Influence of bioaugmentation and biostimulation on PAH degradation in aged contaminated soils: Response and dynamics of the bacterial community.

Polycyclic aromatic hydrocarbons (PAHs) represent a group of hazardous compounds that are ubiquitous and persistent. The main aim of this study was to investigate the degradation of PAHs in chronically contaminated, aged and weathered soils obtained from a former gas plant of Australia. Biostimulation and bioaugmentation using individual isolates (Rhodococcus sp. (NH2), Achromobacter sp. (NH13), Oerskovia paurometabola (NH11), Pantoea sp. (NH15), Sejongia sp. (NH20), Microbacterium maritypicum (NH30) and Arthrobacter equi (NH21)) and a consortium of these isolates were tested during mesocosm studies. A significant reduction (99%) in PAH concentration was observed in all the treatments. In terms of the abundance of PAH-degrading genes and microbial community structure during PAH degradation, qPCR results revealed that Gram-positive bacteria were dominant over other bacterial communities in all the treatments. 16S sequencing results revealed that the inoculated organisms did not establish themselves during the treatment. However, substantial bacterial community changes during the treatments were observed, suggesting that the natural community exhibited sufficient resilience and diversity to enable an active, but changing degrading community at all stages of the degradation process. Consequently, biostimulation is proposed as the best strategy to remediate PAHs in aged, weathered and chronically contaminated soils.

Spatial Distribution of Novel and Legacy Brominated Flame Retardants in Soils Surrounding Two Australian Electronic Waste Recycling Facilities.

Informal recycling of electronic waste (e-waste) has been shown to cause significant brominated flame retardant (BFR) contamination of surrounding soils in a number of Asian and West African countries. However, to the authors' knowledge, there have been no published studies demonstrating polybrominated diphenyl ether (PBDE) and novel brominated flame retardant (NBFR) soil contamination from regulated "formal" e-waste processing facilities in developed countries. This study reports on PBDEs (-28, -47, -99, -100, -153, -154, -183, and -209) and NBFRs (PBT, PBEB, HBB, EH-TBB, BTBPE and DBDPE) in 36 soil samples surrounding two Australian e-waste recycling plants and a further eight reference soils. Overall ∑PBDE concentrations ranged 0.10-98 000 ng/g dw (median; 92 ng/g dw) and ∑NBFRs ranged ND-37 000 ng/g dw (median 2.0 ng/g dw). Concentrations in soils were found to be significantly negatively associated with distance from one of the e-waste facilities for ∑penta-BDEs, BDE-183, BDE-209, and ∑NBFR compound groups. ANOVA tests further illustrated the potential for e-waste recycling to significantly elevate concentrations of some BFRs in soils over distances up to 900 m compared to references sites. This study provides the first evidence of soil contamination with PBDEs and NBFRs originating from formal e-waste recycling facilities in Australia, which may have implications for e-waste recycling practices throughout the world.

Winery biomass waste degradation by sequential sonication and mixed fungal enzyme treatments.

To increase the efficiency of winery-derived biomass biodegradation, grape pomace was ultrasonicated for 20min in the presence of 0.25M, 0.5Mand1.0MKOH and 1.0MNaOH. This was followed by treatment with a 1:1 (v/v) mix of crude enzyme preparation derived from Phanerochaete chrysosporium and Trametes versicolor for 18h and a further 18h treatment with a 60:14:4:2 percent ratio combination of enzymes derived from Aspergillus niger: Penicillium chrysogenum: Trichoderma harzianum: P. citrinum, repsectively. Process efficiency was evaluated by its comparison to biological only mixed fungal degradation over 16days. Ultrasonication treatment with 0.5MKOH followed by mixed enzyme treatment yielded the highest lignin degradation of about 13%. Cellulase, ß-glucosidase, xylanase, laccase and lignin peroxidase activities of 77.9, 476, 5,390.5, 66.7 and 29,230.7U/mL, respectively, were observed during biomass degradation. Gas chromatography-mass spectrometry (GC-MS) analysis of the degraded material identified commercially important compounds such as gallic acid, lithocholic acid, glycolic acid and lactic acid which were generated in considerable quantities. Thus, the combination of sonication pre-treatment and enzymatic degradation has the potential to considerably improve the breakdown of agricultural biomass and produce commercially useful compounds in markedly less time (<40h) with respect to biological only degradation (16days).

