23 replies to this topic

[virginiap]

Hi all What a relief to find this community.

 

I have been experiencing intense withdrawal symptoms while still taking the same dose, 60 mg. I have been taking Cymbalta for 3.5 years and have been wanting to get off for a while. Last week I did a "meditation" and told my body to "take what it needs but forget the rest," from the capsule. Then I began experiencing withdrawal symptoms. My psych has prescribed me gabapentin to manage the symptoms and then we are going to begin the taper. 

 

I am confused as to why this is happening. I recently have been working with a clinical nutritionist to address my CAEBV, Chronic Active Epstein Barr Virus, and have been taking a lot of supplements, e.g., b complex, magnesium, antioxidants. I am always scrupulous to ensure that there will not be any contraindications. Is it possible because my body is beginning to heal that now it is metabolizing the duloxetine differently? Any shared experiences comments or advice are welcome. 

 

It is very scary to feel this way and not know what is going on. I am so sorry we are all struggling. Love to all, thank you xo.

 

p.s. this morning when I took the cymbalta I told my body to "take this and use it to balance," hoping that helps. 

[fishinghat]

Welcome Virginia

 

Many vitamins and minerals effect Cymbalta absorption. Things like vitamin B6, magnesium, calcium, iron, vitamin C and others either directly effect the same CYP enzymes that process Cymbalta or the pH of the digestive tract which will also effect absorption. Recent weight gain will decrease Cymbalta in the blood and store it in the new fat tissue. Weight loss will cause Cymbalta in the fat tissue to be released and will increase the blood levels in the blood. These are just examples of things that can increase or decrease your blood levels or impact the generation of neurotransmitters.  If you would wish to post the list of your supplements and there dosage I will be glad to look over it in the morning.

[invalidusername]

Hi Virginia.

 

Not much at all to add to what Hat has said, but I would put good money on it being the supplements that you are taking which will be affecting the absorption of the Cymbalta. If these supplements must be taken then you need to take them at least two hours apart from the Cymbalta. 

 

If the timing of the supplements is set in stone, then you might consider changing the time you take the Cymbalta which needs to be done slowly, not 8am one day and 6pm the next, you would need to move a couple of hours at a time and space it over a week or so. You could also spread your Cymbalta dose and take half every 12 hours if that helps with the timing.

[virginiap]

Wow!! Thank you both so much. I hate cymbalta! Ha! I am excited but nervous to begin the taper in a few weeks. After this last week though I think I am prepared. And I am so grateful to have found this community as well.

 

So the question remains, do I halt the supplements that have given me back my health and vigor because I am a slave to a pharmaceutical? At this time, it seems that yes, yes I do. 

 

I have experienced both weight gain and weight loss while taking cymbalta. I have done a little research in regards to the CYP enzymes but I guess I need to do more as I do not fully understand the mechanism yet. I imagine so many things affect the PH levels of our digestive tract, what an unstable, immensely powerful drug to prescribe to millions of people! I will post my full list of supplements, that is incredibly generous of you fishinghat, thank you so much. Do you think what invalid has suggested will ensure proper absorption and thus sufficient generation of neurotransmitters? I have been taking most of these supplements for over 2 months and it is only in the last few weeks that I have noticed mood changes and then these intense withdrawal symptoms. I also have been experiencing the intense abdominal pain that I first experienced when initially prescribed duloxetine in 2017. I believe it is due to the HCL in the capsule. Any familiarity with this? I have started making sure I have enough food in my stomach before taking the duloxetine, which is what I did back then as well. I do not know why I have started experiencing this again, maybe because my gut has started to heal after all of the damage. As the cymbalta is extended release will the supplements affect the absorption no matter what? What a frustrating thing! Again I am so grateful for both of your responses and knowledge. Neither the clinical nutritionist nor the psychiatrist I am working with have mentioned any of this.. And of course the initial prescriber said no such thing.. 

 

I have one final question, what about THC? I am a routine user of low thc:cbd organic marijuana. It has helped me with the physical symptoms of my prolonged fight with epstein barr as well as the mental and emotional. I know it is psychoactive and acts on the CNS so is not ideal. I have also heard that cigarette smoke can have an effect on cymbalta metabolism. I no longer smoke cigarettes, but is this true with marijuana smoke as well? I have not been smoking the last week or so because of my withdrawal symptoms but I would like to again in the future. I know THC is not great for the brain but it has to be better than this godforsaken drug. Again, I have been smoking and/or eating edibles while taking the duloxetine for a few years and this is the first time I have noticed such intense withdrawal symptoms.

 

Thank you both again. I will post my supplements below, I am very appreciative and grateful. Bless you both. 

[virginiap]

Pardon some of the notes, this was initially for the psychiatrist. I am trying to figure out a way to share the supplement facts that list the specific vitamins in each supplement.

 

Duloxetine Hcl, 67.3 mg, equivalent to 60mg duloxetine, 9am or 9:30am, have been on since August 2017. Store at 77 degrees F, has not been stored at that temperature, says “excursions permitted to 59-86 degrees F. Maybe it got too cold and efficacy has diminished. Withdrawal symptoms worsen as the day goes on, around 2:30 pm and then also 1am-2am last night. Feel OK upon waking, possible my body is metabolising it differently due to improved nutritional status? Or capsules are compromised. 

 

NAC (pure encapsulations), 1800 MG 3x per day per Kasia Kines, phD functional clinical nutritionist. Working with her for CAEBV, Chronic Active Epstein Barr Virus, have been taking NAC dose for two months or so. 

 

https://kasiakines.com/epstein-barr/

 

Chaste tree/vitex (gaia herbs), 100 mg in AM, have been taking for a while.

 

Ashwagandha (gaia herbs), 350 mg in AM and PM, also has withanolides 2.5 mg.

 

Nutrametrix, isotonic vitamins, (highly bioavailable probably to blame):

Activated b complex, 2x a day, 3 during times of high stress. Have not been taking 3 the last week due to withdrawal symptoms from duloxetine.

Magnesium, 2x a day.

Immune, 1x a day

OPC3, 2x a day

ORAC, 1x a day

Bromelain, 1x a day

 

Heart Health Fish oil, 3000mg, 2x a day, 3x in “times of crisis,” i.e. now. 

 

Pure encapsulations DIM Detox, 2x a day. Have been taking this for over a year, stopped taking it a few days ago due to l-methionine, 200 mg and possible interaction (same liver pathway)? Thinking now it may actually be helpful.

