“Cannabis sativa L. (C. sativa) contains an array of plant-derived (phyto) cannabinoids and terpenes that are predominantly located in the trichome cavity of the plant. Terpenes, aromatic organic hydrocarbons characterized for their role in plant protection/pollination, are gaining attention for their potential as novel therapeutics in many areas of biomedicine. This Viewpoint will explore the exciting recent evidence that terpenes have anti-inflammatory/antioxidant propensity by targeting inflammatory signaling mechanisms relevant to human disease. Given their anti-inflammatory properties, terpenes may contribute to the effects of current cannabinoid-based therapies.”
Tag Archives: phytocannabinoids
Cannabis and the exocannabinoid and endocannabinoid systems. Their use and controversies.
“Cannabis (marijuana) is one of the most consumed psychoactive substances in the world. The term marijuana is of Mexican origin. The primary cannabinoids that have been studied to date include cannabidiol and delta-9-tetrahydrocannabinol, which is responsible for most cannabis physical and psychotropic effects. Recently, the endocannabinoid system was discovered, which is made up of receptors, ligands and enzymes that are widely expressed in the brain and its periphery, where they act to maintain balance in several homeostatic processes. Exogenous cannabinoids or naturally-occurring phytocannabinoids interact with the endocannabinoid system. Marijuana must be processed in a laboratory to extract tetrahydrocannabinol and leave cannabidiol, which is the product that can be marketed. Some studies suggest cannabidiol has great potential for therapeutic use as an agent with antiepileptic, analgesic, anxiolytic, antipsychotic, anti-inflammatory and neuroprotective properties; however, the findings on cannabinoids efficacy and cannabis-based medications tolerability-safety for some conditions are inconsistent. More scientific evidence is required in order to generate recommendations on the use of medicinal cannabis.”
Decreased sensitivity in adolescent versus adult rats to the antidepressant-like effects of cannabidiol.
“Cannabidiol is a non-psychoactive phytocannabinoid with great therapeutic potential in diverse psychiatric disorders; however, its antidepressant potential has been mainly ascertained in adult rats.
OBJECTIVES:
To compare the antidepressant-like response induced by cannabidiol in adolescent and adult rats and the possible parallel modulation of hippocampal neurogenesis.
RESULTS:
Cannabidiol induced differential effects depending on the age and dose administered, with a decreased sensitivity observed in adolescent rats: (1) cannabidiol (30 mg/kg) decreased body weight only in adult rats; (2) cannabidiol ameliorated behavioral despair in adolescent and adult rats, but with a different dose sensitivity (10 vs. 30 mg/kg), and with a different extent (2 vs. 21 days post-treatment); (3) cannabidiol did not modulate anxiety-like behavior at any dose tested in adolescent or adult rats; and (4) cannabidiol increased sucrose intake in adult rats.
CONCLUSIONS:
Our findings support the notion that cannabidiol exerts antidepressant- and anorexigenic-like effects in adult rats and demonstrate a decreased potential when administered in adolescent rats. Moreover, since cannabidiol did not modulate hippocampal neurogenesis (cell proliferation and early neuronal survival) in adolescent or adult rats, the results revealed potential antidepressant-like effects induced by cannabidiol without the need of regulating hippocampal neurogenesis.”
https://www.ncbi.nlm.nih.gov/pubmed/32086540
https://link.springer.com/article/10.1007%2Fs00213-020-05481-4
Phytocannabinoids promote viability and functional adipogenesis of bone marrow-derived mesenchymal stem cells through different molecular targets.
“The cellular microenvironment plays a critical role in the maintenance of bone marrow-derived mesenchymal stem cells (BM-MSCs) and their subsequent cell lineage differentiation. Recent studies suggested that individuals with adipocyte-related metabolic disorders have altered function and adipogenic potential of adipose stem cell subpopulations, primarily BM-MSCs, increasing the risk of heart attack, stroke or diabetes.
In this study, we explored the potential therapeutic effect of some of the most abundant non-euphoric compounds derived from the Cannabis sativa plant (or phytocannabinoids) including tetrahydrocannabivarin (THCV), cannabidiol (CBD), cannabigerol (CBG), cannabidiolic acid (CBDA) and cannabigerolic acid (CBGA), by analysing their pharmacological activity on the viability of endogenous BM-MSCs as well as their ability to alter BM-MSC proliferation and differentiation into mature adipocytes.
