Its low critical temperature allows extraction of thermolabile compounds without their prior thermal decomposition 17,18. As an additional advantage of SFE, all the devices that constitute the plant are hermetic, so the process is carried out without oxygen access which protects bioactive compounds against oxidation . This is possible by choosing the suitable extraction method and optimizing the proper process parameters . To access the paper and deliver your review, click on the link in the invitation email you received which will bring you to the submission/reviewing system. Your review will be managed via an Elsevier submission system such as Editorial Manager. The critical thinking and assessment required for peer-review are outside the scope of generative AI and AI-assisted technologies, and there is a risk that the technology will generate incorrect, incomplete or biased conclusions. Since peer review is confidential, you also must not share information about the review with anyone without permission from the editors and authors. If you do decline the invitation, it would be helpful if you could provide suggestions for alternative reviewers. The goal of this analysis was to verify the possibilities of optimization simultaneously with two different criteria. Additionally, the final results also confirm the necessity to study the influence of more than one input variables on a chosen response as well as their interactions. Pressure has the strongest impact on the TFC content and the value of optimal pressure determine the optimal temperature (which was also confirmed by the regression equation and the coefficients in equation). In nine out of 10 studies (94.5% of subjects) purified THC was inhaled using the Volcano™ vaporizer (Storz‐Bickel, Tuttlingen, Germany). All healthy volunteers who participated in the studies were mild cannabis users, defined as a frequency of cannabis use of maximum once a week in the past year. Some studies were interaction studies, but only the treatment arms that involved administration of either THC alone or placebo alone were taken into account. It is worth noting that the flavonoids content was higher in the sample obtained under optimal TFC conditions specified for that group of compounds. The analyzed compounds were separated with good resolution and peak shapes in a short time analysis (3 min). The effectiveness of this technique in the extraction of flavonoids from plant material was also confirmed by many other studies, for example on Maydis stigma, Scutellaria baicalensis and Ginkgo leaves . However, the total content of phenolic compounds was lower in extract obtained during SFE (20.20 mg GAE/g DM) compared to maceration with 96% ethanol at 80°C (26.16 mg GAE/g DM). • articles that present proportions of original and/or counterfeit and/or substandard drugs • peer-reviewed original articles with full-text available The detailed search and screening strategy has been published within the review protocol . Trust in the seller is described as the key criterion for protection against counterfeit drugs . The Folin-Ciocalteau (F-C) method was used for determination of the total phenolics content where100 µL of sample were added to 1.5 mL deionized water and 100 μL F-C phenol reagent. After achieving the required extraction parameters, the supercritical CO2 was passed through to the extractor. Supercritical fluid extraction was performed using quarter-technical plant (SITEC-Sieber Engineering AG, Switzerland) placed in New Chemical Syntheses Institute in Puławy, Poland (Figure 2a). RevMan: Systematic review and meta-analysis tool for researchers worldwide The main subjective effects of THC consist of feeling high and changes in perception.To further determine the proportions of fake AAS found on the black market, we conducted a systematic literature review and meta-analysis of analytical test results for those substances within the published literature.The obtained results indicate that the extraction efficiency of polar bioactive compounds from M.There is some evidence within the analyzed literature that the amount of seized or confiscated compounds increased over the observation period 26, 34, with one documented significant, i.e. 5.2-fold increase of seized anabolic steroids (1,468/282) over a 5 year period .The subjective effects of cannabis and its main psychoactive component Δ9‐tetrahydrocannabinol (THC) have played an important part in determining the therapeutic potential of cannabinoid agonists and antagonists.We demonstrate that visual inspection of the package, label, and internal content to identify preliminary signs of counterfeiting of AAS have shown to be mostly ineffective. A few studies showed a distribution during the placebo condition that was distinctly different from the other studies (based on visual comparison), and these were excluded from further analysis. Data from 10 studies performed by the Centre for Human Drug Research (CHDR) in which THC was administered to a total of 217 healthy volunteers were selected to perform an exploratory analysis on the measurements of the subjective effects of THC. In this analysis, the effects of THC on these VASs were compared within a total of 217 subjects who participated in 10 different studies. (2) the product is too expensive to make; (3) controlled or restricted substances; (4) radio-labeled compounds; (5) the product is under patent protection in customer’s country. All data generated or analyzed during this study is included in this published article and its supplementary information files. Results of analysis of variance of obtained values and the comparison of predicted and experimental values of each evaluation index. The main criterion was to achieve the highest content of each response. The correlation of all input factors is crucial, and all of the input variables have impact of the maximum TPC content (which is confirmed by significance of all T, P and F in polynomial equation). Total phenolics content increases with pressure and decreases with the increase of solvent flow rate. Firstly, the yield of the process increases with pressure, but after achieving maximum, it decreases. These items may represent what Ashton (2001) describes as “dysphoric reactions” (“dysphoria”). VAS “voices”, “meaning” and “suspicious” are included in the third common factor within the effects of THC. The main four items can be seen as mental aspects of sedation (“relaxation”), whereas the two related items are more physical aspects of sedation. The pressure effect on the extraction efficiency is lower but more complex. The yield of the process increases with the increase of temperature and solvent flow rate (which also has been proven by the regression equations, where significant model terms are T and F). These changes improve the selectivity of the extraction of polar constituents. Those factors strictly depend on the values of extraction temperature and pressure. Concluded, values of temperature and pressure have a decisive influence on the yield of the extraction and the composition of the final product. Moreover, the scCO2 density decreases with increasing temperature, so the extraction of non-polar compounds decreases too. We also used high values of temperature up to 80 °C to check the temperature effect on the content of polar compounds (Table 2). Share this: The final cluster selection was based on what the different clustering methods have in common. The combinations of items found with these different methods were then compared on their ability to predict the drug condition (THC or placebo). For the items that showed a significant dose–response relationship, different methods were applied to determine the combination of (weighted) items that could best describe “the subjective effect of THC”. Subsequently, all administrations during each study day were considered if the dosing interval was at least 60 minutes, which covered more observations and a larger dose range. Data collection We're always working to keep our product images current, but occasionally the manufacturer might update the design. (Updated January 2026) These are the best-reviewed games released each year in the 21st century. This medicine data has been created by - We reviewed literature that assessed the quality and quantity of AAS found on the black market. These substances can easily be acquired over the internet, leading to a substantial black market. Do not forget that, even after finalizing your review, you must treat the article and any linked files or data as confidential documents. If the study included more than one sex/gender, ensure data are reported for all the options that were recorded and that data disaggregated by sex/gender are reported in full, in the main text or in the appendix or supplementary materials. 