Project description:There has been an increased use of medical Cannabis in the United States of America as more states legalize its use. Complete chemical analyses of this material can vary considerably between producers and is often not fully provided to consumers. As phytochemists in a state with legal medical Cannabis we sought to characterize the accumulation of phytochemicals in material grown by licensed commercial producers. We report the development of a simple extraction and analysis method, amenable to use by commercial laboratories for the detection and quantification of both cannabinoids and terpenoids. Through analysis of developing flowers on plants, we can identify sources of variability of floral metabolites due to flower maturity and position on the plant. The terpenoid composition varied by accession and was used to cluster cannabis strains into specific types. Inclusion of terpenoids with cannabinoids in the analysis of medical cannabis should be encouraged, as both of these classes of compounds could play a role in the beneficial medical effects of different cannabis strains.
Project description:Synthetic cannabinoids are one of the most significant groups within the category new psychoactive substances (NPS) and in recent years new compounds have continuously been introduced to the market of recreational drugs. A sensitive and quantitative screening method in urine with metabolites of frequently seized compounds in Norway (AB-FUBINACA, AB-PINACA, AB-CHMINACA, AM-2201, AKB48, 5F-AKB48, BB-22, JWH-018, JWH-073, JWH-081, JWH-122, JWH-203, JWH-250, PB-22, 5F-PB-22, RCS-4, THJ-2201, and UR-144) using ultra-high pressure liquid chromatography-quadrupole time of flight-mass spectrometry (UHPLC-QTOF-MS) has been developed. The samples were treated with ß-glucuronidase prior to extraction and solid-phase extraction was used. Liquid handling was automated using a robot. Chromatographic separation was achieved using a C18-column and a gradient of water and acetonitrile, both with 0.1% formic acid. Each sample was initially screened for identification and quantification followed by a second injection for confirmation. The concentrations by which the compounds could be confirmed varied between 0.1 and 12 ng/mL. Overall the validation showed that the method fulfilled the set criteria and requirements for matrix effect, extraction recovery, linearity, precision, accuracy, specificity, and stability. One thousand urine samples from subjects in drug withdrawal programs were analyzed using the presented method. The metabolite AB-FUBINACA M3, hydroxylated metabolite of 5F-AKB48, hydroxylated metabolite of AKB48, AKB48 N-pentanoic acid, 5F-PB-22 3-carboxyindole, BB-22 3-carboxyindole, JWH-018 N-(5-hydroxypentyl), JWH-018 N-pentanoic acid, and JWH-073 N-butanoic acid were quantified and confirmed in 2.3% of the samples. The method was proven to be sensitive, selective and robust for routine use for the investigated metabolites.
Project description:ImportanceOver the last decade, cannabis has become more accessible through the proliferation of dispensaries in states that have legalized its use. Most patients using cannabis for medical purposes report getting advice from dispensaries, yet there has been little exploration of frontline dispensary staff practices.ObjectiveTo describe the practices of frontline dispensary workers who interact with customers purchasing cannabis for medical purposes and assess whether dispensary practices are associated with medicalization of state cannabis laws (degree to which they resemble regulation of prescription or over-the-counter drugs) and statewide adult use.Design, setting, and participantsThis nationwide cross-sectional survey study was conducted from February 13, 2020, to October 2, 2020, using an online survey tool. Potential respondents were eligible if they reported working in a dispensary that sells tetrahydrocannabinol-containing products and interacting with customers about cannabis purchases.Main outcomes and measuresParticipant responses to questions about formulating customer recommendations and talking to customers about risks.ResultsThe 434 survey responses from 351 unique dispensaries were most often completed by individuals who identified as budtenders (40%), managers (32%), and pharmacists (13%). Most respondents reported basing customer recommendations on the customer's medical condition (74%), the experiences of other customers (70%), the customer's prior experience with cannabis (67%), and the respondent's personal experience (63%); fewer respondents relied on clinician input (40%), cost (45%), or inventory (12%). Most respondents routinely advised customers about safe storage and common adverse effects, but few counseled customers about cannabis use disorder, withdrawal, motor vehicle collision risk, or psychotic reactions. A higher state medicalization score was significantly associated with using employer training (odds ratio, 1.41; 95% CI, 1.18-1.67) and physician or clinician input (odds ratio, 1.23; 95% CI, 1.05-1.43) as a basis for recommendation. Medicalization score was not associated with counseling about cannabis risks.Conclusions and relevanceThis survey study provides insight into how frontline dispensary staff base cannabis recommendations and counsel about risks. The findings may have utility for clinicians to counsel patients who purchase cannabis, customers who want to be prepared for a dispensary visit, and policy makers whose decisions affect cannabis laws.