We provide evidence that CBD, CBDA, CBGA and THCV (5 µM) increase the number of viable BM-MSCs; whereas only CBG (5 µM) and CBD (5 µM) alone or in their combination promote their maturation into adipocytes via distinct molecular mechanisms. These effects were revealed both in vitro and in vivo. In addition, phytocannabinoids prevented the insulin signalling impairment induced by palmitate in adipocytes differentiated from BM-MSCs.
Our study highlights phytocannabinoids as a potential novel pharmacological tool to regain control of functional adipose tissue in unregulated energy homeostasis often occurring in metabolic disorders including type 2 diabetes mellitus (T2DM), aging and lipodystrophy.”
https://www.ncbi.nlm.nih.gov/pubmed/32061773
“The promiscuous pharmacology of phytocannabinoids makes them viable candidates for new medicines for the treatment of metabolic syndromes through the simultaneous resolution of collective complications due to impaired development, maintenance, activity and function of the adipose tissue. Furthermore, phytocannabinoids are generally well tolerated in comparison to potent synthetic PPAR agonists, and combination treatments may further improve their efficacy at lower doses.”
https://www.sciencedirect.com/science/article/pii/S0006295220300873?via%3Dihub
Axially-Chiral Cannabinols: A New Platform for Cannabinoid-Inspired Drug Discovery.
“Phytocannabinoids (and synthetic analogs thereof) are gaining significant attention as promising leads in modern medicine. Considering this, new directions for the design of phytocannabinoid-inspired molecules is of immediate interest. In this regard, we have hypothesized that axially-chiral-cannabinols (ax-CBNs), unnatural and unknown isomers of cannabinol (CBN) may be valuable scaffolds for cannabinoid-inspired drug discovery. There are two main factors directing our interest to these scaffolds: (a) ax-CBNs would have ground-state three-dimensionality; ligand-receptor interactions can be more significant with complimentary 3D-topology, and (b) ax-CBNs at their core structure are biaryl molecules, generally attractive platforms for pharmaceutical development due to their ease of functionalization and stability. Herein we report a synthesis of ax-CBNs, examine physical properties experimentally and computationally, and perform a comparative analysis of ax-CBN and THC in mice behavioral studies.”
https://www.ncbi.nlm.nih.gov/pubmed/32061146
https://onlinelibrary.wiley.com/doi/abs/10.1002/cmdc.202000025
Possible therapeutic applications of cannabis in the neuropsychopharmacology field.
“Cannabis use induces a plethora of actions on the CNS via its active chemical ingredients, the so-called phytocannabinoids.
These compounds have been frequently associated with the intoxicating properties of cannabis preparations. However, not all phytocannabinoids are psychotropic, and, irrespective of whether they are psychotropic or not, they have also shown numerous therapeutic properties.
These properties are mostly associated with their ability to modulate the activity of an intercellular communication system, the so-called endocannabinoid system, which is highly active in the CNS and has been found altered in many neurological disorders.
Specifically, this includes the neuropsychopharmacology field, with diseases such as schizophrenia and related psychoses, anxiety-related disorders, mood disorders, addiction, sleep disorders, post-traumatic stress disorder, anorexia nervosa and other feeding-related disorders, dementia, epileptic syndromes, as well as autism, fragile X syndrome and other neurodevelopment-related disorders.
Here, we gather, from a pharmacological and biochemical standpoint, the recent advances in the study of the therapeutic relevance of the endocannabinoid system in the CNS, with especial emphasis on the neuropsychopharmacology field. We also illustrate the efforts that are currently being made to investigate at the clinical level the potential therapeutic benefits derived from elevating or inhibiting endocannabinoid signaling in animal models of neuropsychiatric disorders.”
https://www.ncbi.nlm.nih.gov/pubmed/32057592
https://www.sciencedirect.com/science/article/abs/pii/S0924977X20300365?via%3Dihub
The Epigenetics of the Endocannabinoid System.
“The endocannabinoid system (ES) is a cell-signalling system widely distributed in biological tissues that includes endogenous ligands, receptors, and biosynthetic and hydrolysing machineries.
The impairment of the ES has been associated to several pathological conditions like behavioural, neurological, or metabolic disorders and infertility, suggesting that the modulation of this system may be critical for the maintenance of health status and disease treatment.
Lifestyle and environmental factors can exert long-term effects on gene expression without any change in the nucleotide sequence of DNA, affecting health maintenance and influencing both disease load and resistance. This potentially reversible “epigenetic” modulation of gene expression occurs through the chemical modification of DNA and histone protein tails or the specific production of regulatory non-coding RNA (ncRNA).
