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Cannabis products are widely used for medical and non-medical reasons worldwide and vary in content of cannabinoids such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Resting state functional connectivity offers a powerful tool to investigate the effects of cannabinoids on the human brain. We systematically reviewed functional neuroimaging evidence of connectivity during acute cannabinoid administration. A pre-registered (PROSPERO ID: CRD42020184264) systematic review of 13 studies comprising 318 participants (mean age of 25 years) was conducted and reported using the PRISMA checklist. During THC and THCv exposure vs placebo reduced connectivity with the NAcc was widely reported. Limited evidence shows that such effects are offset by co-administration of CBD. NAcc-frontal region connectivity was associated with intoxication levels. Cannabis intoxication vs placebo was associated with lower striatal-ACC connectivity. CBD and CBDv vs placebo were associated with both higher and lower connectivity between striatal-prefrontal/other regions. Overall, cannabis and cannabinoids change functional connectivity in the human brain during resting state as a function of the type of cannabinoid examined. • Cannabis and cannabinoids alter rsFC as a function of the cannabinoid examined. • In THC intoxication vs placebo reduced connectivity with the NAcc was reported. • Limited evidence shows that such effects are offset by co-administration of CBD. [ABSTRACT FROM AUTHOR]

The estimation of illicit drugs use through wastewater analysis has become an important issue in the last few years due to their large worldwide consumption, which results in economic, social and health costs. The amounts of urinary biomarkers of illicit drugs (selected drugs or their metabolites) measured in wastewater are used to back-calculate the consumption of a particular drug by the population and to monitor temporal and spatial trends of illicit drug use in a community. The reliability of back-calculation depends on different factors, one being the accuracy of correction factors. A wide range of correction factors have been used in different studies and some biases must be expected when comparing results. Most of the correction factors were developed several years ago, so they need to be updated to include the latest information on pharmacokinetics. Moreover, new comprehensive methods to treat data should be adopted. The goal of this study is to refine current correction factors for back-calculation of the most widely used illicit drugs: amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and tetrahydrocannabinol (THC). The mean percentages of excretion of the parent drugs and their metabolites were calculated for each route of administration, utilizing all accessible pharmacokinetic studies in the literature. This allowed to select the most suitable drug target residue and a refined correction factor was obtained for each substance considering the most frequent route of administration. The refined correction factors we propose can be used in wastewater based epidemiology to standardize the back-calculation of these drugs. These results can be included in the best practice protocol currently adopted in EU studies in order to reduce uncertainty and improve the comparability of results. [ABSTRACT FROM AUTHOR]

In the current study, a novel double-layer gold nanoparticles-electrochemical immunosensor electrode immobilized with tetrahydrocannabinol (THC) antibody derived from Balb/c mice was developed. To increase the fixed quantity of antibodies and electrochemical signals, an electrochemical biosensing signal amplification system was utilized with gold nanoparticles-thionine-chitosan absorbing horseradish peroxidase (HRP). In addition, a transmission electron microscope (TEM) was used to characterize the nanogold solution. To evaluate the quality of the immunosensor, the amperometric I-t curve method was applied to determine the THC in PBS. The results showed that the response current had a good linear correlation with the THC concentration range from 0.01~103 ng/mL with a correlation coefficient of 0.9986. The lowest detection limit for THC was 3.3 pg/mL (S/N = 3). Moreover, it was validated with high sensitivity and reproducibility. Apparently, the immunosensor may be a very useful tool for monitoring the THC. [ABSTRACT FROM AUTHOR]

Cannabinoids have shown to have a variety effects on body systems. Through CB1 and CB2 receptors, amongst other, they exert an effect by modulating neurotransmitter and cytokine release. Current research in the role of cannabinoids in the immune system shows that they possess immunosuppressive properties. They can inhibit proliferation of leucocytes, induce apoptosis of T cells and macrophages and reduce secretion of pro-inflammatory cytokines. In mice models, they are effective in reducing inflammation in arthritis, multiple sclerosis, have a positive effect on neuropathic pain and in type 1 diabetes mellitus. They are effective as treatment for fibromyalgia and have shown to have anti-fibrotic effect in scleroderma. Studies in human models are scarce and not conclusive and more research is required in this field. Cannabinoids can be therefore promising immunosuppressive and anti-fibrotic agents in the therapy of autoimmune disorders. [ABSTRACT FROM AUTHOR]

Short overviews are presented on the historical uses of cannabis in the Middle East and on the more recent scientific and medical research on phytocannabinoids and the endocannabinoid system, with emphasis on research contributions from Israel. These are followed by examples of research projects and clinical trials with cannabinoids and by a short report on the regulation of medical marijuana in Israel, which at present is administered to over 22,000 patients. [ABSTRACT FROM AUTHOR]

