Plants with traditional uses and activities, relevant to the management of Alzheimer’s disease and other cognitive disorders.

“In traditional practices of medicine, numerous plants have been used to treat cognitive disorders, including neurodegenerative diseases such as Alzheimer’s disease (AD) and other memory related disorders. An ethnopharmacological approach has provided leads to identifying potential new drugs from plant sources, including those for memory disorders. There are numerous drugs available in Western medicine that have been directly isolated from plants, or are derived from templates of compounds from plant sources. For example, some alkaloids from plant sources have been investigated for their potential in AD therapy, and are now in clinical use (e.g. galantamine from Galanthus nivalis L. is used in the United Kingdom).

 Various other plant species have shown favourable effects in AD, or pharmacological activities indicating the potential for use in AD therapy.

This article reviews some of the plants and their active constituents that have been used in traditional medicine, including Ayurvedic, Chinese, European and Japanese medicine, for their reputed cognitive-enhancing and antidementia effects. Plants and their constituents with pharmacological activities that may be relevant to the treatment of cognitive disorders, including enhancement of cholinergic function in the central nervous system, anti-cholinesterase (anti-ChE), antiinflammatory, antioxidant and oestrogenic effects, are discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/12557240

Medicinal plants and Alzheimer’s disease: from ethnobotany to phytotherapy.

“The use of complementary medicines, such as plant extracts, in dementia therapy varies according to the different cultural traditions. In orthodox Western medicine, contrasting with that in China and the Far East for example, pharmacological properties of traditional cognitive- or memory-enhancing plants have not been widely investigated in the context of current models of Alzheimer’s disease. An exception is Gingko biloba in which the gingkolides have antioxidant, neuroprotective and cholinergic activities relevant to Alzheimer’s disease mechanisms. The therapeutic efficacy of Ginkgo extracts in Alzheimer’s disease in placebo controlled clinical trials is reportedly similar to currently prescribed drugs such as tacrine or donepezil and, importantly, undesirable side effects of Gingko are minimal. Old European reference books, such as those on medicinal herbs, document a variety of other plants such as Salvia officinalis (sage) and Melissa officinalis (balm) with memory-improving properties, and cholinergic activities have recently been identified in extracts of these plants. Precedents for modern discovery of clinically relevant pharmacological activity in plants with long-established medicinal use include, for example, the interaction of alkaloid opioids in Papaver somniferum (opium poppy) with endogenous opiate receptors in the brain. With recent major advances in understanding the neurobiology of Alzheimer’s disease, and as yet limited efficacy of so-called rationally designed therapies, it may be timely to re-explore historical archives for new directions in drug development. This article considers not only the value of an integrative traditional and modern scientific approach to developing new treatments for dementia, but also in the understanding of disease mechanisms. Long before the current biologically-based hypothesis of cholinergic derangement in Alzheimer’ s disease emerged, plants now known to contain cholinergic antagonists were recorded for their amnesia- and dementia-inducing properties.”

http://www.ncbi.nlm.nih.gov/pubmed/10411211

Cannabis May Offer Alzheimer’s Hope, Study Says

“Marijuana compounds offer an alternative approach for treating the neurodegeneration associated with Alzheimer’s disease (AD)…

Investigators at the Trinity College, Institute for Neuroscience, in Dublin report that cannabinoids have been shown to protect neurons from the deleterious effects of amyloid plaque – the primary pathological hallmark of Alzheimer’s. Cannabinoids also demonstrate a propensity to reduce oxidative stress and inflammation, while also promoting neurogenesis (the birth of new neuronal cells), authors report.

Authors write: “In recent years the proclivity of cannabinoids to exert a neuroprotective influence has received substantial interest as a means to mitigate the symptoms of neurodegenerative conditions. … [C]annabinoids offer a multi-faceted approach for the treatment of Alzheimer’s disease by providing neuroprotection and reducing neuroinflammation, whilst simultaneously supporting the brain’s intrinsic repair mechanisms by augmenting neurotrophin expression and enhancing neurogenesis. … Manipulation of the cannabinoid pathway offers a pharmacological approach for the treatment of AD that may be efficacious than current treatment regimens.”

Preclinical studies have demonstrated that cannabinoids can delay disease progression in animal models of several neurodegenerative diseases, including multiple sclerosis and amyotrophic lateral sclerosis (Lou Gehrig’s disease).”-

Paul Armentano, NORML  http://norml.org/news/2007/09/20/cannabis-may-offer-alzheimers-hope-study-says

Full text of the study, “Alzheimer’s disease; taking the edge off with cannabinoids?” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190031/

Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease.

“A placebo-controlled crossover design to investigate effects of dronabinol (THC) in patients with a diagnosis of probable Alzhemer’s disease who were refusing food. 

These results indicate that dronabinol is a promising novel therapeutic agent which may be useful not only for treatment of anorexia but also to improve disturbed behavior in patients with Alzheimer’s disease.”

http://www.ncbi.nlm.nih.gov/pubmed/9309469

Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia.

Psychopharmacology

“Nighttime agitation occurs frequently in patients with dementia and represents the number one burden on caregivers today. Current treatment options are few and limited due to substantial side effects.

OBJECTIVES:

The aim of the study was to measure the effect of the cannabinoid dronabinol (THC) on nocturnal motor activity.

RESULTS:

Compared to baseline, dronabinol led to a reduction in nocturnal motor activity. These findings were corroborated by improvements in Neuropsychiatric Inventory total score as well as in subscores for agitation, aberrant motor, and nighttime behaviors . No side effects were observed.

