I'm not sure I follow most of these studies, but it seems alprazolam could have some benefits to bodybuilders by lowering cortisol and increasing GH without affecting PRL...am I reading these correctly? I was just switched to alprazolam after being prescribed diazepam for about 2 years, so I was interested in what it may do...

J Clin Endocrinol Metab. 2005 Aug;90(8):4777-83. Epub 2005 May 31.
Effects of dehydroepiandrosterone and alprazolam on hypothalamic-pituitary responses to exercise.
Deuster PA, Faraday MM, Chrousos GP, Poth MA.

MPH, Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814-4799, USA. pdeuster@usuhs.mil

CONTEXT: The hypothalamic-pituitary-adrenal axis (HPA) is restrained by activation of gamma-amino-butyric acid receptors. Alprazolam (APZ) and dehydroepiandrosterone (DHEA) are purported to be gamma-amino-butyric acid agonists and antagonists, respectively. OBJECTIVE: Our objective was to examine the effects of APZ and DHEA alone and in combination on HPA axis activity. DESIGN: This was a double-blind, crossover, placebo-controlled study. SETTING: The study setting was the general community. PARTICIPANTS: Subjects consisted of 15 men (age, 20-45 yr) with a body mass index of 20-25 kg/m2. INTERVENTIONS: DHEA (100 mg/d) or placebo was given for 4 wk, followed by a 2-wk washout; participants ingested 0.5 mg APZ or placebo 10 and 2 h before high-intensity exercise. OUTCOME MEASURES: We measured basal and exercise-induced ACTH, arginine vasopressin (AVP), cortisol, DHEA, and GH responses. It was hypothesized that DHEA would enhance and APZ would blunt exercise-induced ACTH and cortisol release. Results: DHEA significantly increased the AVP response to exercise (P < 0.01). APZ treatment significantly increased basal GH and blunted plasma cortisol, ACTH, AVP, and DHEA responses to exercise (P < 0.05). DHEA and APZ in combination significantly increased the GH response to exercise (P < 0.01). CONCLUSIONS: DHEA may alter a subset of receptors involved in AVP release. Together DHEA and APZ may up-regulate GH during exercise by blunting a suppressive (HPA axis) and potentiating an excitatory (glutamate receptor) system.

PMID: 15928250 [PubMed - indexed for MEDLINE]

Psychopharmacology (Berl). 1989;98(3):369-71.
Effects of chronic alprazolam treatment on plasma concentrations of glucocorticoids, thyroid hormones, and testosterone in cardiomyopathic hamsters.
Ottenweller JE, Tapp WN, Natelson BH.

Primate Neuro-Behavioral Unit, VA Medical Center, East Orange, NJ 07019.

In the first of two experiments, young male cardiomyopathic hamsters were injected intraperitoneally twice a day for 29 days with 8 mg alprazolam/kg body weight or saline. Three hours after the same injections on day 30, they were sacrificed and plasma hormone levels were measured. Alprazolam increased cortisol, total glucocorticoid and triiodothyronine levels. It did not affect corticosterone, thyroxine or testosterone levels. The same protocol was used in a second experiment, except the controls received vehicle and a third group was treated with 48 mg diazepam/kg body weight. Alprazolam again increased cortisol and total glucocorticoid levels, but not those of corticosterone. On the other hand, diazepam increased both cortisol and corticosterone levels. These experiments suggest that chronic benzodiazepine treatment can affect adrenocortical function and perhaps some aspects of thyroid function.

PMID: 2501814 [PubMed - indexed for MEDLINE]

ScientificWorldJournal. 2006 Jan 17;6:1-11.Click here to read
Neuroregulation of the hypothalamus-pituitary-adrenal (HPA) axis in humans: effects of GABA-, mineralocorticoid-, and GH-Secretagogue-receptor modulation.
Giordano R, Pellegrino M, Picu A, Bonelli L, Balbo M, Berardelli R, Lanfranco F, Ghigo E, Arvat E.

Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Italy.

The hypothalamus-pituitary-adrenal (HPA) axis exerts a variety of effects at both the central and peripheral level. Its activity is mainly regulated by CRH, AVP, and the glucocorticoid-mediated feedback action. Moreover, many neurotransmitters and neuropeptides influence HPA axis activity by acting at the hypothalamic and/or suprahypothalamic level. Among them, GABA and Growth Hormone Secretagogues (GHS)/GHS-receptor systems have been shown to exert a clear inhibitory and stimulatory effect, respectively, on corticotroph secretion. Alprazolam (ALP), a GABA-A receptor agonist, shows the most marked inhibitory effect on both spontaneous and stimulated HPA axis activity, in agreement with its peculiar efficacy in panic disorders and depression where an HPA axis hyperactivation is generally present. Ghrelin and synthetic GHS possess a marked ACTH/cortisol-releasing effect in humans and the ghrelin/GHS-R system is probably involved in the modulation of the HPA response to stress and nutritional/metabolic variations. The glucocorticoid-mediated negative feedback action is mediated by both glucocorticoid (GR) and mineralocorticoid (MR) receptors activation at the central level, mainly in the hippocampus. In agreement with animal studies, MRs seem to play a crucial role in the maintenance of the circadian ACTH and cortisol rhythm, through the modulation of CRH and AVP release. GABA agonists (mainly ALP), ghrelin, as well as MR agonists/antagonists, may represent good tools to explore the activity of the HPA axis in both physiological conditions and pathological states characterized by an impaired control of the corticotroph function.

PMID: 16432622 [PubMed - indexed for MEDLINE]

J Endocrinol Invest. 2002 May;25(5):420-5.
Alprazolam, a benzodiazepine, blunts but does not abolish the ACTH and cortisol response to hexarelin, a GHRP, in obese patients.
Grottoli S, Arvat E, Gauna C, Maccagno B, Ramunni J, Giordano R, Maccario M, Deghenghi R, Ghigo E.

Department of Internal Medicine, University of Torino, Italy.

GH secretagogues (GHS) act on specific receptors at the pituitary and hypothalamic level and possess potent GH-releasing activity but also stimulate prolactin (PRL), ACTH and cortisol (F) secretion. However, hyperactivity of the HPA axis in obesity has been reported. The objective of this study was to clarify the endocrine activity of GHS in obesity. In nine obese patients (obese OB), 9 F, age, (34.8 +/- 3.7 y, body mass index (BMI), 35.0 +/- 2.2 kg/m2; WHR, 0.9 +/- 0.02), 14 controls (normal subjects, NS), 14 F, 30.4 +/- 0.9 y, 20.0 +/- 0.4 kg/m2), we studied the ACTH, F and GH responses to hexarelin (HEX, 2.0 microg/kg), a peptidyl GHS, alone and preceded by alprazolam (ALP, 0.02 mg/kg), and a benzodiazepine which has an inhibitory effect on corticotroph secretion. The HEX-induced ACTH response in OB was higher than that in n.s., but this difference did not attain statistical significance. In n.s. the HEX-induced ACTH response was abolished by ALP (P < 0.03) which, however, only blunted that in OB (P < 0.02). The GH response to HEX in OB was lower (P < 0.02) than that in n.s.. ALP blunted the GH response to HEX in n.s. (P < 0.03) while it did not modify that in OB. The GABAergic activation by alprazolam abolishes the ACTH response to hexarelin in normal subjects, while it only blunts that in obese subjects. Moreover, alprazolam blunts the GH response to hexarelin in normal but not in obese subjects. Thus, obese patients show partial refractoriness to the inhibitory effect of alprazolam on both corticotroph and somatotroph function.

PMID: 10997633 [PubMed - indexed for MEDLINE]

J Endocrinol Invest. 2002 Sep;25(8):735-47.
Benzodiazepines and anterior pituitary function.
Arvat E, Giordano R, Grottoli S, Ghigo E.