Chemometric Analysis of Lavender Essential Oils Using Targeted and Untargeted GC-MS Acquired Data for the Rapid Identification and Characterization of Oil Quality.

Standard raw material test methods such as the ISO Standard 11024 are focused on the identification of lavender oil and not the actual class/quality of the oil. However, the quality of the oil has a significant effect on its price at market. As such, there is a need for raw material tests to identify not only the type of oil but its quality. This paper describes two approaches to rapidly identifying and classifying lavender oil. First, the ISO Standard 11024 test method was evaluated in order to determine its suitability to assess lavender oil quality but due to its targeted and simplistic approach, it has the potential to miss classify oil quality. Second, utilizing the data generated by the ISO Standard 11024 test methodology, an untargeted chemometric predicative model was developed in order to rapidly assess and characterize lavender oils (Lavandulaangustifolia L.) for geographical/environmental adulteration that impact quality. Of the 170 compounds identified as per the ISO Standard 11024 test method utilizing GC-MS analyses, 15 unique compounds that greatly differentiate between the two classes of lavender were identified. Using these 15 compounds, a predicative multivariate chemometric model was developed that enabled lavender oil samples to be reliably differentiated based on quality. A misclassification analysis was performed and it was found that the predictions were sound (100% matching rate). Such an approach will enable producers, distributers, suppliers and manufactures to rapidly screen lavender essential oil. The authors concede that the validation and implementation of such an approach is more difficult than a conventional chromatographic assay. However, the rapid, reliable and less problematic screening is vastly superior and easily justifies any early implementation validation difficulties and costs.

Chemical Pollutants Sorbed to Ingested Microbeads from Personal Care Products Accumulate in Fish.

The prevalence of microplastics (<5 mm) in natural environments has become a widely recognized global problem. Microplastics have been shown to sorb chemical pollutants from their surrounding environment, thus raising concern as to their role in the movement of these pollutants through the food chain. This experiment investigated whether organic pollutants sorbed to microbeads (MBs) from personal care products were assimilated by fish following particle ingestion. Rainbow fish (Melanotaenia fluviatilis) were exposed to MBs with sorbed polybrominated diphenyl ethers (PBDEs; BDE-28, -47, -100, -99, -153, -154, -183, 200 ng g(-1); BDE-209, 2000 ng g(-1)) and sampled at 0, 21, 42, and 63 days along with two control treatments (food only and food + clean MBs). Exposed fish had significantly higher Σ8PBDE concentrations than both control treatments after just 21 days, and continued exposure resulted in increased accumulation of the pollutants over the experiment (ca. 115 pg g(-1) ww d(-1)). Lower brominated congeners showed the highest assimilation whereas higher brominated congeners did not appear to transfer, indicating they may be too strongly sorbed to the plastic or unable to be assimilated by the fish due to large molecular size or other factors. Seemingly against this trend, however, BDE-99 did not appear to bioaccumulate in the fish, which may be due to partitioning from the MBs or it being metabolized in vivo. This work provides evidence that MBs from personal care products are capable of transferring sorbed pollutants to fish that ingest them.

A candidate reference method using ICP-MS for sweat chloride quantification.

BACKGROUND: The aim of the study was to develop a method for sweat chloride (Cl) quantification using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) to present to the Joint Committee for Traceability in Laboratory Medicine (JCTLM) as a candidate reference method for the diagnosis of cystic fibrosis (CF). METHODS: Calibration standards were prepared from sodium chloride (NaCl) to cover the expected range of sweat Cl values. Germanium (Ge) and scandium (Sc) were selected as on-line (instrument based) internal standards (IS) and gallium (Ga) as the off-line (sample based) IS. The method was validated through linearity, accuracy and imprecision studies as well as enrolment into the Royal College of Pathologists of Australasia Quality Assurance Program (RCPAQAP) for sweat electrolyte testing. RESULTS: Two variations of the ICP-MS method were developed, an on-line and off-line IS, and compared. Linearity was determined up to 225 mmol/L with a limit of quantitation of 7.4 mmol/L. The off-line IS demonstrated increased accuracy through the RCPAQAP performance assessment (CV of 1.9%, bias of 1.5 mmol/L) in comparison to the on-line IS (CV of 8.0%, bias of 3.8 mmol/L). Paired t-tests confirmed no significant differences between sample means of the two IS methods (p=0.53) or from each method against the RCPAQAP target values (p=0.08 and p=0.29). CONCLUSIONS: Both on and off-line IS methods generated highly reproducible results and excellent linear comparison to the RCPAQAP target results. ICP-MS is a highly accurate method with a low limit of quantitation for sweat Cl analysis and should be recognised as a candidate reference method for the monitoring and diagnosis of CF. Laboratories that currently practice sweat Cl analysis using ICP-MS should include an off-line IS to help negate any pre-analytical errors.

