Phytocannabinoids

The post-COVID condition (PCC) is a pathology stemming from COVID-19, and studying its pathophysiology, diagnosis, and treatment is crucial. Neuroinflammation causes the most common manifestations of this disease including headaches, fatigue, insomnia, depression, anxiety, among others. Currently, there are no specific management proposals; however, given that the inflammatory component involves cytokines and free radicals, these conditions must be treated to reduce the current symptoms and provide neuroprotection to reduce the risk of a long-term neurodegenerative disease...

The endogenous cannabinoid system (ECS) plays a critical role in the regulation of various physiological functions, including sleep, mood, and neuroinflammation. Phytocannabinoids such as Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinomimimetics, and some N-acylethanolamides, particularly palmitoyethanolamide, have emerged as potential therapeutic agents for the management of sleep disorders. THC, the psychoactive component of cannabis, may initially promote sleep, but, in the long term, alters sleep architecture, while CBD shows promise in improving sleep quality without psychoactive effects...

Central and peripheral mechanisms of the endocannabinoid system (ECS) favor energy intake and storage. The ECS, especially cannabidiol (CBD) receptors, controls adipocyte differentiation (hyperplasia) and lipid accumulation (hypertrophy) in adipose tissue. In white adipose tissue, cannabidiol receptor 1 (CB1) stimulation increases lipogenesis and inhibits lipolysis; in brown adipose tissue, it decreases mitochondrial thermogenesis and biogenesis. This study compared the availability of phytocannabinoids [CBD and Δ9-tetrahydrocannabinol (THC)] and polyunsaturated fatty acids [omega 3 (ω3) and omega 6 (ω6)] in different hemp seed oils (HSO)...

INTRODUCTION: The involvement of endocannabinoid system (ECS) in the inflammatory cascade, and the ability of phytocannabinoids, endocannabinoids and their synthetic analogues to modulate it has become an interesting research area for new therapeutic approaches in inflammatory skin diseases. Cannabidiol (CBD) appears to be the most promising among phytocannabinoids, due to the lack of psychotropic effects and low toxicity profile. Its anti-inflammatory action has been highlighted in different preclinical models, ranging from experimental colitis to arthritis and neuroinflammation...

Synthetic cannabinoid receptor agonists (SCRAs) remain one the largest classes of new psychoactive substances, and are increasingly associated with severe adverse effects and death compared to the phytocannabinoid Δ9 -tetrahydrocannabinol (THC). In the attempt to circumvent the rapid emergence of novel SCRAs, several nations have implemented 'generic' legislations, or 'class-wide' bans based on common structural scaffolds. However, this has only encouraged the incorporation of new chemical entities, including distinct core and linker structures, for which there is a dearth of pharmacological data...

Phytocannabinoids represent the hallmark of the secondary metabolism of Cannabis sativa . The content of major phytocannabinoids is closely related to genetic variation as well as abiotic elicitors such as temperature, drought, and saline stress. The present study aims to evaluate hemp response to saline irrigation supplied as NaCl solutions with an electrical conductivity (EC) of 2.0, 4.0, and 6.0 dS m-1 (S1, S2, and S3, respectively) compared to a tap water control (S0). In addition, the potential beneficial effect of a plant-based biostimulant (a legume protein hydrolysate) in mitigating the detrimental effects of saline irrigation on crop growth and phytocannabinoid composition was investigated...

Recreational use of synthetic cannabinoid agonists (i.e., "Spice" compounds) that target the Cannabinoid Type 1 receptor (CB 1 ) can cause respiratory depression in humans. However, Δ 9 -tetrahydrocannabinol (THC), the major psychoactive phytocannabinoid in cannabis, is not traditionally thought to interact with CNS control of respiration, based largely upon sparse labeling of CB1 receptors in the medulla and few reports of clinically significant respiratory depression following cannabis overdose. The respiratory effects of CB 1 agonists have rarely been studied in vivo , suggesting that additional inquiry is required to reconcile the conflict between conventional wisdom and human data...

Global cannabis use has risen 23% since 2010, with 209 million reported users, most of whom are males of reproductive age. Delta-9-tetrahydrocannabinol (THC), the main psychoactive phytocannabinoid in cannabis, disrupts pro-homeostatic functions of the endocannabinoid system (ECS) within the male reproductive system. The ECS is highly involved in regulating morpho-functional and intrinsic sperm features that are required for fertilization and pre-implantation embryo development. Previous work by our group demonstrated that THC altered sperm capacitation and the transcriptome, including several fertility-associated microRNAs (miRs)...

Cannabinoids have shown potential in drug-resistant epilepsy treatment; however, we lack knowledge on which cannabinoid(s) to use, dosing, and their pharmacological targets. This study investigated (i) the anticonvulsant effect of Cannabidiol (CBD) alone and (ii) in combination with Delta-9 Tetrahydrocannabinol (Δ9 -THC), as well as (iii) the serotonin (5-HT)1A receptor's role in CBD's mechanism of action. Seizure activity, induced by 4-aminopyridine, was measured by extracellular field recordings in cortex layer 2/3 of mouse brain slices...

Endocannabinoid system plays a pivotal role in controlling neuroinflammation, and modulating this system may not only aid in managing symptoms of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Epilepsy, Central and Peripheral neuropathic pain, but also, have the potential to target these diseases at an early-stage. In the present study, six different pharmacophore hypotheses were generated from Cannabidiol (CBD)-Cannabinoid Receptor subtype-2 (CB2) and then Zinc database was screened for identification of hit molecules...