 

Ortho Molecular products, liquid Vitamin D3 with K2, taking 5000mcg-10,000mcg a day. Did a few days of 20,000mcg re: MS study involving high doses of vitamin D. Back to 5,000 mcg now. Don’t think this can affect duloxetine metabolism. I don’t know.

 

Garden of Life Once Daily Women’s probiotics, switched from “Mood probiotics” same brand. A few days off last week while waiting for Women’s probiotics. Maybe this has an effect, doesn’t seem likely. 

 

NOW liquid Melatonin, 1.5mg to 3mg nightly.

 

Sunsoil CBD Oil, full spectrum hemp extract, 15-30mg daily.

[virginiap]

Here is a link to a google doc with the supplement facts, I am unable to share the images here. The link is available to be viewed by anyone. Thank you again and of course no pressure to review any of this. I realize that I also typically start the day with warm water with lemon, usually within 2 hours of taking my cymbalta. This surely affects the PH in my digestive tract.

 

Invalid, I think you have won the bet! I have the capsules with a lot of beads inside of them. I opened one last week in a moment of desperation but I currently don't have the wherewithal to count them out. Thank you so much for the invaluable advice. What is cymbalta like in the UK? I was on trazadone in the past while I stayed in the french Caribbean for 4 months and I had to wean myself off as they don't prescribe trazadone in France I guess. What a novel thought ! I didn't realize trazadone was also an antidepressant at the time, I thought it was just a sedative so my mood was quite unstable for a while. Do you think if I continue to take the supplements but provide a window of at least two hours my absorption will be okay? Also, where does the 2 hours come from? I feel I have so much learning and catching up to do. Thanks again.

[fishinghat]

IUN's suggestion may not fully resolve the issues but certainly should help.

 

"I believe it is due to the HCL in the capsule. Any familiarity with this?"

I doubt this as most medications are in the HCL form in order to make them easier on the stomach. The primary stomach acid is HCL.

 

"As the cymbalta is extended release will the supplements affect the absorption no matter what?"

Unlikely as the pH in the intestines (that is where Cymbalta is absorbed) is much higher than in the stomach.  But that is why the suggestion of at least a two hour suggestion. This gives better separation between the supplements and the Cymbalta in your digestive tract.

 

 "I have also heard that cigarette smoke can have an effect on cymbalta metabolism. I no longer smoke cigarettes, but is this true with marijuana smoke as well? "

That is a new one on me. i will have to check into it. Of course stopping smoking while on cigarettes can cause nicotine withdrawal which could add to any concurrent Cymbalta withdrawal.

 

"Withdrawal symptoms worsen as the day goes by, goes on, around 2:30 pm and then also at 1am-2am last night."

This is very interesting that your withdrawal symptoms worsen after you take the Cymbalta. This is the opposite of the normal situation. Normally shortly after taking the Cymbalta withdrawal lessens as the increase in Cymbalta brings some relief. Then later in the day as your blood levels of Cymbalta start to decrease the withdrawal intensifies again. It may be that your body is no longer tolerating the Cymbalta. Just a guess.

   

 "I have also heard that cigarette smoke can have an effect on cymbalta metabolism. I no longer smoke cigarettes, but is this true with marijuana smoke as well? "

That is a new one on me. i will have to check into it. Of course stopping smoking while on cigarettes can cause nicotine withdrawal which could add to any concurrent Cymbalta withdrawal.

 

"Withdrawal symptoms worsen as the day goes by, goes on, around 2:30 pm and then also at 1am-2am last night."

This is very interesting that your withdrawal symptoms worsen after you take the Cymbalta. This is the opposite of the normal situation. Normally shortly after taking the Cymbalta withdrawal lessens as the increase in Cymbalta brings some relief. Then later in the day as your blood levels of Cymbalta start to decrease the withdrawal intensifies again. It may be that your body is no longer tolerating the Cymbalta. Just a guess.

   

Details on the supplements will be forthcoming.

[fishinghat]

Right now the site will not let me post anything long. Will try again later.

[fishinghat]

Well I guess I will have to post this in sections. Here goes.

 

Thank you so much Virginia as this could have serious effects on Cymbalta withdrawal.

 

 

https://pubmed.ncbi....h.gov/30192450/

 

Differences in Duloxetine Dosing Strategies in Smoking and Nonsmoking Patients: Therapeutic Drug Monitoring Uncovers the Impact on Drug Metabolism

 

Abstract

Background: For certain psychotropic drugs, such as clozapine or olanzapine, the influence of smoking on drug metabolism is well studied. Tobacco smoke increases the metabolism of drugs that are substrates for cytochrome P450 (CYP) 1A2 due to CYP induction. The antidepressant duloxetine, acting as a serotonin-norepinephrine reuptake inhibitor, is mainly metabolized via CYP1A2. To date, little is known about the influence of smoking on serum duloxetine concentrations.

 

Methods: A therapeutic drug monitoring database consisting of plasma concentrations of duloxetine collected from January 2013 to June 2017 was analyzed. A group of nonsmoking patients undergoing treatment with duloxetine (n = 89) was compared to a group of active smokers also receiving duloxetine (n = 36). Serum concentrations of duloxetine and dose-adjusted serum concentrations were compared using non-parametric tests.

 

Results: Groups did not differ concerning sex (P = .063), but the group of active smokers was younger (P < .001) and received higher daily doses of duloxetine (P = .001). Smokers showed significantly lower median serum duloxetine concentrations (38.4% lower, P = .002) and 53.6% lower dose-adjusted serum concentrations (0.325 [ng/mL]/[mg/d] in smokers vs 0.7 [ng/mL]/[mg/d] in nonsmokers, P < .001).

 

Conclusions: Despite higher daily doses, smokers had considerably lower serum duloxetine concentrations. The induction of CYP1A2 by tobacco smoke is a clinically relevant factor for drugs that are substrates for CYP1A2. Clinicians should actively assess smoking status, inform patients about the effect of smoking on duloxetine metabolism, and anticipate higher serum concentrations in the case of smoking cessation. Therapeutic drug monitoring ensures treatment efficacy by enabling the personalizing of treatment, as smokers need higher duloxetine doses to target serum concentrations within the therapeutic reference range.

