Whole cannabis flower extracts inhibited three Alzheimer’s-related enzymes and improved cell viability under oxidative stress in laboratory experiments. The researchers studied multi-component extracts containing diverse cannabis compounds, examining their ability to act on several disease-related targets.
The extracts inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), enzymes that break down acetylcholine, a chemical messenger important for memory. They also inhibited BACE1, an enzyme involved in producing amyloid-beta. Cholinesterase inhibition exceeded that of galantamine under the tested assay conditions, with activity depending on extract composition.
Researchers also tested the extracts in PC12 cells exposed to hydrogen peroxide and amyloid-beta, finding improved viability under oxidative stress. Together, these findings identify whole cannabis flower extracts as promising candidates for investigating combined enzyme-inhibiting and cell-protective approaches to Alzheimer’s disease.
“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.”
https://pubmed.ncbi.nlm.nih.gov/42934778
“Taken together, the study highlights the promise of cannabis inflorescence extracts, especially from Type II and III chemovars and fractions, as promising in-vitro multi-target candidates for further investigation in AD related models. By combining cholinesterase inhibition, BACE1 inhibition, and neuroprotection against oxidative and amyloid stress, cannabis-derived compounds may offer a more comprehensive approach compared to current single-target drugs.”
https://link.springer.com/article/10.1186/s42238-026-00479-9