Treating methamphetamine-induced anxiety with valproic acid

[vanboy5]

Due to an extremely heavy workload (12-16 hours a day, for the past 2.5 weeks), I use benzodiazepines as anxiolytics PRN throughout the day. however, I decided to try something non-habit forming and doesn't cause tolerance. I tried taking 300mg of valproic acid last night. Anyone have any thoughts?

 

[MeDieViL]

The combo of nebivolol and candesartan works excellent for amphetamine anxiety (not meth tough) YMMV

 

[P A]

candesartan

...orlynow? Do tell.

nebivolol

Not something I'd recommend to anyone who's using repeated doses of what I have to assume are moderate-high doses of methamphetamine.

not meth tough

Yes meth though. As it relates to feasible human doses within the non-addict range, meth and speed are essentially pharmacologically identical, half-lives and mg-by-mg potency notwithstanding. On the other hand, an angiotensin inhibitor and an atypical beta-blocker are neither clinically anxiolytic, nor likely to satisfy the OP's needs in the least. I can think of no mechanistic explanation nor even a tenuous suggestion in principle that either would be helpful for anything related to either 1) anxiety [aside from stage fright, which isn't relevant] or 2) blood pressure reduction in the context of sympathomimetic use [which is also completely irrelevant to the OP's predicament], nor can I find so much as a case report of anecdotal efficacy for either drug in this particular context; this of course, is aside from a rather brazen post on SAS similarly touting the combination's efficacy as though confidently recommending such a cocktail [on a message board replete with anxious depressives with considerably less knowledge than yourself regarding the biochemical substrates of drug action, no less] after a single anecdotal 'trial' is a conscionable thing to do.

I only take the time to mention any of this out of spite for your potentially dangerous and most assuredly useless recommendation, and in the spirit of harm reduction, as per this site's supposed foundational purpose. Firstly: under virtually any circumstance, the haphazard combination of two hypotensive drugs with markedly differing mechanisms is a terrible idea, and a risk not worth taking for anything other than the stiffest and bulgiest of arteries. Second: beta-blockers are contraindicated with high-dose sympathomimetic stimulants, period. If you don't already know this MeDieVil, I suggest you read moar before coingesting obscure pharmaceutical drugs on what seem to amount to fleeting whims, then recommending them to others as though they are theoretically backed by anything other than your 'experience.'

I tried taking 300mg of valproic acid last night.

Did it work?

Anyone have any thoughts?

Good idea. Other than a handful of annoying side effects in some users, valproate is a solid, tolerable anxiolytic with very minor potential for addiction if used in moderation. Better yet, you could try alternating it day-to-day with benzos in order the maximize and retain the potency of both.

 

[MeDieViL]

^^ Yes you are absolutely correct that nebivilol can be unsafe in combination with recreational doses of stimulants, that slipped out my mind since i usually recommend the combination for people that take therapeutic doses of amphetamine, carvedilol a combined alpha / beta blocker is a safe alternative tough.

The reason why i recommend beta blockers for stimulant anxiety is because stimulant anxiety is partionally mediated to the beta adrenergic receptors.

Norepinephrine signaling through beta-adrenergic receptors is critical for expression of cocaine-induced anxiety.
Schank JR, Liles LC, Weinshenker D.

Department of Human Genetics, Emory University, Atlanta, GA 30322, USA.
Comment in:

Biol Psychiatry. 2008 Jun 1;63(11):1005-6.
Abstract
BACKGROUND: Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety.

METHODS: In this study, we evaluated the performance of dopamine beta-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety.

RESULTS: We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/-) mice, as measured by a decrease in open arm exploration. The Dbh -/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +/- mice following administration of disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/- and wild-type C57BL6/J mice, while the alpha(1) antagonist prazosin and the alpha(2) antagonist yohimbine had no effect.

CONCLUSIONS: These results indicate that noradrenergic signaling via beta-adrenergic receptors is required for cocaine-induced anxiety in mice.

Now the reason behind the arb blocker is that AT1 antagonists increase angiotensin II several fold wich leads to increased AT2, that and increased breakdown of substance P likely contribute to the anxiolytic effect.

Ive experimented extensively with both and both they significantly inhibit stimulant paranoia, combined where it no longer is an issue.

Regarding your concern recommending 2 anti hypertensives take in mind that the doses i recommend are low and that they both can be safely combined.

If you have any evidence showing combining a beta blocker and a ARB blocker is hazardous please post that, but from my research i concluded its a safe combination.

