THC and its analogues may provide an improved therapeutic for Alzheimer’s disease

Abstract

Alzheimer’s disease is the leading cause of dementia among the elderly, and with the ever-increasing size of this population, cases of Alzheimer’s disease are expected to triple over the next 50 years. Consequently, the development of treatments that slow or halt the disease progression have become imperative to both improve the quality of life for patients as well as reduce the health care costs attributable to Alzheimer’s disease. Here, we demonstrate that the active component of marijuana, Δ9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid β-peptide (Aβ) aggregation, the key pathological marker of Alzheimer’s disease. Computational modeling of the THC-AChE interaction revealed that THC binds in the peripheral anionic site of AChE, the critical region involved in amyloidgenesis. Compared to currently approved drugs prescribed for the treatment of Alzheimer’s disease, THC is a considerably superior inhibitor of Aβ aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.

Clinical Trials, Studies and Publications:

A Molecular Link Between the Active Component of Marijuana and Alzheimer’s Disease Pathology

The Potential Therapeutic Effects of THC on Alzheimer’s Disease

Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on β-amyloid-induced toxicity in PC12 cells

Cannabidiol reduces Aβ-induced neuroinflammation and promotes hippocampal neurogenesis through PPARγ involvement

Alzheimer’s disease; taking the edge off with cannabinoids?

The influence of mast cell mediators on migration of SW756 cervical carcinoma cells

Abstract

The role of mast cell mediators on cervical cancer cell migration was assessed using an in vitro assay of scratch wound healing onto monolayers of HPV18-positive cervical carcinoma cells (SW756). Migration of SW756 cells was accelerated by co-culture with the mast cell line LAD2. This effect was inhibited by the H1R antagonist pyrilamine and the cannabinoid agonists 2-arachidonylglycerol (2AG) and Win 55,212-2. Therefore, the specific effects of histamine and cannabinoids on SW756 migration and LAD2 activation were analyzed. Histamine added to the in vitro assay of scratch wound healing either increased or inhibited SW756 migration rate by acting either on H1R or H4R, respectively. Cannabinoids acted on CB1 receptors to inhibit SW756 migration. Supernatants from SW756 cells stimulated LAD2 cell degranulation, which in turn was inhibited by cannabinoids acting via CB2 receptors. RT-PCR showed that SW756 expressed mRNA for CB1, CB2, H1R, H2R, and H4R. On the other hand, LAD2 expressed mRNA for all four HRs and CB2. The results suggest that mast cells could be contributing to cervical cancer cell invasion and spreading by the release of histamine and cannabinoids. Therefore, therapeutic modulation of specific mast cell mediators may be beneficial for cervical cancer treatment.

Clinical Trials, Studies and Publications:

The influence of mast cell mediators on migration of SW756 cervical carcinoma cells

Cannabidiol inhibits cancer cell invasion via upregulation of tissue inhibitor of matrix metalloproteinases-1

Abstract

Although cannabinoids exhibit a broad variety of anticarcinogenic effects, their potential use in cancer therapy is limited by their psychoactive effects. Here we evaluated the impact of cannabidiol, a plant-derived non-psychoactive cannabinoid, on cancer cell invasion. Using Matrigel invasion assays we found a cannabidiol-driven impaired invasion of human cervical cancer (HeLa, C33A) and human lung cancer cells (A549) that was reversed by antagonists to both CB(1) and CB(2) receptors as well as to transient receptor potential vanilloid 1 (TRPV1). The decrease of invasion by cannabidiol appeared concomitantly with upregulation of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). Knockdown of cannabidiol-induced TIMP-1 expression by siRNA led to a reversal of the cannabidiol-elicited decrease in tumor cell invasiveness, implying a causal link between the TIMP-1-upregulating and anti-invasive action of cannabidiol. P38 and p42/44 mitogen-activated protein kinases were identified as upstream targets conferring TIMP-1 induction and subsequent decreased invasiveness. Additionally, in vivo studies in thymic-aplastic nude mice revealed a significant inhibition of A549 lung metastasis in cannabidiol-treated animals as compared to vehicle-treated controls. Altogether, these findings provide a novel mechanism underlying the anti-invasive action of cannabidiol and imply its use as a therapeutic option for the treatment of highly invasive cancers.

Clinical Trials, Studies and Publications:

Cannabidiol inhibits cancer cell invasion via upregulation of tissue inhibitor of matrix metalloproteinases-1

Survey of Current Cannabidiol Use in Pediatric Treatment-Resistant Epilepsy

Severe childhood epilepsies are characterized by a high seizure burden and are often associated with neuro-developmental delays. When traditional medications fail to control a child’s seizures, families look to alternative treatments to help their children. One of these alternative treatments that has become more widespread involves the use of a compound from the Cannabis plant, Cannabidiol (CBD). CBD is a non-psychoactive compound that has been shown to have anticonvulsive properties in a number of animal models of epilepsy. In limited human adult trials, CBD has shown promise as an anticonvulsant with very few negative side effects. The purpose of this survey was to understand current use of CBD in children with treatment-resistant epilepsy.

Clinical Trials, Studies and Publications:

Survey of Current Cannabidiol Use in Pediatric Treatment-Resistant Epilepsy

Decreased prevalence of diabetes in marijuana users: cross-sectional data from the National Health and Nutrition Examination Survey

Abstract

Objective: To determine the association between diabetes mellitus (DM) and marijuana use. Design: Cross-sectional study. Setting: Data from the National Health and Nutrition Examination Survey (NHANES III, 1988e1994) conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention.

Clinical Trials, Studies and Publications:

Decreased prevalence of diabetes in marijuana users

Cannabis use was highly prevalent in the study population (57.4%) and was statistically associated with lower body mass index (BMI), lower % fat mass, lower fasting insulin

Abstract

To ascertain the relationship between cannabis use, obesity, and insulin resistance.

Clinical Trials, Studies and Publications:

Cannabis use in relation to obesity and insulin resistance in the Inuit population