3. Extractions Plan According to Box-Behnken Design (BBD) • Levels of active pharmaceutical ingredients (AI) detected are between the defined range of the declared formulation defined by the individual studya (quantitative) Classification of prohibited substances coded according to the WADA prohibited list (updated version as of 01 January 2021) Furthermore, we assessed the different analytical methods used to determine the quality and quantity of AAS on the black market. Classification of prohibited substances are according to the world anti-doping agency (WADA) prohibited list (Updated version as of 01 January 2021) (Table 2). Both products exhibited an interesting AOC by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power assays. This journal provides immediate open access to its content on the principle that making research freely available to the public supports a greater global exchange of knowledge. No use, distribution or reproduction is permitted which does not comply with these terms. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY NC 4.0), which permits non-comercial use, distribution, and reproduction in any medium, provided the original publication is properly cited. All the results and statistical analysis were accomplished using Design Expert 11.0 (Stat-Ease, Inc., Minneapolis, MN, USA). The complete design comprises fifteen experimental steps at the different process conditions (Table 1). To take into account the effect of high temperature on the quality of plant material, the level of bioactive compounds in the extracts obtained as a result of maceration carried out at different temperature values was compared. Due to the high value of pressure, the surface tension on the phase boundary can be negligible and the extraction of phenols and flavonoids may be efficient despite of the small solubility in scCO2. For qualitative determination of polar compounds in SFE extract, the supercritical fluid chromatography (SFC) was applied. Although it might sound late, given that the research has already been concluded and the data analyzed, the peer review process can still play an important role in ensuring effective, transparent and complete sex and gender reporting. Then we publish the results and expert reviews for free, so you can buy the right products for you. The economics of process is always crucial, especially when the extraction is carried out at larger scale than laboratory (in our study it was quarter-technical plant). We applied pressures up to 80 MPa which allows studies of the extractability of polar compounds in the extensive range of process parameters. The total phenolic content in the obtained product under optimal conditions was 20.20 mg GAE/g DM. In order to verify the accuracy of the process modeling, extractions in optimal parameters at quarter-technical plant for all three responses separately were carried out. The highest concentration of total flavonoids can be achieved in the extraction carried out at high values of all process parameters. The optimal conditions, obtained as a result of extraction of lucerne at quarter-technical plant, and analyzed data by RSM and ANOVA were determined and summarized in the Table 5. The value of temperature has a complex impact on the extraction of phenolics constituents because the highest and the lowest value of determined group of bioactive compounds was obtained for the same T value. This section collects any data citations, data availability statements, or supplementary materials included in this article. All authors contributed to refinement of the literature review and approved the final manuscript. AC provided methodological expertise on biochemical analysis of the samples. LF/PB provided statistical and methodological expertise of the review. This also may have led either to over or under estimation of certain proportions of the estimates of “substandard” or “counterfeit” anabolic androgenic steroids and their subclassifications and sub-analyses. Corms based on DESI mass spectrometry imaging techniqueJ. This study reports the nutraceutical potential of two new types of Adps. Total phenolic and total flavonoid contents (TPC and TFC, respectively) and their changes along the different harvesting periods of the year were also examined. If the study included only one sex/gender, ensure this has been justified. The term “sex” should be used as a classification of male or female based on biological distinction to the extent that this is possible to confirm. The use of common definitions will improve the ability to conduct meta-analyses of published and archived data. Nevertheless, we recommend referees to consider if sex and gender are relevant to the topic of the study, and whether the study follows relevant guidelines, wherever applicable. Access powerful tools for efficient data management, analysis, and reporting. Convert reviews, ratings and other eCommerce data into actionable insights within minutes. Skip over manual tagging and analysis processes. For this analysis, the maximum response following intrapulmonary administration of THC was used to select items and the data from the study that was performed most recently were exclusively used for cross‐validation. ‘Drug checking’ allows people who consume illegal and legal drugs acquired from unregulated drug markets to submit samples for chemical analysis and receive feedback on the quantity, quality, and purity of those substances. In this systematic review we demonstrate that the real composition, the type of production, concentration, quantity, quality, and purity are often not declared on the label, and labels are even misleading. With this systematic review and meta-analysis, we present significant findings for fake AAS on the black market. There is a broad availability of different analytical tools used to identify counterfeit AAS on the black market, as included in this systematic review. The SFC final analysis was performed at 25 °C on ACQUITY UPC BEH column (100 × 3 mm, 1.7 μm, Waters, Milford, MA). SFC analysis was performed using an Acquity UPC2 system (Waters, Milford, MA) with a binary solvent pump, a column oven, an autosampler, PDA detector and backpressure regulator (BPR). The total flavonoids content (TFC) was calorimetrically determined by using aluminum chloride (AlCl3). Importantly, whenever anabolic agents were analyzed with other classes of substances, anabolic agents made the highest proportion of analyzed classes. In addition, other countries from this region (Switzerland, France, Italy, United Kingdom, Czech Republic and Slovakia, Austria, and Belgium) are represented in our list of included studies. The country with the highest number of included studies in this region is Germany with a total of three studies. In 18 articles, counterfeit substances and only in eight articles, substandard substances were presented. Some articles also included other classes of substances in their analysis, such as WADA classes S2, S3, S4, S5, dietary supplements, stimulants, and