Cannabis is one of the oldest cultivated crops in the history for food, fiber and drugs for thousands of years. Extension of cannabis genetic variation developed in a wide- ranging choice of varieties with various complementary phenotypes and secondary metabolites. Cannabis grow practices is very diverse, especially indoor cultivation factors, such as different lighting conditions, pot size, humidity, fertilizers. These growth factors influence a lot on the production of cannabinoids. For medical or pharmaceutical purposes, ratio of CBD or THC is very important. Plants traits and metabolic compounds are related to various conditions produced by microbes. Investigating this crosstalk between plants and microbes can play a vital role not only for stimulating the biosynthetic and signaling pathways of the host plants for the production of agronomically or pharmaceutically essential metabolic compounds but also against pathogens. This study emphasis on decoding the crosstalk between cannabis and associated microbes in the belowground environmental niches that would unravel the complexity of stabilizing cannabinoid production.

Worldwide, approximately 15 million people per year suffer from stroke. With about 5 million deaths, stroke is the second most common cause of death and a major cause of long-term disability. It is estimated that about 25% of people older than 85 years will develop stroke. Cannabis sativa and derived cannabinoids are used for recreational and medical purposes for many centuries. However, due to past legal status, research faced restrictions and cannabis use was stigmatized for potential negative impacts on health. With the legalization of cannabis in many countries of the world, cannabis and cannabis-derived substances such as cannabinoids and terpenes have gained more interest in medical research. Several medical effects of cannabis have been scientifically proven and potential risks were identified. In the context of stroke, the role of cannabis is controversial. Negative impact of cannabis use on stroke has been reported through anecdotal case reports and some population-based studies. However, potential beneficial effects of specific cannabinoids are described in animal studies under certain conditions. In this review, the existing body of evidence regarding the negative and positive impacts of cannabis use prior to stroke will be critically appraised.

The purpose of the study was to describe and compare the pharmacokinetics of five commercial edible marijuana products, determine the influence of body composition on pharmacokinetics, and, in light of epidemiology suggesting marijuana may offer diabetes protection, explore the influence of edible marijuana on glucose tolerance. Seven regular users of marijuana self-administered five edible products in a randomized crossover design; each product contained 10mg of delta-9-tetrahydrocannabinol (THC). 30-minutes following marijuana ingestion, participants imbibed a 75g glucose beverage. Time-to-peak plasma THC concentration ranged between 35 and 90 minutes; maximal plasma THC concentration (Cmax) ranged between 3.2 and 5.5 ng/mL. Differences between products in plasma THC concentration during the first 20-to-30 minutes were detected (P=0.019). Relations were identified between body composition and pharmacokinetic parameters for some products; however, none of these body composition characteristics were consistently related to pharmacokinetics across all five of the products. Edible marijuana had no effect on oral glucose tolerance compared with a marijuana-free control (Matsuda Index; P>0.395). Commercially available edible marijuana products evoke different plasma THC concentrations shortly after ingestion, but do not appear to influence acute glucose regulation. These data may allow marijuana users to make informed decisions pertaining to rates of edible marijuana ingestion and avoid overdose.

Cannabis (Cannabis Sativa L.) is now legally produced in many regions worldwide. Cannabis flourishes under high light intensities (LI); making it an expensive commodity to grow in controlled environments, despite its exceptionally high market value. It is commonly believed that cannabis secondary metabolite levels may be enhanced both by increasing LI and by exposing crops to ultraviolet radiation (UV). However, there is sparse scientific evidence to guide cultivators. Therefore, the impact of LI and UV on yield and quality must be elucidated to enable cultivators to optimize their lighting protocols. We explored the effects of LI, ranging from 350 to 1400 μmol m^-2 s^-1 and supplemental UV spectra on cannabis yield and potency. There were no spectrum effects on inflorescence yield, but harvest index under UVA+UVB was reduced slightly (1.6%) vs. the control. Inflorescence yield increased linearly from 19.4 to 57.4 g/plant and harvest index increased from 0.565 to 0.627, as LI increased from 350 to 1400 μmol m^-2 s^-1. Although there were no UV spectrum effects on total equivalent Δ⁹-tetrahydrocannabinol (T-THC) content in leaves, the neutral form, THC, was 30% higher in UVA+UVB vs. control. While there were no LI effects on inflorescence T-THC content, the content of the acid form (THCA) increased by 20% and total terpenes content decreased by 20% as LI increased from 350 to 1400 μmol m^-2 s^-1. High LI can substantially increase cannabis yield and quality, but we found no commercially-relevant benefits of adding supplemental UV radiation to indoor cannabis production.