Department of Internal Medicine, University of Turin, Italy. e.arvat@libero.it

Benzodiazepines (BDZ) are one of the most prescribed classes of drugs because of their marked anxiolytic, anticonvulsant, muscle relaxant and hypnotic effects. The pharmacological actions of BDZ depend on the activation of 2 specific receptors. The central BDZ receptor, present in several areas of the central nervous system (CNS), is a component of the GABA-A receptor, the activation of which increases GABAergic neurotransmission and is followed by remarkable neuroendocrine effects. The peripheral benzodiazepine receptors (PBR), structurally and functionally different from the GABA-A receptor, have been shown in peripheral tissues but also in the CNS, in both neurones and glial cells, and in the pituitary gland. BDZ receptors bind to a family of natural peptides called endozepines, firstly isolated from neurons and glial cells in the brain and then in several peripheral tissues as well. Endozepines modulate several central and peripheral biological activities, including some neuroendocrine functions and synthetic BDZ are likely to mimic them, at least partially. BZD, especially alprazolam (AL), possess a clear inhibitory influence on the activity of the HPA axis in both animals and humans. This effect seems to be mediated at the hypothalamic and/or suprahypothalamic level via suppression of CRH. The strong negative influence of AL on hypothalamicpituitary-adrenal (HPA) axis agrees with its peculiar efficacy in the treatment of panic disorders and depression. BZD have also been shown to increase GH secretion via mechanisms mediated at the hypothalamic or supra-hypothalamic level, though a pituitary action cannot be ruled out. Besides the impact on HPA and somatotrope function, BDZ also significantly affect the secretion of other pituitary hormones, such as gonadotropins and PRL, probably acting through GABAergic mediation in the hypothalamus and/or in the pituitary gland. In all, BDZ are likely to represent a useful tool to investigate GABAergic activity and clarify its role in the neuroendocrine control of anterior pituitary function; their usefulness probably overrides what had been supposed before.

PMID: 12240908 [PubMed - indexed for MEDLINE]

Diazepam reduces cortisol too.


Cortisol response to diazepam: its relationship to age, dose, duration of treatment, and presence of generalized anxiety disorder.
Pomara N, Willoughby LM, Sidtis JJ, Cooper TB, Greenblatt DJ.Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Building 35, Orangeburg, NY 10962, USA. pomara@nki.rfmh.org

OBJECTIVE: Acute diazepam administration has been shown to decrease plasma cortisol levels consistent with decreased activity of the hypothalamic-pituitary-adrenal axis, especially in individuals experiencing stress. However, the effects of chronic diazepam treatment on cortisol have been less studied, and the relationship to age, anxiety, duration of treatment, and dose are not well understood. METHOD: This double-blind placebo-controlled study examined acute and chronic effects of diazepam on plasma cortisol levels in young (19-35 years) and elderly (60-79 years) individuals with and without generalized anxiety disorder (GAD). Subjects received single oral challenges of placebo or diazepam (2.5 mg or 10 mg) in a placebo-controlled cross-over design, followed by 3 weeks of chronic daily treatment with 2.5 mg or 10 mg diazepam or placebo taken at 10 p.m., and then by a final acute challenge with a single oral dose of the same study medication received during chronic treatment. RESULTS: The elderly experienced significant reductions in plasma cortisol levels compared to placebo both in the initial challenge and during chronic treatment, but the young did not. However, cortisol response to drug was comparable in both groups. Final challenge did not produce any significant cortisol effects in either group and the cortisol response in the elderly was significantly reduced compared to the initial challenge. GAD status was not a factor in plasma cortisol responses to diazepam. CONCLUSIONS: Diazepam reduced cortisol both acutely and during chronic treatment, but not during final challenge, consistent with some tolerance development. This effect was most apparent in the elderly compared with the young adults and was not modulated by GAD status or dosage, and was not related to drug effects on performance and on self-ratings of sedation and tension.

