Francois Olivier Hebert

Background: Cannabidiol (CBD) is widely consumed in low-dose products. However, evidence for its psychotropic effects at non-clinical doses is sparse and inconsistent. Aims: To characterise the acute behavioural effects of low-dose synthetic CBD in healthy volunteers. We hypothesised that 200 mg of CBD would produce a greater peak pleasant drug effect than a placebo. Methods: In a triple-blind, randomised, crossover trial at the CHUM research centre, Montreal, Canada, 70 healthy occasional cannabis users received single oral doses of 20, 50, 100 and 200 mg synthetic CBD and placebo immediately after a high-fat meal. The primary outcome, a participant-rated visual analogue scale of pleasant drug effect (0–100), was assessed at five timepoints post-dosing during each visit. Other measurements included additional participant ratings of drug effects, as well as positive and negative affect, dissociation, anxiety, blood pressure, heart rate, and respiratory rate. Results: Two hundred milligrams of synthetic CBD dose produced an average 12.8% [95% CI = 3.8% to 21.8%] higher peak pleasant drug effect score compared to placebo (Cohen’s d = 0.479 [0.089 to 0.869], p _corr = 0.044). No other dose of CBD showed a significant effect for the primary outcome versus placebo. All adverse events were mild or moderate in severity. Conclusions: The highest dose of CBD tested produced a slight but perceptible pleasurable subjective drug effect. This effect may differ based on prandial state and in clinical populations and populations with heavier cannabis use. Single doses of 100 mg synthetic CBD or less are unlikely to produce any discernible psychoactive effect in healthy, occasional users. Clinical trial registration: The study was registered on ClinicalTrials.gov (NCT05407285).

Background: Cannabidiol (CBD), a phytocannabinoid produced by Cannabis sativa , is widely consumed and interacts with components of the endocannabinoid system, including enzymes and receptors, through indirect and complex mechanisms. However, how CBD influences endogenous cannabinoids such as anandamide (AEA), and related N-acylethanolamines like N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA), remains poorly understood. This study investigates the acute impact of marketed CBD doses on the plasmatic levels of these signaling lipids in occasional cannabis users, addressing a critical gap in understanding the biological effects of low-dose CBD in non-therapeutic contexts. Methods: In a triple-blind, placebo-controlled, randomized crossover trial, 70 healthy volunteers received ten sequences of four oral CBD doses (20, 50, 100, 200 mg) and placebo. Blood was sampled at baseline and five timepoints post-dose. Plasma AEA, PEA, and OEA were quantified by LC–MS, and dose–response assessed with linear mixed-effects models on plasma concentrations (model 1) and Area Under the Curve to increase (AUCi, model 2), including participant ID (nested in sequence) as random effect, and visit, sequence, sex, and baseline levels as fixed effects. Results: Model 2 revealed a significant effect of CBD dose on AUCi of PEA and OEA, but not AEA. Pairwise comparisons showed that placebo was associated with significantly higher AUCi values than the 50 mg dose ( p < 0.05; moderate effect sizes), and trended higher than the 200 mg dose ( p < 0.10; small-to-moderate effect sizes). No differences were observed for other dose contrasts. Importantly, sex emerged as a significant factor: sub-group analyses indicated that these reductions in AUCi were driven by female participants, with lower PEA and OEA exposure confirmed at both 50 mg and 200 mg (only PEA) compared to placebo. No corresponding effects were observed in males. All plasma levels decreased overall throughout each visit, at every dose of CBD and placebo. Conclusions: This study revealed that among healthy adults who consume cannabis occasionally, low-dose oral CBD formulations were able to significantly decrease the cumulative plasma levels of PEA and OEA in a female-specific fashion, confirming the importance of sex-differences in cannabinoid response, and emphasizing the relevance of a personalized approach to cannabis consumption and its effects, as well as public health messaging. Trial registration: (ClinicalTrials.gov, registration: NCT05407285, Registration date: 2022–06-02).