sexual performance enhancers. Most samples (74%) originated from seized compounds by the police, custom authorities, or justice departments and a minority of samples were bought directly from the black market or provided by gyms and users themselves. Most included study designs (95%) were nonclinical laboratory studies. In some cases, the published data had to be manually adapted and transferred to fit our classification system. This may have resulted in some bias of the studies included and a bias in our statistical summary and conclusions. Drug testing services can be an effective harm reduction service that may strengthen surveillance of the black-market drugs that are used and can accurately inform users about the quality and quantity of black market AAS prior to use . One strategy could entail the controlled use and availability of these substances through proper health channels. In the case of Europe, the studies are divided among several countries. Research in the Americas was only done in Brazil, which alone includes 7 of the 19 studies. The geographic scope of the included studies is limited to two world regions, where 37% and 63% respectively were conducted, and these studies reported findings from the Americas (AMR) and Europe (EUR). The peer-reviewed literature of qualitative and quantitative analyses of AAS has considerably increased in the last few years. All study characteristics can be viewed in detail in Table 4. The aim of this work was to optimize conditions for extraction of phenolics compounds from Medicago sativa L. So far, there has been no comprehensive investigation about the extraction of polar compounds with supercritical fluid extraction, especially by using carbon dioxide in a supercritical state as a solvent. The SFE extraction of plant materials which leads to obtain product rich in polar components is mostly carried out with polar co-solvent, usually methanol or ethanol solutions 21,22,23,24. Effective harm reduction strategies, evidence-based guidelines and interventions are urgently needed to protect users from counterfeit products found on the black market, and to support the development of effective services. We searched PubMed/Medline, Embase and Google Scholar for studies published before March 29, 2022 that analyzed the quality and quantity of AAS to determine the proportions of substandard and counterfeit products found on the black market. We further elaborated and highlighted reasons for the vast amount of substandard and counterfeit AAS, the individual and public health impact of those mislabeled products and the possible positive impact of harm reduction strategies for this user population. With this systematic review and meta-analysis on black-market AAS, we have demonstrated that substantial mean proportions may be of substandard quality or counterfeit. Considering the results of maceration and supercritical fluid extraction for the highest tested temperature (80 °C), we can conclude that flavonoids are more susceptible for thermal decomposition than phenolics.This study reports the nutraceutical potential of two new types of Adps.This journal provides immediate open access to its content on the principle that making research freely available to the public supports a greater global exchange of knowledge.Optimized elution strength of supercritical fluid (SF) and the solute solubility in the SF have a crucial impact on the extraction efficiency.Optimal extraction conditions were determined by analysis of variance (ANOVA) based on the obtained responses 26,27.In some studies, the contained active ingredients in “under-concentrated” preparations was much lower than 50% of that indicated (e.g. 0.5–1.5% , 9% or 16% ) if quantitative data was available.Due to the high value of pressure, the surface tension on the phase boundary can be negligible and the extraction of phenols and flavonoids may be efficient despite of the small solubility in scCO2. An inverse predictive check was performed for the individual items and the possible combinations of items to compare the probability to identify the original treatment. A stopping criterion of 0.1% improvement was used for forward and combined analysis and a stopping criterion of −0.5% improvement (either any improvement or a maximum of 0.5% worsening) for backward analysis. Linear stepwise DA is another method to find combinations of items that are able to predict the subjective effect of THC. In our study, the range of pressure up to 800 bars was investigated. However, due to limitations of most applied devices, there are no investigations where extractions were conducted under range of pressure over 550 bars. Secondly, under suitable conditions, the high value of the vapour pressure of polar solute may have a significant influence on the process and it determines extractive properties and efficiency 17,18. Therefore, SFE with pure scCO2 may seem to be a great separation technique for polar compounds under higher conditions than mostly investigated. Can I use this product alongside other medications? The mechanism of action of sativol is not fully defined but is thought to involve disruption of microbial cell membranes and scavenging of free radicals. It is known for its pleasant aroma and potential biological activities, including antimicrobial and antioxidant effects. Such distinct effect profiles could provide quantitative information on different neurophysiological effects of THC, and on different sensitivities of individuals to such effects. The subjective effects of cannabis and THC are relevant, considering their putative therapeutic potential and pathophysiological significance. In combination, the 13 VAS described by Bowdle and the 16 scales used by Bond and Lader cover most of the subjective effects of cannabis and THC that were summarized by Ashton (2001), with the exception of the effects on appetite. Zuurman et al. (2008) used the VAS Bowdle to measure the subjective effects of THC. Bowdle et al. (1998) described a composite scale for psychedelic effects (hereafter VAS Bowdle, see Table 1), consisting of 13 questions with the extremes of “not at all” and “extremely”, and validated this scale in a group of healthy volunteers who received ketamine. News, information on our forthcoming books, author content and discounts. Essential science news, reviews and insights into developments affecting research communities globally. This carefully curated content educates and inspires future scientists, supports global collaboration, and addresses the world’s greatest challenges. Pitchfork may earn a portion of sales from products that are purchased through our site as part of our Affiliate Partnerships with retailers. Mobile Processors (ARM) This may help explain the actions of abused substances, advance fundamental receptor activation studies and design better medicines. The obtained extraction residue can be used as feedstock and the extract, enriched in bioactive compounds, can be implemented as a functional food additive and human diet supplement. All the obtained data have proved that the optimization of supercritical carbon dioxide extraction of Medicago sativa L. The SFC analysis of extracts obtained under optimal conditions for TFC and TPC revealed that the extracts have higher content of individuals group of flavonoids and phenolic acids, respectively. All of the investigated extraction parameters i.e., temperature, pressure and flow rate had an influence on yield, total phenolics content and total flavonoids content. Drugs are used for reducing side effects of AAS abuse and/or boosting AAS effects. This is especially concerning when those substances are injected into the muscle as it poses a risk of forming abscesses in the muscle and skin necrosis 36, 61. Graham and colleagues demonstrated contamination with bacterial skin commensals during microbiological analysis of their samples. This can, taken unknowingly, lead