Cannabidiol (CBD), the second most prevalent phytocannabinoid in Cannabis sativa, potentially offers numerous therapeutic benefits without psychoactive effects. Research into CBD's therapeutic applications must be supported by an understanding of the time course of CBD concentrations in the body and how these concentrations relate to CBD's safety and efficacy. This study aimed to develop a simplified protocol for quantifying CBD, Δ9-Tetrahydrocannabinol (THC) and its metabolites in human plasma and urine, eliminating complex and time-consuming sample preparation, especially for urine samples, while maintaining accuracy comparable to traditional methods. This protocol was used to assess the influence of an oral capsule of CBD (BSPG CBD BRAINS Bioceutical laboratories) on the pharmacokinetics of CBD and its metabolites in plasma and urine relative to an FDA approved CBD formulation (Epidiolex®). The method development focused on optimizing mass spectrometry (MS) conditions with an ultra-high performance liquid chromatography (UHPLC) C18 column. Plasma and urine were collected at fourteen and eight time points, respectively, across 24 h and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify CBD and its metabolites. Additionally, (THC) and its metabolites were examined, with no detectable levels found in either plasma or urine. This newly developed analytical method successfully quantified CBD and its metabolites in both plasma and urine, contributing valuable data to the understanding of CBD pharmacokinetics in different oral products. This study's findings have important implications for optimizing CBD administration and assessing therapeutic outcomes.

Background: As cannabis legalization expands and professional sports organizations reassess cannabinoid policies, elite contact sport athletes are increasingly exposed to cannabis use for therapeutic, recovery, and recreational purposes. Despite these shifts, limited evidence-based education and persistent stigma may hinder informed decision-making and athlete-clinician communication. Hypothesis: Professional and elite-level contact sport athletes exhibit inconsistent knowledge and perspectives regarding cannabis use, shaped by stigma, inadequate education, and regulatory ambiguity. Study Design: Qualitative descriptive study. Level of Evidence: Level 4. Methods: A total of 10 semi-structured interviews were conducted with current or former elite contact sport athletes from professional and collegiate leagues, including the National Hockey League, National Football League, National Basketball Association, American Hockey League, National Collegiate Athletic Association, and USports. Interviews explored athletes’ knowledge, attitudes, and experiences related to cannabis and cannabinoid products in sport. Transcripts were analyzed using Braun and Clarke’s 6-step thematic analysis framework to identify recurring patterns and themes. Results: A total of 5 primary themes emerged: (1) athletes use cannabis; (2) insufficient education and lack of credible information sources; (3) persistent stigma and fear of judgment; (4) limited trust and communication with medical staff; and (5) inconsistency in laws, policies, and organizational responses. Athletes reported cannabis use for pain management, sleep, recovery, and mental health, typically with deliberate control over dosage, timing, and administration methods. Across interviews, participants emphasized the need for accessible, evidence-based education for both athletes and medical personnel. Conclusion: Elite contact sport athletes use cannabis intentionally for recreational, therapeutic, and recovery purposes but face systemic barriers related to misinformation, stigma, and inconsistent policy guidance. Enhancing athlete and clinician education and standardizing cannabis-related regulations across leagues may support safer, evidence-informed practices. Clinical Relevance: This study identifies critical educational and policy gaps regarding cannabis in elite sport and underscores the need for multidisciplinary collaboration to guide responsible cannabinoid use among athletes.