 

[Jamshyd]

Talk about using a chainsaw to scratch your back

 

[vanboy5]

PA: I thank you so much for your time and input. I am grateful for people like you. I'm in the midst of opening up a new hotel so I have chosen to use this powerful cns stimulant for support. Yes I was very well aware of the fact that beta blockers are contraindicated for stimulant-induced hypertension. Instead, I've been using long-acting 4mg doxazosin for hypertension at night (I find it also helps with sleep), long-acting ASA for its anticoagulant properties, and 120mg of long-acting dextromethorphan as a partial NMDA-antagonist for tolerance reduction.

I spoke to my psychiatrist about what I've been doing yesterday (he treats me not with pharmacotherapy but instead, psychodynamic psychotherapy) and he says he can't be sure but like you doesn't believe there to be any contraindications between valproic acid and meth.

Sorry for straying away from the point of this thread buti just want to thank you so much again for your strongfully worded and clearly heartfelt comments. A kickass reminder of what this site was meant for in the first place: harm reduction.

 

[Lolie]

The amount you're taking is at the low end of the therapeutic range, but if you're going to take it on a daily basis for any length of time it would be wise to get your liver enzymes checked every now and then.

As the OP is male, this doesn't apply to them but it may be relevant to others wishing to try valproic acid/sodium valproate for the same purpose. It is strongly contraindicated for use by pregnant women and women intending to become pregnant due to a significant increase in birth defects.

 

[melange]

this is a little tip I live my life by


ALWAYS HAVE HIGH PROOF ETHANOL ON HAND NO MATTER WHAT

 

[MeDieViL]

Regarding the anxiolytic effects of cardesartan, there is some evidence in rodents altough they havent been tested specifically on stimulant induced anxiety like propranolol, still consider they can be safely combined with low doses of beta blockers and they worked excellent in my case i tought they were worth recommending.

Blockade of brain angiotensin II AT(1) receptors ameliorates stress, anxiety, brain inflammation and ischemia: Therapeutic implications.
Saavedra JM, Sánchez-Lemus E, Benicky J.

Section on Pharmacology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, 10 Center Drive, Building 10, Room 2D-57, Bethesda, MD 20892, United States.
Abstract
Poor adaptation to stress, alterations in cerebrovascular function and excessive brain inflammation play critical roles in the pathophysiology of many psychiatric and neurological disorders such as major depression, schizophrenia, post traumatic stress disorder, Parkinson's and Alzheimer's diseases and traumatic brain injury. Treatment for these highly prevalent and devastating conditions is at present very limited and many times inefficient, and the search for novel therapeutic options is of major importance. Recently, attention has been focused on the role of a brain regulatory peptide, Angiotensin II, and in the translational value of the blockade of its physiological AT(1) receptors. In addition to its well-known cardiovascular effects, Angiotensin II, through AT(1) receptor stimulation, is a pleiotropic brain modulatory factor involved in the control of the reaction to stress, in the regulation of cerebrovascular flow and the response to inflammation. Excessive brain AT(1) receptor activity is associated with exaggerated sympathetic and hormonal response to stress, vulnerability to cerebrovascular ischemia and brain inflammation, processes leading to neuronal injury. In animal models, inhibition of brain AT(1) receptor activity with systemically administered Angiotensin II receptor blockers is neuroprotective; it reduces exaggerated stress responses and anxiety, prevents stress-induced gastric ulcerations, decreases vulnerability to ischemia and stroke, reverses chronic cerebrovascular inflammation, and reduces acute inflammatory responses produced by bacterial endotoxin. These effects protect neurons from injury and contribute to increase the lifespan. Angiotensin II receptor blockers are compounds with a good margin of safety widely used in the treatment of hypertension and their anti-inflammatory and vascular protective effects contribute to reduce renal and cardiovascular failure. Inhibition of brain AT(1) receptors in humans is also neuroprotective, reducing the incidence of stroke, improving cognition and decreasing the progression of Alzheimer's disease. Blockade of AT(1) receptors offers a novel and safe therapeutic approach for the treatment of illnesses of increasing prevalence and socioeconomic impact, such as mood disorders and neurodegenerative diseases of the brain.

Ann N Y Acad Sci. 2008 Dec;1148:360-6.
Peripherally administered angiotensin II AT1 receptor antagonists are anti-stress compounds in vivo.
Pavel J, Benicky J, Murakami Y, Sanchez-Lemus E, Saavedra JM.

