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Synthetic cannabinoid receptor agonists (SCRAs) may be used as an alternative to natural cannabis; however, they may carry a greater risk of problematic use and withdrawal. This study aimed to characterise the withdrawal symptom profile of SCRAs and compare their profile of effect with high-potency herbal cannabis. Global Drug Survey data (2015 and 2016) were used to access a clinically relevant sample of people reporting use of SCRAs >10 times in the past 12-months, a previous SCRA quit attempt, and lifetime use of high-potency herbal cannabis. Participants completed an 11-item SCRA withdrawal symptom checklist and compared SCRAs and high-potency herbal cannabis on their onset and duration of effects, speed of the development of tolerance, severity of withdrawal, and difficulty with dose titration. Participants (n = 284) reported experiencing a mean of 4.4 (95% CI: 4.1, 4.8) withdrawal symptoms after not using SCRAs for >1 day; most frequently reported were sleep issues (59.2%), irritability (55.6%), and low mood (54.2%). Withdrawal symptoms were significantly associated with frequency (>51 vs. 11–50 times per year: IRR = 1.43, 95% CI: 1.16, 1.77, p = 0.005) and quantity (grams per session: IRR = 1.13, 95% CI: 1.05, 1.22, p = 0.001) of SCRA use. Compared to high-potency herbal cannabis, SCRAs were rated as having a faster onset and shorter duration of effects, faster development of tolerance, and more severe withdrawal (p’s

BACKGROUND AND AIMS: The United Kingdom (UK) Psychoactive Substances Act (PSA), implemented on the 26 th May 2016, made the production, supply and sale of all non-exempted psychoactive substances illegal. The aim of this study was to measure trends in hospital presentations for severe toxicity following analytically confirmed synthetic cannabinoid receptor agonist (SCRA) exposure before and after implementation of the PSA. DESIGN: Observational study.SETTING: Thirty-four hospitals across the UK participating in the Identification of Novel Psychoactive Substances (IONA) study.PARTICIPANTS: A total of 627 (79.9% male) consenting individuals who presented to participating hospitals between July 2015 and December 2019 with severe acute toxicity and suspected novel psychoactive substances exposure.MEASUREMENTS: Toxicological analyses of patient samples were conducted using liquid-chromatography tandem mass-spectrometry. Time-series analysis was conducted on the monthly number of patients with and without analytically confirmed SCRA exposure using Poisson segmented regression.FINDINGS: SCRAs were detected in 35.7% (n = 224) of patients. After adjusting for seasonality and the number of active sites, models showed no clear evidence of an upward or downward trend in the number of SCRA exposure cases in the period before (incidence rate ratio [IRR], 1.12; 95% CI, 0.99-1.26; P = 0.068) or after (IRR, 0.97; 95% CI, 0.94-1.01; P = 0.202) the implementation of the PSA. There was also no clear evidence of an upward or downward trend in non-SCRA exposure cases before (IRR, 1.12; 95% CI, 0.98-1.27; P = 0.105) or after (IRR, 1.01; 95% CI, 0.98-1.04; P = 0.478) implementation of the PSA.CONCLUSIONS: There is no clear evidence of an upward or downward trend in the number of patients presenting to UK hospitals with severe acute toxicity following analytically confirmed synthetic cannabinoid receptor agonist exposure since the implementation of the Psychoactive Substances Act.

The current systematic review aimed to summarize the literature on the prevalence of routes of administration and cannabis products used among youth and young adults in Canada and the United States (US).Five academic databases were searched in April 2020 and February 2021. Peer-reviewed articles were included if they were a population-based quantitative observational study describing the prevalence of a cannabis product or route of administration among youth and young adults in Canada or the US. Risk of bias was assessed using Hoy and colleagues' risk of bias assessment tool. A narrative review was conducted.Twenty-six studies were identified for the following routes of administration: smoking (n = 16), vaping (n = 21), dabbing (n = 3), oral (n = 13), topical (n = 1); and products: dried flower (n = 2), and concentrates (n = 8). Smoking had the highest prevalence rates among youth and young adults; however, rates of use appeared to reduce over time. Conversely, prevalence of vaping appeared to increase over time. Fewer studies focused on oral or dabbed cannabis but those that did reported prevalence estimates of approximately a third among recent cannabis consumers.The heterogeneity of cannabis routes of administration restricted our ability to collate average prevalence estimates. In jurisdictions where non-medical cannabis is legal, policymakers should provide guidance and education to youth on each type of product and routes of administration.Funding for this study was provided by a Canadian Institutes of Health Research (PJT-153342). The current review was registered with PROSPERO (CRD42020169275).

