⚠️ Piperine (Black Pepper Extract) and its CYPnnn Inhibition

[Chip (OP)]

🔥 Piperine Synergy & Potentiation

Piperine is the primary active alkaloid in black pepper (Piper nigrum) and functions as a powerful bioavailability enhancer, modulating both Phase I (CYP450) and Phase II (glucuronidation) metabolic pathways.


🧬 Key Mechanisms

• Inhibits CYP3A4, CYP2D6, CYP2E1 – Slows drug metabolism
  
• Blocks UDP-glucuronosyltransferase (UGT) – Prevents rapid excretion
  
• Enhances absorption via intestinal epithelial permeability
  
• Increases thermogenesis and blood flow in the gut
  

⚡ Optimal Dosage

Formulation	Typical Dose
Piperine extract (BioPerine®)	5–20 mg
Black pepper (powdered spice)	250–500 mg

🧠 Therapeutic effect begins at 5 mg of standardized piperine extract. Doses over 20 mg may cause GI irritation.


🔥 Substances Potentiated by Piperine

🧠 Nootropics & Neuromodulators

• Curcumin – Up to 2000% ↑ absorption
  
• Resveratrol – Higher blood plasma retention
  
• 5-HTP – Slower breakdown, stronger mood support
  
• L-DOPA / Mucuna – Prolonged dopaminergic effect
  
• Phenethylamine (PEA) – Longer duration, stronger stimulation
  
• Hordenine – Extended TAAR1 activity
  
• Caffeine – Slower metabolism, extended half-life
  
• Modafinil – Mild potentiation of wakefulness
  

💊 Supplements & Adaptogens

• Berberine – Enhanced glucose modulation
  
• Quercetin – Amplified antioxidant effects
  
• Bacopa Monnieri – Improved cognitive support
  
• CoQ10 – Greater mitochondrial delivery
  
• Melatonin – Longer sleep duration
  
• Fat-soluble Vitamins (A, D, E, K) – Improved absorption
  

🌿 Cannabinoids

• CBD / THC – Increased potency and duration
  ⚠️ May raise anxiety levels at high doses
  

⏱️ Timeline of Effects

Time After Ingestion	Effect
0–10 min	Initial absorption in GI tract begins
10–30 min	CYP/UGT enzyme inhibition takes effect
30–45 min	Peak potentiation of target substances
1–3 hours	Sustained enhancement of absorption/metabolism
3–6 hours	Gradual return to baseline enzyme activity

🚨 ⚠️ Pharmaceutical Interactions ⚠️ 🚨

Due to CYP and UGT inhibition, Piperine may dangerously increase levels of:

• Benzodiazepines (Diazepam, Clonazepam)
  
• SSRIs / SNRIs (Sertraline, Venlafaxine)
  
• Opioids (Morphine, Oxycodone)
  
• Beta-blockers (Metoprolol, Atenolol)
  
• MAO inhibitors – Hypertensive risk
  
• Anticoagulants (Warfarin) – Bleeding risk
  

❗ Avoid combining piperine with narrow therapeutic index medications unless supervised by a medical professional.


⚙️ Integration Tips

• Dose 10–15 minutes before target compound
  
• Use 5–10 mg Piperine extract, or 250–300 mg black pepper powder
  
• Cycle use to avoid enzyme over-inhibition or tolerance

🧠 Notes for Formulators

• Piperine is lipophilic – combine with fats or oils for best effect
  
• Highly synergistic with methyl donors, dopaminergics, and anti-inflammatory agents
  
• Acts as a natural AMPK modulator, supporting metabolic and neuroprotective stacks
  

Created for Neurostack Optimization — by Chipper 
🔗 GitHub Repo: NeuroOverride Stack