[fishinghat]

https://pubmed.ncbi....h.gov/18651344/

The influence of smoking on the serum level of duloxetine

 

Abstract

Duloxetine is a dual acting antidepressant (selective serotonin and norepinephrine reuptake inhibitor). Existing data suggest that the advisable therapeutic serum level of duloxetine ranges between 20 and 80 ng/mL. In a naturalistic setting we determined duloxetine serum levels within a steady state in a sample of depressive inpatients by high performance liquid chromatography (HPLC). The mean serum levels in 28 patients at the time of the first TDM analysis were 52.0+/-67 ng/mL. Eight of the patients were smokers and showed a considerably lower serum level of 24.3+/-18.8 ng/mL. In the further course of treatment the difference was compensated by application of higher doses in smokers. These findings suggest that smoking is associated with lower duloxetine serum levels due to an induction of CYP1A2 by polycylic hydrocarbons which are contained in tobacco smoke. Therefore in smokers higher doses of duloxetine (about 15%) seem to be necessary to reach adequate serum levels.

 

 

https://www.japha.or...0007-8/fulltext

 

Smoking cessation and duloxetine toxicity: A case report

 

Abstract

Objective

Psychiatric medications are among the drugs affected by cigarette smoke, and because of the high prevalence of smoking in the psychiatric community, psychiatric patients are particularly at risk when entering the smoke-free environment of a hospital.

 

Case summary

Polycyclic aromatic hydrocarbons present in cigarette smoke are well-known inducers of cytochrome P450 (CYP) enzymes. CYP1A2 induction by cigarette smoking increases metabolic clearance of substrates of this enzyme; smoking cessation results in a decrease in CYP1A2 activity, which causes an increase in serum substrate levels. Although these effects are well documented, the effect of smoking cessation remains a hidden danger, in part, because computerized drug interaction surveillance systems are not designed to alert clinicians when an offending agent is discontinued.

 

Practice implication

To raise awareness and demonstrate the importance of a thorough assessment of smoking status, we present a case in which the temporal relationship of smoking cessation to the emergence of nausea, vomiting, and tachycardia 3 days later (day 3); the development of myoclonic jerks by day 5; and the resolution of symptoms on reduction of duloxetine dosage on day 44 implicates duloxetine toxicity in a patient with ischemic cardiomyopathy awaiting implantation of a left ventricular assist device.

[fishinghat]

And lastly about smoking...

 

 

https://pubmed.ncbi....h.gov/21366359/

 

Duloxetine: clinical pharmacokinetics and drug interactions 

 

Abstract 

Duloxetine, a potent reuptake inhibitor of serotonin (5-HT) and norepinephrine, is effective for the treatment of major depressive disorder, diabetic neuropathic pain, stress urinary incontinence, generalized anxiety disorder and fibromyalgia. Duloxetine achieves a maximum plasma concentration (C(max)) of approximately 47 ng/mL (40 mg twice-daily dosing) to 110 ng/mL (80 mg twice-daily dosing) approximately 6 hours after dosing. The elimination half-life of duloxetine is approximately 10-12 hours and the volume of distribution is approximately 1640 L. The goal of this paper is to provide a review of the literature on intrinsic and extrinsic factors that may impact the pharmacokinetics of duloxetine with a focus on concomitant medications and their clinical implications. Patient demographic characteristics found to influence the pharmacokinetics of duloxetine include sex, smoking status, age, ethnicity, cytochrome P450 (CYP) 2D6 genotype, hepatic function and renal function. Of these, only impaired hepatic function or severely impaired renal function warrant specific warnings or dose recommendations. Pharmacokinetic results from drug interaction studies show that activated charcoal decreases duloxetine exposure, and that CYP1A2 inhibition increases duloxetine exposure to a clinically significant degree. Specifically, following oral administration in the presence of fluvoxamine, the area under the plasma concentration-time curve and C(max) of duloxetine significantly increased by 460% (90% CI 359, 584) and 141% (90% CI 93, 200), respectively. In addition, smoking is associated with a 30% decrease in duloxetine concentration. The exposure of duloxetine with CYP2D6 inhibitors or in CYP2D6 poor metabolizers is increased to a lesser extent than that observed with CYP1A2 inhibition and does not require a dose adjustment. In addition, duloxetine increases the exposure of drugs that are metabolized by CYP2D6, but not CYP1A2. Pharmacodynamic study results indicate that duloxetine may enhance the effects of benzodiazepines, but not alcohol or warfarin. An increase in gastric pH produced by histamine H(2)-receptor antagonists or antacids did not impact the absorption of duloxetine. While duloxetine is generally well tolerated, it is important to be knowledgeable about the potential for pharmacokinetic interactions between duloxetine and drugs that inhibit CYP1A2 or drugs that are metabolized by CYP2D6 enzymes. 

 

Note - Furthermore, as shown below, nicotine has significant effects on serotonin and norepinephrine which not only could but probably would effect Cymbalta withdrawal.

 

https://pubmed.ncbi....h.gov/19452140/

 

Abstract 

Duloxetine, a potent reuptake inhibitor of serotonin (5-HT) and norepinephrine, is effective for the treatment of major depressive disorder, diabetic neuropathic pain, stress urinary incontinence, generalized anxiety disorder and fibromyalgia. Duloxetine achieves a maximum plasma concentration (C(max)) of approximately 47 ng/mL (40 mg twice-daily dosing) to 110 ng/mL (80 mg twice-daily dosing) approximately 6 hours after dosing. The elimination half-life of duloxetine is approximately 10-12 hours and the volume of distribution is approximately 1640 L. The goal of this paper is to provide a review of the literature on intrinsic and extrinsic factors that may impact the pharmacokinetics of duloxetine with a focus on concomitant medications and their clinical implications. Patient demographic characteristics found to influence the pharmacokinetics of duloxetine include sex, smoking status, age, ethnicity, cytochrome P450 (CYP) 2D6 genotype, hepatic function and renal function. Of these, only impaired hepatic function or severely impaired renal function warrant specific warnings or dose recommendations. Pharmacokinetic results from drug interaction studies show that activated charcoal decreases duloxetine exposure, and that CYP1A2 inhibition increases duloxetine exposure to a clinically significant degree. Specifically, following oral administration in the presence of fluvoxamine, the area under the plasma concentration-time curve and C(max) of duloxetine significantly increased by 460% (90% CI 359, 584) and 141% (90% CI 93, 200), respectively. In addition, smoking is associated with a 30% decrease in duloxetine concentration. The exposure of duloxetine with CYP2D6 inhibitors or in CYP2D6 poor metabolizers is increased to a lesser extent than that observed with CYP1A2 inhibition and does not require a dose adjustment. In addition, duloxetine increases the exposure of drugs that are metabolized by CYP2D6, but not CYP1A2. Pharmacodynamic study results indicate that duloxetine may enhance the effects of benzodiazepines, but not alcohol or warfarin. An increase in gastric pH produced by histamine H(2)-receptor antagonists or antacids did not impact the absorption of duloxetine. While duloxetine is generally well tolerated, it is important to be knowledgeable about the potential for pharmacokinetic interactions between duloxetine and drugs that inhibit CYP1A2 or drugs that are metabolized by CYP2D6 enzymes. 