Synthetic cannabinoid receptor agonists (SCRAs) may be used as an alternative to natural cannabis; however, they may carry a greater risk of problematic use and withdrawal. This study aimed to characterise the withdrawal symptom profile of SCRAs and compare their profile of effect with high-potency herbal cannabis. Global Drug Survey data (2015 and 2016) were used to access a clinically relevant sample of people reporting use of SCRAs10 times in the past 12-months, a previous SCRA quit attempt, and lifetime use of high-potency herbal cannabis. Participants completed an 11-item SCRA withdrawal symptom checklist and compared SCRAs and high-potency herbal cannabis on their onset and duration of effects, speed of the development of tolerance, severity of withdrawal, and difficulty with dose titration. Participants (n = 284) reported experiencing a mean of 4.4 (95% CI: 4.1, 4.8) withdrawal symptoms after not using SCRAs for1 day; most frequently reported were sleep issues (59.2%), irritability (55.6%), and low mood (54.2%). Withdrawal symptoms were significantly associated with frequency (51 vs. 11-50 times per year: IRR = 1.43, 95% CI: 1.16, 1.77, p = 0.005) and quantity (grams per session: IRR = 1.13, 95% CI: 1.05, 1.22, p = 0.001) of SCRA use. Compared to high-potency herbal cannabis, SCRAs were rated as having a faster onset and shorter duration of effects, faster development of tolerance, and more severe withdrawal (p's 0.001). In conclusion, SCRA withdrawal symptoms are more likely to occur after greater SCRA exposure. The effects of SCRA indicate a more severe withdrawal syndrome and a greater risk of problematic use than natural cannabis.

BackgroundAs new cannabis products and administration methods proliferate, patterns of use are becoming increasingly heterogeneous. However, few studies have explored different profiles of cannabis use and their association with problematic use.MethodsLatent class analysis (LCA) was used to identify subgroups of past-year cannabis users endorsing distinct patterns of use from a large international sample (n = 55 240). Past-12-months use of six different cannabis types (sinsemilla, herbal, hashish, concentrates, kief, edibles) were used as latent class indicators. Participants also reported the frequency and amount of cannabis used, whether they had ever received a mental health disorder diagnosis and their cannabis dependence severity via the Severity of Dependence Scale (SDS).ResultsLCA identified seven distinct classes of cannabis use, characterised by high probabilities of using: sinsemilla & herbal (30.3% of the sample); sinsemilla, herbal & hashish (20.4%); herbal (18.4%); hashish & herbal (18.8%); all types (5.7%); edibles & herbal (4.6%) and concentrates & sinsemilla (1.7%). Relative to the herbal class, classes characterised by sinsemilla and/or hashish use had increased dependence severity. By contrast, the classes characterised by concentrates use did not show strong associations with cannabis dependence but reported greater rates of ever receiving a mental health disorder diagnosis.ConclusionsThe identification of these distinct classes underscores heterogeneity among cannabis use behaviours and provides novel insight into their different associations with addiction and mental health.