Bioremediation potential of diesel-contaminated Libyan soil.

Bioremediation is a broadly applied environmentally friendly and economical treatment for the clean-up of sites contaminated by petroleum hydrocarbons. However, the application of this technology to contaminated soil in Libya has not been fully exploited. In this study, the efficacy of different bioremediation processes (necrophytoremediation using pea straw, bioaugmentation and a combination of both treatments) together with natural attenuation were assessed in diesel contaminated Libyan soils. The addition of pea straw was found to be the best bioremediation treatment for cleaning up diesel contaminated Libyan soil after 12 weeks. The greatest TPH degradation, 96.1% (18,239.6mgkg(-1)) and 95% (17,991.14mgkg(-1)) were obtained when the soil was amended with pea straw alone and in combination with a hydrocarbonoclastic consortium respectively. In contrast, natural attenuation resulted in a significantly lower TPH reduction of 76% (14,444.5mgkg(-1)). The presence of pea straw also led to a significant increased recovery of hydrocarbon degraders; 5.7log CFU g(-1) dry soil, compared to 4.4log CFUg(-1) dry soil for the untreated (natural attenuation) soil. DGGE and Illumina 16S metagenomic analyses confirm shifts in bacterial communities compared with original soil after 12 weeks incubation. In addition, metagenomic analysis showed that original soil contained hydrocarbon degraders (e.g. Pseudoxanthomonas spp. and Alcanivorax spp.). However, they require a biostimulant (in this case pea straw) to become active. This study is the first to report successful oil bioremediation with pea straw in Libya. It demonstrates the effectiveness of pea straw in enhancing bioremediation of the diesel-contaminated Libyan soil.

Biosurfactant from red ash trees enhances the bioremediation of PAH contaminated soil at a former gasworks site.

Polycyclic aromatic hydrocarbons (PAHs) are persistent contaminants that accumulate in soil, sludge and on vegetation and are produced through activities such as coal burning, wood combustion and in the use of transport vehicles. Naturally occurring surfactants have been known to enhance PAH-removal from soil by improving PAH solubilization thereby increasing PAH-microbe interactions. The aim of this research was to determine if a biosurfactant derived from the leaves of the Australian red ash (Alphitonia excelsa) would enhance bioremediation of a heavily PAH-contaminated soil and to determine how the microbial community was affected. Results of GC-MS analysis show that the extracted biosurfactant was significantly more efficient than the control in regards to the degradation of total 16 US EPA priority PAHs (78.7% degradation compared to 62.0%) and total petroleum hydrocarbons (TPH) (92.9% degradation compared to 44.3%). Furthermore the quantification of bacterial genes by qPCR analysis showed that there was an increase in the number of gene copies associated with Gram positive PAH-degrading bacteria. The results suggest a commercial potential for the use of the Australian red ash tree as a source of biosurfactant for use in the accelerated degradation of hydrocarbons.

Assimilation of polybrominated diphenyl ethers from microplastics by the marine amphipod, Allorchestes compressa.

Microplastic particles (MPPs; <5 mm) are found in skin cleansing soaps and are released into the environment via the sewage system. MPPs in the environment can sorb persistent organic pollutants (POPs) that can potentially be assimilated by organisms mistaking MPPs for food. Amphipods (Allorchestes compressa) exposed to MPPs isolated from a commercial facial cleansing soap ingested ≤45 particles per animal and evacuated them within 36 h. Amphipods were exposed to polybrominated diphenyl ether (PBDEs) congeners (BDE-28, -47, -99, -100, -153, -154, and -183) in the presence or absence of MPPs. This study has demonstrated that PBDEs derived from MPPs can be assimilated into the tissue of a marine amphipod. MPPs reduced PBDE uptake compared to controls, but they caused greater proportional uptake of higher-brominated congeners such as BDE-154 and -153 compared to BDE-28 and -47. While MPPs in the environment may lower PBDE uptake compared to unabsorbed free chemicals, our study has demonstrated they can transfer PBDEs into a marine organism. Therefore, MPPs pose a risk of contaminating aquatic food chains with the potential for increasing public exposure through dietary sources. This study has demonstrated that MPPs can act as a vector for the assimilation of POPs into marine organisms.