to substantial drug-related side effects. GC–MS with or without 40, 46 prior derivatization of the AAS has also been successfully used to screen and quantify AAS, based on their fragmentation patterns and retention times.We further elaborated and highlighted reasons for the vast amount of substandard and counterfeit AAS, the individual and public health impact of those mislabeled products and the possible positive impact of harm reduction strategies for this user population.Primary outcomes are proportions of counterfeit and substandard substances.If you do decline the invitation, it would be helpful if you could provide suggestions for alternative reviewers.If the study included only one sex/gender, ensure this has been justified.To provide the minimum cost of the optimization process, the statistical and mathematical methods were used to optimize the number of experiments.News, information on our forthcoming books, author content and discounts.Data from 10 studies performed by the Centre for Human Drug Research (CHDR) in which THC was administered to a total of 217 healthy volunteers were selected to perform an exploratory analysis on the measurements of the subjective effects of THC.Since most studies included several different consecutive doses on each individual study occasion, it was possible to assess a dose–response relationship, which was performed in two steps. Our knowledgeable pharmacists are available to help our patients find the right products for their needs and to answer any questions they may have about over-the-counter medication or supplements. Our pharmacy is stocked with a comprehensive selection of products to meet the diverse needs of our patients, including vitamins, pain relievers, allergy medication, and more. Our prescription medication products are available to patients who have been prescribed medication by their physician. Each of our pharmacy products is carefully selected to meet the diverse needs of our patients, and we are dedicated to providing personalized and compassionate care to ensure that our patients receive the right medication at the right dosage. At Second Medic, we offer a wide range of high-quality pharmacy products to support our patients' health and wellbeing. No significant difference was found in caloric content (4 kcal/g). Results demonstrated a high content of proteins (23-30 g/100 g FDJ and g/100 g RM), crude fiber (29 g/100 g RM), and minerals (such as sodium, calcium, iron, and zinc). Alfalfa (Medicago sativa) has been extensively used as animal feed, due to its fiber, protein, minerals, and vitamins, being also a useful source of phenolic compounds with potential therapeutic benefits. After the quality appraisal stage, an overall number of 19 full-text articles were included for data extraction and analysis. For one study, the study design (retrospective database analysis) did not qualify for the analysis by ToxRtool and was individually assessed by the study team . The detailed data extraction and data analysis plan have been published elsewhere . Login to add this product to My List For compounds distributed in the corms, the highest abundance was found in corms from Shanghai, followed by Zhejiang and the lowest from Anhui. L-Citruline, phenylacetylglycine, sativol, and geniposide were specifically distributed in the corms. Methods A method based on desorption electrospray ionization mass spectrometry imaging and optimized sample pretreatment was developed for directly visualize metabolites in C. Contact us today to learn more about our comprehensive selection of pharmacy products and how we can support your ongoing medical care. We are committed to ensuring that our patients have access to the highest quality pharmacy products available. That's why we offer a wide range of medical supplies, including wound care products, diabetic supplies, and more. Oil-based preparations were directly extracted with the appropriate solvent, while tablets and capsules were grounded into a fine powder before extraction. The sample preparation for LC–MS/MS or GC–MS is simple and was mostly based on an extraction with organic solvents, usually methanol 43, 46, 47, 49, 51, followed by sonication. Among the included studies, most approaches are based on liquid chromatography coupled to mass spectrometry (LC–MS/MS) 32, 42, 47, 49, 50, or gas chromatography coupled to mass spectrometry (GC–MS) 32, 35, 40, 42, 47, 49, 51–54. Firstly, defined ranges of declared labels could vary massively between articles, had a quantitative analysis been performed, with defined ranges between 50–200% , 80–130% , 80–120% or 90–110% . Proportions of substandard anabolic androgenic steroids from 8 studies, grouped by geographical region In two articles, the authors analyzed mixed samples, but the proportion of AAS was above 75%, as described in the inclusion criteria published in the study protocol 34–36. The CO2 molecule has a small polarity but due to the presence of a quadrupole moment, it can dissolve some polar compounds at higher values of the process parameters . Recent studies have been focused on the selective SFE separation of different groups of compounds from plant materials like waxes from vegetable matters 19,20. Due to the advantages of scCO2, SFE has been commercially used in the production of food and feed additives or nutraceuticals and pharmaceuticals. The counterfeit drug market can affect all drugs and is estimated to be a multimillion dollar business . This provides the perfect foundation for a counterfeit drug market for all IPEDs. In 18 articles, proportions of counterfeit substances and in eight articles, proportions of substandard substances were presented. Half of the studies presenting data on substandard substances were sub-analyzed into over-concentrated and under-concentrated samples. The full extraction form can be found in Supplementary file 2; the summary form used for data analysis can be found in Supplementary file 3. One study was a retrospective database analysis of the Brazilian federal police database . Characteristics of 19 published studies presenting qualitative and quantitative data of fake AAS on the black-market Among the included studies, the majority (53%) were published in the last five years of this current study (2017–2022) and the vast majority (79%) were published within the last decade (2012–2022) of this current study. These subjective effects, which are largely attributable to THC, can be quite diverse. These distinct subjective clusters could represent effects on various systems in the brain, which can be used to further differentiate the involvement of endocannabinoid systems in health and disease. These results provide experimental evidence that THC can evoke different classes of effects. KCA is a disjoint clustering method, in which all items are distributed within a pre‐defined number of separated clusters to minimize within‐cluster variability and maximize between‐cluster variability (Hartigan and Wong, 1979). PCA and FA were therefore performed using the maximum response in the THC condition, after a mean subtraction for all VAS items and log‐transformation for VAS Bowdle items. Both techniques can be applied to a dataset that is jointly normally distributed and are sensitive to the relative scaling of the original variables. MCA is an exploratory technique that uses logical indicators (true or false), which makes it more suitable for data that is not normally distributed or categorical (Greenacre, 2007). Rather, those products are produced in clandestine underground laboratories lacking the necessary knowledge or equipment to produce these compounds in adequate quantity and quality, as also described by other authors 26, 35, 38. But in addition, products that contain the labeled substances can still be over-concentrated or under-concentrated. Rather than caused by study design issues, the differing proportions of counterfeit