Section on Pharmacology, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
Abstract
Angiotensin II AT(1) receptor blockers (ARBs) are commonly used in the clinical treatment of hypertension. Subcutaneous or oral administration of the ARB candesartan inhibits brain as well as peripheral AT(1) receptors, indicating transport across the blood-brain barrier. Pretreatment with candesartan profoundly modifies the response to stress. The ARB prevents the peripheral and central sympathetic activation characteristic of isolation stress and abolishes the activation of the hypothalamic-pituitary-adrenal axis during isolation. In addition, candesartan prevents the isolation-induced decrease in cortical corticotropin-releasing factor 1 and benzodiazepine receptors induced by isolation. When administered before cold-restraint stress, candesartan totally prevents the production of gastric ulcerations. This preventive effect of candesartan is the consequence of profound anti-inflammatory effects, reduction of sympathetic stimulation, and preservation of blood flow to the gastric mucosa. The ARB does not reduce the hypothalamic-pituitary-adrenal axis stimulation during cold restraint. Preservation of the effects of endogenous glucocorticoids is essential for protection of the gastric mucosa during cold restraint. Administration of the ARB to nonstressed rats decreases anxiety in the elevated plus-maze. Our results demonstrate that Angiotensin II, through AT(1) receptor stimulation, is a major stress hormone, and that ARBs, in addition to their antihypertensive effects, may be considered for the treatment of stress-related disorders.

A centrally acting, anxiolytic angiotensin II AT1 receptor antagonist prevents the isolation stress-induced decrease in cortical CRF1 receptor and benzodiazepine binding.
Saavedra JM, Armando I, Bregonzio C, Juorio A, Macova M, Pavel J, Sanchez-Lemus E.

Section on Pharmacology, National Institute of Mental Health, National Institutes of Health, DHHS, Bethesda, MD 20892, USA. [email protected]
Abstract
Long-term pretreatment with an angiotensin II AT1 antagonist blocks angiotensin II effects in brain and peripheral organs and abolishes the sympathoadrenal and hypothalamic-pituitary-adrenal responses to isolation stress. We determined whether AT1 receptors were also important for the stress response of higher regulatory centers. We studied angiotensin II and corticotropin-releasing factor (CRF) receptors and benzodiazepine binding sites in brains of Wistar Hannover rats. Animals were pretreated for 13 days with vehicle or a central and peripheral AT1 antagonist (candesartan, 0.5 mg/kg/day) via osmotic minipumps followed by 24 h of isolation in metabolic cages, or kept grouped throughout the study (grouped controls). In another study, we determined the influence of a similar treatment with candesartan on performance in an elevated plus-maze. AT1 receptor blockade prevented the isolation-induced increase in brain AT1 receptors and decrease in AT2 binding in the locus coeruleus. AT1 receptor antagonism also prevented the increase in tyrosine hydroxylase mRNA in the locus coeruleus. Pretreatment with the AT1 receptor antagonist completely prevented the decrease in cortical CRF1 receptor and benzodiazepine binding produced by isolation stress. In addition, pretreatment with candesartan increased the time spent in and the number of entries to open arms of the elevated plus-maze, measure of decreased anxiety. Our results implicate a modulation of upstream neurotransmission processes regulating cortical CRF1 receptors and the GABA(A) complex as molecular mechanisms responsible for the anti-anxiety effect of centrally acting AT1 receptor antagonists. We propose that AT1 receptor antagonists can be considered as compounds with possible therapeutic anti-stress and anti-anxiety properties.

Regul Pept. 2005 Jun 30;128(3):227-38.
Anti-stress and anti-anxiety effects of centrally acting angiotensin II AT1 receptor antagonists.
Saavedra JM, Ando H, Armando I, Baiardi G, Bregonzio C, Juorio A, Macova M.

Section on Pharmacology, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-1514, USA. [email protected]
Abstract
The brain and the peripheral (hormonal) angiotensin II systems are stimulated during stress. Activation of brain angiotensin II AT(1) receptors is required for the stress-induced hormone secretion, including CRH, ACTH, corticoids and vasopressin, and for stimulation of the central sympathetic activity. Long-term peripheral administration of the angiotensin II AT(1) antagonist candesartan blocks not only peripheral but also brain AT(1) receptors, prevents the hormonal and sympathoadrenal response to isolation stress and prevents the formation of stress-induced gastric ulcers. The mechanisms responsible for the prevention of stress-induced ulcers by the AT(1) receptor antagonist include protection from the stress-induced ischemia and inflammation (neutrophil infiltration and increase in ICAM-1 and TNF-alpha) in the gastric mucosa and a partial blockade of the stress-induced sympathoadrenal stimulation, while the protective effect of the glucocorticoid release during stress is maintained. AT(1) receptor antagonism prevents the stress-induced decrease in cortical CRH(1) and benzodiazepine binding and is anxiolytic. Blockade of brain angiotensin II AT(1) receptors offers a novel therapeutic opportunity for the treatment of anxiety and other stress-related disorders.

