Philip L Wylie, Jessica Westland, Mei Wang, Mohamed M Radwan, Chandrani G Majumdar, Mahmoud A ElSohly
{"title":"Screening for More than 1,000 Pesticides and Environmental Contaminants in Cannabis by GC/Q-TOF.","authors":"Philip L Wylie, Jessica Westland, Mei Wang, Mohamed M Radwan, Chandrani G Majumdar, Mahmoud A ElSohly","doi":"10.1159/000504391","DOIUrl":"10.1159/000504391","url":null,"abstract":"<p><p>A method has been developed to screen cannabis extracts for more than 1,000 pesticides and environmental pollutants using a gas chromatograph coupled to a high-resolution accurate mass quadrupole time-of-flight mass spectrometer (GC/Q-TOF). An extraction procedure was developed using acetonitrile with solid phase extraction cleanup. Before analysis, extracts were diluted 125:1 with solvent. Two data mining approaches were used together with a retention-time-locked Personal Compound Database and Library (PCDL) containing high-resolution accurate mass spectra for pesticides and other environmental pollutants. (1) A Find-by-Fragments (FbF) software tool extracts several characteristic exact mass ions within a small retention time window where the compound elutes. For each compound in the PCDL, the software evaluates the peak shape and retention time of each ion as well as the monoisotopic exact mass, ion ratios, and other factors to decide if the compound is present or not. (2) A separate approach used Unknowns Analysis (UA) software with a peak-finding algorithm called SureMass to deconvolute peaks in the chromatogram. The accurate mass spectra were searched against the PCDL using spectral matching and retention time as filters. A subset PCDL was generated containing only pesticides that are most likely to be found on foods in the US. With about 250 compounds in the smaller PCDL, there were fewer hits for non-pesticides, and data review was much faster. Organically grown cannabis was used for method development. Twenty-one confiscated cannabis samples were analyzed and ten were found to have no detectable pesticides. The remaining 11 samples had at least one pesticide and one sample had seven detectable residues. Quantitative analysis was run on the confiscated samples for a subset of the pesticides found by screening. Two cannabis samples had residues of carbaryl and malathion that were estimated to be about 10 times greater than the highest US Environmental Protection Agency tolerance set for food and about 4,000 times greater than the Canadian maximum residue limits for dried cannabis flower.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"3 1","pages":"14-24"},"PeriodicalIF":0.0,"publicationDate":"2020-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000504391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39539458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Gabriela Hounie, Marco Agassiz Almeida Vasques
{"title":"Neurological Improvement with Medical Cannabis in a Progressive Supranuclear Palsy Patient: A Case Report.","authors":"Ana Gabriela Hounie, Marco Agassiz Almeida Vasques","doi":"10.1159/000503864","DOIUrl":"10.1159/000503864","url":null,"abstract":"<p><p>Progressive supranuclear palsy (PSP) is a severe, debilitating, and often fatal disease resembling other neurodegenerative disorders, namely Alzheimer's (AD) and Parkinson's (PD) diseases, which have been successfully treated with cannabinoids. We herein report the case of a 71-year-old woman diagnosed with PSP, displaying severe impairment of motor and language functions which progressively improved after treatment with medical cannabis. Before treatment, the patient was unable to move her limbs, was fed soft food, and was unable to speak or move her eyes. The patient has regained horizontal eye movement, is able to walk with assistance, has returned to physiotherapy, started to eat solid food, and has had a remarkable improvement in her speech. The possible mechanisms of this improvement are discussed.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"2 2","pages":"65-68"},"PeriodicalIF":0.0,"publicationDate":"2019-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489313/pdf/mca-0002-0065.