or substandard AAS reflect the selection of the tested AAS samples, with real differences in the quality of AAS found on the black market. Not many subjects show an effect on these items, but if these scales are affected, the effects seem to be clear. This clustering of feeling high and the other items follows the description of the most typical THC effects by Ashton (2001). The other items that had high individual predictive values describe effects on time perception and cognitive functions (controlling of thoughts and mental slowness), which are also well known and frequent effects of cannabis and THC (Ashton, 2001). This analysis explored the characteristics of the scope of subjective effects of THC as measured on different VASs. As VAS “high” was expected to have a large impact on the outcomes, the analysis was repeated without this item, resulting in a combination of VAS “lethargic”, “dreamy”, “thoughts” and “colours” in case of forward DA and the same items together with VAS “sound” in case of backward DA. The American Sociological Review does not publish book reviews. We want to do everything we can to support reviewers (also sometimes known as "referees") and to recognize their contribution. At Wiley we believe that peer review is the foundation for safeguarding the quality and integrity of scientific and scholarly research. Information and guidelines on reviewing book proposals, manuscripts and published books Everything you need to know about reviewing a journal article Disagreements in study eligibility, data extraction, and quality assessment were resolved by consensus between the two reviewers. To further determine the proportions of fake AAS found on the black market, we conducted a systematic literature review and meta-analysis of analytical test results for those substances within the published literature. With this systematic review and meta-analysis, we demonstrate that substantial mean proportions of black-market AAS are counterfeit and of substandard quality. Track products and prioritize features based on data. There seems to be a subset of individuals (even among occasional cannabis users) who respond to THC with dysphoric reactions and another small group of individuals who do not experience the typical “high” effects of THC. These findings correspond with previous descriptions of the subjective effects of THC and cannabis. The main subjective effects of THC consist of feeling high and changes in perception. The clear separation between items from VAS Bond and Lader and from VAS Bowdle that was seen with most methods is interesting. The finding that a combination of items of the VAS Bond and Lader, which has an approximately normal distribution, explains most of the variation in effect is therefore important. • to increase the homogeneity, article with mixed samples (e.g., if the analysis includes different classes of IPED) in which data on AAS are Quality assessment for bias of analytical studies was conducted using the ToxRtool for in-vitro studies and was assessed by two reviewers (RM and PB) independently. Each study was screened by title and abstract based on predefined eligibility criteria (Table 1). We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA) statement . To our knowledge, this is the first systematic literature review analyzing fake black-market AAS within the published literature. Even though this cluster of items does not seem highly predictive of the effect of THC, this aspect might correlate with other important predictors for the effect of THC such as the occurrence of adverse events.The very wide range in proportions of counterfeit or substandard black market AAS puts the user in a situation of unpredictable uncertainty.For use in future studies, the authors would recommend the addition of scales for hunger and appetite.For other data visualizations, there may be other ways of inspecting the files.The lowest level among the tested phenolic compounds was observed for ferulic acid.The pooled proportions for primary outcomes and corresponding 95% confidence interval (CI) were calculated using a random-effect model, using the procedure for meta-analysis of single proportions “metaprop” from the library “meta”, provided in R software for statistical computing.The factors that determine the intensity of each of these effects have not been investigated in detail, but the subjective effects of THC seem to differ among users, and probably also between occasions of use or doses and modes of administration.Effective harm reduction strategies, evidence-based guidelines and interventions are urgently needed to protect users from counterfeit products found on the black market, and to support the development of effective services. Compare journals within and between research fields on several aspects such as duration of first review round and decision time for desk rejections. Journal popularity scores are calculated based on the number of visits to the journal page, and editorial information is provided by the editor. To gain the energy back for an active life, SBLs sativol is a dependable and rejuvenating tonic for nerves. The authors would like to thank Marieke Liem‐Moolenaar and Linda Klumpers for their support in data collection. VAS Bond and Lader and VAS Bowdle are frequently used in CNS drug research and capture most of the subjective effects that have been described with cannabis or THC. As THC is the main component of cannabis and the elicited subjective effects of THC are comparable to the subjective effects of cannabis described in the literature, the findings might be applicable to cannabis. THC and cannabis have a rather broad range of effects, which can differ between subjects, doses and use circumstances. From the different combinations of items, only those found with DA resulted in a better predictive value as a composite scale. Importantly, there are more than 60 different anabolic androgenic steroids listed on the WADA prohibited list and novel compounds are frequently detected on the market. We demonstrate that visual inspection of the package, label, and internal content to identify preliminary signs of counterfeiting of AAS have shown to be mostly ineffective. AAS were the most dominant group within all analyzed products, and they were almost exclusively analyzed within the WADA class S1. The very wide range in the proportions of counterfeit or substandard AAS from the black market shows the uncertainty about quality, thus leaving users with unpredictable risks. Although these proportions must be interpreted with caution due to some methodological challenges and high heterogeneity, one must acknowledge the unreliable nature of those substances acquired from the black market. With this systematic review we aim to further elaborate on these threats and suggest evidence-based approaches to reduce harms for this user population. Besides the well-known side effects of anabolic steroids, new individual and public health threats arise due to fake drugs from the black market. Counterfeit products can potentially lead to negative health outcomes and are considered an individual and public health threat . Optimise product listings and drive world class SEO.In order to verify the influence of the temperature on the concentration of polar compounds, conventional macerations with 96% ethanol solution at defined in BBD plan values of temperature, were performed.