Analysis of the volatile organic compounds from leaves, flower spikes, and nectar of Australian grown Agastache rugosa.

BACKGROUND: The foraging choices of honey bees are influenced by many factors, such as floral aroma. The composition of volatile compounds influences the bioactivity of the aromatic plants and honey produced from them. In this study, Agastache rugosa was evaluated as part of a project to select the most promising medicinal plant species for production of bioactive honey. METHODS: Headspace solid-phase microextraction HS-SPME /GC-MS was optimized to identify the volatile bioactive compounds in the leaves, flower spikes, and for the first time, the flower nectar of Australian grown A. rugosa. RESULTS: Methyl chavicol (= estragole) was the predominant headspace volatile compound in the flowers with nectar, flower spikes, and leaves, with a total of 97.16%, 96.74% and 94.35%, respectively. Current results indicate that HS-SPME/GC-MS could be a useful tool for screening estragole concentration in herbal products. CONCLUSION: Recently, estragole was suspected to be carcinogenic and genotoxic, according to the European Union Committee on Herbal Medicinal Products. Further studies are needed on safe daily intake of Agastache as herbal tea or honey, as well as for topical uses.

A novel method for reducing the effect of tonic muscle activity on the gamma band of the scalp EEG.

Neural oscillations in the gamma band are of increasing interest, but separating them from myogenic electrical activity has proved difficult. A novel algorithm has been developed to reduce the effect of tonic scalp and neck muscle activity on the gamma band of the EEG. This uses mathematical modelling to fit individual muscle spikes and then subtracts them from the data. The method was applied to the detection of motor associated gamma in two separate groups of eight subjects using different sampling rates. A reproducible increase in high gamma (65-85 Hz) magnitude occurred immediately after the motor action in the left central area (p = 0.02 and p = 0.0002 for the two cohorts with individually optimized algorithm parameters, compared to p = 0.03 and p = 0.16 before correction). Whilst the magnitude of this event-related gamma synchronisation was not reduced by the application of the EMG reduction algorithm, the baseline left central gamma magnitude was significantly reduced by an average of 23 % with a faster sampling rate (p < 0.05). In comparison, at left and right temporo-parietal locations the gamma amplitude was reduced by 60 and 54 % respectively (p < 0.05). The reduction of EMG contamination by fitting and subtraction of individual spikes shows promise as a method of improving the signal to noise ratio of high frequency neural oscillations in scalp EEG.

What can we learn about schizophrenia from studying the human model, drug-induced psychosis?

When drug-induced psychoses were first identified in the mid-20th century, schizophrenia was considered a discrete disease with a likely genetic cause. Consequently, drug-induced psychoses were not considered central to understanding schizophrenia as they were thought to be phenocopies rather than examples of the illness secondary to a particular known cause. However, now that we know that schizophrenia is a clinical syndrome with multiple component causes, then it is clear that the drug-induced psychoses have much to teach us. This article shows how the major neuropharmacological theories of schizophrenia have their origins in studies of the effects of drugs of abuse. Research into the effects of LSD initiated the serotonergic model; amphetamines the dopamine hypothesis, PCP and ketamine the glutamatergic hypothesis, while most recently the effects of cannabis have provoked interest in the role of endocannabinoids in schizophrenia. None of these models account for the complete picture of schizophrenia; rather the various drug models mimic different aspects of the illness. Determining the different molecular effects of those drugs whose pharmacological effects do and do not mimic the various aspects of schizophrenia has much to teach us concerning the pathogenesis of the illness.

Cannabis, the mind and society: the hash realities.