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39539456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Abstracts - 4th International Medical Cannabis Conference (CannX 2019) Tel Aviv, Israel, September 9-10, 2019","authors":"","doi":"10.1159/000502323","DOIUrl":"https://doi.org/10.1159/000502323","url":null,"abstract":"","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"2 1","pages":"84 - 103"},"PeriodicalIF":0.0,"publicationDate":"2019-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000502323","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46944648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Construction and Validation of Quantification Methods for Determining the Cannabidiol Content in Liquid Pharma-Grade Formulations by Means of Near-Infrared Spectroscopy and Partial Least Squares Regression.","authors":"Joan Espel Grekopoulos","doi":"10.1159/000500266","DOIUrl":"https://doi.org/10.1159/000500266","url":null,"abstract":"<p><p>There is an increasing interest in cannabinoids as they are being proved to effectively treat the symptoms of a variety of medical conditions. Commercialization of cannabinoid-based pharmaceutical products is expected to grow in the near future, favored by the recent changes in medical regulations in many developed countries. Hence, robust and reliable analytical methods for determining the content of the active pharmaceutical ingredient will be needed, as this is one of the most relevant parameters for the decision to release the final pharmaceutical product into the market. The aim of this work was to demonstrate that near-infrared (NIR) spectroscopy fulfills the needed requirements for this purpose, as well as to provide a methodology to be applied to other cannabinoid-based products. We present two validated methods for the quantification of different liquid pharma-grade cannabidiol (CBD) formulations based on NIR spectroscopy and partial least squares regression modelling. The methods were constructed and validated with spectra belonging both to production samples and to laboratory samples specifically made for this purpose, and they fulfill European Medicines Agency and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guideline requirements. These methods allow determining the CBD content with results comparable to the usual method of choice while saving reagent- as well as time-related costs.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"2 1","pages":"43-55"},"PeriodicalIF":0.0,"publicationDate":"2019-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000500266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39542022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cannabinoids in Gynecological Diseases.","authors":"Petra Luschnig, Rudolf Schicho","doi":"10.1159/000499164","DOIUrl":"https://doi.org/10.1159/000499164","url":null,"abstract":"<p><p>The endocannabinoid system (ECS) is a multifunctional homeostatic system involved in many physiological and pathological conditions. The ligands of the ECS are the endo-cannabinoids, whose actions are mimicked by exogenous cannabinoids, such as phytocannabinoids and synthetic cannabinoids. Responses to the ligands of the ECS are mediated by numerous receptors like the classical cannabinoid receptors (CB<sub>1</sub> and CB<sub>2</sub>) as well as ECS-related receptors, e.g., G protein-coupled receptors 18 and 55 (GPR18 and GPR55), transient receptor potential ion channels, and nuclear peroxisome proliferator-activated receptors. The ECS regulates almost all levels of female reproduction, starting with oocyte production through to parturition. Dysregulation of the ECS is associated with the development of gynecological disorders from fertility disorders to cancer. Cannabinoids that act at the ECS as specific agonists or antagonists may potentially influence dysregulation and, therefore, represent new therapeutic options for the therapy of gynecological disorders.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"2 1","pages":"14-21"},"PeriodicalIF":0.0,"publicationDate":"2019-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000499164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39542019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Abstracts - The 2nd International Annual Congress on Controversies on Cannabis-Based Medicines, Barcelona, Spain, May 23-24, 2019","authors":"","doi":"10.1159/000500623","DOIUrl":"https://doi.org/10.1159/000500623","url":null,"abstract":"","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"2 1","pages":"69 - 83"},"PeriodicalIF":0.0,"publicationDate":"2019-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000500623","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41374630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Esther Uchendu, Hemant Lata, Suman Chandra, Ikhlas A Khan, Mahmoud A ElSohly