Project description:The majority of adults in the U.S. now have state-legal access to medical or recreational cannabis products, despite their federal prohibition. Given the wide array of pharmacologically active compounds in these products, it is essential that their biochemical profile is measured and reported to consumers, which requires accurate laboratory testing. However, no universal standards for laboratory testing protocols currently exist, and there is controversy as to whether all reported results are legitimate. To investigate these concerns, we analyzed a publicly available seed-to-sale traceability dataset from Washington state containing measurements of the cannabinoid content of legal cannabis products from state-certified laboratories. Consistent with previous work, we found that commercial Cannabis strains fall into three broad chemotypes defined by the THC:CBD ratio. Moreover, we documented systematic differences in the cannabinoid content reported by different laboratories, relative stability in cannabinoid levels of commercial flower and concentrates over time, and differences between popular commercial strains. Importantly, interlab differences in cannabinoid reporting persisted even after controlling for plausible confounds. Our results underscore the need for standardized laboratory methodologies in the legal cannabis industry and provide a framework for quantitatively assessing laboratory quality.
Project description:Heavy cannabis users display smaller amygdalae and hippocampi than controls, and genetic variation accounts for a large proportion of variance in liability to cannabis dependence (CD). A single nucleotide polymorphism in the cannabis receptor-1 gene (CNR1), rs2023239, has been associated with CD diagnosis and intermediate phenotypes, including abstinence-induced withdrawal, cue-elicited craving, and parahippocampal activation to cannabis cues. This study compared hippocampal and amygdalar volumes (potential CD intermediate phenotypes) between heavy cannabis users and healthy controls, and analyzed interactions between group, rs2023239 variation, and the volumes of these structures. Ninety-four heavy cannabis users participated, of whom 37 (14 men, 23 women; mean age=27.8) were matched to 37 healthy controls (14 men, 23 women; mean age=27.3) for case-control analyses. Controlling for total intracranial volume and other confounding variables, matched cannabis users had smaller bilateral hippocampi (left, p=0.002; right, p=0.001) and left amygdalae (p=0.01) than controls. When genotype was considered in the case-control analyses, there was a group by genotype interaction, such that the rs2023239 G allele predicted lower volume of bilateral hippocampi among cannabis users relative to controls (both p<0.001). This interaction persisted when all 94 cannabis users were compared to controls. There were no group by genotype interactions on amygdalar volume. These data replicate previous findings of reduced hippocampal and amygdalar volume among heavy cannabis users, and suggest that CNR1 rs2023239 variation may predispose smaller hippocampal volume after heavy cannabis use. This association should be tested in future studies of brain volume differences in CD.
Project description:Background: For cannabis-dependent subjects, the relationship between cannabis withdrawal syndrome (CWS) severity and the urine cannabinoid concentrations are unclear; we investigated this using a commercial point-of-care (POC) enzyme immunoassay detecting 11-nor-9-carboxy-Delta-9-tetrahydrocannabinol (THC-COOH). Methods: Observational study of 78 adult chronic cannabis-dependent subjects assessed over a 24-day inpatient detoxification treatment, with 13 serial measurement days. Repeated Measures Correlation and Multilevel Linear Models were employed. Results: Absolute urinary THC-COOH levels significantly correlated with Marijuana Withdrawal Checklist (MWC) scores across the entire study duration (r = 0.248; p < 0.001). Correlation between serial creatinine-adjusted THC-COOH ratios and serial MWC scores emerged as significant only in the sample with higher MWC scores (>11 points) at admission (n = 21; r = 0.247; p = 0.002). The aforementioned significant relationships have persisted when replacing the absolute THC-COOH-levels with the (relative) day-to-day change in urinary THC-COOH levels. MWC scores were significantly correlated with the Clinical Global Impression-Severity (CGI-S; r = 0.812; p < 0.001). Females showed a significantly slower decline in urine THC-COOH levels and prolonged CWS course characterized by substantial illness severity (per CGI-S), occurring in nearly 30% of cases. Conclusion: Urine cannabinoid levels (THC-COOH) determined by POC assay significantly predicted CWS severity (moderate correlation), guiding detoxification treatment duration. In patients with MWC > 11 points upon admission, creatinine-adjusted THC-COOH ratios also significantly predicted CWS severity-again with moderate effect size. Females showed prolonged urinary THC-COOH elimination and cannabis withdrawal.