HIV-associated neurocognitive disorders (HAND) persist despite the advent of antiretroviral therapy (ART), suggesting underlying systemic and central nervous system (CNS) inflammatory mechanisms. The endogenous cannabinoid receptors 1 and 2 (CB1 and CB2) modulate inflammatory gene expression and play an important role in maintaining neuronal homeostasis. Cannabis use is disproportionately high among people with HIV (PWH) and may provide a neuroprotective effect for those on ART due to its anti-inflammatory properties. However, expression profiles of CB1 and CB2 in the brains of PWH on ART with HAND have not been reported. In this study, biochemical and immunohistochemical analyses were performed to determine CB1 and CB2 expression in brain specimens of HAND donors. Immunoblot revealed CB1 and CB2 were differentially expressed in frontal cortices from HAND brains compared to neurocognitively unimpaired (NUI) brains from PWH. CB1 expression levels negatively correlated with memory and information processing speed. CB1 was primarily localized to neuronal soma in HAND brains versus a more punctate distribution on neuronal processes of NUI brains. CB1 expression was increased in cells with glial morphology and showed increased colocalization with an astroglial marker. These results suggest that targeting the endocannabinoid system may be a potential therapeutic strategy for HAND.

Objectives: The mechanism of action of drugs that depress the central nervous system (CNS) was unknown until molecular pharmacology discovered each drug's exact role. The benefit of knowing the mechanism of action is to design a new drug that could have the same efficacy as the prototype drug but with fewer side effects. Some of the available CNS depressant drugs that were abused or illegally used could be modified to make them used medically. Methods: We reviewed various published articles in PubMed and Google Scholar that focused on CNS depressants' molecular pharmacology.Results: It was clear that at specific plasma concentrations of ethyl alcohol showed almost same mode of action of propofol by targeting the extrasynaptic GABA-A receptors, which causes tonic GABAergic inhibition. Besides, the High affinity of some benzodiazepines (e.g., midazolam) to α1 subunit of GABA-A receptor causes sedative, hypnotic, amnesic, and some antiepileptic effects; however, some other benzodiazepines (e.g., diazepam) have high affinity to α3 subunits, which causes anxiolytic, muscle relaxant, and strong antiepileptic effects. The CB1 receptor partial agonism effect of tetrahydrocannabinol has a sedative advantage over full agonism due to desensitization of CB1 receptors. Conclusion: From the molecular pharmacology prospect, it is possible to design new drugs with more specific CNS depressants effect and fewer side effects by targeting particular receptors with a precise reaction.

Neuropathic pain (NP) affects about the 8% of the general population. Current analgesic therapies have limited efficacy, making NP one of the most difficult to treat pain conditions. Evidence indicates that excessive oxidative stress can contribute to the onset of chronic NP and several natural antioxidant compounds have showed promising efficacy in NP models. Thus, the aim of the present study was to investigate the pain-relieving activity of honokiol (HNK)-rich standardized extract of Magnolia officinalis Rehder & E. Wilson bark (MOE), well known for its antioxidant and anti-inflammatory properties, in the spared nerve injury (SNI) model. The molecular mechanisms were investigated in spinal cord samples from SNI mice and in LPS-stimulated BV2. MOE and HNK showed antioxidant activity. MOE (30 mg/kg p.o.), produced an antiallodynic effect in the absence of locomotor impairment. MOE treatment reduced spinal p-p38, p-JNK1, iNOS, p-p65, IL-1ß and Nrf2 overexpression, increased IL-10 and MBP levels and attenuated the Notch signaling pathway by reducing Jagged1 and NEXT. All these effects were prevented by the CB1 antagonist AM251. HNK reduced the proinflammatory state of LPS-stimulated BV2 cells and reduced Jagged1 overexpression. MOE and HNK, by modulating oxidative and proinflammatory responses, might represent interesting candidates for NP management.