[fishinghat]

NAC is a great supplement to take as it has a calming effect on neurotransmitter performance. I am very concerned about that dosage however. Normally I see people taking 600 mg up to twice a day. I will look into this as well.

The highest dose ever evaluated that I could find in the medical journals was 2400 mg/day. (ncbi)

 

https://europepmc.or.../PMC/PMC7892733

This report says that the highest dose evaluated was 3000 mg/day and was well tolerated. 

 

Many members have found it useful during benzo withdrawal.

 

More to follow.

[fishinghat]

Chaste tree/vitex (gaia herbs)

 

https://examine.com/...astus/research/

 

3.1Dopaminergic Neurotransmission

There appears to be dopaminergic agonists (D2 receptor assays) in the ethanolic:water extract BNO-1095.[10] When testing isolated molecules, B115 was the most potent at 1uM having similar binding affinity to 218nM dopamine but the two clerodadienol structures appeared to be more practically relevant due to a higher concentrations; with their aspect of the extract exerting 5.7-fold more dopaminergic action than B115 and accounting for over 50% of dopaminergic action of Vitex Agnus.[10] The water, butanol, and chloroform extract do not actually appear to possess any significant dopaminergic activity as all activity is concentrated in hexane or ethanolic extracts.[9]

 

Beyond the clerodadeinol compounds, others that may contribute to dopaminergic effects are linoleic acid (IC50 of 40+/-12ug/mL), Rotundifuran (45+/-7ug/mL), and 6β,7β-diacetoxy-13-hydroxy-labda-8,14-diene (IC50 of 79+/-12ug/mL).[9] 

 

3.2Melatonergic Neurotransmission

In men, Vitex Agnus appears to have dose-dependent effects on inducing melatonin secretion.[24] 120mg and 480mg of a 5:1 extract (0.6g and 2.4g dry extract equivalent) increased Melatonin AUC in serum approximately 20%, with more significance during sleep, in an open label trial.[24]

 

3.3Opioidergic Neurotransmission

A basic 90% methanolic extract of Vitex Agnus Castus (VAC) has an IC50 of 88.4+/-8.47µg/mL on the Gamma-Opioid receptor, and the potency of the chloroform subset appeared to be enhanced with an IC50 of 23.8+/-2.81µg/mL and the EtOAc with an IC50 of 62.2+/-18.5µg/mL; no affinity was found in the water extract for either Gamma or Delta receptors.[25] IC50 of the methanolic, chloroform, and EtOAc extracts against the Delta-Opioid receptor were 43.0+/-7.78µg/mL, 21.4+/-3.84µg/mL, and 20.7+/-16.9µg/mL; respectively.[25] Interaction with the Opioid receptors appears to be noncompetitive.

The flavonoids of apigenin, luteolin, 3-methylkaempferol, and casticin have been reported to have dose-dependent agonistic properties on Gamma and Delta opioid receptors with isokaempferide having no effect[25][17] and the effects on the Delta opioid receptor possibly only coming from Casticin;[25] the opioid activating ingredients appear to be present in chloroform or ethanolic extracts for the most part.[4][25][17]

 

Casticin appears to be the most prominent player here (as defatted extracts do not have affinity, suggesting fatty acids play no role[4]), binding to both receptors with IC50 values on Gamma-Opioid and Delta-Opioid being 2.84+/-0.707uM and 2.05+/-0.631uM while other flavonoids ranged in the 20-40uM range.[25] It is unable to activate the Gamma-Opioid receptor, but activates the Delta-Opioid receptor with an EC50 value of 15.3+/-6.32uM and Emax of 74.6+/-18.2%.[25]

 

Fat soluble compounds in Vitex Agnus appear to have efficacy in interacting with opioid receptors, and Casticin has been demonstrated to activate the opioid receptors

 

Opioid activity may play a role in Hot Flash symptoms due to a decrease of opioid activity preceding adrenergic instability (assessed by withdrawal from Opioid acting drugs)[26][27] with is hypothesized to be normalized with opioid activity.[28] Lower levels of B-endorphin (opioid peptide) has also been noted in menopause,[29][30] and activation of Opioid receptor expressing neurons tends to release B-endorphin compounds.[31][32]

 

Activation of Opioid receptors may release B-endorphin, which is inversely correlated with symptoms of menopause

 

3.4Serotonergic Neurotransmission

In evaluating a variety of bioactives including flavonoids, no molecule appeared to have significant activity through serotonin receptors up to 40µg/mL.[17]

 

One study has noted that binding directly to serotonin receptors failed to occur with Vitex in vitro,[9] yet at least one study suggests a possible increase in anxiety at higher doses (100-300mg/kg rats) of Vitex Agnus via acting as an modulator of 5-HT1A receptors, increasing the anxiogenic effects of 5-HT1A antagonists while attenuating the anxiolytic effects of agonists.[33]

 

May interact with serotonergic mechanisms, but no evidence supports direct agonist roles. Unknown significance for supplementation

 

3.5Miscellaneous Mechanisms

When incubated in vitro with Prolactin cells, extracts from Vitex Agnus appear to suppress Prolactin secretion with the potency of one extract at 0.5mg/mL being as effective as 1uM Dopamine (reducing to 10% of control) and the other two at 5mg/mL reducing prolactin secretion to 60% of control.[10] Diterpenoid structures present in these extracts appear to be rotundifuran and clerodadienols, with the latter outperfoming dopamine (1nM) when itself was at a slightly higher concentration of 86uM (underperforming at 43uM).[10]

 

Histamine, which may influence prolactin, does not have its receptor (H1) affected with incubated Vitex Agnus.[9] This release of prolactin appears to be a downstream effect of activation of Dopamine D2 receptors.[34][35]

 

In vitro, reductions of prolactin appear to be apparent which may be mediated via D2 (dopamine) activation

 

