Category

Cognitive Aging

Cannabinoids in late‐onset Alzheimer’s disease

By | Cognitive Aging, Dementia

Authors:

AIA Ahmed, MA van der Marck, GAH van den Elsen, MGM Olde Rikkert


Published in Clinical Pharmacology & Therapeutics

8 March 2015

 

Abstract

Given the lack of effective treatments for late-onset Alzheimer’s disease (LOAD) and the substantial burden on patients, families, health care systems, and economies, finding an effective therapy is one of the highest medical priorities. The past few years have seen a growing interest in the medicinal uses of cannabinoids, the bioactive components of the cannabis plant, including the treatment of LOAD and other physical conditions that are common in older people. Several in vitro and in vivo studies have demonstrated that cannabinoids can reduce oxidative stress, neuroinflammation, and the formation of amyloid plaques and neurofibrillary tangles, the key hallmarks of LOAD. In addition, in population-based studies, cannabinoids reduced dementia-related symptoms (e.g., behavioral disturbances). The current article provides an overview of the potential of cannabinoids in the treatment of LOAD and related neuropsychiatric symptoms in older people. We also discuss the efficacy, safety, and pharmacokinetics of cannabinoid-based drugs in older people with dementia.

 

DOI: 10.1002/cpt.117

PAYWALL

Citation:

Ahmed A, Marck MVD, Elsen GVD, Rikkert MO. Cannabinoids in late-onset Alzheimers disease. Clinical Pharmacology & Therapeutics. 2015;97(6):597-606. doi:10.1002/cpt.117.

A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice

By | Cognitive Aging, Dementia

Authors:

Andras Bilkei-Gorzo, Onder Albayram, Astrid Draffehn, Kerstin Michel, Anastasia Piyanova, Hannah Oppenheimer, Mona Dvir-Ginzberg, Ildiko Rácz, Thomas Ulas, Sophie Imbeault, Itai Bab, Joachim L Schultze, Andreas Zimmer


Published in Nature Medicine

8 May 2017

 

Abstract

The balance between detrimental, pro-aging, often stochastic processes and counteracting homeostatic mechanisms largely determines the progression of aging. There is substantial evidence suggesting that the endocannabinoid system (ECS) is part of the latter system because it modulates the physiological processes underlying aging. The activity of the ECS declines during aging, as CB1 receptor expression and coupling to G proteins are reduced in the brain tissues of older animals and the levels of the major endocannabinoid 2-arachidonoylglycerol (2-AG) are lower. However, a direct link between endocannabinoid tone and aging symptoms has not been demonstrated. Here we show that a low dose of Δ9-tetrahydrocannabinol (THC) reversed the age-related decline in cognitive performance of mice aged 12 and 18 months. This behavioral effect was accompanied by enhanced expression of synaptic marker proteins and increased hippocampal spine density. THC treatment restored hippocampal gene transcription patterns such that the expression profiles of THC-treated mice aged 12 months closely resembled those of THC-free animals aged 2 months. The transcriptional effects of THC were critically dependent on glutamatergic CB1 receptors and histone acetylation, as their inhibition blocked the beneficial effects of THC. Thus, restoration of CB1 signaling in old individuals could be an effective strategy to treat age-related cognitive impairments.

 

DOI: 10.1038/nm.4311

PAYWALL

Citation:

Bilkei-Gorzo A, Albayram O, Draffehn A, et al. A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice. Nature Medicine. 2017;23(6):782-787. doi:10.1038/nm.4311.