(Updated January 2026) These are the best-reviewed games released each year in the 21st century.This would suggest that THC does not affect mood in a stricter sense, which is consistent with the review by Zuurman et al. (2009).The supercritical fluid extraction as a separation technique is very suitable for the separation according to “green chemistry” standards, especially when carbon dioxide is used as a solvent.To gain the energy back for an active life, SBLs sativol is a dependable and rejuvenating tonic for nerves.Measurements performed in the first 60 minutes after THC administration were pooled to identify items that are sensitive to THC.All rights are reserved, including those for text and data mining, AI training, and similar technologies. Get leading brands of Homeopathic products, and connect online with over 800 homeopaths across India. Find affordable medicine substitutes, save up to 50% on health products, up to 80% off on lab tests and free doctor consultations. All products displayed on HomeoAyurPlus are procured from verified and licensed pharmacies. The three dimensions can be used as the basis of an evidence‐based composite scale (see Table 4, which could also include effects on hunger and appetite), to further explore and differentiate the involvement of endocannabinoid systems in health and disease and to quantify the subjective effects of THC and cannabis in clinical research. In summary, the current analysis provides experimental evidence that the subjective effects of THC in mild cannabis users have three main dimensions (consistent over a variety of statistical techniques). All these items are included in the “alertness” clusters as described by Bond and Lader (1974). All these items were a part of the cluster “external perception” as described by Zuurman et al. (2008), except “high” which was treated by Zuurman et al. (2008) as a separate cluster because of its predominance. The items with high predictive values could be grouped into three distinct factors of effect. The full-text screening stage of 24 articles led to 21 potential articles relevant in this systematic review and were thus eligible for quality appraisal. Meta-regression analyses provided in R software were conducted to explore the association between studies’ publication year and outcome measures . The pooled proportions for primary outcomes and corresponding 95% confidence interval (CI) were calculated using a random-effect model, using the procedure for meta-analysis of single proportions “metaprop” from the library “meta”, provided in R software for statistical computing. To find clusters within the dataset, multiple correspondence analysis (MCA), PCA, factor analysis (FA), k‐means cluster analysis (KCA), hierarchical cluster analysis (HCA), variable clustering (VC) and discriminant analysis (DA) were used. Initially, only the first administration of THC during each study day was taken into account, which assured the absence of carry‐over effects and tolerance. Since most studies included several different consecutive doses on each individual study occasion, it was possible to assess a dose–response relationship, which was performed in two steps. Most of these studies had a design where multiple doses of THC were administered on each study day, with a fixed time interval between administrations. To determine possible dose–response relationships for the different VAS items that are sensitive for the effect of THC, the studies that used intrapulmonary administration of THC were selected. In all these studies, several administrations were given during a study day to prolong the effect of THC. Individual VAS items are compared on sensitivity to the effects of THC, including a possible dose–response relationship. The aim of the current analysis is to identify distinct profiles within the spectrum of characteristic subjective effects of THC as measured using well‐known sets of VAS. Once you have delivered your review, you might want to make use of Elsevier’s Reviewer Hub to ensure that you receive credit for your work. The submission system provides reviewers with a notification of the final decision, if the journal has opted in to this functionality. The journal for which you are reviewing might have a specific format (e.g., questionnaire) or other instructions for how to structure your feedback. You should indicate whether your comments are your own opinion or are reflected by the data and evidence. Your comments should be courteous and constructive, and should not include any ad hominem remarks or personal details including your name (unless the journal you are invited to review for employs open peer review). It also contains minerals such as Mg, Ca, Cu, Zn, Fe, Mn, P. Due to high content of bioactive nutrients, preparations from alfalfa have antifungal, antibacterial, insecticidal and nematicidal properties 1,2,3,4. Alfalfa has been considered as functional food due to low content of saturated fat, cholesterol and sodium and high concentration of different nutrients (like folate). The SFC analysis revealed a proper separation of flavonoids and phenolics acids for dedicated TFC and TPC optimal parameters. The obtained results indicate that the extraction efficiency of polar bioactive compounds from M. This data proved the accuracy of the process optimization with individual criteria separately, as well as the according to different criteria at the same time. In the extract, obtained under optimal conditions for the maximum yield of the process, the total flavonoids content was analyzed. Results of total phenolics content (TPC) and total flavonoids content (TFC) in M. Maceration with polar co-solvents is well described and has been dedicated for polar compounds separation . In order to verify the influence of the temperature on the concentration of polar compounds, conventional macerations with 96% ethanol solution at defined in BBD plan values of temperature, were performed. In the case of our work, we have worked at the quarter-technical plant where the amount of the feedstock and obtained product allows work with pure supercritical fluid. In this paper, extraction with supercritical carbon dioxide of alfalfa was performed. There are many ways in which the (subjective) effects of cannabis and THC can be measured. The factors that determine the intensity of each of these effects have not been investigated in detail, but the subjective effects of THC seem to differ among users, and probably also between occasions of use or doses and modes of administration. Other effects are impairments of reaction time, short‐term memory and motor coordination. Less frequently, there can also be effects that are reminiscent of psychosis, like distorted perceptions of colour, space and time. It is described as continuous or chronic AAS use, despite prominent adverse medical, psychological, or social effects . Surprisingly, we did not identify any studies from the US, Middle East, Oceania, Asia, or Africa. We further show a limited geographical scope of included studies, with all studies being from countries in Europe or Brazil. Quality and quantity of anabolic androgenic steroids found on the black market However, a new dimension for application of lucerne products can be added thanks to supercritical extraction by obtaining a pure extract enriched with bioactive nutrients. Wherethrough the great content of the bioactive compounds, the alfalfa product has been used as a food and feed additives and medicine supplements. Qualitative analysis of products was performed with supercritical fluid chromatography (SFC). For MCA, the dataset was recoded into responders and non‐responders, and the final item selection was based on the inertia of the items. The role of co-solvent is to increase the polarity and the elution strength of a supercritical fluid with maintaining the same process parameters without significantly changing the scCO2 selectivity 17,18. The extractive properties of the supercritical carbon dioxide can be manipulated by adding a defined amount of a polar co-solvent during the process. The most common described SFE procedures, applied in the industry, are coffee decaffeination, extraction of hops or hemps, preparation of Serenoa repens extract, flower extracts, or natural pesticides . There is also no need to evaporate the solvent, as after the end of process it changes into gaseous state and leaves the process environment