In the present study we investigated the effect of ethephon on changes in the amount of many terpenoid compounds including, tetrahydrocannabinol (THC), cannabidiol (CBD), chlorophyll, carotenoids, α-tocopherol and pyruvate as one of substrate in plastidic terpenoids biosynthesis inCannabis sativaat vegetative stage. Treatment with 1 and 100 µM ethephon increased THC content up to 9 fold in vegetative stage. Plants treated with 10 µM ethephon had more CBD content in comparison with control plants. The amount of CBD decreased in plants subjected to 5 and 100 µM ethephon. Leave area in plant treated with ethephon did not show significant changes in comparison to control plants. Ethephon treatment caused a declined in the amount of α-tocopherol. The levels of chlorophylls and carotenoids raised in treated plants with 1 µM ethephon. With regard to the fact that ethephon had not negative effect on the surface of leaves and chlorophyll content thus its application can be a suitable way for increasing of THC and α-tocopherol inCannabis sativaL. [ABSTRACT FROM AUTHOR]

Recent studies highlight the therapeutic virtues of cannabidiol (CBD). Furthermore, due to their molecular enriched profiles, cannabis inflorescences are biologically superior to a single cannabinoid for the treatment of various health conditions. Thus, there is flourishing demand for Cannabis sativa varieties containing high levels of CBD. Additionally, legal regulations around the world restrict the cultivation and consumption of tetrahydrocannabinol (THC)-rich cannabis plants for their psychotropic effects. Therefore, the use of cannabis varieties that are high in CBD is permitted as long as their THC content does not exceed a low threshold of 0.3%–0.5%, depending on the jurisdiction. These chemovars are legally termed 'hemp'. This controlled cannabinoid requirement highlights the need to detect low levels of THC, already in the field. In this review, cannabis profiling and the existing methods used for the detection of cannabinoids are firstly evaluated. Then, selected valuable biosensor technologies are discussed, which suggest portable, rapid, sensitive, reproducible, and reliable methods for on-site identification of cannabinoids levels, mainly THC. Recent cutting-edge techniques of promising potential usage for both cannabis and hemp analysis are identified, as part of the future cultivation and agricultural improvement of this crop. • Demand for Cannabis sativa L. strains containing high levels of cannabidiol (CBD). • Restrictions of tetrahydrocannabinol (THC)-rich cannabis for psychotropic effects. • Cannabis profiling and the existing methods used for the detection of cannabinoids. • Portable biosensors for on-site identification of cannabinoids are discussed. • Optical, gas, and electrochemical techniques for both cannabis and hemp analysis. [ABSTRACT FROM AUTHOR]

Cannabis sativa is an economically important source of durable fibers, nutritious seeds, and psychoactive drugs but few economic plants are so poorly understood genetically., Marijuana and hemp were crossed to evaluate competing models of cannabinoid inheritance and to explain the predominance of tetrahydrocannabinolic acid ( THCA) in marijuana compared with cannabidiolic acid ( CBDA) in hemp. Individuals in the resulting F2 population were assessed for differential expression of cannabinoid synthase genes and were used in linkage mapping. Genetic markers associated with divergent cannabinoid phenotypes were identified., Although phenotypic segregation and a major quantitative trait locus ( QTL) for the THCA/ CBDA ratio were consistent with a simple model of codominant alleles at a single locus, the diversity of THCA and CBDA synthase sequences observed in the mapping population, the position of enzyme coding loci on the map, and patterns of expression suggest multiple linked loci. Phylogenetic analysis further suggests a history of duplication and divergence affecting drug content., Marijuana is distinguished from hemp by a nonfunctional CBDA synthase that appears to have been positively selected to enhance psychoactivity. An unlinked QTL for cannabinoid quantity may also have played a role in the recent escalation of drug potency. [ABSTRACT FROM AUTHOR]

Fractality, represented as self-similar repeating patterns, is ubiquitous in nature and the brain. Dynamic patterns of hippocampal spike trains are known to exhibit multifractal properties during working memory processing; however, it is unclear whether the multifractal properties inherent to hippocampal spike trains reflect active cognitive processing. To examine this possibility, hippocampal neuronal ensembles were recorded from rats before, during and after a spatial working memory task following administration of tetrahydrocannabinol (THC), a memory-impairing component of cannabis. Multifractal detrended fluctuation analysis was performed on hippocampal interspike interval sequences to determine characteristics of monofractal long-range temporal correlations (LRTCs), quantified by the Hurst exponent, and the degree/magnitude of multifractal complexity, quantified by the width of the singularity spectrum. Our results demonstrate that multifractal firing patterns of hippocampal spike trains are a marker of functional memory processing, as they are more complex during the working memory task and significantly reduced following administration of memory impairing THC doses. Conversely, LRTCs are largest during resting state recordings, therefore reflecting different information compared to multifractality. In order to deepen conceptual understanding of multifractal complexity and LRTCs, these measures were compared to classical methods using hippocampal frequency content and firing variability measures. These results showed that LRTCs, multifractality, and theta rhythm represent independent processes, while delta rhythm correlated with multifractality. Taken together, these results provide a novel perspective on memory function by demonstrating that the multifractal nature of spike trains reflects hippocampal microcircuit activity that can be used to detect and quantify cognitive, physiological, and pathological states. [ABSTRACT FROM AUTHOR]

