17 replies to this topic

[OneScrewLoose]

I've been trying to figure out why over the last week textures are making me a lot more nervous, I've been more nervous, and I've been sweating in my hands a lot. I just realized that I've been taking around 40-80mg of propanolol (as needed) a day for my anxiety, as per my doctor. I'm wondering if this recent bout of anxiety is because of upregulation of beta receptors...am I just making things worse by taking the propanolol?

[shaggy]

Using propranolol is a vicious circle.... It actually up regulates Beta receptors, so when you stop taking it you'll be in a worse position.

Not sure how long this effect lasts though....??

[Lufega]

I agreed. I just finished a surgery rotation and I was using 10-20 mg propranolol a day to get me through. Now comes the bad part. The rebound effect is nasty but 1 gram magnesium per day helps. I've also read that forskolin can downregulate B-receptors. This is an area that needs further research.

[OneScrewLoose]

I agreed. I just finished a surgery rotation and I was using 10-20 mg propranolol a day to get me through. Now comes the bad part. The rebound effect is nasty but 1 gram magnesium per day helps. I've also read that forskolin can downregulate B-receptors. This is an area that needs further research.

Why does magnesium help?

[Lufega]

I agreed. I just finished a surgery rotation and I was using 10-20 mg propranolol a day to get me through. Now comes the bad part. The rebound effect is nasty but 1 gram magnesium per day helps. I've also read that forskolin can downregulate B-receptors. This is an area that needs further research.

Why does magnesium help?

I think by reducing sympathetic action (adrenaline), which is what activates B-receptors in the first place. This should help while your receptors down-regulate.

[OneScrewLoose]

I just had a couple packs of this "natural calm" magnesium sample packs I get from iherb. Soon I'll be going to accupuncture and when I get back I'll do what I did yesterday (my first day without propanolol), kava, ativan and ashwaghanda.

[medicineman]

people on propranalol due just fine if they taper down the dosage when they are coming off. when taking propranalol in an as needed basis, especially at doses this high, you create this problem of upregulation... also make sure you are not taking any benadryl or ketotifen, because they upregulate beta receptors even further..

[OneScrewLoose]

How does benadryl upregulate beta receptors?

Edited by OneScrewLoose, 15 March 2009 - 04:23 AM.

[Happy Gringo]

I think forskolin works by a different mechanism than using beta receptors. I have over-the-counter access to albuterol at about 20 cents per tab down here in Costa Rica, so I use this to preserve muscle tissue (also helps with fat-loss) when I take a 10 day break from weight training every 6 weeks. It down-regulates beta receptors, so I take benadryl a day before and a day after the albuterol to up-regulate and try to balance. I also have no idea how the benadryl up-regulates, maybe it is no more than an old wives tale around the bodybuilding circles?

[StrangeAeons]

Benadryl in an anticholinergic, so it leads to increased sympathetic tone; I imagine then that this should (in theory) lead to andrenergic receptor downregulation, though it's iffy.
As per everything you're doing, OSL, I'd have to imagine evaluating all the other measures you're taking to modify your receptors is gonna be pointless if you're taking ativan; benzos are gonna chill you out no matter what.
EDIT: Oh yeah, forskolin works by downregulating cAMP, which has to do with certain neurons in the brain only firing when they're hyperpolarized-- it's a little confusing.

Edited by PetaKiaRose, 15 March 2009 - 08:44 PM.

[Lufega]

Two distinct pathways for cAMP-mediated down-regulation of the beta 2-adrenergic receptor. Phosphorylation of the receptor and regulation of its mRNA level.
Bouvier M, Collins S, O'Dowd BF, Campbell PT, de Blasi A, Kobilka BK, MacGregor C, Irons GP, Caron MG, Lefkowitz RJ.

Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.

We have studied cyclic AMP-mediated regulation of the beta 2-adrenergic receptor (beta 2AR). The effects of cAMP were assessed in Chinese hamster fibroblast (CHW) cells expressing either the wild type human beta 2AR receptor (CH-beta 2) or mutated forms of the receptor lacking the consensus sequences for phosphorylation by the cAMP-dependent protein kinase. Treatment of the CH-beta 2 cells with the cAMP analogue dibutyryl cAMP (Bt2cAMP) induces a time-dependent "down-regulation" of the number of beta 2AR. This down-regulation of the receptors is accompanied by a decline in the steady state level of beta 2AR mRNA. Moreover, the treatment with Bt2cAMP induces an increase in the phosphorylation level of the membrane-associated beta 2AR. Both the reduction in beta 2AR mRNA and the enhanced phosphorylation of the receptor are rapid and precede the loss of receptor. The down-regulation of beta 2AR induced by Bt2cAMP is concentration-dependent and mimicked by the other biologically active cyclic nucleotide analogue, 8-Br-cAMP, by forskolin, and by the phosphodiesterase inhibitor, isobutylmethylxanthine. In the CHW cell lines expressing receptors lacking the putative protein kinase A phosphorylation sites, the Bt2cAMP-induced phosphorylation of beta 2AR is completely abolished. In these cells the down-regulation of beta 2AR receptor number produced by cAMP is significantly slowed, whereas the reduction in beta 2AR mRNA level is equivalent to that observed in CH-beta 2 cells. These data indicate that there are at least two pathways by which cAMP may decrease the number of beta 2ARs in cells: one involves phosphorylation of the receptor by the cAMP-dependent protein kinase and the other leads to a reduction in steady state beta 2AR mRNA levels.