The inhibition of prolactin release from isolated Casticin has been noted in vivo, where injections of 10, 20, and 40mg/kg for a week reduced prolactin levels by 33.9%, 54.3%, and 64.7%;[36] 1mg/kg Bromocriptine used as a reference was approximately as effective as 15mg/kg (measuring at a 44.9% reduction).[36] Another study in rats (800,1600mg/kg ethanolic extract) only noted this decrease of prolactin in rats undergoing experimental menopause (-30.44% and -37.83% at respective doses) and failed to find influence on otherwise normal female rats.[37]

 

This reduction of prolactin may be mediated via the flavonoid Casticin, although due to other compounds exerting dopaminergic actions (Clerodane Diterpenoids) it may not be the only active ingredient

 

In otherwise healthy males an extract (BP1095E1) at 120, 240, and 480mg daily for 14 days was associated with an increase in prolactin (24 hour AUC and also in response to a TRH-stimulation test) was noted with 120mg but reductions were noted with 480mg.[38]

 

Note - This supplement has numerous effects on neurotransmitters and would undoubtably effect Cymbalta withdrawal but in what way I am not certain. 

 

https://pubmed.ncbi....h.gov/27435374/

 

Antinociceptive and antidepressant-like effects of the crude extract of Vitex megapotamica in rats 

Abstract 

 

Ethnopharmacological relevance: Vitex megapotamica (Spreng) Moldenke has been used in South American folk medicine to treat inflammatory diseases. However, the effects of V. megapotamica on animal models of nociception and depression have not been evaluated. 

 

Aim of the study: This study investigated whether the crude leaf extract of V. megapotamica exhibits antinociceptive and antidepressant-like effects in a Freund's adjuvant-induced chronic inflammation and depression model. 

Materials and methods: Chronic inflammation was induced in rats by the intraplantar administration of complete Freund's adjuvant (CFA; 100μl). The effect of oral crude extract of V. megapotamica (VmE; 3-30mg/kg, p.o.) on nociception (thermal hyperalgesia, mechanical allodynia and arthritis score), inflammation (edema, myeloperoxidase activity), immobility (forced swimming test), locomotor activity (open field), gastrointestinal transit, hyperalgesia and naloxone-precipitated morphine withdrawal syndrome was evaluated. Naloxone (0.4mg/kg, i.p.) was used to investigate the involvement of opioid system in the currently described effects of VmE. 

 

Results: Crude extract caused antinociceptive/antidepressant-like effects in the CFA-induced chronic inflammation model, which was prevented by naloxone. The VmE extract (10mg/kg, p.o.) did not alter the locomotor activity, gastrointestinal function and inflammatory parameters and did not cause hyperalgesia. 

 

Conclusion: V. megapotamica induces opioid-dependent antinociception and antidepressant-like effect, without anti-inflammatory activity. The results support the use of VmE as analgesic and antidepressant. 

 

Note - There are similar antidepressant effects from other members of the Vitex family of plants. It seems to have additive effects to other antidepressants. Way too little is know about this supplement.

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[fishinghat]

Ashwagandha

(Withania somnifera )

 

 

https://www.ncbi.nlm...pubmed/25405876

All five studies concluded that WS intervention resulted in greater score improvements (significantly in most cases) than placebo in outcomes on anxiety or stress scales. 

 

https://www.ncbi.nlm...pubmed/26068424

Our results provide evidence indicating that key constituents in WS may have an important role in the development of pharmacological treatments for neurological disorders associated with GABAergic signaling dysfunction such as general anxiety disorders, sleep disturbances, muscle spasms, and seizures.

 

https://www.ncbi.nlm...pubmed/19718255

300 mg twice a day.

Final BAI scores (anxiety test) decreased by 56.5% in the Ashwagandha group. Significant differences between groups were also observed in mental health, concentration, fatigue, social functioning, vitality, and overall quality of life with the Ashwagandha group exhibiting greater clinical benefit. No serious adverse reactions were observed in either group.

 

http://www.ncbi.nlm....pubmed/24497737

250 mg 2x/day

 

http://www.ncbi.nlm....pubmed/24330893

500 mg/day for bipolar, effective.

 

http://www.ncbi.nlm....pubmed/23439798

Each capsule contained 300 mg of high-concentration full-spectrum extract from the root of the Ashwagandha plant. Each person took 2 capsules a day. The treatment group that was given the high-concentration full-spectrum Ashwagandha root extract exhibited a significant reduction in scores on all the stress-assessment scales on Day 60, relative to the placebo group. The serum cortisol levels were substantially reduced in the Ashwagandha group, relative to the placebo group. No serious adverse events were reported.

 

http://www.ncbi.nlm....pubmed/22546655

W. somnifera extract is effective in treating obsessive compulsive disorder

https://www.ncbi.nlm...pubmed/18697607

The results suggest the protective effect of WS in the management of ethanol (alcohol)withdrawal reactions.

 

https://www.ncbi.nlm...pubmed/17585686

Preliminary results suggest that Withania root extract can be used in the management sleep loss and associated oxidative stress.

 

http://www.ncbi.nlm....pubmed/19363747

Effective for anxiety

 

http://www.ncbi.nlm....pubmed/11194174

WSG also exhibited an antidepressant effect, comparable with that induced by imipramine in the 'behavioural despair' and 'learned helplessness' tests. The investigations support the use of WS as a mood stabilizer in clinical conditions of anxiety and depression 

 

http://www.ncbi.nlm....les/PMC3252722/

It has a Cognition Promoting Effect and was useful in children with memory deficit and in old age people loss of memory. It was also found useful in neurodegenerative diseases such as Parkinson's, Huntington's and Alzeimer's diseases. It has GABA mimetic effect and was shown to promote formation of dendrites. It has anxiolytic effect and improves energy levels and mitochondrial health. It is an anti-inflammatory and anti-arthritic agent and was found useful in clinical cases of Rheumatoid and Osteoarthritis.

 

http://www.ncbi.nlm....les/PMC3487234/

1,250 mg/day × 10 days

All volunteers tolerated WS without any adverse event. 

Safety and side effects

 

https://www.ncbi.nlm...les/PMC2958355/

250 mg twice a day.

At 6 weeks, significantly more patients met a priori response criteria in the drug group (88.2%) as compared with the placebo group (50%). The drug was well-tolerated and did not occasion more adverse effects than did placebo. It is concluded that this ethanolic extract of Withania somnifera has useful anxiolytic potential and merits further investigation. This product is comparative to lorazepam in its ability to control anxiety.