Rationale: Data on safety, pharmacodynamics, and pharmacokinetics of tetrahydrocannabinol (THC) are lacking in dementia patients. Methods: In this randomized, double-blind, placebo-controlled, crossover trial, we evaluated the safety, pharmacodynamics, and pharmacokinetics of THC in ten patients with dementia (mean age 77.3 ± 5.6). For 12 weeks, participants randomly received oral THC (weeks 1-6, 0.75 mg; weeks 7-12, 1.5 mg) or placebo twice daily for 3 days, separated by a 4-day washout period. Results: Only 6 of the 98 reported adverse events were related to THC. Visual analog scale (VAS) feeling high, VAS external perception, body sway-eyes-open, and diastolic blood pressure were not significantly different with THC. After the 0.75-mg dose, VAS internal perception (0.025 units; 95 % CI 0.010-0.040) and heart rate (2 beats/min; 95 % CI 0.4-3.8) increased significantly. Body sway-eyes-closed increased only after 1.5 mg (0.59°/s; 95 % CI 0.13-1.06). Systolic blood pressure changed significantly after both doses of THC (0.75 mg, −7 mmHg, 95 % CI −11.4, −3.0; 1.5 mg, 5 mmHg, 95 % CI 1.0-9.2). The median T was 1-2 h, with THC pharmacokinetics increasing linearly with increasing dose, with wide interindividual variability (CV% up to 140 %). The mean C (ng/mL) after the first dose (0-6 h) was 0.41 (0.18-0.90) for the 0.75-mg dose and 1.01 (0.53-1.92) for the 1.5-mg dose. After the second dose (6-24 h), the C was 0.50 (0.27-0.92) and 0.98 (0.46-2.06), respectively. Conclusions: THC was rapidly absorbed and had dose-linear pharmacokinetics with considerable interindividual variation. Pharmacodynamic effects, including adverse events, were minor. Further studies are warranted to evaluate the pharmacodynamics and efficacy of higher THC doses in older persons with dementia. [ABSTRACT FROM AUTHOR]

Recreational cannabis use in adults with epilepsy is widespread. The use of cannabis for medicinal purposes is also becoming more prevalent. For this purpose, various preparations of cannabis of varying strengths and content are being used. The recent changes in the legal environment have improved the availability of products with high cannabidiol (CBD) and low tetrahydrocannabinol (THC) concentrations. There is some anecdotal evidence of their potential efficacy, but the mechanisms of such action are not entirely clear. Some suspect an existence of synergy or “entourage effect” between CBD and THC. There is strong evidence that THC acts via the cannabinoid receptor CB 1 . The mechanism of action of CBD is less clear but is likely polypharmacological. The scientific data support the role of the endocannabinoid system in seizure generation, maintenance, and control in animal models of epilepsy. There are clear data for the negative effects of cannabis on the developing and mature brain though these effects appear to be relatively mild in most cases. Further data from well-designed studies are needed regarding short- and long-term efficacy and side effects of CBD or high-CBD/low-THC products for the treatment of seizures and epilepsy in children and adults. [ABSTRACT FROM AUTHOR]

Abstract: Low striatal dopamine D2/3 receptor (D2/3) availability and low ventrostriatal dopamine release have been observed in alcoholism, cocaine and heroin dependence. Multiple studies to date have examined D2 availability in cannabis dependence and have consistently failed to demonstrate alterations. In addition, the response of the dopamine system to an amphetamine challenge and to a stress challenge has also been examined, and did not show alterations. We review these studies here and conclude that cannabis dependence is an exception among commonly abused drugs in that it is not associated with blunting of the dopamine system. [Copyright &y& Elsevier]

Abstract: The cannabinoid acids are a structurally heterogeneous group of compounds some of which are endogenous molecules and others that are metabolites of phytocannabinoids. The prototypic endogenous substance is N-arachidonoyl glycine (NAgly) that is closely related in structure to the cannabinoid agonist anandamide. The most studied phytocannabinoid is Δ9-THC-11-oic acid, the principal metabolite of Δ9-THC. Both types of acids have in common several biological actions such as low affinity for CB1 anti-inflammatory activity and analgesic properties. This suggests that there may be similarities in their mechanism of action, a point that is discussed in this review. Also presented are reports on analogs of the acids that provide opportunities for the development of novel therapeutic agents, such as ajulemic acid. [Copyright &y& Elsevier]