Epilepsy is characterized by repeated spontaneous reactions caused by hyper-excitability and neurons firing in high synchronization in the central nervous system. It seriously affects the quality of life of epileptic patients and nearly 30% of individuals are refractory to treatment of antiepileptic drugs. Therefore, there is an urgent need to develop new medicines to manage and control the refractory epilepsy. Cannabinoid ligands including selective cannabinoid receptor subtype (CB1 or CB2 receptor) ligands and non-selective cannabinoid (synthetic and endogenous) ligands may serve as the novel candidates for this need. Cannabinoid systems appear to regulating seizure activity in the brain through the activation of CB1 and CB2 cannabinoid receptors (CB1R and CB2R). An abundant series of cannabinoid analogues have been tested in various animal models, including a rat pilocarpine model of acquired epilepsy, in vitro hippocampal neuronal culture models of acquired epilepsy and status epilepticus, a pentylenetetrazole model of myoclonic seizures in mice and a penicillin-induced model of epileptiform activity in the rats. The accumulating lines of evidence show that cannabinoid ligands exhibit significant benefits to control seizure activity in different epileptic models. For this reason, we summarize the relationship between brain CB2 receptors and seizures, and emphasize the potential mechanisms of their therapeutic effects involving affecting neurons, astrocytes, and microglia cells. The unique features of CB2Rs, such as lower expression levels under physiological conditions and high inducibility under epileptic conditions, make it an important target for future research on drug-resistant epilepsy.

The endocannabinoid system has been found to be pervasive in mammalian species. It has also been described in invertebrate species primitive as the Hydra. Insects apparently are devoid of this otherwise ubiquitous system that provides homeostatic balance to the nervous and immune systems, as well as many other organ systems. The endocannabinoid system (ECS) has been defined to consist of three parts: 1. Endogenous ligands, 2. G-protein coupled receptors (GPCRs), and 3. Enzymes to degrade and recycle the ligands. Two endogenous molecules have been identified as ligands in the ECS to date. These are the endocannabinoids: Anandamide (arachidonoyl ethanolamide) and 2-AG (2-arachidonoyl glycerol). Two G-coupled protein receptors have been described as part of this system, with other putative GPC being considered. Coincidentally, the phytochemicals produced in large quantities by the Cannabis sativa L plant, and in lesser amounts by other plants, can interact with this system as ligands. These plant-based cannabinoids are termed, phytocannabinoids. The precise determination of the distribution of cannabinoid receptors in animal species is an ongoing project, with the canine cannabinoid receptor distribution currently receiving the most interest in non-human animals.