CONCLUSIONS:

The study suggests that dronabinol (THC) was able to reduce nocturnal motor activity and agitation in severely demented patients. Thus, it appears that dronabinol (THC) may be a safe new treatment option for behavioral and circadian disturbances in dementia.”

http://www.ncbi.nlm.nih.gov/pubmed/16521031

https://link.springer.com/article/10.1007%2Fs00213-006-0343-1

Cannabinoid system in neurodegeneration: new perspectives in Alzheimer’s disease.

“Alzheimer’s disease is a chronic and progressive neurodegenerative disorder. The presence of functional cannabinoid CB2 receptors in central nervous system (CNS) has provoked that this receptor and its agonist ligands are now considered as promising pharmacological targets for neurological diseases. Herein, we review the evidences supporting the potential role of the ECS as a therapeutic target, focused on CB2 receptor and its ligands, for the treatment of Alzheimer’s disease.”

http://www.ncbi.nlm.nih.gov/pubmed/19456285

Cannabinoids and neurodegenerative diseases.

“Although significant advances have taken place in recent years on our understanding of the molecular mechanisms of different neurodegenerative diseases, its translation into effective therapeutic treatments has not been as successful as could be expected. There is still a dramatic lack of curative treatments for the most frequent disorders and only symptomatic relief for many others. Under this perspective, the search for novel therapeutic approaches is demanding and significant attention and efforts have been directed to studying additional neurotransmission systems including the endocannabinoid system (ECS).

The neuroprotective properties of exogenous as well as endogenous cannabinoids have been known for years and the underlying molecular mechanisms have been recently unveiled. As discussed later, antioxidative, antiglutamatergic and antiinflammatory effects are now recognized as derived from cannabinoid action and are known to be of common interest for many neurodegenerative processes.

 Thus, these characteristics make cannabinoids attractive candidates for the development of novel therapeutic strategies.

 The present review will focus on the existing data regarding the possible usefulness of cannabinoid agents for the treatment of relevant neurological pathologies for our society such as Alzheimer’s disease, multiple sclerosis, Huntington’s disease and amyotrophic lateral sclerosis.”

http://www.ncbi.nlm.nih.gov/pubmed/19839933

CB1 agonist ACEA protects neurons and reduces the cognitive impairment of AβPP/PS1 mice.

“The present study shows that chronic administration of the cannabinoid receptor type 1 (CB1) receptor agonist arachidonyl-2-chloroethylamide (ACEA) at pre-symptomatic or at early symptomatic stages, at a non-amnesic dose, reduces the cognitive impairment observed in double AβPP(swe)/PS1(1dE9) transgenic mice from 6 months of age onwards…

… targeting the CB1 receptor could offer a versatile approach for the treatment of Alzheimer’s disease.”

http://www.ncbi.nlm.nih.gov/pubmed/22451318

Protective effect of cannabinoid CB1 receptor activation against altered intrinsic repetitive firing properties induced by Aβ neurotoxicity.

Neuroscience Letters

“The amyloid β (Aβ) protein is believed to be the key pathological mediator of Alzheimer’s disease (AD) which is the first and most well known type of dementia. Despite a growing body of evidence indicating that Aβ neurotoxicity induces changes in synaptic function, little effort, if any, has been made to investigate the effect of in vivo Aβ treatment on intrinsic neuronal properties. The present study was designed to examine the effects that in vivo Aβ treatment have on the intrinsic repetitive firing properties of CA1 pyramidal neurons, using whole cell patch clamp recording. Protective effect of cannabinoid CB1 receptor activation was also investigated against Aβ-induced alterations in evoked electrophysiological activities. The findings from present study demonstrated that a bilateral injection of Aβ into the prefrontal cortex causes robust changes in activity-dependent electrophysiological responses in hippocampal CA1 pyramidal neurons. The effects of Aβ treatment alone was almost completely prevented by combined treatment with Aβ and ACEA, a selective CB1 receptor agonist. It can be concluded Aβ treatment reduces evoked neuronal activity and activation of CB1 cannabinoid receptors may have beneficial preventative effects on Aβ-induced electrophysiological changes.”

http://www.ncbi.nlm.nih.gov/pubmed/22172925

https://www.sciencedirect.com/science/article/abs/pii/S0304394011015667

Nonpsychoactive Cannabidiol Prevents Prion Accumulation and Protects Neurons against Prion Toxicity

“Creutzfeldt–Jakob disease (CJD) in humans belongs to a group of fatal neurodegenerative disorders called transmissible spongiform encephalopathies (TSEs) or prion diseases. No therapeutic treatments against TSEs are currently available. The urgent need to find effective anti-prion therapies has been strengthened by the emergence of variant CJD (vCJD) caused by contaminated beef consumption …

Our results suggest that CBD may protect neurons against the multiple molecular and cellular factors involved in the different steps of the neurodegenerative process, which takes place during prion infection. When combined with its ability to target the brain and its lack of toxic side effects, CBD may represent a promising new anti-prion drug.

Overall, CBD is a promising therapeutic drug against the TSEs because it combines several crucial characteristics. It has a low toxicity and lack of psychotropic side effects as well as in vivo neuroprotective, anti-inflammatory, and anti-PrPres properties. Because CBD easily crosses the BBB, it also has the potential to be effective after prion infection has reached the CNS. Finally, prolonged treatments with CBD do not induce tolerance, a phenomenon frequently observed with THC. Additional investigations should be performed to define the optimal dose, route, frequency, and duration of the in vivo CBD treatment necessary to prevent TSE infection…”

http://www.jneurosci.org/content/27/36/9537.full