are really trial-and-error. Therefore when you finally find a medication that works for you, it's understandable to not want to go off, even if there are risks.

 

In my case I've also had the thought that Lorazepam is lesser evil than drinking alcohol for my anxiety or something.

 

I've been following the pipeline for new and innovative mental health drugs for 18 years, what has changed in that time, nothing, nada, the most promising drugs all failed in phase III when it comes to anxiety, depression and psychotic spectrum disorders. The ones that got through I tried and it's the same crap as already available. 

 

I've been alcoholic for 5 years in the past, if you drink everyday it's comparable to taking a very high dose of anti anxiety and antidepressant medication but it's far more dangerous to the mind and body in the long term.

 

I don't know what the roots of your anxiety is but have you looked into psychedelics as a treatment option, it's very promising for depression and anxiety.


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#27 Galaxyshock

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Posted 03 June 2023 - 10:39 AM

I've been alcoholic for 5 years in the past, if you drink everyday it's comparable to taking a very high dose of anti anxiety and antidepressant medication but it's far more dangerous to the mind and body in the long term.

 

I was daily drinker back in 2016. Beer mostly, a lot of it. I had basically given up when it comes to medications, supplements and nootropics. I was on Escitalopram and Diazepam without any effect on anxiety or anhedonia. Now I'm in a better place but still tend to enjoy beer a bit too much at times lol. Naltrexone has helped to reduce it though.

 

Have you ever tried Kava? I find it very nice mildly recreational herb with deeply calming effect. But it's unfortunately controlled substance in Finland. Also a problem with Kava is that it tastes really bad and the effects from one dose last only like one to two hours.


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#28 YoungSchizo

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Posted 03 June 2023 - 11:00 AM

I was daily drinker back in 2016. Beer mostly, a lot of it. I had basically given up when it comes to medications, supplements and nootropics. I was on Escitalopram and Diazepam without any effect on anxiety or anhedonia. Now I'm in a better place but still tend to enjoy beer a bit too much at times lol. Naltrexone has helped to reduce it though.

 

Have you ever tried Kava? I find it very nice mildly recreational herb with deeply calming effect. But it's unfortunately controlled substance in Finland. Also a problem with Kava is that it tastes really bad and the effects from one dose last only like one to two hours.

 

Same here bud, I also started in 2016 to 2021 and also beer and lots of it. Even though I'm not alcoholic anymore I'm still attracted to enjoy to much beer from time to time. In 2021 I started to wage a war against psychiatry (see my thread in the mental health section). In those 2 years I've become fat again because I'm not carrying bag but a mountain on my shoulders and therefore I sometimes resort to beer to un-stress.

 

Those dumb fucks didn't even allow me to use Naltrexone, what I read about it it's seems like a great drug, not only to drink less but also the effects on mental health.

 

I completely stopped my own experiments with supplements, nootropics and whatnot. The only thing on my list I want to try is Lumateperone. Europe is always 5 years behind the US when it comes to new medication. I also follow some promising new drugs but those can take 2-3 years before it hits the market.



#29 Galaxyshock

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Posted 03 June 2023 - 01:27 PM

Same here bud, I also started in 2016 to 2021 and also beer and lots of it. Even though I'm not alcoholic anymore I'm still attracted to enjoy to much beer from time to time. In 2021 I started to wage a war against psychiatry (see my thread in the mental health section). In those 2 years I've become fat again because I'm not carrying bag but a mountain on my shoulders and therefore I sometimes resort to beer to un-stress.

 

Those dumb fucks didn't even allow me to use Naltrexone, what I read about it it's seems like a great drug, not only to drink less but also the effects on mental health.

 

I completely stopped my own experiments with supplements, nootropics and whatnot. The only thing on my list I want to try is Lumateperone. Europe is always 5 years behind the US when it comes to new medication. I also follow some promising new drugs but those can take 2-3 years before it hits the market.

 

I'm overweight too, mostly it's belly fat. I do have muscle too from years of lifting - it doesn't all seem to disappear despite not training. But some kind of exercise regimen would probably be a good idea now that I'm going to try live without tranquilizers.

 

Well that sucks, Naltrexone is generally well-tolerated med that can help with addictions and indeed may even have other benefits on mental health.

 

Looks like Lumateperone may be a good anti-psychotic as it lacks anticholinergic and antihistamine effects. It's good that they keep developing these new drugs since the current options leave much to be desired. I'm looking forward to some sort of breakthrough in anhedonia treatments.


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#30 gamesguru

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Posted 03 June 2023 - 02:09 PM

Also a problem with Kava is that it tastes really bad and the effects from one dose last only like one to two hours.

 

It shouldn't taste bad. I get an organic dehydrated juice that is slightly peppery/gingery. And concentrated capsules with 50+ mg kavalactones.

 

The acute effects may only last a few hours. But the adaptogenic qualities linger for days.

 

 

I'm overweight too, mostly it's belly fat. I do have muscle too from years of lifting - it doesn't all seem to disappear despite not training. But some kind of exercise regimen would probably be a good idea now that I'm going to try live without tranquilizers.

 

Well that sucks, Naltrexone is generally well-tolerated med that can help with addictions and indeed may even have other benefits on mental health.

 

In terms of weight gain, you need to monitor metabolic effects of antidepressant treatment. It may be caused by some medications.

 

Salvia and psilocybin are also good for addiction, likely due to their partial agonism at the D2 receptor site.

Recent research indicates that the dopamine D2 receptor partial agonists, such as aripiprazole, also shows useful ancillary efficacy in several animal models of psychostimulant and opioid addiction. Notably, these findings suggest that unlike full dopamine receptor agonists and antagonists these compounds have low abuse liability and are generally well tolerated.

 

 

Though part of the anti-addiction effect may be due to the wild perceptual alterations and this later making it harder to rationalize addiction, there is investigation into semi-synthetic salvinorin derivatives with a longer duration of effect and also (maybe one day) ones without the psychedelic effect.

 

13. Kivell BM, Ewald AW, Prisinzano TE. Salvinorin A analogs and other kappa-opioid receptor compounds as treatments for cocaine abuse. Adv Pharmacol. (San Diego, Calif). (2013) 69:481–511. doi: 10.1016/B978-0-12-420118-7.00012-3

14. Morani AS, Ewald A, Prevatt-Smith KM, Prisinzano TE, Kivell BM. The 2-methoxy methyl analogue of salvinorin A attenuates cocaine-induced drug seeking and sucrose reinforcements in rats. Eur J Pharmacol. (2013) 720:69–76. doi: 10.1016/j.ejphar.2013.10.050







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