Recent studies have shown that the endogenous cannabinoid system (ECS) of the brain is essentially involved in the pathogenesis of Parkinson's disease (PD), influencing its symptoms by regulating the level of endogenous cannabinoids and altering the activation of cannabinoid receptors (CBR). Therefore, modulation of ECS with new drugs developed for this purpose may prove to be a promising strategy in the treatment of PD. However, fine regulation of ECS is quite a challenge due to the functional diversity of CBR in the basal ganglia. Our review analyses the effects of ECS modulators on experimental PD models and in patients with PD, as well as presents the outlooks for the development of new cannabinoid drugs for the treatment of motor and non-motor symptoms in PD.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the lack of estrogen receptors (ER), progesterone receptors, and HER-2 receptors. Thus, TNBC tumours do not benefit from the current therapies targeting ER or HER-2. Therefore, there is an urgent need to develop novel treatment for this subtype of breast cancer. Marijuana is a common name given to Cannabis plants, a group of plants in the Cannabis genus of the Cannabaceae family. Cannabis plants are among the oldest cultivated crops, traced back at least 12,000 years and are well known for their multi-purpose usage, including medicinal purposes. The main active compounds extracted from Cannabis plants are 21-carbon-containing terpenophenolics, which are referred to as phytocannabinoids. Of these, the tetrahydrocannabinol (THC) group contains highly potent cannabinoids, including delta-9-tetrahydrocannabinol (∆9-THC) and delta-8-tetrahydrocannabinol (∆8-THC), which are the most abundant THCs and are largely responsible for psychological and physiological effects of marijuana. The use of Cannabis plants for medicinal purposes was first recorded in 2337 BC in China, where Cannabis plants were used to treat pains, rheumatism, and gout. Recently, several cannabinoids have been approved for a number of treatments, one of which is the treatment of nausea and vomiting caused by chemotherapy in cancer patients. Furthermore, increasing evidence shows that cannabinoids not only attenuate side effects due to cancer treatment, but might also potentially possess direct antitumor effects in several cancer types, including breast cancer. However, anti-tumour activity of marijuana has been variable in different studies and even promoted tumour growth in some cases. In addition, the mechanisms of cannabinoid action in cancer remain unclear. This review summarizes evidence about the mixed actions of cannabinoids in cancer in general and triple-negative breast cancer in particular.

Introduction: Dental health problems including dental plaque are common health problems affecting people of different age groups globally. Air-polishing is a safe tooth polishing technique used by dental professionals for stain and plaque removal and as preventive procedure for dental health. Here we report the technical improvisation of existing air-polishing technique by supplementing cannabinoid powder into the classic polishing powder for effective removal of supragingival and subgingival plaque and inhibition of plaque forming bacteria. Methods: The cannabidiol (CBD) powder was added to the tooth polishing powder (AIR-N-GO, classic) at 1% (wt/wt) ratio. The study was conducted on 12 patients, of which 6 received regular polishing treatment and 6 received CBD-supplemented polishing treatment. The dental plaque samples were collected before and after each treatment and subjected to in vitro microbiological analysis and the colony forming units (CFU) were analyzed using automated colony counter. Results: Based on in vitro microbiological analysis, the average CFU of interdental space samples collected from post-CBD-supplemented polishing treatment was significantly reduced (linear fold change between 3.9-18.4) compared to that of post-regular polishing (linear fold change between 1.0-2.6) treatment. Conclusions: CBD-supplemented polishing powder can help in effective removal and killing of dental plaque bacteria during the polishing treatment. CBD powder can be added as enhancing supplement to the existing polishing powders.

Fatty Acid Amide Hydrolase (FAAH) is one of the enzymes responsible of endocannabinoids metabolism. The inhibition of FAAH is a useful and indirect strategy to raise endogenous cannabinoid concentrations, which would be useful for the treatment of various pathological processes in which cannabinoid concentrations are lowered. In the present work, we present an extensive 3D-QSAR/CoMSIA study on a series of 90 irreversible inhibitors of FAAH of pyrimidinyl-piperazine-carboxamide structure. The final model obtained was extensively validated (q2 = 0.734; r2test = 0.966; r2m = 0.723), and based on the information derived from the contour maps we reported a series of 10 new compounds designed as powerful FAAH inhibitors (pIC50 of the best-proposed compounds = 12.196; 12.416).