Cannabis sativa is increasingly being grown around the world for medicinal, industrial, and recreational purposes. As in all cultivated plants, cannabis is exposed to a wide range of pathogens, including powdery mildew (PM). This fungal disease stresses cannabis plants and reduces flower bud quality, resulting in significant economic losses for licensed producers. The Mildew Locus O ( MLO ) gene family encodes plant-specific proteins distributed among conserved clades, of which clades IV and V are known to be involved in susceptibility to PM in monocots and dicots, respectively. In several studies, the inactivation of those genes resulted in durable resistance to the disease. In this study, we identified and characterized the MLO gene family members in five different cannabis genomes. Fifteen Cannabis sativa MLO ( CsMLO ) genes were manually curated in cannabis, with numbers varying between 14, 17, 19, 18, and 18 for CBDRx, Jamaican Lion female, Jamaican Lion male, Purple Kush, and Finola, respectively (when considering paralogs and incomplete genes). Further analysis of the CsMLO genes and their deduced protein sequences revealed that many characteristics of the gene family, such as the presence of 7 transmembrane domains, the MLO functional domain, and particular amino acid positions, were present and well conserved. Phylogenetic analysis of the MLO protein sequences from all five cannabis genomes and other plant species indicated seven distinct clades (I through VII), as reported in other crops. Expression analysis revealed that the CsMLOs from clade V, CsMLO1 and CsMLO4 , were significantly upregulated following Golovinomyces ambrosiae infection, providing preliminary evidence that they could be involved in PM susceptibility. Finally, the examination of variation within CsMLO1 and CsMLO4 in 32 cannabis cultivars revealed several amino acid changes, which could affect their function. Altogether, cannabis MLO genes were identified and characterized, among which candidates potentially involved in PM susceptibility were noted. The results of this study will lay the foundation for further investigations, such as the functional characterization of clade V MLOs as well as the potential impact of the amino acid changes reported. Those will be useful for breeding purposes in order to develop resistant cultivars.

We present five cases of pediatric drug-resistant epilepsy (DRE) that failed management using high cannabidiol (CBD) doses, but had significant reduction in seizure frequency with reintroduction or increasing doses of tetrahydrocannabinol (THC). There is growing evidence supporting the use of whole-plant CBD-rich extracts (containing THC and other cannabinoids) in the treatment of pediatric DRE. Based on our experiences and reports in the literature, we propose that, in patients who fail management with an initial trial of high-dose CBD-focused therapy, there may be a role for add-on THC-focused formulations.

Because they generate more wood per area and time, short rotation plantations are likely to play an increasing role in meeting the global increase in the demand for wood fiber. To be successful, high-yield plantations require costly intensive silviculture regimes to ensure the survival and maximize yields. While hybrid poplar (Populus spp.) is frequently used in intensive, short rotation forestry, it is particularly sensitive to competition and resource levels. Mechanical site preparation is thus of great importance to create microsites that provide sufficient light levels and adequate soil water and nutrient availability. We conducted an experiment in Québec (Canada) to compare two intensive site preparation treatments commonly used to establish hybrid poplar. We compared the effects of double-blade site preparation (V-blade), mounding and a control on hybrid poplar growth and nutritional status four growing seasons after planting on recently harvested forested sites. We also evaluated the effects of site preparation and planted poplar on inorganic soil N. Our results confirmed general positive effects of site preparation on the early growth of hybrid poplar clones. After four growing seasons, survival was higher in the mounding treatment (99%) than in the V-blade (91%) and the control (48%). Saplings planted in the V-blade and in the mounding treatments had mean diameters that were respectively 91% and 155% larger than saplings planted in the control plots. Saplings were 68% taller in the mounding treatment than the control plots, but differences between the V-blade and controls were not significant. We did not detect significant effects of site preparation or the presence of planted hybrid poplar on soil inorganic N. Sapling foliar nutrient concentrations were not influenced by the site preparation treatments. Based on these results, mounding appears to be a good management approach to establish hybrid poplar plantations under the ecological conditions we have studied, as it is less likely to cause erosion because of the localized nature of the treatment. However, these environmental benefits need to be balanced against economic and social considerations.