Highlights: [•] CB1 blockade in the PVN increases fasting-induced hyperphagia. [•] CB1 blockade in the PVN enhances the orexigenic effect of ghrelin. [•] CB1 blockade potentiates ghrelin-induced PVN hypoactivity. [Copyright &y& Elsevier]

Highlights: [•] Cannabinoids attenuate SIN-1 toxicity to oligodendrocytes via CB2R activation. [•] CB52 reduces inflammation and provides neuroprotection in EAE mice. [•] Activation of CB1R contributes to the beneficial effects of CB52 in EAE animals. [Copyright &y& Elsevier]

Abstract: Tetrahydrocannabinol (THC), a psychoactive component of marijuana, is known to exert cytotoxicity in immune cells. In the present study, we examined the cytotoxicity of Δ8-THC in mouse macrophage J774-1 cells and a possible involvement of cannabinoid receptors and stress-responsive mitogen-activated protein kinases (MAPKs) in the cytotoxic process. J774-1 cells were treated with Δ8-THC (0–20μM) for up to 6h. As measured by the MTT and LDH assays, Δ8-THC induced cell death of J774-1 cells in a concentration- and/or exposure time-dependent manner. Δ8-THC-induced cell damage was associated with vacuole formation, cell swelling, chromatin condensation, and nuclear fragmentation. The cytotoxic effect of Δ8-THC was significantly prevented by a caspase-1 inhibitor Ac-YVAD-cmk but not a caspase-3 inhibitor z-DEVD-fmk. The pretreatment with SR144528, a CB2 receptor-selective antagonist, effectively suppressed Δ8-THC-induced cytotoxicity in J774-1 cells, which exclusively expressed CB2 receptors as indicated by real-time polymerase chain reaction analysis. In contrast, AM251, a CB1 receptor-selective antagonist, did not affect the cytotoxicity. Pertussis toxin and α-tocopherol significantly attenuated Δ8-THC-induced cytotoxicity suggesting that Gi/o protein coupling signal transduction and oxidative stress are responsible for the cytotoxicity. Δ8-THC stimulated the phosphorylation of p38 MAPK and c-Jun N-terminal kinase (JNK) in J774-1 cells, which were effectively antagonized by the pretreatment with SR144528. In addition, SB203580, a p38 MARK inhibitor, significantly attenuated the cytotoxic effect of Δ8-THC, whereas SP600125, a JNK inhibitor, significantly enhanced the cytotoxicity. These results suggest that the cytotoxicity of Δ8-THC to J774-1 cells is exerted mediated through the CB2 receptor followed by the activation of p38 MAPK. [Copyright &y& Elsevier]

Abstract: Methamphetamine use disorders remain a significant public health concern. Methamphetamine produces its behavioral effects by facilitating release of monoamines like dopamine (DA) and serotonin (5-HT). Results from animal studies show that acute pretreatment with DA and 5-HT antagonists attenuates the effects of methamphetamine, but this area remains largely unexplored in humans. This study sought to assess whether aripiprazole, a partial agonist at D2/5-HT1A receptors and an antagonist at 5-HT2A receptors, would attenuate the reinforcing and subject-rated effects of oral methamphetamine. Seven subjects with histories of recreational stimulant use completed a placebo-controlled, crossover, double-blind protocol in which they first sampled doses of oral methamphetamine (0, 4, 8 or 16mg) following acute pretreatment with aripiprazole (0 and 15mg). During each Sampling Session, subjects also completed a battery of subject-rated, cardiovascular, and other performance measures. In subsequent Self-Administration Sessions, subjects were provided the opportunity to earn the previously sampled methamphetamine dose on a progressive-ratio procedure. Methamphetamine functioned as a reinforcer, and produced prototypical stimulant-like subject-rated and cardiovascular effects (e.g., increased ratings of Stimulated; elevated blood pressure). Aripiprazole reduced methamphetamine self-administration and attenuated some of the positive subject-rated effects of methamphetamine (e.g., ratings of Like Drug). These results indicate that acute aripiprazole pretreatment attenuates the abuse-related effects of methamphetamine. [Copyright &y& Elsevier]