The endocannabinoid system (eCB) began to be studied from the identification of the molecular structures present in the cannabis sativa plant. The ECS is constituted of cannabinoid receptors, endogenous ligands and all the associated enzymatic apparatus responsible for maintaining homeostasis. Several physiological effects of cannabinoids are exerted through interaction with various receptors such as CB1 and CB2 receptors, vanilloid receptors, and the recently discovered [GPCRs (GPR55, GPR3, GPR6, GPR12 and GPR19). Endogenous ligands such anandamide and 2-arachidonoylglycerol might modulate these receptors. eCB has proved to play a critical role in some human diseases and has been extensively studied due to its wide therapeutic potential and because it is a promising target for the development of new drugs. Phytocannabinoids and synthetic cannabinoids have shown varied affinities to eCB, which are relevant to the treatment of various diseases. They may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases. Furthermore, Integrative and Complementary Health Practices (ICHP) appear to influence the endocannabinoid system through modulation. This review will show a description of ECS components and discuss how phytocannabinoids, other exogenous compounds, and PICS may operate the eCB balance.

Fifty years on from the classical fluid-mosaic model of Singer and Nicolson, current views of the plasma membrane portray a much more complex view of this interface region. Compartmentalization, together with transbilayer and lateral asymmetries, provide the structural foundation for functional specializations at the cell surface, including the active role of the lipid microenvironment in the modulation of membrane-bound proteins. The chemical synapse, the site where neurotransmitter-coded signals are decoded by neurotransmitter receptors, adds another layer of complexity to the plasma membrane architectural intricacy, mainly due to the need to accommodate a sizeable number of molecules in a minute subcellular compartment with dimensions barely reaching the micrometer. In this review, we discuss how Nature has developed suitable adjustments to accommodate different types of membrane-bound receptors and scaffolding proteins via membrane microdomains, and how this “efford-sharing” mechanism has evolved to optimize crosstalk or separation or coupling where/when appropriate. To this end, we use a fast ligand-gated neurotransmitter receptor, the nicotinic acetylcholine receptor, and a second-messenger G-protein coupled receptor, the cannabinoid receptor, as paradigmatic example.

Single-particle tracking with quantum dots (QDs) constitutes a powerful tool to track the nanoscopic dynamics of individual cell membrane components unveiling their membrane diffusion characteristics. Here we tested the possibility of extracting from the nano-resolved (16 ms and 30 nm) population dynamics of several quantum dots, time-binned at the second time-scale, the rapid structural changes of the cell membrane surface. We used for this proof-of-concept study bright, small and stable biofunctional QD nanoconstructs recognizing the neuronal cannabinoid type 1 (CB1) receptor and a commercial point-localization microscope to reconstruct in 3D the dynamics of the plasma membrane surface of cultured cells with a spatial resolution of tens of nanometers. CB1 receptor was chosen because it’s a highly expressed and fast diffusing membrane protein. Therefore, rapid QD diffusion on the axonal plasma membrane of cultured hippocampal neurons allowed highly precise reconstruction of the membrane surface in less than one minute. QD nanoconstructs diffused into the membrane of synaptic clefts allowing the entire topological reconstruction of the presynaptic component. In addition, we demonstrated successful reconstruction of the remarkably high dynamics of membrane surface topology at the second time-scale both in HEK-293 cell filopodia and axons. Our results show that this novel technique, which we named nanoPaint, is a powerful precision tool for the study of the structural plasticity of cell membrane surfaces.