Many parasites with complex life cycles modify their intermediate hosts’ behaviour, presumably to increase transmission to their final host. The threespine stickleback ( Gasterosteus aculeatus ) is an intermediate host in the cestode Schistocephalus solidus life cycle, which ends in an avian host, and shows increased risky behaviours when infected. We studied brain gene expression profiles of sticklebacks infected with S . solidus to determine the proximal causes of these behavioural alterations. We show that infected fish have altered expression levels in genes involved in the inositol pathway. We thus tested the functional implication of this pathway and successfully rescued normal behaviours in infected sticklebacks using lithium exposure. We also show that exposed but uninfected fish have a distinct gene expression profile from both infected fish and control individuals, allowing us to separate gene activity related to parasite exposure from consequences of a successful infection. Finally, we find that Selective Serotonin Reuptake Inhibitor (SSRI)-treated sticklebacks and infected fish do not have similarly altered gene expression, despite their comparable behaviours, suggesting that the serotonin pathway is probably not the main driver of phenotypic changes in infected sticklebacks. Taken together, our results allow us to predict that if S . solidus directly manipulates its host, it could target the inositol pathway.

Glossy buckthorn (Frangula alnus Mill.) is an alien species in Canada that is invading many forested areas. Glossy buckthorn has impacts on the biodiversity and productivity of invaded forests. Currently, we do not know much about the species’ ecology and no thorough study of its distribution in temperate forests has been performed yet. As is often the case with invasive plant species, the phenology of glossy buckthorn differs from that of other indigenous plant species found in invaded communities. In the forests of eastern Canada, the main phenological difference is a delay in the shedding of glossy buckthorn leaves, which occurs later in the fall than for other indigenous tree species found in that region. Therefore, our objective was to use that phenological characteristic to map the spatial distribution of glossy buckthorn over a portion of southern Québec, Canada, using remote sensing-based approaches. We achieved this by applying a linear temporal unmixing model to a time series of the normalized difference vegetation index (NDVI) derived from Landsat 8 Operational Land Imager (OLI) images to create a map of the probability of the occurrence of glossy buckthorn for the study area. The map resulting from the temporal unmixing model shows an agreement of 69% with field estimates of glossy buckthorn occurrence measured in 121 plots distributed over the study area. Glossy buckthorn mapping accuracy was limited by evergreen species and by the spectral and spatial resolution of the Landsat 8 OLI.

The social environment encountered early during development can temporarily or permanently influence life history decisions and behaviour of individuals and correspondingly shape molecular pathways. In the highly social cichlid fish Neolamprologus pulcher, deprivation of brood care permanently affects social behaviour and alters the expression of stress axis genes in juveniles and adults. It is unclear when gene expression patterns change during early life depending on social experience, and which genes are involved. We compared brain gene expression of N. pulcher at two time points during the social experience phase when juveniles were reared either with or without brood care, and one time point shortly afterwards. We compared (a) whole transcriptomes and (b) expression of 79 genes related to stress regulation, in order to define a neurogenomic state of stress for each fish. At developmental day 75, that is, after the social experience phase, 43 genes were down‐regulated in fish having experienced social deprivation, while two genes involved in learning and memory and in post‐translational modifications of proteins (PTM), respectively, were up‐regulated. Down‐regulated genes were mainly associated with immunity, PTM and brain function. In contrast, during the experience phase no genes were differentially expressed when assessing the whole transcriptome. When focusing on the neurogenomic state associated with the stress response, we found that individuals from the two social treatments differed in how their brain gene expression profiles changed over developmental stages. Our results indicate that the early social environment influences the transcriptional activation in fish brains, both during and after an early social experience, possibly affecting plasticity, immune system function and stress axis regulation.

Two subspecies of Asian gypsy moth (AGM), Lymantria dispar asiatica and L. dispar japonica, pose a serious alien invasive threat to North American forests. Despite decades of research on the ecology and biology of this pest, limited AGM-specific genomic resources are currently available. Here, we report on the genome sequences and functional content of these AGM subspecies. The genomes of L.d. asiatica and L.d. japonica are the largest lepidopteran genomes sequenced to date, totaling 921 and 999 megabases, respectively. Large genome size in these subspecies is driven by the accumulation of specific classes of repeats. Genome-wide metabolic pathway reconstructions suggest strong genomic signatures of energy-related pathways in both subspecies, dominated by metabolic functions related to thermogenesis. The genome sequences reported here will provide tools for probing the molecular mechanisms underlying phenotypic traits that are thought to enhance AGM invasiveness.