Abstract: Inflammation in the central nervous system (CNS) is a complex process that involves a multitude of molecules and effectors, and it requires the transmigration of blood leukocytes across the blood–brain barrier (BBB) and the activation of resident immune cells. Cannabidiol (CBD), a non-psychotropic cannabinoid constituent of Cannabis sativa, has potent anti-inflammatory and immunosuppressive properties. Yet, how this compound modifies the deleterious effects of inflammation in TMEV-induced demyelinating disease (TMEV-IDD) remains unknown. Using this viral model of multiple sclerosis (MS), we demonstrate that CBD decreases the transmigration of blood leukocytes by downregulating the expression of vascular cell adhesion molecule-1 (VCAM-1), chemokines (CCL2 and CCL5) and the proinflammatory cytokine IL-1β, as well as by attenuating the activation of microglia. Moreover, CBD administration at the time of viral infection exerts long-lasting effects, ameliorating motor deficits in the chronic phase of the disease in conjunction with reduced microglial activation and pro-inflammatory cytokine production. Adenosine A2A receptors participate in some of the anti-inflammatory effects of CBD, as the A2A antagonist ZM241385 partially blocks the protective effects of CBD in the initial stages of inflammation. Together, our findings highlight the anti-inflammatory effects of CBD in this viral model of MS and demonstrate the significant therapeutic potential of this compound for the treatment of pathologies with an inflammatory component. [Copyright &y& Elsevier]

Objective: To describe bath salts and synthetic tetrahydrocannabinol (THC) exposures in the US from 2009 to 2012, hypothesizing a yearly increase. Study design: All exposures reported to American Association of Poison Control Centers between January 1, 2009, and April 30, 2012, were extracted from the National Poison Data System using generic and product codes. Results: Bath salts and synthetic THC exposures totaled 7467 and 11 561, respectively. Bath salts exposures were 0 in 2009, 298 in 2010, and 6062 in 2011. Synthetic THC exposures were 14 in 2009, 2821 in 2010, and 6255 in 2011. First-tertile bath salts exposures were lower in 2012 (n = 1007) than in 2011 (n = 2027), and synthetic THC exposures were higher in 2012 (n = 2389) than in 2011 (n = 1888). Most exposures occurred in the midwest and southeast regions (64.8% of bath salts and 58% of synthetic THC exposures). Male subjects comprised 69% (n = 5153) of bath salts users and 74% (n = 8505) of synthetic THC users. Exposure to bath salts were highest in subjects 20-29 years of age (n = 2943), and exposure to synthetic THC was highest for subjects 13-19 years of age (n = 5349). Intentional abuse and inhalation were most common reason for and mode of exposure, respectively. Conclusions: Bath salts and synthetic THC abuse increased from 2009 to 2011. Synthetic THC emerged first and has more reported exposures than bath salts. In 2012, bath salts abuse declined and synthetic marijuana abuse increased. Young men intentionally abusing the drug via inhalation make up the majority of users. [Copyright &y& Elsevier]

With the recent legalization of marijuana in several countries for recreational use, a controversial belief is spreading about it being "safe". In this systematic review, we decided to investigate this belief and present the adverse effects of marijuana and tobacco smoking on the cardiovascular system. We carried out an electronic search on databases including PubMed, PubMed Central, and Medline. Medical Subject Headings (MeSH) terms and different keywords were used for data collection. We included studies published in the last 10 years that were in English. All types of study subjects were accepted. Grey literature, books, case reports and case series, overlapping and duplicate studies, and studies older than 10 years were excluded. In this review, we included 18 studies, which we then separated into the "tobacco and cardiovascular disease" arm and the "cannabinoids and cardiovascular disease" arm. We had 11 and seven studies for each of the arms, respectively. The types of articles included in this review were traditional and systematic reviews and meta-analyses. After reviewing all the data included in this article, we found out that cannabinoid consumption has a more devastating effect on the cardiovascular system when compared to tobacco. The shocking fact was that in several cases, deadly adverse effects were observed in patients within a few hours after consumption or even during their first time using cannabinoids., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Abu Jad et al.)

Cannabis use and depression management have been studied, with a preponderance of exacerbating effects, but there are few studies on postpartum depression (PPD). Depression affects a significant number of women, with a portion of it manifesting as PPD in childbearing women in the United States each year. The pharmacologic management approaches have disadvantages such as side effects, cost-benefit ratio, contraindications, use reluctance, medication adherence, and stigmatization in patients. Anecdotal claims of medical cannabis' therapeutic benefits have led to widespread legalization in several regions, making cannabis and its extracts a possible alternative. Cannabis is widely used during pregnancy and in general. Even though substance use disorders exacerbating depression symptoms have been reported, there are increasing reports and evidence about the therapeutic benefit of dose-dependent cannabis or its extracts in some depression symptoms, such as acute psychosocial stress relief, its purported anxiolytic effect, appetite, and sleep quality, thus stimulating more interest that may be inferred to depression. PPD marijuana use is unclear. This paper reviewed works of literature that claimed cannabis' therapeutic benefit in treating depression and, by extension, PPD. Our findings show the link between cannabis and PPD has not been fully explored. Self-reported studies link marijuana uses to positive mood, anxiety relief, sleep regulation, nausea and vomiting reduction, and appetite stimulation-all PPD symptoms. Others opposed postpartum marijuana use., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Ayisire et al.)

