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51

Treatment, Recovery and Rehabilitation / NAC (N-Acetyl-Cysteine) Treatment for Drug Induced Liver Damage

« Last post by Chip on January 15, 2024, 07:13:11 AM »

I just bought a whole bunch of this stiff since I've been an alcoholic and Methamphetamine user.

https://www.hindawi.com/journals/omcl/2021/3320325/?fbclid=IwAR1DsG021bkzg3CDvsFumaDF0CdSoyyzUBRL4Rkh1yl_woiRLeeDi_I30dg

52

Antipsychotics / Neuroleptics / New AP - Brexpiprazole: so far so good - the new partial antagonist

« Last post by Chip on January 15, 2024, 06:06:30 AM »

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749739/#:~:text=Brexpiprazole%20has%20antipsychotic%2Dlike%20activity,of%20aripiprazole%20%5BMaeda%20et%20al.

53

Antidepressants / Antidepressant effects of combination of brexpiprazole and fluoxetine

« Last post by Chip on January 15, 2024, 06:00:59 AM »

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5263204/

54

Treatment, Recovery and Rehabilitation / Methamphetamine and Protection Against Cardiotoxicity

« Last post by Chip on January 15, 2024, 05:58:02 AM »

I already have Atrial Fibrillation but chronic users could benefit from this study.

Dapagliflozin Protects Methamphetamine-Induced Cardiomyopathy by Alleviating Mitochondrial Damage and Reducing Cardiac Function Decline in a Mouse Model:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301370/#:~:text=Dapagliflozin%20Reduces%20Myocardial%20Injury%20and%20Adverse%20Fibrotic%20Remodeling%20Caused%20by%20Methamphetamine%20Exposure

Dapagliflozin:

https://en.m.wikipedia.org/wiki/Dapagliflozin

And don't forget the humble CAN OF SMOKED OYSTERS too

55

Treatment, Recovery and Rehabilitation / Re: Reversing or Protecting Against Methamphetamine's Neurotoxic's Effects

« Last post by Chip on January 12, 2024, 07:34:33 PM »

Key Vitamins and Supplements for Meth Recovery:

https://www.harmonyridgerecovery.com/vitamins-supplements-meth-recovery/

One well informed person's complete stack of daily supplements:

**__AM__**
* **Synthroid** *(levothyroxine sodium)* 100mcg
* **Mydayis** *(mixed amphetamine salts, 3-bead ER)* 50mg
* **MethylPro® B Complex** *(thiamine mononitrate, riboflavin 5' phosphate, niacinamide, pyridoxine hydrochloride and pyridoxal 5' phosphate, L-5-methylfolate calcium, methylcobalamin, biotin, calcium D-pantothenate, choline bitartrate, inositol, para-aminobenzoic acid)*
* **NALT** *(N-acetyl-L-tyrosine)* 350mg
* **ALCAR** *(acetyl-L-carnitine)* 500mg
* **L-Citrulline** 1,300mg
* **TeaCrine®** *(theacrine)* 100mg
* **Cognizin®** *(citicoline)* 250mg
* **CoQH-CF™** *(ubiquinol)* 100mg
* **Magtein®** *(magnesium L-threonate)* 1,334mg / 96mg elemental magnesium
* **Cognance™** *(Bacopa monnieri extract, whole plant)* 100mg *(10% Ebelin lactone [1])*
* **AvailOm®** *(omega-3 PUFA / L-Lysine complex)* 1000mg *(245mg DHA / 205mg EPA FFA) [2]*
* **PrimaVie®** *(purified shilajit)* 250mg
* **Longvida® Curcumin** *(optimized Curcuma longa extract, rhizome)* 400mg *(23% curcuminoids)*
* **Tongkat Ali Extract** *(Eurycoma longifolia extract, root)* 100mg *(10% eurycomanone)*
* **Horny Goat Weed Extract** *(Epimedium brevicornum extract, leaf)* 500mg *(10% icariin)*
* **Tribulus Extract** *(Tribulus terrestris extract, fruit)* 500mg *(20% protodioscin)*

**__Noon__**
* **NALT** *(N-acetyl L-tyrosine)* 350mg
* **Cognizin®** *(citicoline)* 250mg

**__PM__**
* **Depakote ER** *(divalproex sodium, 24-hr ER)* 1500mg
* **Crestor** *(rosuvastatin calcium)* 5mg
* **Vitamin D3** *(cholecalciferol)* 125mcg Mon-Fri | 250mcg Sat-Sun
* **Xyzal** *(levocetirizine dihydrochloride)* 5mg
* **Truvada** *(emtricitabine-tenofovir disoproxil fumarate)* 200mg-300mg
* **Magtein®** *(magnesium L-threonate)* 667mg / 48mg elemental magnesium
* **Magnesium glycinate** *(magnesium bisglycinate chelate monohydrate)* 1,067mg / 133mg elemental magnesium
* **LiOr** *(lithium orotate)* 20mg
* **NACET 100mg + Cofactors** *(N-acetyl-L-cysteine ethyl ester, L-selenomethionine, Molybdenum, Glycine)*
* **Pregnenolone** *(micronized)* 5mg
* **Beta-ecdysterone** *(Cyanotis arachnoidea extract, root)* 500mg *(50% beta-ecdysterone/20-hydroxyecdysone)*
* **Licorice Extract** *(Glycyrrhiza glabra extract, root)* 25mg *(98% Isoliquiritigenin [3])*
* **Noble Kava Extract** *(Piper methysticum extract, root)* 1,000mg *(10% kavalactones [4])*

**__As-Needed__**
* **Klonopin** *(clonazepam)* Up to 1mg/d
* **Lunesta** *(eszopiclone)* 2mg qhs
* **Cialis** *(tadalafil)* 20mg/d

56

Tolerance / My latest take on how tolerance works

« Last post by Chip on January 12, 2024, 04:27:51 PM »

Tolerance may develop when a drug is used repeatedly because metabolism of the drug speeds up (often because the liver enzymes involved in metabolising drugs become more active) and because the number of sites (cell receptors) that the drug attaches to or the strength of the bond (affinity) between the receptor and drug decreases.

