Cannabis flower extracts as a multi-target agent in Alzheimer's disease: Inhibition of AChE, BChE, and BACE1 with cell-protective effects in a PC12 cell model.

Shitrit A.; Khattib A.; Khatib S. · Journal of cannabis research · 2026

**Background & Methods** This in vitro review study investigated whole cannabis flower extracts for multi-target enzyme inhibition relevant to Alzheimer's disease pathology. Researchers used spectrophotometric assays to measure inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE1), and evaluated neuroprotective effects in PC12 cells exposed to hydrogen peroxide and amyloid-β (Aβ₁₋₄₂) to simulate AD-related oxidative stress conditions. **Key Findings** • Cannabis flower extracts demonstrated superior inhibition of cholinergic enzymes (AChE and BChE) compared to the standard AD medication Galantamine, with efficacy varying based on extract composition. Extract fractionation identified components with potent dual inhibitory activity against both BChE and BACE1. • Cannabis extracts showed significant BACE1 inhibition, representing among the first evidence of this effect in cannabis-based preparations. This is particularly notable given that BACE1 inhibition represents a major therapeutic target in current AD drug development. • Extracts enhanced PC12 cell viability under oxidative stress conditions, demonstrating cell-protective effects that suggest neuroprotective potential beyond simple enzyme inhibition. **Dosage & Administration** Not reported. This was an in vitro study examining extract compositions and concentrations in cell-based assays without human dosing information. **Safety & Adverse Effects** Not reported. Safety evaluation was limited to cell culture models; no human safety data or adverse effect profiles were documented. **Evidence Quality** This study represents preliminary in vitro evidence with significant limitations. As a laboratory-based investigation using cell culture models, findings cannot be directly extrapolated to human efficacy or safety. The PC12 cell line, while useful for neurotoxicity screening, does not fully recapitulate the complex pathophysiology of Alzheimer's disease in vivo. No human trials were conducted, and the multi-component nature of cannabis extracts complicates identification of specific active compounds responsible for observed effects. Extract composition variability and lack of standardization limit reproducibility. The study provides mechanistic insights warranting further investigation but represents early-stage research; substantial additional preclinical and clinical work would be required before therapeutic applications could be considered.

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