Abstract: The results of an indoor hydroponic Cannabis growth study are presented. It is intended that this work will be of assistance to those with an interest in determining an estimation of yield and value of Cannabis crops. Three cycles of six plants were grown over a period of 1 year in order to ascertain the potential yield of female flowering head material from such an operation. The cultivation methods used were selected to replicate typical indoor hydroponic Cannabis growing operations, such as are commonly encountered by the New Zealand Police. The plants were also tested to ascertain the percentage of the psychoactive chemical Δ-9 tetrahydrocannabinol (THC) present in the flowering head material, and were genetically profiled by STR analysis. Phenotypic observations are related to the data collected. The inexperience of the growers was evidenced by different problems encountered in each of the three cycles, each of which would be expected to negatively impact the yield and THC data obtained. These data are therefore considered to be conservative. The most successful cycle yielded an average of 881g (31.1oz) of dry, groomed female flowering head per plant, and over the whole study the 18 plants yielded a total of 12,360g (436.0oz), or an average of 687g (24.2oz) of dry head per plant. THC data shows significant intra-plant variation and also demonstrates inter-varietal variation. THC values for individual plants ranged from 4.3 to 25.2%. The findings of this study and a separate ESR research project illustrate that the potency of Cannabis grown in New Zealand has dramatically increased in recent years. DNA analysis distinguished distinct groups in general agreement with the phenotypic variation observed. One plant however, exhibiting a unique triallelic pattern at two of the five loci tested, while remaining phenotypically indistinguishable from three other plants within the same grow. [Copyright &y& Elsevier]

E-cigarette, or vaping, product use–associated lung injury (EVALI) outbreak was linked to vitamin E acetate (VEA) used as a solvent for tetrahydrocannabinol (THC). Several studies were conducted to assess the products of VEA (and THC/VEA mixtures) thermal degradation as a result of vaporizing/aerosolizing from a traditional type (coil—cotton wick) and ceramic type coil vape pens. The particle size distribution (PSD) of VEA aerosol and the temperature VEA and THC/VEA mixtures are heated to were also measured for a few types of traditional and ceramic vape pens. The current study assessed the PSD of the aerosol generated from THC, VEA, and a number of THC/VEA mixtures using a dab-type vape pen under two different temperature settings and two puffing flow rates. Thermal degradation of THC, VEA, and THC/VEA mixtures were also assessed, and coil temperature was measured. Results showed the dependence of the PSD upon the chemical content of the aerosolized mixture as well as upon the puffing flow rate. Minimal thermal degradation was observed. Flaws in the vape pen's design, which most likely affected results, were detected. The suitability of VEA, THC, and THC/VEA mixtures with certain types of vape pens was discussed. [ABSTRACT FROM AUTHOR]

Abstract: Marijuana smoking is associated with a number of abnormal findings in the lungs of habitual smokers. Previous studies revealed that Δ9-tetrahydrocannabinol (THC) caused mitochondrial injury in primary lung epithelial cells and in the cell line, A549 [Sarafian, T. A., Kouyoumjian, S., Khoshaghideh, F., Tashkin, D. P., and Roth, M. D. (2003). Delta 9-tetrahydrocannabinol disrupts mitochondrial function and cell energetics. Am J Physiol Lung Cell Mol Physiol 284, L298–306; Sarafian, T., Habib, N., Mao, J. T., Tsu, I. H., Yamamoto, M. L., Hsu, E., Tashkin, D. P., and Roth, M. D. (2005). Gene expression changes in human small airway epithelial cells exposed to Delta9-tetrahydrocannabinol. Toxicol Lett 158, 95–107]. The role of cannabinoid receptors in this injury was unclear, as was the potential impact on cell function. In order to investigate these questions, A549 cells were engineered to over-express the type 2 cannabinoid receptor (CB2R) using a self-inactivating lentiviral vector. This transduction resulted in a 60-fold increase in CB2R mRNA relative to cells transduced with a control vector. Transduced cell lines were used to study the effects of THC on chemotactic activity and mitochondrial function. Chemotaxis in response to a 10% serum gradient was suppressed in a concentration-dependent manner by exposure to THC. CB2R-transduced cells exhibited less intrinsic chemotactic activity (p <0.05) and were 80- to 100-fold more sensitive to the inhibitory effects of THC. Studies using SR144528, a selective CB2R antagonist, verified that these effects were mediated by the CB2R. Marijuana smoke extract, but not smoke extracts from tobacco or placebo marijuana cigarettes, reproduced these effects (p <0.05). THC decreased ATP level and mitochondrial membrane potential (Ψ m) in both control and CB2R-transduced cells. However, these decreases did not play a significant role in chemotaxis inhibition since cyclosporine A, which protected against ATP loss, did not increase cell migration. Moreover, CB2R-transduced cells displayed higher Ψ m than did control cells. Since both Ψ m and chemotaxis are regulated by intracellular signaling, we investigated the effects of THC on the activation of multiple signaling pathways. Serum exposure activated several signaling events of which phosphorylation of IκB-α and JNK was regulated in a CB2R- and THC-dependent manner. We conclude that airway epithelial cells are sensitive to both CB2R-dependent and independent effects mediated by THC. [Copyright &y& Elsevier]

