A Proteomic View of Cellular and Molecular Effects of Cannabis

Abstract

Cannabis (Cannabis sativa), popularly known as marijuana, is the most commonly used psychoactive substance and is considered illicit in most countries worldwide. However, a growing body of research has provided evidence of the therapeutic properties of chemical components of cannabis known as cannabinoids against several diseases including Alzheimer’s disease (AD), multiple sclerosis (MS), Parkinson’s disease, schizophrenia and glaucoma; these have prompted changes in medicinal cannabis legislation. The relaxation of legal restrictions and increased socio-cultural acceptance has led to its increase in both medicinal and recreational usage. Several biochemically active components of cannabis have a range of effects on the biological system. There is an urgent need for more research to better understand the molecular and biochemical effects of cannabis at a cellular level, to understand fully its implications as a pharmaceutical drug. Proteomics technology is an efficient tool to rigorously elucidate the mechanistic effects of cannabis on the human body in a cell and tissue-specific manner, drawing conclusions associated with its toxicity as well as therapeutic benefits, safety and efficacy profiles. This review provides a comprehensive overview of both in vitro and in vivo proteomic studies involving the cellular and molecular effects of cannabis and cannabis-derived compounds.

Key Genes and Biochemical Networks in Various Brain Regions Affected in Alzheimer’s Disease

“…Another common down-regulated pathway between the AD sensitive brain regions was the retrograde endocannabinoid signaling pathway. The endocannabinoid system (ECS) is comprised of endocannabinoids (eCBs) that are endogenous lipid-based neurotransmitters, along with their receptors such as cannabinoid receptor 1 (CB1R) and cannabinoid receptor 2 (CB2R), and the enzymes that are involved in their synthesis and degradation [49]. Arachidonoyl ethanolamide (anandamide or AEA) and 2-arachidonoylglycerol (2-AG) are the two main endocannabinoids [49].…”

“…The endocannabinoid system (ECS) is comprised of endocannabinoids (eCBs) that are endogenous lipid-based neurotransmitters, along with their receptors such as cannabinoid receptor 1 (CB1R) and cannabinoid receptor 2 (CB2R), and the enzymes that are involved in their synthesis and degradation [49]. Arachidonoyl ethanolamide (anandamide or AEA) and 2-arachidonoylglycerol (2-AG) are the two main endocannabinoids [49]. ECS plays a vital role in the central nervous system function and in the regulation of the endocrine and immune systems [50,51].…”

Fingolimod effects on the brain are mediated through biochemical modulation of bioenergetics, autophagy, and neuroinflammatory networks

“…Retrograde eCB signaling is one of the major altered pathways in several neurodegenerative diseases such as AD, PD, and MS [34][35][36].…”

“…CB, cerebellum; FC, frontal cortex system has been shown to activate anti-inflammatory signaling pathways that modulate immune cell functions; such as modulation of microglial activation in different neurodegenerative diseases [43]. Currently cannabinoid-based drugs are being used to treat symptoms of several neurodegenerative diseases particularly MS [35,44]. Interestingly, cannabinoids also induce autophagy in an AMPK-dependent manner, via their anti-inflammatory actions [45].…”

Regulation of DNA Methylation by Cannabidiol and Its Implications for Psychiatry: New Insights from In Vivo and In Silico Models

“…It is now known that CBD binds to a wide variety of targets, including receptors (primarily PPARγ, GPR55, TRPV1, 5-HT1A, 5-HT3, mu-opioid, A2 and GABA A ), enzymes (MAGL and FAAH), transporters (monoamines, glutamate and eCB) and ion channels, among others [ 14 , 42 ] ( Figure 3 ). This might explain the multitude of CBD effects on neurotransmitter release, cell signaling, gene expression and protein levels, cell cycle control, oxidative stress and inflammation [ 43 ]. Altogether, the polypharmacology of CBD may explain its ability to be effective against diverse pathologies by recruiting different mechanisms depending on the system compromised in the given condition [ 14 , 43 , 44 ].…”