PMID: 15338100 [PubMed - indexed for MEDLINE]


Alprazolam also,supposed to be a unique benzo for its antidepressant properties as well as anxiety reducing;

http://en.wikipedia.org/wiki/Alprazolam

There is some evidence for antidepressant treatment of clinical depression in out patient settings, evidence for inpatients is lacking;^[9] other benzodiazepines are not known to have antidepressant activity.

Also;

[Alprazolam in the treatment of anxiety disorders and mixed anxiety and depressive disorders. Results of multicenter clinical trial]
[Article in Polish]

Kiejna A, Małyszczak K, Rzewuska M, Sobucka K, Florkowski A, Rajewski A, Rajewska J, Wojtanowska M, Dabkowski M, Brzeziński R, Rybakowski J, Sep-Kowalikowa B, Gałuszko P, Nowicki Z.Katedry i Kliniki Psychiatrii AM we Wrocławiu.

Alprazolam is one of the most commonly prescribed psychotropics drug all over the world. This suggests that alprazolam is very effective and safe. A multicentre clinical trial was carried out for assessing its efficacy and side effects. 130 patients suffering from anxiety disorders, mixed anxiety and depressive disorders and dysthtymia were involved in the trial. During 6 weeks they used to take from 1.5 to 2.5 mg. of alprazolam daily. Mental state has been assessed with Hamilton rating scales of anxiety and depression, Montgomery Asberg scale of depression and CGI scales. At the endpoint good recovery was found in 75% of the patients, mild recovery in 19%, and 6% got worse. The effect of treatment depends on individual patients' traits rather than on initial mental state. Adverse events were noted in a half of patients, were not severe and were going down during the treatment. 4.6% of patients dropped out because of adverse events, the others tolerated alprazolam well.

PMID: 9132771 [PubMed - indexed for MEDLINE]

True, but diazepam just makes me lazy for way too long.

Am I missing something here? (honestly im no pro at this stuff) But thats like giving a 220lb man 400 bars. That seems just a wee bit excessive. 1/2 a bar and im Tom Tankredo'd. Whats the known LD50 on ALZ?

(forgive me if I missed something)

EDIT:suck at quotes

LOL Yeah, a little excessive, eh?

QQ

What?

Swtichching from diaz to alprazolam will be interestig - note that the short half life of alprazolam if quite difference from the 24 hr .. 48 hr half life of diaz (this inculdes the various derivatives that some people think (thought?) were the primary actives.
If you are taking it for anxiety, you will need to does it frequently.

In fact, I know someone who might get mild panic attacks when they thought that they had missed a dose.

I've been doing .5mg 2-3x a day, and doing just fine. I was prescribed 2mg twice a day but I don't need nearly that much.

It's actually almost impossible to cause a lethal reaction by overdose of most of the anxiolytic benzos.

This was their advantage over the barbiturates.

The acute LD50 of alprazolam in rats is 331 to 2171 mg/kg. Other animal experiments have shown that direct intravenous introduction of doses over 195 mg/kg.

X2 you have to take A LOT to die from benzos.

Wait a second, you may not die from toxicity, but what about respiratory failure? I'm pretty sure you wouldn't need ~150mg per kilogram to cause that.

http://www.fda.gov/cder/foi/label/2003/21434_xanax_lbl.pdf

OK? Why did you bold depersonalization? Are you saying I've been depersonalized?

Ha no. I found it funny it was a "Frequent" side effect. Aside from rare conditions I think benzos should be avoided.

Oh ok...but those are the side effects of physical dependence, not just from it's use. It may well be a frequent side effect of withdraw/dependence, I'm just not there yet.

choke them on it!




via the benzodiazepine's mechanism of action, it stops being effective once you take enough and additional alprazolam does almost nil. that's why you need that much -- just about an impossible feat for a human