Δ9-Tetrahydrocannabinol (THC) is the primary cannabinoid of marijuana and has been shown to either potentiate or inhibit tumor growth, depending on the type of cancer and its pathogenesis. Little is known about the activity of cannabinoids like THC on epidermal growth factor receptor-overexpressing lung cancers, which are often highly aggressive and resistant to chemotherapy. In this study, we characterized the effects of THC on the EGF-induced growth and metastasis of human non-small cell lung cancer using the cell lines A549 and SW-1573 as in vitro models. We found that these cells express the cannabinoid receptors CB1 and CB2, known targets for THC action, and that THC inhibited EGF-induced growth, chemotaxis and chemoinvasion. Moreover, signaling studies indicated that THC may act by inhibiting the EGF-induced phosphorylation of ERK1/2, JNK1/2 and AKT. THC also induced the phosphorylation of focal adhesion kinase at tyrosine 397. Additionally, in in vivo studies in severe combined immunodeficient mice, there was significant inhibition of the subcutaneous tumor growth and lung metastasis of A549 cells in THC-treated animals as compared to vehicle-treated controls. Tumor samples from THC-treated animals revealed antiproliferative and antiangiogenic effects of THC. Our study suggests that cannabinoids like THC should be explored as novel therapeutic molecules in controlling the growth and metastasis of certain lung cancers.Oncogene (2008) 27, 339–346; doi:10.1038/sj.onc.1210641; published online 9 July 2007 [ABSTRACT FROM AUTHOR]

Cannabis sativa L. (hemp) with minor content of the psychoactive Δ9-tetrahydrocannabinol (THC) was lifted in Germany. Nowadays, a wide variety of hemp food products is offered on the market. As help for evaluation of such products, this article provides information on all aspects of hemp as foodstuff. An introduction to the current law situation in Germany and the European Union (EU) is presented. In particular, suggestions for the food regulatory and food chemical evaluation of hemp food products are made. Between 1998 and 2003, a significant linear decrease in the THC concentrations for the product groups hemp tea (N = 19, R = -0.73, p < 0.0001) and hemp oil (N = 60, R = -0.23, p = 0.05) was observed. The prescribed use of certified hemp seed by the EU and the increase of controls on manufacturers have obviously led to a significant decline of THC concentrations in hemp food products. The maximum THC content in current purchasable hemp food products is ten to a hundred-fold lower than those found in the studies of the 1990s. These levels of THC in hemp food do not cause regulatory or health concern anymore. However, ongoing quality control is needed to maintain low THC levels. This includes both the use of low THC varieties and proper seed cleaning. [ABSTRACT FROM PUBLISHER]

A fully automated procedure using alkaline hydrolysis and headspace solid-phase microextraction (HS-SPME), followed by on-fiber derivatization and gas chromatographic–mass spectrometric (GC–MS) detection has been developed for determination of cannabinoids in hemp food samples. After addition of a deuterated internal standard, the sample was hydrolyzed with sodium hydroxide and submitted to direct HS-SPME. After absorption of analytes for on-fiber derivatization, the fiber was placed directly into the headspace of a second vial containing N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA), before GC–MS analysis. Linearity was good for Δ9-tetrahydrocannabinol (THC), cannabidiol, and cannabinol; regression coefficients were greater than 0.99. Depending on the characteristics of the matrix the detection limits obtained ranged between 0.01 and 0.17 mg kg-1 and the precision between 0.4 and 11.8%. In comparison with conventional liquid–liquid extraction this automated HS-SPME–GC–MS procedure is substantially faster. It is easy to perform, solvent-free, and sample quantities are minimal, yet it maintains the same sensitivity and reproducibility. The applicability was demonstrated by analysis of 30 hemp food samples. Cannabinoids were detected in all of the samples and it was possible to differentiate between drug-type and fiber-type Cannabis sativa L. In comparison with other studies relatively low THC concentrations between 0.01 and 15.53 mg kg-1 were determined. [ABSTRACT FROM AUTHOR]