Psychopharmacology (Berl). 1996 Aug;126(3):206-18.
Effects of the selective angiotensin II receptor antagonists losartan and PD123177 in animal models of anxiety and memory.
Shepherd J, Bill DJ, Dourish CT, Grewal SS, McLenachan A, Stanhope KJ.

Department of Neuropharmacology, Wyeth Research UK Ltd., Berkshire, UK.
Abstract
There is increasing interest in the potential functional role of the octapeptide angiotensin II (AII) in psychiatric and cognitive disorders. The novel angiotensin II (AII) receptor antagonists, losartan and PD123177, selective for the AT1 and AT2 receptor subtypes respectively, constitute important pharmacological tools for the assessment of the behavioural consequences of modulation of AII function. The present series of studies investigated the effects of each compound in two animal models of anxiety, the rat elevated zero-maze and mouse light/dark box, and two models of working memory in the rat, the operant delayed matching to position (DMTP) task and the spatial reinforced alternation test in the T-maze. Our data indicate that both compounds (0.01-10 mg/kg s.c.) were without significant effect in any of the behavioural assays. Using the present methods and strains of laboratory rodents, these findings provide no support for the involvement of AII receptor function in the mediation of anxiety of working memory.

But yeah recommending a pure beta blocker was pretty rheckless, it slipped my mind because i usually recommend those to people that dont take recreational doses, that was a mistake of me.

I have tried many benzo's and other things for stimulant anxiety without any succes and this combination completely abolished it.

 

[P A]

the doses i recommend are low and that they both can be safely combined

I saw no dosing guidelines nor specific recommendations of any kind, aside "take this, it works!"

Now the reason behind the arb blocker is that AT1 antagonists increase angiotensin II several fold wich leads to increased AT2, that and increased breakdown of substance P likely contribute to the anxiolytic effect.

That's all fine, but none of this means anything within the context of the OP's consideration of using an anxiolytic of relatively well-founded human efficacy for an indication that can be reliably extended from other data once the primary human findings are taken into account.

And while I am aware of the interaction between Substance P and the angiotensin system, I have yet to see any indication outside of rodent literature that SP is crucially implicated in states of human angst, let alone pscyhostimulant-induced anxious arousal, which to my knowledge is either largely or completely independent of inflammatory neuropeptide signalling.

Ive experimented extensively with both and both they significantly inhibit stimulant paranoia, combined where it no longer is an issue.

This is a prime example of how little anecdotal claims mean to anyone other than yourself. Despite having taken repeated, more-than-ample doses of methamphetamine (in some cases alongside potentiators) I've never experienced the marked paranoia and 'anxiety' so commonly reported by many fellow users. Mania and compulsive, stereotyped behavior to be sure, but never the slightest hint of anything resembling fear nor worry. Of course, this isn't to marginalize the experiences of you and the OP - quite the opposite, in fact. Such an observation only further underpins the unquestionable, but statistically unreliable nature of personal, subjective response to a psychoactive drug (or drugs).

I may have spoken too soon regarding beta-blockers and candesartan in specific (I can't find any safety data at all regarding their combination outside of congestive heart failure and clinical hypertension, wherein any risk is often outweighed by putative therapeutic benefit), but my contention nevertheless holds in principle, unless you can succeed in procuring the data where I've failed. When it comes to potential pharmaclogic risk, and the prophylaxis thereof, absence of evidence never constitutes evidence of absence. Show me anything demonstrating a remote chance that AT inhibitors and beta-blockers are safe in combination in humans with good cardiovascular health (i.e. normotensive) and I'll gladly concede your point.

 

[melange]

P A, just because something "loooks right on paper" does not mean it is right

what good is something if it was recommended and did not work for that person? everyone is different

 

[MeDieViL]

And while I am aware of the interaction between Substance P and the angiotensin system, I have yet to see any indication outside of rodent literature that SP is crucially implicated in states of human angst, let alone pscyhostimulant-induced anxious arousal, which to my knowledge is either largely or completely independent of inflammatory neuropeptide signalling.

