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
- 1Natural Compounds and Analytical Chemistry Laboratory, MIGAL – Galilee Research Institute, P.O. Box 831, Kiryat Shmona, 11016 Israel
- 2Department of Biotechnology, Tel-Hai University of Kiryat Shmona in the Galilee, Tel-Hai, Kiryat Shmona, 1220800 Israel
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder marked by progressive cognitive decline. Despite extensive research, its multifactorial nature continues to challenge the development of effective therapies. Current treatments, including anticholinergic agents and amyloid β–targeted drugs, alleviate symptoms but fail to halt disease progression and often produce side effects. Therefore, novel multi-target strategies are urgently needed.
Cannabis (Cannabis sativa L.) has long been recognized for its medicinal properties, yet its potential in AD therapy has only recently gained attention. Previous studies have mainly focused on single cannabinoids or endocannabinoid system modulation. In this study, we investigated whole cannabis flower extracts, rich in diverse active compounds, for their ability to inhibit key AD-related enzymes: acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE1), using spectrophotometric assays. Fractionation of one extract further identified components with potent inhibitory activity against both BChE and BACE1.
Additionally, the extracts were evaluated for their cell-protective potential in PC12 cells exposed to hydrogen peroxide (H₂O₂) and amyloid β (Aβ₁–₄₂), mimicking AD-like oxidative stress conditions. Cannabis extracts showed stronger inhibition of cholinergic enzymes compared to Galantamine, with efficacy depending on extract composition. Importantly, this study is among the first to reveal significant BACE1 inhibition by cannabis extracts. Moreover, the extracts enhanced PC12 cell viability under oxidative stress, indicating cell-protective effects.
Overall, these findings suggest that multi-component cannabis extracts may interact with several AD-related molecular targets in vitro and may serve as promising leads for further mechanistic and preclinical investigation.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s42238-026-00479-9.
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BibTeX
@article{shitrit2026cannabis,
title = {{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}},
author = {Asif Shitrit and Ali Khattib and Soliman Khatib},
journal = {Journal of Cannabis Research},
year = {2026},
month = jul,
doi = {10.1186/s42238-026-00479-9},
url = {https://doi.org/10.1186/s42238-026-00479-9},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Asif Shitrit
AU - Ali Khattib
AU - Soliman Khatib
PY - 2026
DA - 2026/07/31
JO - Journal of Cannabis Research
DO - 10.1186/s42238-026-00479-9
UR - https://doi.org/10.1186/s42238-026-00479-9
AB - Alzheimer’s disease (AD) is a neurodegenerative disorder marked by progressive cognitive decline. Despite extensive research, its multifactorial nature continues to challenge the development of effective therapies. Current treatments, including anticholinergic agents and amyloid β–targeted drugs, alleviate symptoms but fail to halt disease progression and often produce side effects. Therefore, novel multi-target strategies are urgently needed. Cannabis (Cannabis sativa L.) has long been recognized for its medicinal properties, yet its potential in AD therapy has only recently gained attention. Previous studies have mainly focused on single cannabinoids or endocannabinoid system modulation. In this study, we investigated whole cannabis flower extracts, rich in diverse active compounds, for their ability to inhibit key AD-related enzymes: acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE1), using spectrophotometric assays. Fractionation of one extract further identified components with potent inhibitory activity against both BChE and BACE1. Additionally, the extracts were evaluated for their cell-protective potential in PC12 cells exposed to hydrogen peroxide (H₂O₂) and amyloid β (Aβ₁–₄₂), mimicking AD-like oxidative stress conditions. Cannabis extracts showed stronger inhibition of cholinergic enzymes compared to Galantamine, with efficacy depending on extract composition. Importantly, this study is among the first to reveal significant BACE1 inhibition by cannabis extracts. Moreover, the extracts enhanced PC12 cell viability under oxidative stress, indicating cell-protective effects. Overall, these findings suggest that multi-component cannabis extracts may interact with several AD-related molecular targets in vitro and may serve as promising leads for further mechanistic and preclinical investigation. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s42238-026-00479-9.
SN - 2522-5782
ER -