 

https://www.ncbi.nlm...pubmed/28004351

This study provides scientific validation to the anxiolytic, anti-inflammatory and anti-apoptotic properties of ASH-WEX, which may serve as an effective dietary supplement for management of SD induced stress and associated functional impairments.

 

Conclusion Ashwagandha root extract is a natural compound with sleep-inducing potential, well tolerated and improves sleep quality and sleep onset latency in patients with insomnia at a dose of 300 mg extract twice daily. It could be of potential use to improve sleep parameters in patients with insomnia and anxiety, but need further large-scale studies.

 

 

https://www.ncbi.nlm...les/PMC6750292/

An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract

A randomized, double-blind, placebo-controlled study

 

Abstract

 

Background:

Ashwagandha (Withania somnifera (L.) Dunal) is a herb traditionally used to reduce stress and enhance wellbeing. The aim of this study was to investigate its anxiolytic effects on adults with self-reported high stress and to examine potential mechanisms associated with its therapeutic effects.

 

Methods:

In this 60-day, randomized, double-blind, placebo-controlled study the stress-relieving and pharmacological activity of an ashwagandha extract was investigated in stressed, healthy adults. Sixty adults were randomly allocated to take either a placebo or 240 mg of a standardized ashwagandha extract (Shoden) once daily. Outcomes were measured using the Hamilton Anxiety Rating Scale (HAM-A), Depression, Anxiety, and Stress Scale -21 (DASS-21), and hormonal changes in cortisol, dehydroepiandrosterone-sulphate (DHEA-S), and testosterone.

 

Results:

All participants completed the trial with no adverse events reported. In comparison with the placebo, ashwagandha supplementation was associated with a statistically significant reduction in the HAM-A (P = .040) and a near-significant reduction in the DASS-21 (P = .096). Ashwagandha intake was also associated with greater reductions in morning cortisol (P < .001), and DHEA-S (P = .004) compared with the placebo. Testosterone levels increased in males (P = .038) but not females (P = .989) over time, although this change was not statistically significant compared with the placebo (P = .158).

 

Conclusions:

These findings suggest that ashwagandha's stress-relieving effects may occur via its moderating effect on the hypothalamus-pituitary-adrenal axis. However, further investigation utilizing larger sample sizes, diverse clinical and cultural populations, and varying treatment dosages are needed to substantiate these findings.

 

Members Comments

 

Brz - ashwagandha update:

had to stop - bummer.

definitely allergic. just like sk8ermama. i couldn't figure out why my allergies hadn't gone away even after the pollen count dropped way down. stopped the ashwagandha and my congestion and headaches subsided. not to mention i had a very tight chest feeling. very uncomfortable. my side effects are not uncommon from what i've learned. i may try again way down the road but now that i'm battling reflux, i don't want to complicate things. i've heard rhodiola is a similar adaptogen, but don't want to introduce anything new into my system right now. 

 

Polly - The Ashwaganda and Suntheanine is making me feel spaced out but calm - which isn't a bad thing!

 

FH - I noticed that this product has a warning about using it if you have a thyroid condition. It turns out that Ashwag… raises thyroid hormones t3 and t4 BUT the black pepper extract lowers t3 and t4. Due to the instability in the effect of these components there is a thyroid warning. As I an a recovering subclinical hypothyroid patient I will stay away from this supplement. I also found that the piperine (black pepper extract) allows the extra absorbtion of medication in the digestive tract and although extensive research has not been conducted there is a number of medications that it has already been demonstrated to significantly elevate during use. I certainly do not want to start jacking around with my medication absorbtion. For right now the Ashwag… is out.

 

brokedowninohi - "The physical symptoms of anxiety were running rampant this morning and I decided to try ashgawandha. Made a trip to my "local" corporate grocery and picked up some "organic non-GMO" non-certified ashgawandha in 500 mg tablets, advertised as being 10% withanolides. It does not have any black pepper content so I supplemented some out of curiosity.

I swear that single tablet did more in a couple hours for relieving my physical anxiety than 5k run..."

"As for the ash, I've taken 1000 mg for the past two nights and slept like a baby. I haven't woken that refreshed or free of muscular tension in a while."

 

https://www.ncbi.nlm...pubmed/28829155

Lowered TSH, and rasied t3 and t4 (Thyroid enzymes)

 

https://www.ncbi.nlm.../pubmed/9811169

administered daily for 20 days by gastric intubation increased serum 3,3',5-triiodothyronine (T3) and tetraiodothyronine (T4) concentrations 

 

https://www.ncbi.nlm...pubmed/16355578

Thyrotoxicosis following the use of ashwagandha

 

https://www.ncbi.nlm...pubmed/25624699

https://www.ncbi.nlm...pubmed/10619390

 

https://www.ncbi.nlm...9?dopt=Abstract

Ashwagandha-induced liver injury: A case series from Iceland and the US Drug-Induced Liver Injury Network.

In all but one case, normal function was resumed and rhodiola was a possible factor in one case. The final case left unreported - so not quite as bad as it all seems.

 

https://www.ncbi.nlm...pubmed/31728244

 

Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Insomnia and Anxiety: A Double-blind, Randomized, Placebo-controlled Study.

 

Abstract

 

Introduction Insomnia is a prevalent sleep disorder that can profoundly impact a person's physical health and mental wellbeing. Most of the currently available drugs for insomnia exert adverse effects. Hence, alternative herbal therapies could be effective in treating insomnia. Ashwagandha, a proven "Rasayana" from ancient Ayurveda is having the required potential to treat insomnia. Objective To determine the efficacy and safety of Ashwagandha root extract in patients with insomnia and anxiety. Methods This was a randomized, double-blind, placebo-controlled study conducted at Prakruti Hospital, Kalwa, Maharashtra, India. A total of 60 patients were randomly divided into two groups: test (n = 40) and placebo (n = 20) in a randomization ratio of 2:1. Test product was a capsule containing highest concentration full-spectrum Ashwagandha root extract 300 mg, and the placebo was an identical capsule containing starch. Both treatments were given twice daily with milk or water for 10 weeks. Sleep actigraphy (Respironics Philips) was used for assessment of sleep onset latency (SOL), total sleep time (TST), sleep efficiency (SE) and wake after sleep onset (WASO). Other assessments were total time in bed (sleep log), mental alertness on rising, sleep quality, Pittsburgh Sleep Quality Index (PSQI), and Hamilton Anxiety Rating Scale (HAM-A) scales. Results Two patients, one from each group, did not complete study and the per-protocol dataset (n = 58) included 29 and 19 patients from test and placebo, respectively. The baseline parameters were similar in the two groups at baseline. The sleep onset latency was improved in both test and placebo at five and 10 weeks. However, the SOL was significantly shorter (p, 0.019) after 10 weeks with test [29.00 (7.14)] compared to placebo [33.94 (7.65)]. Also, significant improvement in SE scores was observed with Ashwagandha which was 75.63 (2.70) for test at the baseline and increased to 83.48 (2.83) after 10 weeks, whereas for placebo the SE scores changed from 75.14 (3.73) at baseline to 79.68 (3.59) after 10 weeks. Similarly, significant improvement in sleep quality was observed with test compared to placebo (p, 0.002). Significant improvement was observed in all other sleep parameters, i.e., SOL, SE, PSQI and anxiety (HAM-A scores) with Ashwagandha root extract treatment for 10 weeks. Conclusion Ashwagandha root extract is a natural compound with sleep-inducing potential, well tolerated and improves sleep quality and sleep onset latency in patients with insomnia at a dose of 300 mg extract twice daily. It could be of potential use to improve sleep parameters in patients with insomnia and anxiety, but need further large-scale studies.