Cannabis has been known for at least 4,000 years to have profound effects on the mind--effects that have provoked dramatically divergent attitudes towards it. Some societies have regarded cannabis as a sacred boon for mankind that offers respite from the tribulations of everyday life, whereas others have demonized it as inevitably leading to 'reefer madness'. The debate between the protagonists and prohibitionists has recently been re-ignited, but unfortunately this debate continues mainly in ignorance of our new understanding of the effects of cannabis on the brain and of studies that have quantified the extent of the risks of long-term use.

Characterization of tetra-aryl benzene isomers by using preparative gas chromatography with mass spectrometry, nuclear magnetic resonance spectroscopy, and X-ray crystallographic methods.

The present study describes a preparative gas chromatographic (GC) approach employed to study a series of products arising from reaction of phenylacetylene with para-substituted aryl-iodides under Sonogashira catalysis conditions. GC analysis resolves the isomers from each reaction; however, it cannot provide structural details (their MS data are virtually identical). Since classical liquid chromatography cannot resolve the isomers, preparative-scale GC is the only practical approach to provide further spectroscopic characterization of the isomers. The products are well separated by GC so a single thick-film capillary column is adequate for this case, with operation up to approximately +300 degrees C. By collection of 50+ repeat injections, sufficient material could be isolated for (1)H NMR spectral analysis of the isomers, and for one isomer (isomer I) of a number of analogous related catalytic reaction mixtures, X-ray crystal structure determination enabled complete structural elucidation (absolute configuration) of the substitution pattern of the structure of this isomer. This confirmed isomer I to be the 2-para-aryl-substituted 1,3,5-triphenylbenzene product in all cases. (1)H NMR spectra of isomer I products generally had similar patterns but differed markedly from the second major isomer product (isomer II).

Cannabis points to the synaptic pathology of mental disorders: how aberrant synaptic components disrupt the highest psychological functions
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Cannabis can elicit an acute psychotic reaction, and its long-term use is a risk factor for schizophrenia. The main active psychoactive ingredient ∆9-tetrahydrocannabinol (Δ9-THC) activates cannabinoid 1 (CB1) receptors, which are localized to the terminals of glutamate and GABA neurons in the brain. The endogenous cannabinoids are involved in information processing and plasticity at synapses in the hippocampus, basal ganglia, and cerebral cortex. Exogenously applied CB1 receptor agonists disrupt neuronal dynamics and synaptic plasticity, resulting in cognitive deficits and impairment of the highest psychological functions. Various other pro-psychotic drugs, such as ketamine and methamphetamine, exert their effects in the same microdomain of synaptic spines as Δ9-THC. Additionally, many of the most robust findings in psychiatric genetics include components that localize to dendritic spines and have important roles in information processing and plasticity.
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La cannabis puede provocar una reacción psicótica aguda y su empleo a largo plazo es un factor de riesgo para esquizofrenia. El principal componente psicoactivo ∆9-tetrahidrocannabinol (Δ9-THC) estimula los receptores cannabinoides CB1, que se localizan en las terminales de las neuronas de glutamato y de GABA cerebrales. Los cannabinoides endógenos participan en el procesamiento de la información y la plasticidad en las sinapsis del hipocampo, los ganglios basales y la corteza cerebral. Los agonistas de CB1 administrados de forma exógena interrumpen la dinámica neuronal y la plasticidad sináptica, lo que se traduce en déficits cognitivos y deterioro de las funciones psicológicas más altas. Varias otras drogas propsicóticas, como la ketamina y la metanfetamina, ejercen sus efectos en el mismo microdominio de espinas sinápticas que el Δ9-THC. Además, muchos de los hallazgos más consistentes en genética psiquiátrica incluyen componentes que se localizan en las espinas dendríticas y tienen funciones importantes en el procesamiento y la plasticidad de la información.

Le cannabis peut provoquer une réaction psychotique aiguë et sa consommation à long terme est un facteur de risque de schizophrénie. Le ∆9-tétrahydrocannabinol (Δ9-THC), principal ingrédient psychoactif, active les récepteurs cannabinoïdes CB1 situés aux extrémités des neurones glutamatergiques et GABAergiques dans le cerveau. Les cannabinoïdes endogènes participent au traitement de l'information et à la plasticité des synapses dans l'hippocampe, les ganglions de la base et le cortex cérébral. Les agonistes CB1 exogènes perturbent la dynamique neuronale et la plasticité synaptique, entraînant des déficits cognitifs et une altération des fonctions psychologiques les plus hautes. D'autres drogues propsychotiques, telles la kétamine et la méthamphétamine, agissent dans le même micro-domaine des épines synaptiques que le Δ9-THC. De plus, de nombreuses recherches en génétique psychiatrique ont mis en évidence des composés qui jouent un rôle important dans le traitement de l'information et la plasticité en se fixant sur les épines dendritiques.