Recent findings demonstrate the epigenetic modulation of the ES in biological tissues; in the same way, endocannabinoids, phytocannabinoids, and cannabinoid receptor agonists and antagonists induce widespread or gene-specific epigenetic changes with the possibility of trans-generational epigenetic inheritance in the offspring explained by the transmission of deregulated epigenetic marks in the gametes.
Therefore, this review provides an update on the epigenetics of the ES, with particular attention on the emerging role in reproduction and fertility.”
Cannabinoid Signaling in Glioma Cells.
“Cannabinoids are a group of structurally heterogeneous but pharmacologically related compounds, including plant-derived cannabinoids, synthetic substances and endogenous cannabinoids, such as anandamide and 2-arachidonoylglycerol.
Cannabinoids elicit a wide range of central and peripheral effects mostly mediated through cannabinoid receptors. There are two types of specific Gi/o-protein-coupled receptors cloned so far, called CB1 and CB2, although an existence of additional cannabinoid-binding receptors has been suggested. CB1 and CB2 differ in their predicted amino acid sequence, tissue distribution, physiological role and signaling mechanisms.
Significant alterations of a balance in the cannabinoid system between the levels of endogenous ligands and their receptors occur during malignant transformation in various types of cancer, including gliomas.
Cannabinoids exert anti-proliferative action in tumor cells.
Induction of cell death by cannabinoid treatment relies on the generation of a pro-apoptotic sphingolipid ceramide and disruption of signaling pathways crucial for regulation of cellular proliferation, differentiation or apoptosis. Increased ceramide levels lead also to ER-stress and autophagy in drug-treated glioblastoma cells.
Beyond blocking of tumor cells proliferation cannabinoids inhibit invasiveness, angiogenesis and the stem cell-like properties of glioma cells, showing profound activity in the complex tumor microenvironment. Advances in translational research on cannabinoid signaling led to clinical investigations on the use of cannabinoids in treatments of glioblastomas.”
https://www.ncbi.nlm.nih.gov/pubmed/32034716
https://link.springer.com/chapter/10.1007%2F978-3-030-30651-9_11
“Cannabinoids exert anti-proliferative action in tumor cells.” https://www.ncbi.nlm.nih.gov/pubmed/22879071
“A glioma is a primary brain tumor that originates from the supportive cells of the brain, called glial cells.” http://neurosurgery.ucla.edu/body.cfm?id=159
“Remarkably, cannabinoids kill glioma cells selectively and can protect non-transformed glial cells from death.” http://www.ncbi.nlm.nih.gov/pubmed/15275820
Cannabinoids in the Pathophysiology of Skin Inflammation.
“Cannabinoids are increasingly-used substances in the treatment of chronic pain, some neuropsychiatric disorders and more recently, skin disorders with an inflammatory component.
This paper aims to detail and clarify the complex workings of cannabinoids in the molecular setting of the main dermatological inflammatory diseases, and their interactions with other substances with emerging applications in the treatment of these conditions. Also, the potential role of cannabinoids as antitumoral drugs is explored in relation to the inflammatory component of skin cancer.
In vivo and in vitro studies that employed either phyto-, endo-, or synthetic cannabinoids were considered in this paper. Cannabinoids are regarded with growing interest as eligible drugs in the treatment of skin inflammatory conditions, with potential anticancer effects, and the readiness in monitoring of effects and the facility of topical application may contribute to the growing support of the use of these substances.
Despite the promising early results, further controlled human studies are required to establish the definitive role of these products in the pathophysiology of skin inflammation and their usefulness in the clinical setting.”
https://www.ncbi.nlm.nih.gov/pubmed/32033005
https://www.mdpi.com/1420-3049/25/3/652
“Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429381/
Abrupt withdrawal of cannabidiol (CBD): A randomized trial.
“The rationale of this study was to assess occurrence of withdrawal symptoms induced by abrupt cessation of cannabidiol (CBD) after prolonged administration in healthy volunteers.
CONCLUSION:
In healthy volunteers, no evidence of withdrawal syndrome was found with abrupt discontinuation of short-term treatment with CBD.”
https://www.ncbi.nlm.nih.gov/pubmed/32036242
“There was no evidence of a physical withdrawal syndrome after abrupt cessation of CBD.”
https://www.epilepsybehavior.com/article/S1525-5050(19)31116-3/fulltext
“Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa” https://www.ncbi.nlm.nih.gov/pubmed/19690824