 

Note - These results may be statistically significant but I am not impressed. The improvement on sleep averages around 5% more than placebo and this is in healthy individuals not someone going through withdrawal. Also, like many have noted on this site, the effects tend to wear off after a few weeks.

 

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[fishinghat]

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Nutrametrix, isotonic vitamins:

Note - according to the Nutrametric website this is a custom blended product. With out specific ingredients and dose I could not give you any applicable information.

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Activated b complex, 2x a day, 3 during times of high stress. 

Again, depends on which B vitamins and the dose.

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Magnesium, 2x a day.

What dose? Many members have reported issues taking magnesium during withdrawal. 

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Immune, 1x a day

???

Can you give me the exact product name and/or manufacturer?

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OPC3, 2x a day

I assume it is the Isotonix product?

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ORAC, 1x a day

ORAC stands for Oxygen Radical Absorbance Capacity??

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[fishinghat]

Bromelain

 

https://examine.com/...osition_sources

Bromelain is a crude extract that comes from pineapples, particularly the stems or immature fruits; thus Bromelain is sometimes referred to as Pineapple extract.

 

3 Digestion and the Intestinal Tract

The general idea of Bromelain and digestion, as well as the entire protease class, is that they may contribute for an otherwise impaired digestive system.[17] Bromelain has some other effects extending beyond its activities as a protease, however.

 

3.1 Gastric

Bromelain has been shown effective in reducing dyspepsia in persons without heliobactor pylori infections when in conjunction with other nutraceuticals.[18]

 

3.2 Intestional

Via its protease activities, bromelain can slow down intestinal motility in rats and in vitro.[19] Its activities are inhibited by PAR-2 (receptor sensitive to proteases) as well as PDE4 and PLC downstream of the receptor, suggesting mechanisms of action.[19]

 

3.3 Colonic

An oral dose of 2-20mg bromelain in drinking water once daily is able to reduce inflammation in a murine model of colonic inflammation, and theoretically may aid inflammatory bowel disease (IBD).[20] Controlled doses of 2mg and 5mg showed benefit, although 2mg was too low to be significantly different than control.[20

 

Side-effects with moderate to higher dosages (400-800mg) tend to be gastrointestinal in nature, including pasty feces and farting.[6]

 

https://www.rxlist.c...supplements.htm

Are there any interactions with medications?

Amoxicillin (Amoxil, Trimox)Interaction Rating: Moderate Be cautious with this combination. Talk with your health provider.

Taking bromelain with amoxicillin might increase how much amoxicillin is in the body. This might increase the effects and side effects of amoxicillin.

 

Medications that slow blood clotting (Anticoagulant / Antiplatelet drugs)Interaction Rating: Moderate Be cautious with this combination. Talk with your health provider.

 

Bromelain might slow blood clotting. Taking bromelain along with medications that also slow clotting might increase the chances of bruising and bleeding.

 

Some medications that slow blood clotting include aspirin, clopidogrel (Plavix), diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, indomethacin (Indocin), ticlopidine (Ticlid), warfarin (Coumadin), and others.

 

Antibiotics (Tetracycline antibiotics)Interaction Rating: Minor Be cautious with this combination.T alk with your health provider.

Taking bromelain might increase how much antibiotic the body absorbs. Taking bromelain along with some antibiotics called tetracyclines might increase effects and side effects of these antibiotics.

Some tetracyclines include demeclocycline (Declomycin), minocycline (Minocin), and tetracycline (Achromycin).

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[fishinghat]

Heart Health Fish oil, 3000mg, 2x a day, 3x in “times of crisis,” i.e. now. 

I assume this is the Heart Health™ Essential Omega III Fish Oil with Vitamin E?

The manufacturer list 3 other "Omega III Fish Oil" products.

 

 

Pure encapsulations DIM Detox, 2x a day. 

To me this is a horrible product for anyone. Just a few notes on what I see on the surface here. Interferes with many cyp enzymes, Contains calcium which lowers magnesium and iron, contains more Omega 3 and NAC, contains Milk thistle which in incompatible with many anxiety medications as well as some antidepressants (Cymbalta is not listed as one that I could find), 7-hydroxymatairesinol which acts like estrogen and acts on dopamine receptors. L-Methionine effects the absorption of vitamin B6, B12, choline, folic acid and magnesium, and also inhibits the bodies usage of l-leucine, and phosphatidylcholine which can increase atherosclerosis in mice through the production of choline, trimethylamine oxide, and betaine. I don't even know where to begin in describing this product. 

[fishinghat]

Ortho Molecular products, liquid Vitamin D3 with K2, taking 5000mcg-10,000mcg a day. Did a few days of 20,000mcg re: MS study involving high doses of vitamin D. Back to 5,000 mcg now. Don’t think this can affect duloxetine metabolism. I don’t know.

Vitamin D toxicity is on the increase due to over use/overdose of Vitamin D. Currently Vitamin D supplementation is very popular and routine levels of your vitamin D should be performed if you are taking the supplements.

 

Vitamin D can raise calcium with long term use.

The RDA for Vitamin D3 is 600 iu per day but the NHS is considering taking that up to 1000 IU per day. Vitamin D toxicity has increased significantly in the last few years as mega doses of Vitamin D is gaining in popularity. According to the Institute of Medicine, 4000 IU is the safe upper level of daily vitamin D intake. 