{"title":"Cryopreservation of Shoot Tips of Elite Cultivars of <i>Cannabis sativa</i> L. by Droplet Vitrification.","authors":"Esther Uchendu, Hemant Lata, Suman Chandra, Ikhlas A Khan, Mahmoud A ElSohly","doi":"10.1159/000496869","DOIUrl":"https://doi.org/10.1159/000496869","url":null,"abstract":"<p><p><i>Cannabis sativa</i> L. (marijuana or hemp) is recognized worldwide for its psychoactive properties as well as for fiber production. This study focused on the evaluation of 3 droplet vitrification protocols for long-term conservation of shoot tips in liquid nitrogen (LN). Shoot tips (∼0.5 mm) were excised from 3- to 4-week-old in vitro-grown shoots of 3 cultivars (MX, VI-20, and B-5: high tetrahydrocannabinol [THC], high cannabidiol [CBD], and intermediate THC∼CBD, respectively) and pretreated on 5% dimethyl sulfoxide agar plates for 48 h. The shoot tips were then vitrified in LN using 3 separate cryoprotectant (plant vitrification solutions [PVS] #2, #3, and #4) droplets on an aluminum cryoplate. There was no significant difference between the regrowth of cryopreserved shoot tips exposed to PVS2 for 15 and 20 min, but regrowth of all 3 cultivars significantly declined after 20 min of exposure. Exposure duration of 15 min was adapted for subsequent experiments. Regrowth of cryopreserved MX was significantly higher with PVS2 (63%) than with PVS3 and PVS4 (≤5%). Regrowth of cryopreserved VI-20 was highest with PVS2 (57%) and significantly higher than with PVS3 and PVS4 (≤25%). The regrowth of cryopreserved shoot tips of B-5 was significantly different between all 3 protocols with PVS2 > PVS4 > PVS3. Both PVS2 and PVS4 produced regrowth above 55%, while regrowth with PVS3 was significantly lower (31%). These results indicate that 15-20 min of exposure to PVS2 are most suitable for cryopreservation of these varieties. This is the first report on protocol development for the cryopreservation of organized tissues of <i>C. sativa</i> L. for germplasm conservation.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"2 1","pages":"29-34"},"PeriodicalIF":0.0,"publicationDate":"2019-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000496869","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39542021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of a Novel Nano-emulsion Formulation to Improve Intestinal Absorption of Cannabidiol.","authors":"Yukako Nakano, Masataka Tajima, Erika Sugiyama, Vilasinee Hirunpanich Sato, Hitoshi Sato","doi":"10.1159/000497361","DOIUrl":"https://doi.org/10.1159/000497361","url":null,"abstract":"<p><strong>Background: </strong>Cannabidiol (CBD) is highly lipophilic, and its oral bioavailability is known to be very low in humans. In this study, we developed a novel nanoemulsion preparation of CBD (CBD-NE) to improve the poor solubility and absorption of CBD. The pharmacokinetic profiles of CBD in rats were evaluated after oral administrations of CBD oil and CBD-NE, and the effect of bile secretion on CBD absorption was also evaluated.</p><p><strong>Methods: </strong>The CBD-NE formulation developed in this study consisted of vitamin E acetate, ethanol, Tween-20, and distilled water (1.7/3.8/70/24.5, w/w%). A CBD oil formulation (CBD oil, control) 100 mg/kg or CBD-NE 50 mg/kg was orally administered to rats, and the blood samples were collected over time. Moreover, the CBD oil or CBD-NE was orally administered to bile-fistulated rats, and the pharmacokinetic profiles of CBD were also evaluated. CBD concentrations in plasma were measured using LC-MS/MS.</p><p><strong>Results: </strong>The particle size of CBD-NE was 35.3 ± 11.8 nm. Mean T<sub>max</sub> of CBD-NE was shortened significantly by the factor of 3 (from 8.00 to 2.40 h, <i>p</i> < 0.001) and AUC<sub>0-</sub><sub>∞</sub>/dose increased by 65% (from 0.272 ± 0.045 to 0.448 ± 0.087 h L/kg) compared with CBD oil. AUC<sub>0-</sub><sub>∞</sub>/dose and C<sub>max</sub>/dose after oral administration of CBD oil were significantly reduced by the factor of 27 and 23 (<i>p</i> < 0.05 and <i>p</i> < 0.01), respectively, in bile-fistulated rats compared with the untreated rats. In contrast, all pharmacokinetic parameters after oral administration of CBD-NE were not significantly different between the untreated and bile-fistulated rats. Therefore, these results demonstrated that conventional CBD oil formulation but not CBD-NE requires bile-mediated micelle formation.</p><p><strong>Conclusions: </strong>The novel NE formulation developed in this study successfully improved the absorption of CBD regardless of bile secretion. The newly developed oral CBD-NE preparation could be useful to achieve a more stable and quicker onset of action by CBD.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"2 1","pages":"35-42"},"PeriodicalIF":0.0,"publicationDate":"2019-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000497361","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39542023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Barbara Broers, Zacharie Patà, Aline Mina, James Wampfler, Christian de Saussure, Sophie Pautex
