Low-dose combinations administered systemically have been reported to modulate amyloid pathology and improve cognitive performance. For example, intraperitoneal administration of CBD (0.273 mg/kg) and THC (0.205 mg/kg) for 28 days in 5xFAD mice improved spatial memory and altered plaque ...

April 23, 2026 - Preclinical studies show that CBD and THC reduce β-amyloid accumulation, attenuate tau phosphorylation, and regulate neuroinflammatory responses, often associated with improvements in learning and memory.

August 10, 2022 - In APP/PS1 transgenic mice, chronic treatment with various CBD doses (5–50 mg/kg) reversed and (at 20 mg/kg) prevented the development of several cognitive deficits (Cheng et al., 2014a,b; Coles et al., 2020; Watt et al., 2020b). Interestingly, CBD only moderately reduced insoluble Aβ40 and pro-inflammatory cytokines and had no other effects on AD brain pathology. In a tauopathy model of AD (i.e., TAU58/2 transgenic mice), CBD improved spatial memory of 14-month-old female mice (but not of 4-month-old males).

May 28, 2026 - Low doses of THC have been shown to inhibit amyloid aggregation and even block an enzyme (acetylcholinesterase) involved in plaque formation. Some mouse studies found amyloid reductions at strikingly low THC doses.

March 13, 2025 - Preclinical and clinical studies ... properties, may have neuroprotective effects. The combination of THC and CBD has shown promising results in improving memory and reducing β-amyloid plaque deposition in animal models....

Results of the radial arm water maze (RAWM) test demonstrated that treatment with 0.02 and 0.2 mg/kg of THC for three months significantly improved the spatial learning performance of aged APP/PS1 mice in a dose-dependent manner. Results of protein analyses revealed that low-dose THC treatment ...

Inhalational and intranasal ... and slowed cognitive decline, indicating that enhanced bioavailability can shift the effective dose range downward (Fihurka et al., 2022; Sadaka et al., 2023). Oral administration (via gavage) in preclinical models introduced greater variability, with beneficial effects observed across a wider dose range. Low oral THC doses (1–2.5 mg/kg/day) improved working memory in aged rodents, whereas higher ...

July 25, 2025 - A study based on cell and transgenic mice suggests that low doses (0.02 and 0.2 mg/kg) of THC administered over three months significantly reduce the levels of Aβ oligomers, phosphorylated tau protein and total tau protein.

May 20, 2025 - Therefore, in this work we have demonstrated a wide spectrum of beneficial effects induced by CBD, ranging from the molecular to the behavioral level, and which may be based on the reduction of the formation of beta-amyloid plaques and the prevention of phosphorylated Tau tangles [48]. More studies are required to underscore the mechanisms of action of CBD and to translate the preclinical studies into clinical assays.

A two-week course of high doses of CBD helps restore the function of two proteins key to reducing the accumulation of beta-amyloid plaque, a hallmark of Alzheimer’s disease, and improves cognition in an experimental model of early onset familial Alzheimer’s, investigators report. The proteins TREM2 and IL-33 are important to the ability of the brain’s immune cells to literally consume dead cells and other debris like the beta-amyloid plaque that piles up in patients’ brains, and levels of both are decreased in Alzheimer’s.

In vitro studies have found CBD to increase Aβ clearance and reduce tau hyperphosphorylation (reviewed in [8,9]). Furthermore, CBD reversed a spatial reference memory deficit in a pharmacological mouse model of AD [10]. Our own work expanded on these initial findings by utilising a double transgenic APPswe/PS1∆9 (APP/PS1) mouse, which co-expresses amyloid precursor protein (APP) and presenilin 1 (PS1) mutant genes. This transgenic AD mouse model demonstrates construct and face validity for AD, including age-dependent amyloid pathology and AD-relevant behavioural deficits including cognitive impairments [11,12].

February 19, 2014 - Confirming these observations, a recent study reported a marked reduction in neurofibrillary tangles in parkin-null, human tau overexpressing (PK-/-/TauVLW) mice, a model of complex frontotemporal dementia, parkinsonism, and lower motor neuron disease, after prolonged exposure to Sativex®, an already approved medicine based on mixed Δ9-THC and CBD natural extracts (Casarejos et al., 2013). The authors suggested the cannabinoid potentiation of autophagy or improvement of redox state as likely mechanisms accounting for the reduction in tau deposition.

In a preliminary study, we examined the effect of two low doses of CBD (0.1 mg/kg, 1 mg/kg) on performance in emotional and cognitive tests in STZ-treated animals. We found similar therapeutic effects for both doses (Fig. S4); therefore, we proceeded with the lower dose of 0.1 mg/kg. We assessed protein levels in the CA1 and DG regions. In the CA1, a two-way ANOVA revealed significant effects on Aβ protein levels (Fig. 2a) and p-Tau (Fig.

June 17, 2021 - Activation of both CB1 and cannabinoid receptor 2 (CB2) has revealed beneficial neuroprotective effects reducing β-amyloid deposition and tau phosphorylation. It should also be noted that low doses of Δ9-tetrahydrocannabinol (THC) showed several beneficial effects by inducing hippocampal neurogenesis and reducing Aβ toxicity (i.e., plaque deposition) in rodents, as well as in other dementia-related symptoms in both pre-clinical and clinical studies [13,14]. Furthermore, (i) the phytocannabinoid cannabidiol, (ii) the activation of the CB2 receptors, and (iii) the modulation of the endogenous

Importantly, Sativex reduced Aβ and tau deposition in the hippocampus and cerebral cortex as well as increasing autophagy (Casarejos et al., 2013), thus implying, that although the mouse model is not directly related to AD, the therapeutic benefits are. The second study conducted by Aso et al. (2015) compared the effect of CBD, THC and a CBD-THC combination in the APPxPS1 mouse model, in the early symptomatic phase (~6 months). This study found that all treatments improved memory deficits in the two-object recognition task but only the CBD-THC combination prevented the learning deficit seen in the active avoidance task.

April 6, 2023 - However, CBDA- and THCA-treated mice showed decreased hippocampal Aβ and p-tau and superior cognitive function compared with Aβ1–42-treated mice. In addition, CBDA and THCA lowered Aβ and p-tau levels, alleviated calcium dyshomeostasis, ...

October 1, 2025 - The current study builds upon previously published work demonstrating that CBD treatment improves cognitive performance, reduces Aβ plaque burden, and enhances acetylcholine signaling in the 5XFAD mouse model of AD (Oakley et al., 2006; Schneider ...