Adolescents have access to a wide range of cannabis products with patterns of use becoming increasingly diverse. This study aimed to identify subgroups of adolescents in the general population who use similar types of cannabis and their association with psychotic experiences. Data on cannabis use were obtained from 467 adolescents aged between 16 and 17 years. Latent class analysis (LCA) identified groups of adolescents based on the type of cannabis used in the past 12 months. Univariate analysis explored differences in socio-demographics, substance use and mental health symptoms between groups. Multivariate analysis examined associations between class membership and psychotic experiences controlling for frequency and amount of cannabis. Finally, we explored the association between motives for cannabis and class membership using multi-nominal logistic regression. LCA identified 3 classes of adolescents: (i) herbal only (47.9%); (ii) skunk only (20.8%) and (3) mixed use (31.3%). Relative to non-users, skunk only use was associated with a 2-fold increase in paranoia (OR = 2.45, 95% CI = 1.29–4.63), along with, sleep disturbance and anxiety. Monthly cannabis use and consuming 2 or more joints on one occasion was associated with a 2-fold increase in hallucinations (OR = 2.2; 95% CI = 1.0–4.8 and OR = 1.9; 95% CI = 1.2–3.2), but did not reach the Bonferroni corrected p-value. Expansion and conformity motives differentiated the mixed cannabis class from the herbal only class. The findings suggest that different subgroups of cannabis users exist in adolescence as defined by the type of cannabis consumed and are differentially related to psychotic experiences and motives for use.

BACKGROUND AND AIMS Cannabis products with high delta-9-tetrahydrocannabinol (THC) concentrations carry an increased risk of addiction and mental health disorders, while it has been suggested that cannabidiol (CBD) may moderate the effects of THC. This study aimed to systematically review and meta-analyse changes in THC and CBD concentrations in cannabis over time (PROSPERO registration: CRD42019130055). DESIGN Embase, MEDLINE® and Epub Ahead of Print, In-Process and Other Non-Indexed Citations and Daily, Global Health, PsycINFO and Scopus were searched from inception to 27/03/2019 for observational studies reporting changes in mean THC and/or CBD concentration in cannabis over at least three annual time points. Searches and extraction were conducted by two independent reviewers. Random effects meta-regression models estimated annual changes in THC and CBD for each product within each study; these estimates were pooled across studies in random effects models. RESULTS We identified 12 eligible studies from the USA, UK, Netherlands, France, Denmark, Italy and New Zealand. For all herbal cannabis, THC concentrations increased by 0.29% each year (95% CI: 0.11, 0.47), P

Summary Background A substantial and unmet clinical need exists for pharmacological treatment of cannabis use disorders. Cannabidiol could offer a novel treatment, but it is unclear which doses might be efficacious or safe. Therefore, we aimed to identify efficacious doses and eliminate inefficacious doses in a phase 2a trial using an adaptive Bayesian design. Methods We did a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial at the Clinical Psychopharmacology Unit (University College London, London, UK). We used an adaptive Bayesian dose-finding design to identify efficacious or inefficacious doses at a-priori interim and final analysis stages. Participants meeting cannabis use disorder criteria from DSM-5 were randomly assigned (1:1:1:1) in the first stage of the trial to 4-week treatment with three different doses of oral cannabidiol (200 mg, 400 mg, or 800 mg) or with matched placebo during a cessation attempt by use of a double-blinded block randomisation sequence. All participants received a brief psychological intervention of motivational interviewing. For the second stage of the trial, new participants were randomly assigned to placebo or doses deemed efficacious in the interim analysis. The primary objective was to identify the most efficacious dose of cannabidiol for reducing cannabis use. The primary endpoints were lower urinary 11-nor-9-carboxy-δ-9-tetrahydrocannabinol (THC-COOH):creatinine ratio, increased days per week with abstinence from cannabis during treatment, or both, evidenced by posterior probabilities that cannabidiol is better than placebo exceeding 0·9. All analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov ( NCT02044809 ) and the EU Clinical Trials Register (2013-000361-36). Findings Between May 28, 2014, and Aug 12, 2015 (first stage), 48 participants were randomly assigned to placebo (n=12) and to cannabidiol 200 mg (n=12), 400 mg (n=12), and 800 mg (n=12). At interim analysis, cannabidiol 200 mg was eliminated from the trial as an inefficacious dose. Between May 24, 2016, and Jan 12, 2017 (second stage), randomisation continued and an additional 34 participants were allocated (1:1:1) to cannabidiol 400 mg (n=12), cannabidiol 800 mg (n=11), and placebo (n=11). At final analysis, cannabidiol 400 mg and 800 mg exceeded primary endpoint criteria (0·9) for both primary outcomes. For urinary THC-COOH:creatinine ratio, the probability of being the most efficacious dose compared with placebo given the observed data was 0·9995 for cannabidiol 400 mg and 0·9965 for cannabidiol 800 mg. For days with abstinence from cannabis, the probability of being the most efficacious dose compared with placebo given the observed data was 0·9966 for cannabidiol 400 mg and 0·9247 for cannabidiol 800 mg. Compared with placebo, cannabidiol 400 mg decreased THC-COOH:creatinine ratio by −94·21 ng/mL (95% interval estimate −161·83 to −35·56) and increased abstinence from cannabis by 0·48 days per week (0·15 to 0·82). Compared with placebo, cannabidiol 800 mg decreased THC-COOH:creatinine ratio by −72·02 ng/mL (−135·47 to −19·52) and increased abstinence from cannabis by 0·27 days per week (−0·09 to 0·64). Cannabidiol was well tolerated, with no severe adverse events recorded, and 77 (94%) of 82 participants completed treatment. Interpretation In the first randomised clinical trial of cannabidiol for cannabis use disorder, cannabidiol 400 mg and 800 mg were safe and more efficacious than placebo at reducing cannabis use. Funding Medical Research Council.