Be careful with forskolin though. It raises testosterone and as a result, will make you bald. At least it did for me, silently and on top of the head where I couldn't see it. Luckily, someone pointed it out. I'll add Saw palmetto to offset the effect of DHT. Hopefully, this should solve the problem. Grrrrrrrrrr....

Edited by Lufega, 16 March 2009 - 01:06 AM.

[Lufega]

Effects of lithium on the beta-adrenergic receptor-adenylate cyclase system in rat cerebral cortical membranes.
Odagaki Y, Koyama T, Matsubara S, Yamashita I.

Department of Psychiatry and Neurology, Hokkaido University School of Medicine, Sapporo, Japan.

The effects of lithium on the beta-adrenoceptor-adenylate cyclase system in cerebral cortical membranes of rats were investigated. Lithium chloride inhibited adenylate cyclase activity in a concentration-dependent manner in vitro. However, relatively high concentrations of lithium were needed for this inhibition; and at 1 mM, no significant reduction in adenylate cyclase activity was seen under any condition. Administration of lithium carbonate for 21 days decreased the maximum number of [3H]dihydroalprenolol binding sites without changing the apparent dissociation constant. Activation of adenylate cyclase by (-)-isoproterenol in the presence of 1 microM guanyl-5'-ylimidodiphosphate (Gpp(NH)p) was significantly attenuated in lithium-treated rats compared with the controls. Lithium treatment reduced the Gpp(NH)p-stimulated adenylate cyclase activity in the presence of 10 microM (-)-isoproterenol, but not in the absence of this beta-adrenergic receptor agonist. Basal activity or adenylate cyclase activity stimulated by forskolin or manganese was not affected, whereas the activity stimulated by sodium fluoride was significantly attenuated by long-term lithium treatment. These results indicate that chronic lithium treatment induces subsensitivity in the beta-adrenoceptor-adenylate cyclase system, for which down-regulation of beta-adrenergic receptors is chiefly responsible.

Edited by Lufega, 16 March 2009 - 01:11 AM.

[Happy Gringo]

Personally, I think more testosterone is GOOD! Saw Palmetto has estrogenic properties, so I would look at pygeum to stop DHT conversion.

[OneScrewLoose]

Benadryl in an anticholinergic, so it leads to increased sympathetic tone; I imagine then that this should (in theory) lead to andrenergic receptor downregulation, though it's iffy.
As per everything you're doing, OSL, I'd have to imagine evaluating all the other measures you're taking to modify your receptors is gonna be pointless if you're taking ativan; benzos are gonna chill you out no matter what.
EDIT: Oh yeah, forskolin works by downregulating cAMP, which has to do with certain neurons in the brain only firing when they're hyperpolarized-- it's a little confusing.

I'm just using the ativan and the other things to keep me calm until my beta receptors downregulate, since I went off cold turkey.

[BlueCloud]

.. I've also read that forskolin can downregulate B-receptors. ..

Any source for that ? I'm under the impression that it may actually do the opposite :

Effect of forskolin on beta-adrenergic hyporesponsiveness in skin.

De Vries GW, Amdahl LD, Lowe N, Wheeler LA.

Author information

Abstractbeta-Adrenergic receptor hyporesponsiveness has been observed in psoriasis and after exposure of epidermis to phorbol esters. It was the purpose of our studies to determine if forskolin, which is known to act synergistically with receptor agonists in elevating endogenous levels of cyclic AMP, could return these responses to those seen under control conditions. It was observed that topical application of phorbol ester to mouse ears in vivo led to a significant reduction in isoproterenol stimulation of cyclic AMP in vitro. Low doses of forskolin (10(-7) M) were able to enhance isoproterenol's effect under these conditions. Similarly, human keratinocyte cell cultures treated with phorbol esters and human psoriatic epidermis in vitro were both hyporesponsive to isoproterenol. Again, pretreatment of these samples with forskolin restored the beta-agonist stimulation to control values. These data indicate that forskolin is still able to act synergistically with beta-agonists in hyporesponsive systems and suggest that forskolin may be a useful probe in defining the mechanism of this decreased responsiveness both in phorbol-ester-treated skin and in psoriasis.

http://www.ncbi.nlm..../pubmed/2856180

[jadamgo]

Any drug that has troublesome rebound should be tapered down. Also, propranolol is not appropriate for daily chronic use, as you've found. (The only exception is that a month-long course of propranolol can be used after a traumatic event to reduce the chances of developing PTSD. For any other use, be it psychiatric or cardiovascular, there are better drugs available.)

To get off it without being miserable, you need 2 things:
1. A coping mechanism "toolbox" to help deal with the anxiety in safer ways. This should include behavioral techniques like deep breathing, distraction, or mindfulness meditation, and probably also helpful supplements or drugs like aniracetam, chamomile tea, or (es-)citalopram.

2. You need to switch to a lower dose of propanolol as you taper down. Switch to 10mg tablets, and take them only as needed to take the edge off the rebound symptoms. It would be okay to take multiple tablets when needed since they're so much weaker than the capsules you're already taking.

In a week or two you'll be able to quit completely, without ever having made yourself totally miserable. That's as long as you've found another way to deal with the anxiety, of course -- if you just stop treating it, then the "rebound anxiety" would actually mostly be the re-appearance of the original anxiety symptoms.

[BlueCloud]

In a week or two you'll be able to quit completely, without ever having made yourself totally miserable.

Lol... The OP's post is 6 years old. I'm sure he has quit by now :-))))
And I just noticed it myself..

Edited by BlueCloud, 15 February 2014 - 01:02 AM.

[jadamgo]

Facepalm! And I almost always notice necroposts!