There is a growing amount of evidence to suggest that cannabis and individual cannabinoids may be effective in suppressing certain symptoms of multiple sclerosis and spinal cord injury, including spasticity and pain. Anecdotal evidence is to be found in newspaper reports and also in responses to questionnaires. Clinical evidence comes from trials, albeit with rather small numbers of patients. These trials have shown that cannabis, Δ9-tetrahydrocannabinol, and nabilone can produce objective and/or subjective relief from spasticity, pain, tremor, and nocturia in patients with multiple sclerosis (8 trials) or spinal cord injury (1 trial). The clinical evidence is supported by results from experiments with animal models of multiple sclerosis. Some of these experiments, performed with mice with chronic relapsing experimental allergic encephalomyelitis (CREAE), have provided strong evidence that cannabinoid-induced reductions in tremor and spasticity are mediated by cannabinoid receptors, both CB1 and CB2. Endocannabinoid concentrations are elevated in the brains and spinal cords of CREAE mice with spasticity, and in line with this observation, spasticity exhibited by CREAE mice can be ameliorated by inhibitors of endocannabinoid membrane transport or enzymic hydrolysis. Research is now needed to establish whether increased endocannabinoid production occurs in multiple sclerosis. Future research should also be directed at obtaining more conclusive evidence about the efficacy of cannabis or individual cannabinoids against the signs and symptoms of these disorders, at devising better modes of administration for cannabinoids and at exploring strategies that maximize separation between the sought-after therapeutic effects and the unwanted effects of these drugs. [Copyright &y& Elsevier]

New data strengthen the idea of a prominent role for endocannabinoids in the modulation of a wide variety of neurobiological functions. Among these, one of the most important is the control of movement. This finding is supported by 3 lines of evidence: (1) the demonstration of a powerful action, mostly inhibitory in nature, of synthetic and plant-derived cannabinoids and, more recently, of endocannabinoids on motor activity; (2) the presence of the cannabinoid CB1 receptor subtype and the recent description of endocannabinoids in the basal ganglia and the cerebellum, the areas that control movement; and (3) the fact that CB1 receptor binding was altered in the basal ganglia of humans affected by several neurological diseases and also of rodents with experimentally induced motor disorders. Based on this evidence, it has been suggested that new synthetic compounds that act at key steps of endocannabinoid activity (i.e., more-stable analogs of endocannabinoids, inhibitors of endocannabinoid reuptake or metabolism, antagonists of CB1 receptors) might be of interest for their potential use as therapeutic agents in a variety of pathologies affecting extrapyramidal structures, such as Parkinson''s and Huntington''s diseases. Currently, only a few data exist in the literature studying such relationships in humans, but an increasing number of journal articles are revealing the importance of this new neuromodulatory system and arguing in favour of the funding of more extensive research in this field. The present article will review the current knowledge of this neuromodulatory system, trying to establish the future lines for research on the therapeutic potential of the endocannabinoid system in motor disorders. [Copyright &y& Elsevier]

The leading cause of irreversible blindness is glaucoma, a disease normally characterized by the development of ocular hypertension and consequent damage to the optic nerve at its point of retinal attachment. This results in a narrowing of the visual field, and eventually results in blindness. A number of drugs are available to lower intraocular pressure (IOP), but, occasionally, they are ineffective or have intolerable side-effects for some patients and can lose efficacy with chronic administration. The smoking of marijuana has decreased IOP in glaucoma patients. Cannabinoid drugs, therefore, are thought to have significant potential for pharmaceutical development. However, as the mechanism surrounding their effect on IOP initially was thought to involve the CNS, issues of psychoactivity hindered progress. The discovery of ocular cannabinoid receptors implied an explanation for the induction of hypotension by topical cannabinoid applications, and has stimulated a new phase of ophthalmic cannabinoid research. Featured within these investigations is the possibility that at least some cannabinoids may ameliorate optic neuronal damage through suppression of N-methyl-D-aspartate receptor hyperexcitability, stimulation of neural microcirculation, and the suppression of both apoptosis and damaging free radical reactions, among other mechanisms. Separation of therapeutic actions from side-effects now seems possible through a diverse array of novel chemical, pharmacological, and formulation strategies. [Copyright &y& Elsevier]

Cannabinoids recently have been shown to control the cell survival/death decision. Thus, cannabinoids induce growth arrest or apoptosis in a number of transformed neural and non-neural cells in culture. In addition, cannabinoid administration induces regression of malignant gliomas in rodents by a mechanism that may involve sustained ceramide generation and extracellular signal-regulated kinase activation. In contrast, most of the experimental evidence indicates that cannabinoids may protect normal neurons from toxic insults, such as glutamatergic overstimulation, ischaemia, and oxidative damage. Regarding immune cells, low doses of cannabinoids may enhance proliferation, whereas high doses of cannabinoids usually induce growth arrest or apoptosis. The potential therapeutic applications of these findings are discussed. [Copyright &y& Elsevier]