The Cannabinoids, CBDA and THCA, Rescue Memory Deficits and Reduce Amyloid-Beta and Tau Pathology in an Alzheimer’s Disease-like Mouse Model

Abstract

Most studies related to hemp are focused on Cannabidiol (CBD) and Tetrahydrocannabinol (THC); however, up to 120 types of phytocannabinoids are present in hemp. Hemp leaves contain large amounts of Cannabidiolic acid (CBDA) and Tetrahydrocannabinolic acid (THCA), which are acidic variants of CBD and THC and account for the largest proportion of CBDA. In recent studies, CBDA exhibited anti-hyperalgesia and anti-inflammatory effects. THCA also showed anti-inflammatory and neuroprotective effects that may be beneficial for treating neurodegenerative diseases. CBDA and THCA can penetrate the blood–brain barrier (BBB) and affect the central nervous system. The purpose of this study was to determine whether CBDA and THCA ameliorate Alzheimer’s disease (AD)-like features in vitro and in vivo. The effect of CBDA and THCA was evaluated in the Aβ1–42-treated mouse model. We observed that Aβ1–42-treated mice had more hippocampal Aβ and p-tau levels, pathological markers of AD, and loss of cognitive function compared with PBS-treated mice. 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, and exhibited neuroprotective effects in primary neurons. Our results suggest that CBDA and THCA have anti-AD effects and mitigate memory loss and resilience to increased hippocampal Ca2+, Aβ, and p-tau levels. Together, CBDA and THCA may be useful therapeutic agents for treating AD.

Therapeutic‐like activity of cannabidiolic acid methyl ester in the MK‐801 mouse model of schizophrenia: Role for cannabinoid CB1 and serotonin‐1A receptors

“…Previous research showed that NMDAR antagonism can induce immobility in the FST (Langen et al, 2012), and our study corroborates the findings that compounds such as CBD and HU-580 can significantly reduce immobility behaviour (Dlugosz et al, 2023;Sales et al, 2019Sales et al, , 2020. Moreover, CBD (Felipe et al, 2013;Leweke et al, 2021;Osborne et al, 2017) and CBDA (Kim et al, 2023) improve or rescue cognitive performance in psychiatric and neurological disorders. Regarding behavioural amelioration, conclusions about receptor correlates seem to be complex.…”

An ethnobotanical survey on the therapeutic use of Cannabis sativa L. in the province of Taounate, Morocco

“…Among these various uses, therapeutic use was presented by a cultural index value of 40 %. The plant's therapeutic properties that have been experimentally demonstrated by several studies carried out in vitro and in vivo (Haddou et al 2023, Kim et al 2023, Breijyeh et al 2021. Our survey reported 11 diseases 2 c treated by cannabis.…”

Análise terapêutica do canabidiol para o tratamento de Alzheimer

“…(Mannucci et al, 2017). Research, Society andDevelopment, v. 13, n. 2, e6513245006, 2024 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v13i2.45006 In a recent in vivo study, using rats as models, Kim et al (2023) raises that, in addition to decreasing levels of βA and TAU protein in primary neurons and hippocampus, treatment with CBD and THC decreases cell death and modulates calcium levels. In patients with AD, elevated calcium concentration interferes with signaling pathways, resulting in impaired learning and memory.…”