Yeah i'm still a little unclear by what mechanism they show their anxiolytic effect, the abstracts i posted above you also point to a differend mechenism, for example it appears that AT1 activation is reguared for stress induced hormone secretion.

Angiotensin also appears to modulate GABA and dopamine i suspect NE too, i'l look into it.

 

[P A]

Quasi-doublepost. All apologies.

PA: YOU ROCK! I'd like to email you my new hotel's grand opening. Just a simple gesture of my sincere gratitude.

I'm truly touched. And by all means, I'd love to know how it turns out for you; I wish you [and of course, your hotel] the very best of luck.

As an aside, when it comes to the self-pharmacotherapy, you seem to know what you're doing. Keep it up. But I have to know, if you're willing to share: having never met nor even heard of anyone post-1950s receiving clinical psychodynamic therapy...how is it working out for you?

ALWAYS HAVE HIGH PROOF ETHANOL ON HAND NO MATTER WHAT

Hear, hear. Wise words.

Regarding the anxiolytic effects of cardesartan, there is some evidence in rodents altough they havent been tested specifically on stimulant induced anxiety like propranolol

Having read a couple of those studies myself, I fully agree. AT inhibitors appear to be efficacious for particular types of experimentally induced anxiety in rats.

I have tried many benzo's and other things for stimulant anxiety without any succes

That's surprising. They seem to work quite well for that purpose in the majority of rats, and if I understand correctly, the majority of humans. And don't get me wrong, I'm glad that it works well for you - my vitriol was directed entirely at your ideas, not your personal pharmacotherapeutic successes, which I understand to have been oft-referenced across multiple boards.

P A, just because something "loooks right on paper" does not mean it is right

what good is something if it was recommended and did not work for that person? everyone is different

Try again, this time addressing the right person. Otherwise...?

 

[P A]

Angiotensin also appears to modulate GABA and dopamine i suspect NE too, i'l look into it.

I'd be interested to see what you find, if anything. AT has never really been an object of intensive interest for me. I'd actually be surprised if there was much else than what you referenced above.

P A, just because something "loooks right on paper" does not mean it is right

...or maybe you're referring to my comments regarding the reasonably well-regarded effectiveness of valproate in states of acute and chronic anxiety? I was talking 'multiple placebo-controlled trials' effective, not "eh, looks good in rat studies, guess I'll just throw down a few caps with whatever else is on hand and hope for the best."

 

[blues runner]

For speed-induced anxiety, I use a beta blocker. 40 mg of Inderal (propranolol) pretty much eliminates all the somatic symptoms. No more tachycardia, efficient breathing rhythm...helps quite a bit. Nearly all the physical symptoms of my anxiety disappear. I never found benzos particularly effective for this. I've tried up to 40 mg Valium, 6 mg Klonopin, 4 mg Xanax...experimented with benzos with different half-lives all to no avail.

ETA: Although the propranolol seems to work nicely for me, I must admit I'm not that big on stimulants in general (heroin addict), so I'm sure I don't ever take anywhere near the levels that a true speed user probably does. Also, I usually tend to have a couple of drinks whenever I "crash" on any stimulant. Strange then that the benzos don't really seem to do much for me (since their action in the brain is very similar to that of ethanol). Oh well.

 

[vanboy5]

pa: thanks for your compliment, although my knowledge is indeed quite superficial. I've psychodynamic psychotherapy is still widely practised, although its efficacy is limited to the amount of time you can spare. However, it can still be extremely useful in treating many mental disorders. I like my pdoc in that he is extremely open and has become almost a mentor if you will in psychology - a great passion of mine. Second to that, of course, is psychopharmacology.

Sorry for totally straying from the topic of my own thread. I would like to say that in cases of psychostimulant psychosis such as paranoid ideation benzos would likely have limited efficacy. However, if it is purely the "sketch" or anxiety - perhaps even as severe as a panic attack, then benzos with strong anxiolytic properties such as alprazolam, clonazepam, and bromazepam etc would certainly relieve a user of some of the emotional stress caused by hyperactivity in the dopaminic neurotransmitters (please let me know if I should go back to basic drug discussion as my efforts to sound as technically eloquent as the rest of you seem very feeble). However, I started this thread in the first place because I was looking for alternative solutions to gaba-agonising drugs due to tolerance and withdrawal.

 

[MeDieViL]

I'd be interested to see what you find, if anything. AT has never really been an object of intensive interest for me. I'd actually be surprised if there was much else than what you referenced above.