Studies have demonstrated the neuroprotective effect of cannabidiol (CBD) and other Cannabis sativa L. derivatives on diseases of the central nervous system caused by their direct or indirect interaction with endocannabinoid system-related receptors and other molecular targets, such as the 5-HT1A receptor, which is a potential pharmacological target of CBD. Interestingly, CBD binding with the 5-HT1A receptor may be suitable for the treatment of epilepsies, parkinsonian syndromes and amyotrophic lateral sclerosis, in which the 5-HT1A serotonergic receptor plays a key role...

Cannabichromene (CBC) is a nonpsychoactive phytocannabinoid well-known for its wide-ranging health advantages. However, there is limited knowledge regarding its human metabolism following CBC consumption. This research aimed to explore the metabolic pathways of CBC by various human liver cytochrome P450 (CYP) enzymes and support the outcomes using in vivo data from mice. The results unveiled two principal CBC metabolites generated by CYPs: 8'-hydroxy-CBC and 6',7'-epoxy-CBC, along with a minor quantity of 1″-hydroxy-CBC...

Production of phytocannabinoids remains an area of active scientific interest due to the growing use of cannabis by the public and the underexplored therapeutic potential of the over 100 minor cannabinoids. While phytocannabinoids are biosynthesized by Cannabis sativa and other select plants and fungi, structural analogs and stereoisomers can only be accessed synthetically or through heterologous expression. To date, the bioproduction of cannabinoids has required eukaryotic hosts like yeast since key, native oxidative cyclization enzymes do not express well in bacterial hosts...

Hyperalgesia resulting from sleep deprivation (SD) poses a significant a global public health challenge with limited treatment options. The nucleus accumbens (NAc) plays a crucial role in the modulation of pain and sleep, with its activity regulated by two distinct types of medium spiny neurons (MSNs) expressing dopamine 1 or dopamine 2 (D1-or D2) receptors (referred to as D1-MSNs and D2-MSNs, respectively). However, the specific involvement of the NAc in SD-induced hyperalgesia remains uncertain. Cannabidiol (CBD), a nonpsychoactive phytocannabinoid, has demonstrated analgesic effects in clinical and preclinical studies...

Cannabidiol (CBD), a prominent phytocannabinoid found in various Cannabis chemotypes, is under extensive investigation for its therapeutic potential. Moreover, because it is nonpsychoactive, it can also be utilized as a functional ingredient in foods and supplements in certain countries, depending on its legal status. From a chemical reactivity point of view, CBD can undergo conversion into different structurally related compounds both during storage and after the consumption of CBD-based products. The analytical determination of these compounds is of paramount concern due to potential toxicity and the risk of losing the active ingredient (CBD) title...

BACKGROUND: The cannabis plant contains several cannabinoids, and many terpenoids that give cannabis its distinctive flavoring and aroma. Δ9 -Tetrahydrocannabinol (Δ9 -THC) is the plant's primary psychoactive constituent. Given the abuse liability of Δ9 -THC, assessment of the psychoactive effects of minor cannabinoids and other plant constituents is important, especially for compounds that may be used medicinally. This study sought to evaluate select minor cannabinoids and terpenes for Δ9 -THC-like psychoactivity in mouse Δ9 -THC drug discrimination and determine their binding affinities at CB1 and CB2 receptors...

BACKGROUND: The primary components driving the current commercial fascination with cannabis products are phytocannabinoids, a diverse group of over 100 lipophilic secondary metabolites derived from the cannabis plant. Although numerous phytocannabinoids exhibit pharmacological effects, the foremost attention has been directed towards Δ9 -tetrahydrocannabinol (THC) and cannabidiol, the two most abundant phytocannabinoids, for their potential human applications. Despite their structural similarity, THC and cannabidiol diverge in terms of their psychotropic effects, with THC inducing notable psychological alterations...

The endocannabinoid system is widely expressed throughout the body and is comprised of receptors, ligands, and enzymes that maintain metabolic, immune, and reproductive homeostasis. Increasing interest in the endocannabinoid system has arisen due to these physiologic roles, policy changes leading to more widespread recreational use, and the therapeutic potential of Cannabis and phytocannabinoids. Rodents have been the primary preclinical model of focus due to their relative low cost, short gestational period, genetic manipulation strategies, and gold-standard behavioral tests...

The first detailed phytochemical analysis of the cannabigerol (CBG)-rich chemotype IV of Cannabis sativa L. resulted in the isolation of the expected cannabigerolic acid/cannabigerol (CBGA/CBG) and cannabidiolic acid/cannabidiol (CBDA/CBD) and of nine new phytocannabinoids ( 5 - 13 ), which were fully characterized by HR-ESIMS and 1D and 2D NMR. These included mono- or dihydroxylated CBGA/CBG analogues, a congener with a truncated side chain ( 10 ), cyclocannabigerol B ( 11 ), and the CBD derivatives named cannabifuranols ( 12 and 13 )...

With recent evolution of cannabis legalization around the world, cannabis edibles are booming, and determining their concentration in Δ9-tetrahydrocannabinol (Δ9-THC), the regulated psychoactive substance, remains a challenge for toxicology laboratories, which must prove the legal status or not of the product. Cannabinoids are a large family of structurally similar and lipophilic molecules, requiring dedicated pre-analytical methods, as well as efficient chromatographic separation to differentiate cannabinoid isomers which are distinguished by their psychoactive properties and their legal status...