Summary Plasmodium infection begins with the bite of an anopheline mosquito, when sporozoites along with saliva are injected into a vertebrate host. The role of the host responses to mosquito saliva components in malaria remains unclear. We observed that antisera against Anopheles gambiae salivary glands partially protected mice from mosquito-borne Plasmodium infection. Specifically, antibodies to A. gambiae TRIO (AgTRIO), a mosquito salivary gland antigen, contributed to the protection. Mice administered AgTRIO antiserum showed lower Plasmodium liver burden and decreased parasitemia when exposed to infected mosquitoes. Active immunization with AgTRIO was also partially protective against Plasmodium berghei infection. A combination of AgTRIO antiserum and antibodies against Plasmodium circumsporozoite protein, a vaccine candidate, further decreased P. berghei infection. In humanized mice, AgTRIO antiserum afforded some protection against mosquito-transmitted Plasmodium falciparum . AgTRIO antiserum reduced the movement of sporozoites in the murine dermis. AgTRIO may serve as an arthropod-based target against Plasmodium to combat malaria.

In March 2020, the ‘Everyone In’ initiative was introduced by the UK government as a public health response to COVID-19. This initiative sought to temporarily accommodate people experiencing rough sleeping in hotels in all local authority areas throughout England. In London, ‘Everyone In’ involved the procurement of vacant accommodation in over 100 hotels and temporarily re-housed approximately 2000 individuals. A rapid qualitative study was undertaken within two hotels to explore experiences of the initiative from the perspective of people accommodated in the hotels. This article describes how standard qualitative methods were adapted and implemented to complete the study whilst meeting COVID-19 social distancing guidelines. The research involved a longitudinal design of a two-stage qualitative interview that sought to capture residents’ experience of ‘Everyone In’ at two points in time (while in the hotel and when residents had left the hotel). Adapted qualitative methods were employed by a team of 13 researchers. These adaptations included socially distanced leaflet dropping, telephone-based participant recruitment, a remote, multistage, longitudinal qualitative telephone interviewing and rapid framework analysis. 35 hotel residents were recruited into the study (two subsequently withdrew participation). A total of 299 (of a possible 330) short interviews were completed by 33 participants (26 male and 7 female) as part of the multi-stage, longitudinal design of the study. This study indicates that adapted qualitative research methods employed during a pandemic can be successfully applied to obtain insights and experiences (of individuals and groups) otherwise difficult to reach and/or complex to understand.