itself. These products pose a considerable individual and public health threat, and the very wide range in proportions of fake black-market AAS puts the user in a situation of unpredictable uncertainty. These items should also receive your attention during the peer review process. As a peer reviewer you may request sub-group analysis if deemed necessary and check if all data are provided disaggregated by sex, as a minimum. Also, the effect profiles can help in quantifying the dose − response relationships for different THC‐effects, for instance to discriminate peripheral and central cannabinoid type 1 antagonists (Klumpers et al., 2013b). For example, the interactions of different constituents of cannabis (i.e. THC and cannabidiol) could be disentangled, by measuring the effects of each component and different combinations of components (Bhattacharyya et al., 2010). For use in future studies, the authors would recommend the addition of scales for hunger and appetite. The effect of THC on appetite is not measured by VAS Bond and Lader or VAS Bowdle and therefore not taken along in the current analysis. Some authors assessed visual inspection of packaging and detection of counterfeiting rate with contradicting results. Counterfeit proportions for oil-based solutions compared to tablets are described as 43–65% vs. 29–37%, respectively 25, 43. Funnel plot for counterfeit AAS (left), funnel plot for substandard AAS (right). If smaller, statistically not significant studies tend to remain unpublished, then an asymmetrical shape may be observed. For “over-concentrated” preparations however, active ingredients could go as much as 200% above that indicated on the label (e.g. 221% or 225% ) if quantitative data was available. The present review can enable us to identify the proper direction, get familiar with new research methods and success of genetic engineering technology in alfalfa, to produce maximally improved cultivars. However, an advance of transgenic approach is contentious, requiring vigilant experimental methods and design to contest bio-safety challenges. There are no reviews yet. Our content is for informational purposes only. Different harm reduction strategies could be employed to limit this user community from either getting in contact with fake AAS from the black market or to promote safer use and informed decision making. Updated numbers are urgently needed, as the popularity of these substances is described to have increased, i.e. in the UK it is estimated that AAS popularity has doubled within the 10 years to 2018 . There is a large and increasing number of individuals who are possibly exposed to these fake AAS on the black market. Manuscripts may also contain database identifiers or accession numbers (e.g., genes) in relation to our database linking program.The optimal conditions, obtained as a result of extraction of lucerne at quarter-technical plant, and analyzed data by RSM and ANOVA were determined and summarized in the Table 5.Firstly, the yield of the process increases with pressure, but after achieving maximum, it decreases.The other items that had high individual predictive values describe effects on time perception and cognitive functions (controlling of thoughts and mental slowness), which are also well known and frequent effects of cannabis and THC (Ashton, 2001).The sample preparation for LC–MS/MS or GC–MS is simple and was mostly based on an extraction with organic solvents, usually methanol 43, 46, 47, 49, 51, followed by sonication.Each of our pharmacy products is carefully selected to meet the diverse needs of our patients, and we are dedicated to providing personalized and compassionate care to ensure that our patients receive the right medication at the right dosage.Also, different multivariate techniques were employed to examine if the clustering of different VAS items elicited distinct response patterns. All the studies had a randomized, cross‐over, placebo‐controlled design and were approved by the local Ethics Committee. The time points and measurements of VAS Bond and Lader and VAS Bowdle, as well as the time points of drug administration and administered dose were used for the analysis. Also, different multivariate techniques were employed to examine if the clustering of different VAS items elicited distinct response patterns. When these profiles are combined in composite scales, they can be used in the design and interpretation of studies assessing the effect of THC or cannabis and to improve our understanding of the endocannabinoid system in health and disease. Rather, those products are produced in clandestine underground laboratories lacking the necessary knowledge or equipment to produce these compounds in adequate quantity and quality, as also described by other authors 26, 35, 38.Skip the sales tricks and user reviews.However, a new dimension for application of lucerne products can be added thanks to supercritical extraction by obtaining a pure extract enriched with bioactive nutrients.Streamline your systematic reviews and meta-analyses with Cochrane's Review Manager (RevMan).In all these studies, several administrations were given during a study day to prolong the effect of THC.It is available as over the counter products without precription. Unknowingly taking the wrong formulation can lead to unexpected side effects, especially when taken over a longer period than intended or in combination with other substances. The most common route of administration is per intramuscular injection and we demonstrate that proportions of counterfeit and substandard substances for injectables compared to oral formulations may be considerably higher. We want to highlight one particular adverse event of those substances that can become a motivator for continued use and an increased risk of continuously being exposed to counterfeit or substandard substances, the “AAS dependence syndrome” . Designed for mainstream PCs and ultra‑thin laptops, the 3610 delivers data-center-class Gen5 performance and efficiency in … Since we first brought the QLC-based PowerStore 3200Q with PowerStoreOS 4.0 into the lab, Dell hasn’t slowed down. All review experiences are provided by registered members of the academic community, and checked for systematic errors by the SciRev team. Many reviews come with a motivation for the overall rating. Assess manuscripts for inclusion of sex-disaggregated data and gender analysis. For qualitative research make sure that a systematic data analysis is presented and sufficient descriptive elements with relevant quotes from interviews are listed in addition to the author’s narrative. These questions address different aspects of the manuscript, such as the quality of the data analysis, reproducibility, and the overall clarity of the manuscript. The same correlation is observed for extract obtain under for conditions optimal for TPC, where the content of salicylic and ferulic acids is the highest (Figure 2b). The lowest level among the tested phenolic compounds was observed for ferulic acid. In the study, the method of analyzing three flavonoids (flavon, apigenin, naringenin) and two phenolic acids (salicylic and ferulic acid) present in Yield, TPC and TFC extracts from M. This affects the band broadening during the chromatographic separation and also affects mass transfer, which includes thermodynamic processes responsible for system selectivity . The quantitative and qualitative analysis was performed under the optimized conditions at 25 °C and 13.7 MPa using methanol as the co-solvent (the gradient as described in Section 2.8). Other interesting statistics include total handling time of accepted manuscripts, journal popularity score, and overall quality of the review process. Data on experienced duration and quality of the review process are provided by researchers. Each journal has its own page with information about the review process. Items that are relatively closer to the right side of the map are items that are more likely to show a response than items that are closer to the left side of the map.Track products and prioritize features based on data.