Ive been investigating the angiotensin system lately, have to go in a few minutes will see wheter i can dig somore usefull things up tomorrow:

Anxiety-like behavior in mice lacking the angiotensin II type-2 receptor.
Okuyama S, Sakagawa T, Chaki S, Imagawa Y, Ichiki T, Inagami T.

1st Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical, 1-403, Yoshinocho, Ohmiya 330-8530, Japan.
Abstract
The main biological role of angiotensin II type 2 receptor (AT2) has not been established. We made use of targeted disruption of the mouse AT2 gene to examine the role of the AT2 receptor in the central nervous system (CNS). AT2-deficient mice displayed anxiety-like behavior compared with wild-type mice. However, AT2-deficient mice showed no depressant-like activity and no change in hexobarbital-induced sleeping time as compared with findings in wild-type mice. Both noradrenergic and corticotropin-releasing factor (CRF) neuronal systems appear to be involved in this anxiety-like behavior. Diazepam, captopril (angiotensin I converting enzyme inhibitor), prazosin (alpha1 antagonist) reversed the anxiety-like behavior in these AT2-deficient mice, whereas yohimbine (alpha2 antagonist), phenylephrine (alpha1 agonist), clonidine (alpha2 agonist), isoproterenol (beta1/beta2 agonist), propranolol (beta1/beta2 antagonist) and alpha-helical CRF9-41 (CRF receptor antagonist) has no apparent effects on anxiety-like behavior in AT2-deficient mice. In addition, concentrations of plasma adrenocorticotropic hormone (ACTH) and corticosterone in AT2-deficient mice did not differ from these in wild-type mice, hence, there are probably no endocrine abnormalities involving the hypothalamic-pituitary-adrenal axis (HPA). The amygdala appears to play an important role in many of the responses to fear and anxiety. The number of [3H]prazosin but not [125I]CRF binding sites in the amygdala was significantly reduced in AT2-deficient mice. These findings indicate that the noradrenergic system is involved in mediating the anxiety-like behavior in AT2-deficient mice.

Copyright 1999 Elsevier Science B.V.

Basicly ARB blockers work against anxiety because of increased AT2 agonism (and not because of the AT1 blockade itself, wich causes a several fold increase in angiotensin leading to increased AT2 agonism, telmisertan a arb that doesnt increase angiotensin II lacked all anxiolytic effects.

This study points to noradrennergic involvement in AT2 deficient mice

 

[P A]

I have another psychiatrist whom I see and present myself with bipolar I symptoms and he prescribes me lots of interesting meds I just keep as part of a collection. I'm an ok actor, I suppose.

That is, unfortunately, an imperative faculty when it comes to acquiring psychotherapeutics outside the range of orthodox prescribing practices, barring the exceptional case of the 'open-minded' psychiatrist.

However, I started this thread in the first place because I was looking for alternative solutions to gaba-agonising drugs due to tolerance and withdrawal.

Sorry, I should have picked up on that. I was planning on suggesting alternatives, but promptly forgot. Your location is listed as 'Asia,' and as such, your options may or may not be limited relative to those available in my country, from whose officially approved pharmacopoeia I derive the majority of my knowledge. Regardless, I regret to let you know that when it comes to psychostimulant-induced anxiety/panic, only the most powerful of remedies are likely to be of significant benefit, and as is so common in pharmacotherapy, the most potent anxiolytics are restricted to a select few classes of drugs, most all of them GABAergic and laden with potential side effects. You likely already know at least something about each of them: the barbiturates, the carbamates, the high-potency benzodiazepines (and maybe high-dose diazepam), ethanol, indirect GABA agonists (like valproate, vigabatrin, or tiagabine), and the adrenergic antagonists, one of which I understand you already use. Apart from those well-founded options, alternatives include the GABA-B agonists (baclofen, phenibut, and hydroxybutyrate) and, if you're desperate, the neuroleptic tranquilizers.

 

[MeDieViL]

That's surprising. They seem to work quite well for that purpose in the majority of rats, and if I understand correctly, the majority of humans. And don't get me wrong, I'm glad that it works well for you - my vitriol was directed entirely at your ideas, not your personal pharmacotherapeutic successes, which I understand to have been oft-referenced across multiple boards.

Benzo's only appear to blunt the anxiety togheter with the euphoria, so it just feels like i took a lower dose, the anti hypertensives i use seem to completely abolish the anxiety while not changing the euphoria.

 

[vanboy5]

PA:

I have never considered GABA-B agonists so thanks for the tip I'll check it out!