Project description:IntroductionWith its legalisation and regulation in Canada in 2018, the proportion of Canadians reporting cannabis use in 2019 increased substantially over the previous year, with half of new users being aged 45+ years. While use in older adults has been low historically, as those born in the 1950s and 1960s continue to age, this demographic will progressively have more liberal attitudes, prior cannabis exposure and higher use rates. However, older adults experience slower metabolism, increased likelihood of polypharmacy, cognitive decline and chronic physical/mental health problems. There is a need to enhance knowledge of the effects of cannabis use in older adults. The following question will be addressed using a scoping review approach: what evidence exists regarding beneficial and harmful effects of medical and non-medical cannabis use in adults >50 years of age? Given that beneficial and harmful effects of cannabis may be mediated by patient-level (eg, age, sex and race) and cannabis-related factors (eg, natural vs synthetic, consumption method), subgroup effects related to these and additional factors will be explored.Methods and analysisMethods for scoping reviews outlined by Arksey & O'Malley and the Joanna Briggs Institute will be used. A librarian designed a systematic search of the literature from database inception to June 2019. Using the OVID platform, Ovid MEDLINE will be searched, including Epub Ahead of Print and In-Process and Other Non-Indexed Citations, Embase Classic+Embase, and PsycINFO for reviews, randomised trials, non-randomised trials and observational studies of cannabis use. The Cochrane Library on Wiley will also be searched. Eligibility criteria will be older adult participants, currently using cannabis (medical or non-medical), with studies required to report a cannabis-related health outcome to be eligible. Two reviewers will screen citations and full texts, with support from artificial intelligence. Two reviewers will chart data. Tables/graphics will be used to map evidence and identify evidence gaps.Ethics and disseminationThis research will enhance awareness of existing evidence addressing the health effects of medical and non-medical cannabis use in older adults. Findings will be disseminated through a peer-reviewed publication, conference presentations and a stakeholder meeting.Trial registration numberDOI 10.17605/OSF.IO/5JTAQ.
Project description:This study examined the genetic association between variation in the cannabinoid receptor 1 (CNR1) gene and cannabis dependence symptoms.Adolescent and young adult subjects were recruited from three settings: a treatment program for youth with substance use disorders, the criminal justice system, and the community. A case-control sample consisted of 224 cases who endorsed at least one dependence symptom and 108 controls who tried cannabis but endorsed no symptoms. A family-based sample of 219 families was also analyzed.Case-control analysis identified a nominal association between SNP rs1049353 and having one or more cannabis dependence symptoms (p=.029), but the association did not hold up in a combined sample. Family-based analysis found a trend for the same SNP (p=.07). We did not replicate a previous report that SNP rs806380 was associated with the development of cannabis dependence.These results provide inconclusive evidence of association between rs1049353/rs806380 and the development of cannabis dependence, and underscore the importance of replicating results of genetic association studies. Additional family-based studies are needed to clarify the role of the CNR1 gene, and its various SNPs, in the development of cannabis use disorders.
Project description:ImportancePediatric health care contacts due to cannabis exposure increased in Colorado and Washington State after cannabis (marijuana) policies became more liberal, but evidence from other US states is limited.ObjectiveTo document the incidence of pediatric cannabis exposure cases reported to the Regional Center for Poison Control and Prevention (RPC) before and after medical marijuana legalization (MML) in Massachusetts.Design, setting, and participantsCross-sectional comparison of pediatric cannabis exposure cases 4 years before and after MML in Massachusetts. The exposure cases included those of 218 children and teenagers aged between 0 and 19 years, as reported to the RPC from 2009 to 2016. Census data were used to determine the incidence. Data analysis was performed from November 12, 2018, to July 20, 2019.ExposureCannabis products.Main outcomes and measuresIncidence of RPC-reported cannabis exposure cases, both single substance and polysubstance, for the age group of 0 to 19 years, and cannabis product type, coingestants, and clinical effects.ResultsDuring the 8-year study period (2009-2016), the RPC received 218 calls involving cannabis exposure (98 single substance, 120 polysubstance) in children and teenagers aged 0 to 19 years, representing 0.15% of all RPC calls in that age group for that period. Of the total exposure cases, males accounted for 132 (60.6%) and females 86 (39.4%). The incidence of single-substance cannabis calls increased from 0.4 per 100?000 population before MML to 1.1 per 100?000 population after (incidence rate ratio, 2.4; 95% CI, 1.5-3.9), a 140% increase. The age group of 15 to 19 years had the highest frequency of RPC-reported cannabis exposures (178 calls [81.7%]). The proportion of all RPC calls due to single-substance cannabis exposure increased overall for all age groups from 29 before MML to 69 afterward. Exposure to edible products increased after MML for most age groups.Conclusions and relevancePediatric cannabis exposure cases increased in Massachusetts after medical marijuana was legalized in 2012, despite using childproof packaging and warning labels. This study provides additional evidence suggesting that MML may be associated with an increase in cannabis exposure cases among very young children, and extends prior work showing that teenagers are also experiencing increased cannabis-related health system contacts via the RPC. Additional efforts are needed to keep higher-potency edible products and concentrated extracts from children and teenagers, especially considering the MML and retail cannabis sales in an increasing number of US states.