Trace metal biomonitoring in the east Gippsland Lakes estuary using the barnacle Amphibalanus variegatus and mussel Mytilus edulis.

The Gippsland Lakes estuary, a Ramsar listed wetland, in Victoria, Australia, is an area of potential concern for metal pollution due to influxes of human population and associated anthropogenic activities. A biomonitoring exercise was undertaken where the concentrations of 9 metals (Cr, Fe, Cu, Zn, As, Se, Ag, Cd and Hg) were analysed in the soft tissue of two common sessile invertebrates: the mussel Mytilus edulis and the barnacle Amphibalanus variegatus from 6 locations on two different occasions throughout the Gippsland Lakes estuary. A salinity gradient exists in the Lakes, from seawater at Lakes Entrance in the east, decreasing down to < 10 PSU in the west at Lake Wellington during times of rainfall, which is a major factor governing the growth and distribution of both species. Dissolved metal levels in general were low; however, Cu at most sites exceeded the 90% trigger values, while all Zn concentrations exceeded the lowest 80% trigger values of the ANZECC marine water quality guidelines for environmental health. Elevated levels of Cu and Zn were found particularly in barnacles at some sites with environmental contamination due to leaching from anti fouling paints and sacrificial zinc anodes. Elevated levels of Ag and Cd were found in mussels at the Hollands Landing site, which is immediately adjacent to a boat ramp, and Cd and Ag at this site are suspected to originate from inland anthropogenic sources. Concentrations of As in M. edulis across all 6 sites in both sampling periods had mean wet weight As concentrations exceeding the maximum level stated in the FSANZ guidelines. A. variegatus contained elevated levels of Hg especially at the North Arm site with a maximum of 13.6 µg Hg/g dry wt., while A. variegatus also showed temporal changes in Hg concentrations across sites. The maximum Hg concentration found in Mytilus edulis was 1.49 µg Hg/g dry wt. at the Hollands Landing site. Previous contaminant studies of biota in the Lakes have targeted sampling of singular predatory or migratory species, such as Black Bream (Acanthopagrus butcheri) and the Burrunan dolphin (Tursiops australis). This is the first biomonitoring study conducted on sessile organisms to assess metal contamination in the system.

Synthetic cannabinoid use in psychiatric patients and relationship to hospitalisation: A retrospective electronic case register study.

INTRODUCTION AND OBJECTIVES: Cannabis use has been associated with psychosis and with poor outcome in patients with mental illness. Synthetic cannabinoids (SCs) have been suggested to pose an even greater risk to mental health, but the effect on clinical outcome has not been directly measured. In this study, we aimed to investigate the demographics and hospitalisation of psychiatric patients who were SC users. METHODS: We searched the Biomedical Research Centre Clinical Record Interactive Search register for SC users and age- and sex-matched SC non-users who had been psychiatric patients under the South London and Maudsley NHS Trust. We recorded diagnosis, homelessness, cannabis use and the total number of days admitted as an inpatient to secondary and tertiary mental-health services. RESULTS: We identified 635 SC users and 635 age- and sex-matched SC non-users. SC users were significantly more likely to be homeless (χ2=138.0; p<0.0001) and to use cannabis (χ2=257.3; p<0.0001) than SC non-users. SC users had significantly more inpatient days after their first recorded use of SCs than controls (M (SD)=85.5 (199.7) vs. 25.4 (92.32); p<0.0001). Post hoc tests revealed that SC non-users who used cannabis had fewer inpatient days than SC users (p<0.0001), and that non-users of both SC and cannabis had fewer inpatient days than SC non-using cannabis users (p=0.02). CONCLUSIONS: SC use may lead to an increase in the number of days spent in hospital in patients with psychiatric illness. This highlights the need for clinicians to ask specifically about SC use.

Cannabidiol for the treatment of cannabis use disorder: a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial.

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.