Probably not an issue.

[fishinghat]

Garden of Life Once Daily Women’s probiotics, switched from “Mood probiotics” same brand. A few days off last week while waiting for Women’s probiotics. Maybe this has an effect, doesn’t seem likely. 

 

This seems like a really good product. Good choice. Should not be a problem.

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NOW liquid Melatonin, 1.5mg to 3mg nightly.

 

Melatonin

 

Studies have shown that the optimal dose for melatonin for sleep is 0.3 mg a night sublingual. Doses greater than 0.75 mg can actually be detrimental to sleep.

 

The human body builds up tolerance to melatonin and its effectiveness usually lasts only 3 to 7 days. 

 

https://www.ncbi.nlm...pubmed/12043836

Inhibition of dopamine release by melatonin has been demonstrated in specific areas of the mammalian central nervous system (hypothalamus, hippocampus, medulla-pons, and retina). Antidopaminergic activities of melatonin have been demonstrated in the striatum.

Many other articles document the decrease in dopamine production with increased levels of melatonin.

 

Note - This would indicate that patients with depression may want to limit their use of melatonin due to possible lowering of dopamine and increased depression.

 

 

https://dailymed.nlm...3b-9faf7ec7e04c

Insert for prescription Melatonin

DIRECTIONS: 1-10 drops under the tongue, 3 times a day or as directed by a health professional. Consult a physician for use in children under 12 years of age.

DESBIO NDC 57520-0729-1 HOMEOPATHIC MELATONIN 1 FL OZ (30 ML)

 

https://www.ncbi.nlm...pubmed/24802882

Optimal dosages for melatonin supplementation therapy in older adults: a systematic review of current literature.

we advise the use of the lowest possible dose of immediate-release formulation melatonin to best mimic the normal physiological circadian rhythm of melatonin and to avoid prolonged, supra-physiological blood levels.

 

https://www.ncbi.nlm...pubmed/15639542

it is suggested that melatonin exerts its analgesic actions not by binding to opioid receptor subtypes but by binding to its own receptors and increasing the release of beta-endorphin.

 

FH - I did a little experiment a couple of days ago. I had ordered some sublingual melatonin to use to take the edge off in case of a major problem developing. It is 30 drops to make 3 mg. Some research has indicated that a smaller dose could be used to treat bouts of anxiety during the day. So a couple days ago I felt a little agitated and decided to try 4 drops (0.4 mg). It kicked in in about 15 minutes. I was a little sleepy for about 30 minutes and then quite calm and relaxed for about 2 or 3 hours. Not to bad. I am glad to have it around as continue to keep trying things it will give me a fall back in case I need one.

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[fishinghat]

Sunsoil CBD Oil, full spectrum hemp extract, 15-30mg daily.

I am not a CND guru. IUN has a lot of knowledge in that subject and I refer you to him for info.

 

 

"I realize that I also typically start the day with warm water with lemon, usually within 2 hours of taking my cymbalta. This surely affects the PH in my digestive tract."

 

The pH of pure lemon juice is 2 to 3 and I assume you mix it with water so the pH is probably higher than that. The pH of stomach acid is 1.5 to 3 so the lemon juice will not make stomach pH more acidic.

[invalidusername]

Hat has got everything covered here, but just from looking at your listing, the b vitamins, the magnesium.. and others, can all affect the means by which your system will absorb the cymbalta.

 

Regarding the CBD, this will not affect the Cymbalta. A lot of interactions will be reported on the internet mistakenly in thinking that CBD includes THC, which as you probably know, is not the case as it is the wrong part of the plant to include such elements. 30mg daily is quite a strong dose and I would advise being on this level for any length of time. People usually use CBD on a situation/as and when basis, a cure rather than a preventative. 

 

One can easily build up a tolerance to CBD - as they can Ashwagandha, so in order to maintain a suitable efficiency, I would advise a regimen which includes a "t-break". The length of this break depends largely on how much you are taking and the frequency. If in doubt, please ask and I will help.

 

IUN

[virginiap]

Thank you both so, so very much. Bless you.

 

I was able to get stabilized on the cymbalta and I have been focused on the CAEBV as I was experiencing MS symptoms. Thankfully I have been able to halt the reactivation of the epstein barr virus and I am almost ready to begin the taper from cymbalta. I really appreciate your wealth of knowledge and insight as well as the time and effort you put in to this research fishinghat. Thank you so much as well IUN, I have been able to manage the supplements by taking them at least 6 hours after my cymbalta dose, which I now take at 8am. 

 

I apologize for the delay in replying, when I am suffering from an EBV reactivation I have no energy or will to do much. I am so very grateful for your support and knowledge. I have not had time to thoroughly review the research you posted fishinghat, I have done a quick scan. As I am now starting to feel better I will be able to dive in.

 

I do have one question IUN, how did you arrive at the 2 hour mark in regards to time bw duloxetine and supplements? Is this the time it takes on average for cymbalta to be metabolized by the liver? The psychiatrist I have been working with first said to wait 12 hours and then 6, but she also didn't really know. Do you know who would be able to help me determine the specific mechanism and time of metabolism for each of these supplements and the cymbalta? I consulted a compounding pharmacist but he said because a lot them haven't been studied he couldn't be certain. Do I need to find a biochemist ha? But for real!

 

Thank you both again, what a phenomenal gift you have both given to the world with this forum. I will follow up again. Happy Tuesday to you both.

 

Virginia

[fishinghat]

The minimum two hour time for the seperation of drugs is a standard reference often seen in the medical research. 

 

As far as "who would be able to help me determine the specific mechanism and time of metabolism for each of these supplements and the cymbalta?" "Do I need to find a biochemist ha? But for real!"

 

Good news !!! You found one. I have a double Bachlor's degree in both Chemistry and Biology as well as a Masters in physiology. I did that kind of research for around 30 years before I retired. Piece of cake.

 

Just post a list of the supplements/drug you want checked out and I will be glad to do so. Also, there is a fair amount of this info in the ebook so you might want to give it a look over.

[invalidusername]

Once the research is in the blood, it becomes like catnip when presented with a challenge

 

Glad to hear that you have paved the way for your withdrawal, and as Hat said, the 2 hour separation time is quite standard. Granted there is some assumption involved, but it is a fairly safe figure to work from to allow one drug to have worked its way through the stomach and reach the lower GI. 

 

Will be interested to hear how the withdrawal goes - and as always - we will do our very best to help you along the way.