The effects of morphine (MOR) and dexmedetomidine (DEX) on the MAC of isoflurane were measured in rats chronically treated with the synthetic cannabinoid WIN 55,212-2 (WIN55). Methods: The MAC of isoflurane was determined in 32 male rats from expiratory samples at the time of tail clamping. The effects of morphine (MAC(ISO+MOR)) and dexmedetomidine (MAC(ISO+DEX)) on the MAC of isoflurane in untreated rats and rats treated for 21 days with WIN 55,212-2 (MAC(ISO+WIN55+MOR)) and (MAC(ISO+WIN55+DEX)) were measured. Prior to the administration of morphine and dexmedetomidine, the MAC of the isoflurane was measured in both untreated rats (MAC(ISO)) and those treated with WIN 55,212-2 (MAC(ISO+WIN55)). Results: The minimum alveolar concentration was measured as 1.32 ± 0.06 in the MAC(ISO) group and 1.69 ± 0.09 in the MAC(ISO+WIN55) group. The MAC of the MAC(ISO+MOR) group was 0.97 ± 0.02 (26% less than the control group, MAC(ISO)). MAC was measured as 1.55 ± 0.08 in the MAC(ISO+WIN55+MOR) group (8% less than the MAC(ISO+WIN55) group), 0.68 ± 0.10 in the MAC(ISO+DEX) group (48% less than the control group, MAC(ISO)), and 0.67 ± 0.08 in the MAC(ISO+WIN55+DEX) group (60% less than the MAC(ISO+WIN55) group). Conclusions: The administration of WIN 55,212-2 for 21 days increases the MAC of isoflurane in rats. The sparing effect on isoflurane of morphine decreases in rats chronically treated with the synthetic cannabinoid, WIN 55,212-2. Dexmedetomidine increases its sparing effect on the minimum alveolar concentration of isoflurane in rats chronically treated with WIN 55,212-2.

Since the recent legalization of medical and recreational use of cannabis (Cannabis sativa L.) in many regions worldwide, there has been high demand for research to improve yield and quality. With the paucity of scientific literature on the topic, this study investigated the relationships between light intensity (LI) and photosynthesis, inflorescence yield, and inflorescence quality of cannabis grown in an indoor environment. After growing vegetatively for 2 weeks under a canopy-level photosynthetic photon flux density (PPFD) of ≈ 425 μmol·m-2·s-1 and an 18-h light/6-h dark photoperiod, plants were grown for 12 weeks in a 12-h light/12-h dark ‘flowering’ photoperiod under canopy-level PPFDs ranging from 120 to 1800 μmol·m-2·s-1 provided by light emitting diodes. Leaf light response curves varied both with localized (i.e., leaf-level) PPFD and temporally, throughout the flowering cycle. Therefore, it was concluded that the leaf light response is not a reliable predictor of whole- plant responses to LI, particularly crop yield. This may be especially evident given that dry inflorescence yield increased linearly with increasing canopy-level PPFD up to 1800 μmol·m-2·s-1, while leaf-level photosynthesis saturated well below 1800 μmol·m-2·s-1. The density of the apical inflorescence and harvest index also increased linearly with increasing LI, resulting in higher-quality marketable tissues and less superfluous tissue to dispose of. There were no LI treatment effects on cannabinoid potency, while there were minor LI treatment effects on terpene potency. Commercial cannabis growers can use these light response models to determine the optimum LI for their production environment to achieve the best economic return; balancing input costs with the commercial value of their cannabis products.

In recent years, there have been frequent reports on the adverse effects of synthetic cannabinoid (SC) abuse. SCs cause psychoactive effects, similar to those caused by marijuana, by binding and activating cannabinoid receptor 1 (CB1R) in the central nervous system. The aim of this study was to establish a reliable quantitative structure-activity relationship (QSAR) model to correlate the structures and physicochemical properties of various SCs with their CB1R-binding affinities. We prepared 15 SCs and their derivatives (tetrahydrocannabinol [THC], naphthoylindoles, and cyclohexylphenols) and determined their binding affinity to CB1R, which is known as a dependence-related target. We calculated the molecular descriptors for dataset compounds using an R/CDK (R package integrated with CDK, version 3.5.0) toolkit to build QSAR regression models. These models were established and statistical evaluations were performed using the mlr and plsr packages in R software. The most reliable QSAR model was obtained from the partial least squares regression method via external validation. This model can be applied in vivo to predict the addictive properties of illicit new SCs. Using a limited number of dataset compounds and our own experimental activity data, we built a QSAR model for SCs with good predictability. This QSAR modeling approach provides a novel strategy for establishing an efficient tool to predict the abuse potential of various SCs and to control their illicit use.