{"title":"Prescription of a THC/CBD-Based Medication to Patients with Dementia: A Pilot Study in Geneva.","authors":"Barbara Broers, Zacharie Patà, Aline Mina, James Wampfler, Christian de Saussure, Sophie Pautex","doi":"10.1159/000498924","DOIUrl":"https://doi.org/10.1159/000498924","url":null,"abstract":"<p><strong>Background: </strong>Dementia is increasing worldwide. No effective medication is currently available for the treatment of the underlying disease and accompanying behavioral symptoms. Cannabinoids might have a beneficial effect, but clinical studies with (low-dose) synthetic THC have not been conclusive.</p><p><strong>Objective: </strong>To test the acceptability, practical aspects, and clinical outcomes of the introduction of a THC/CBD-based oral medication in severely demented patients in a specialized nursing home in Geneva.</p><p><strong>Methods: </strong>This was a prospective observational study.</p><p><strong>Results: </strong>Ten female demented patients with severe behavior problems received oral medication with on average 7.6 mg THC/13.2 mg CBD daily after 2 weeks, 8.8 mg THC/17.6 mg CBD after 1 month, and 9.0 mg THC/18.0 mg CBD after 2 months. The THC/CBD-based oil was preferred. Neuropsychiatric Inventory, Cohen-Mansfield Agitation Inventory score, and a behavior problem visual analog scale decreased by 40% after 2 months, rigidity score by 50%. Half of the patients decreased or stopped other psychotropic medications. The staff appreciated the decrease in rigidity, making daily care and transfers easier, the improved direct contact with the patients, the improvement in behavior, and the decrease in constipation with less opioids. There was no withholding of the medication for reasons of side effects, and the effects persisted after 2 months.</p><p><strong>Conclusions: </strong>An oral cannabis extract with THC/CBD, in higher dosages than in other studies, was well tolerated and greatly improved behavior problems, rigidity, and daily care in severely demented patients.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"2 1","pages":"56-59"},"PeriodicalIF":0.0,"publicationDate":"2019-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000498924","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39542024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthew T Welling, Lei Liu, Arno Hazekamp, Ashley Dowell, Graham J King
{"title":"Developing Robust Standardised Analytical Procedures for Cannabinoid Quantification: Laying the Foundations for an Emerging Cannabis-Based Pharmaceutical Industry.","authors":"Matthew T Welling, Lei Liu, Arno Hazekamp, Ashley Dowell, Graham J King","doi":"10.1159/000496868","DOIUrl":"10.1159/000496868","url":null,"abstract":"<p><p>The plant genus <i>Cannabis</i> is a prolific producer of unique pharmaceutically relevant metabolites, commonly referred to as cannabinoids. Robust and standardised methods for the quantification of cannabinoids within botanical and drug forms is a critical step forward for an emerging <i>Cannabis</i>-based pharmaceutical industry, which is poised for rapid expansion. Despite a growing body of analytical methods for the quantification of cannabinoids, few have been validated using internationally accredited guidelines. Moreover, standardised methods have yet to be developed for application at various stages of manufacture as well as for different levels of processing and refinement. Validation parameters for establishing robust standardised methods for cannabinoid quantification within <i>Cannabis</i>-based drug forms are critically discussed. Determining an appropriate level of specificity (discrimination) among heterogeneous botanical matrices as well as evaluating accuracy (recovery) and inter-laboratory precision (reproducibility) within strict and volatile regulatory environments are potential obstacles to the establishment of robust analytical procedures. We argue that while some of these challenges remain unique to <i>Cannabis</i>, others are common to botanical-based drug development and manufacture. In order to address potential barriers to analytical method standardisation, a collaborative research initiative inclusive of academic and commercial stakeholders is proposed.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"2 1","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2019-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489335/pdf/mca-0002-0001.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39542018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}