This is my understanding of how tolerance works for psychoactive drugs as most people are either ignorant of (novices), confused or simply misunderstand:

It also determines your **withdrawal response**.

Tolerance action evolves differently for each drug and every time period involved will vary as will the responses to the various dosages and their rate of titration or increases. **Dose and frequency** are the two determinants of the gravity of your tolerance or **addictive response** but **frequency carries more weight**.

To further complicate this, **cross-tolerance** develops to different drugs when they share the same mechanism of action and/or by modulating the same neurotransmitter levels in the same way.

Lastly, the **ceiling effect** of certain drugs like the whole class of benzos, the opiate Codeine and the opioid Buprenorphine, **saturates the receptors** and jacks up tolerance to the whole of it's class .

Some non-psychoactive drugs like Paracetemol do not cause tolerance whatsoever.

> The only way to keep your tolerance naive indefinitely is to never poke it like you do when you use a drug more than once or twice contiguously before your physiological response returns to baseline -- and then waiting a little bit longer just to be safe, before your next session -- for example by using Heroin weekly or Methamphetamine no more than every 10 days. However, it always catches up with you eventually.

Everybody is different and their individual tolerances and withdrawal responses can vary significantly as is the case with amphetamines (as most never develop any issues at all but a small majority need regular breaks).

Tolerance is a mammalian homeostatic response to any external molecule that alters neurotransmitter levels or effects nerve transmission rates.

> Tolerance is the mechanism of addiction and is permanent because it's a learned response and is in your best interests for it to quickly try to rebalance your physiology due to the variations of drug-serum levels that happen when you use drugs.

But you can take a break to **reset** it however it not only goes back to where it was before you took that break, but it just goes a little bit faster every time, often imperceptibly.

You can eventually reach a point where it doesn't matter how long that break is so it can't be reset.

> The only way to keep your tolerance naive indefinitely is to never poke it like you do when you use a drug more than once or twice contiguously before your physiological response returns to baseline.ogical effect.

Also, with many drugs, the **range of effects between a perceptible sensation through to profound euphoria keeps narrowing** over time until it's no longer available, much to the disappointment of the user.

So you end up not feeling much at higher doses and as you keep increasing the dosage you then either go to the top end of that range (such as having a blackout like with alcohol) or hit a ceiling and then if you continue on you may suddenly and unexpectedly overdose due to the dimishing warning symptoms.

Understanding various tolerances and their evolution can save your life.

References:

* Mechanisms Underlying Tolerance after Long-Term Benzodiazepine Use

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321276/

* What is a ceiling effect?

*In the context of opioid addiction treatment, the term "ceiling" refers to the ceiling effect, a pharmacological phenomenon that occurs when a drug reaches its maximum effect, and increasing the dose does not result in any further benefits or side effects. This concept is particularly relevant for medications like buprenorphine, which have a ceiling effect that reduces the risk of overdose. Specifically, buprenorphine’s safety is conferred by ceiling effects for respiratory depression, sedation, and subjective measures (euphoria), making it a very safe option for opioid use disorder (OUD) treatment.*

https://ophelia.com/glossary/ceiling-effect#:~:text=Ceiling%20effect-,What%20is%20a%20ceiling%20effect%3F,further%20benefits%20or%20side%20effects.

57

Treatment, Recovery and Rehabilitation / Re: Treatment of Methamphetamine withdrawal (in trauma patients)

« Last post by Chip on January 12, 2024, 04:20:10 PM »

See also the role of drugs like Buprenorphine, stimulant prodrugs and even Venlafaxine, in the search for an effective tool to stop stimulant abuse and to return to recreation level use only - especially in light of the current mess that the world is in with Methamphetamine abuse !

58

Harm Reduction / Re: Meth's Interesting Duality - Neurotoxic and Neuroprotectant Dose Dependency and

« Last post by Chip on January 12, 2024, 04:10:23 PM »

More good stuff as recommended by Bronwyn from the Psychopharmacology Discord server:

The Main Molecular Mechanisms Underlying MethamphetamineInduced Neurotoxicity and Implications for Pharmacological Treatment:

see Table 2 for recommended/current Treatment Options

https://www.frontiersin.org/articles/10.3389/fnmol.2018.00186/full

59

Harm Reduction / Re: Meth's Interesting Duality - Neurotoxic and Neuroprotectant Dose Dependency and

« Last post by Chip on January 10, 2024, 02:18:17 PM »

More good news, concerns and data on dose dependent uses.

It also refers to both (low) doses not exceeding 25 mg in humans and doses not exceeding 2.0 mg/kg in mice.

Long-Term Treatment with Low Doses of Methamphetamine Promotes Neuronal Differentiation and Strengthens Long-Term Potentiation of Glutamatergic Synapses onto Dentate Granule Neurons:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939399/

60

Opiates & Opioids / [BL] smiling and spurts of laughter while withdrawing? does this happen to you?

« Last post by Chip on January 10, 2024, 11:14:45 AM »

This includes my contribution to this interesting bluelight thread:

https://bluelight.org/xf/threads/smiling-and-spurts-of-laughter-while-withdrawing-does-this-happen-to-anybody-else.572598

If you need any help or a chat then IM/PM or email me, Chip