• to increase the homogeneity, article with mixed samples (e.g., if the analysis includes different classes of IPED) in which data on AAS are• articles that present proportions of original and/or counterfeit and/or substandard drugsClassification of prohibited substances coded according to the WADA prohibited list (updated version as of 01 January 2021)Counterfeit products can potentially lead to negative health outcomes and are considered an individual and public health threat .Qualitative and quantitative analysis according to the suggested classification of Neves , and Weber and colleagues into original, substandard or counterfeit and subclassifications with some adaptions for analysisAt Wiley we believe that peer review is the foundation for safeguarding the quality and integrity of scientific and scholarly research. Secondary outcomes are proportions of adulterated, substituted, and inert substances for counterfeit results, and over-concentrated and under-concentrated substances for substandard results. Primary outcomes are proportions of counterfeit and substandard substances. We used a subclassification of “counterfeit” substances to comprise “adulterated”, “substituted” and “inert”; and “substandard” substances to comprise “over- and under- concentrated” (Table 3). We further classified compounds according to the suggested classification of Neves , and Weber and colleagues with adaptions into “original”, “substandard” and “counterfeit”. Substandard and counterfeit products found in our systematic review were most likely produced by manufacturers not in line with good manufacturing practices (GMP’s) . Both the proportion of substandard and counterfeit products are described to be higher in formulations for oil-based solutions used for injectables compared to tablets used for oral administration 25, 26, 36, 43. For counterfeit substances, most studies sub-analyzed data into inert, substituted, and adulterated samples. The authors provided sufficient information in the methods section so that, by consensus between the reviewers (RM/PB/LF), we were confident to include the study for extraction and analysis. A subgroup analysis was conducted for counterfeit AAS (proportions of adulterated, substituted and inert substances), substandard AAS (proportions of over-concentrated and under-concentrated substances) and based on geographical location. Optimized elution strength of supercritical fluid (SF) and the solute solubility in the SF have a crucial impact on the extraction efficiency. Polynominal quadratic equations for all output variables as results of the studies on the Medicago sativa’s extracts. Considering the results of maceration and supercritical fluid extraction for the highest tested temperature (80 °C), we can conclude that flavonoids are more susceptible for thermal decomposition than phenolics. According to Box-Behnken plan data for the SFE experiments (Table 1), for extract no. 1 obtained at 60 °C the determined value of TFC was also the highest. The popularity of these techniques (proved by significant number of publications) is connected with the nature of CO2 and specificity of the obtained product. The supercritical fluid extraction as a separation technique is very suitable for the separation according to “green chemistry” standards, especially when carbon dioxide is used as a solvent. The extraction method has a huge impact on the composition of the final extract, including the concentration of polar constituents, like flavonoids 1,7,8,9. As a result of the extraction of lucerne leaves with ethanol as a solvent, genistin, daidzein, glycitein, genistein and formononetin were also determined . Phenols are valuable components in human diet and serve an important role in nutraceutical potential and health-promoting effects due to their high antioxidant activity. Up until today there is still no effective way to protect AAS users from counterfeit AAS, as there is no formal quality control in place to ensure that what is acquired is real. Due to lack of reporting, precise prevalence and demographic information on the use of these substances is challenging . Historically, the majority of AAS users were professional or competitive athletes, but nowadays survey data has revealed that over 75% of AAS users are non-competitive bodybuilders or athletes, who are mostly motivated by cosmetic benefits over performance enhancement from AAS use 4, 6, 8–13. There is a great need for future prevention and harm-reduction programs to protect users from these substances. Most studies were nonclinical laboratory studies (95%) and provided samples seized by authorities (74%). Your review will help the editor decide whether or not to publish the article. When you sit down to write the review, again make sure you familiarize yourself with any journal-specific guidelines (these will be noted in the journal’s guide for authors). Experiments including patient or animal data should properly be documented. For other data visualizations, there may be other ways of inspecting the files. NB for certain types of visualization, preview tools are available, allowing you to inspect how files will display on ScienceDirect if the manuscript is accepted. The new approach of this study was to extract non-oleic plant with pure scCO2 to obtain product with high efficiency and high level of bioactive compounds as phenolics compounds. Optimal extraction conditions were determined by analysis of variance (ANOVA) based on the obtained responses 26,27. This experiment also allowed to compare the effectiveness of both extraction techniques in obtaining a product enriched in flavonoids and phenolic compounds. Michel Aglietta’s singular trajectory traced from radicalization in Algeria and 1960s Marxism to studies of China and green modelling. An inter-generational exchange between one of the Cold War’s originating thinkers and a young Marxist scholar studying his work. Kevin Cox looks instead at the making of classes—and expropriation of African farmers—in conditions of globalization’s labour shock. Were involved in the data acquisition and interpreted the data; O.W. As no subjective effects are expected during the placebo condition, the scores for the items of the VAS Bond and Lader were expected to be distributed around the middle and the scores for the items of the VAS Bowdle close to a score of 0 mm. In this regard, for each VAS item the data of the placebo condition from different studies were presented as boxplots. Prior to the analysis, a visual quality check of the available data was performed. This study was included as a check of the notion that THC effects are determined by individual sensitivity and brain concentrations, and not by administration route. Similar correlation was observed for extraction of Lepidium sativum freeze-dried sprouts and seeds with different techniques. Sativa with supercritical carbon dioxide is comparable to conventional extraction techniques. The obtained TFC content was 14.56 mg RU/g DM which was under optimal range. Critical issues in research data, which are considered to be major flaws can be related to insufficient data points, statistically non-significant variations and unclear data tables. Manuscripts may also contain database identifiers or accession numbers (e.g., genes) in relation to our database linking program. Please be aware that links to data might therefore be present in the submission files. Authors may add research data, including data visualizations, to their submission to enable readers to interact and engage more closely with their research after publication. Once you are satisfied that the methodology is sufficiently robust, examine any data in the form of figures, tables, or images.