Objective:This study investigates the efficacy of 20:1 cannabidiol:tetrahydrocannabinol (CBD:THC) cannabis herbal extract (CHE) in reducing pain and improving mobility in dogs undergoing tibial plateau leveling osteotomy (TPLO) for cranial cruciate ligament rupture (CCLr). Methods:Forty-eight dogs were enrolled in a randomized, double-blinded, placebo-controlled clinical trial at the Western College of Veterinary Medicine between December 2022 and October 2024. Dogs were assigned to one of the three treatment groups: placebo (flavored olive oil), 2 mg CBD (0.1 mg THC)/kg body weight (bw), or 5 mg CBD (0.25 mg THC)/kg bw. All dogs received a standard peri- and post-operative analgesic protocol consisting of opioids, nerve blocks, non-steroidal anti-inflammatory drugs (NSAIDs), and gabapentin. Veterinary assessments were performed on days +1 and +14 postoperatively and included Glasgow Composite Pain Scores (GCPS), stifle range of motion (ROM), thigh and stifle circumference, and gait symmetry ratios. Owners were advised to complete a modified Canine Brief Pain Inventory (CBPI) on days +3, +7, and +14. Plasma cannabinoid concentrations on days 1 and 14 were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Data were analyzed using linear mixed models and generalized estimating equations. Results:Forty-two dogs completed the study. All dogs had marked improvement in owner-reported pain scores from days +1 to +14, regardless of treatment group. There were no significant differences in outcome measures between treatment groups. Potential treatment × day interactions were noted for ROM and gait symmetry; the high CHE dose group had marginally greater function on day +1, but none of these effects persisted to day +14. No serious adverse events were reported; mild gastrointestinal effects (vomiting or diarrhea) were noted in seven cases. Owners reported the CHE doses were generally well tolerated. Plasma cannabinoid concentrations were highly variable and did not correlate with clinical outcomes. Clinical significance:Overall, administration of an oral 20:1 CBD: THC cannabis herbal extract in addition to a standard analgesic protocol did not improve analgesia and limb function following TPLO surgery in dogs. Minor functional benefits may have occurred in the higher CHE dose group, but only on the first day following surgery. Current multimodal peri- and post-operative analgesic practices were effective, irrespective of CHE administration.

IntroductionCannabis holds therapeutic potential; however, activation of the type 1 cannabinoid receptor (CB1R) via Δ9-tetrahydrocannabinol (THC) is also responsible for the characteristic “high” induced by cannabis. The pharmacology of the less abundant phytocannabinoid, cannabigerol (CBG), is poorly established, though it has been shown to exhibit promising therapeutic properties such as potential anxiolytic effects.MethodsWe assessed the pharmacokinetics (PK) and pharmacodynamics (PD) of CBG in C57BL/6Crl mice, hypothesizing that CBG would produce fewer PD effects than we had previously observed with THC, even when accounting for PK differences. Following oral (p.o.), intraperitoneal (i.p.), and intravenous (i.v.) administration, the PK profile of CBG was assessed via blood sampling at specified time points (10 min, 30 min, 1 h, 3 h, 6 h, 12 h, 18 h, and 24 h). The blood concentrations of CBG were quantified by High-Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS). A separate cohort of mice was treated with CBG and tested for cataleptic, hypothermic, anti-nociceptive, and locomotor effects to correlate the PK profile of CBG with CBG’s observed PD effects.Results and DiscussionOur data reveal that CBG was not intoxicating, even when accounting for the route of administration and blood concentration. Our findings support previous reports that CBG is not intoxicating and reveal that even if CBG were present at sufficiently high concentrations in cannabis products, it would not produce intoxicating effects like those of THC.

Cannabidiol (CBD) is a phytocannabinoid without intoxicating properties. While CBD can improve neurophysiological functions and subjective symptoms, its effect on cognitive function remains unclear. We summarized the available randomized controlled trials investigating CBD administration and cognitive function. A review of the literature was conducted using the following keywords on PubMed/Medline: (cannabis OR cannabidiol OR cannabinoid OR CBD OR Δ 9 -tetrahydrocannabinol OR tetrahydrocannabinol) AND (neurology OR brain OR psychiatric OR neuroscience OR psychology OR cognition) AND (human) AND (randomized controlled trial OR RCT). The search yielded 1038 articles with 36 total included for this literature review. The articles included healthy participants, neurological disease, psychiatric disease, psychosis, paranoia, schizophrenia, and drug-use disorders. Studies with healthy participants included a variety of dosing strategies, suggesting an effect on cognitive function and sleep quality. In Parkinson's disease, 75-300 mg CBD resulted in mild improvements in daily life activities. Decreases in subjective anxiety were found in patients with psychiatric disease using CBD doses ranging from 300 to 400 mg. In patients with psychosis and paranoia, 600 mg CBD showed inconsistent results in cognitive function. In patients with schizophrenia, up to 1000 mg CBD per day had minimal effects on cognition. Finally, up to 800 mg CBD had minimal effects on cognitive function in patients with substance use disorders. The findings are limited by utilization of acute dosing, variations in CBD dose, and different routes of administration. Standardized dosing and CBD formulations are needed to assess its efficacy for improving cognition.

The increasing legalization of Cannabis sativa plant products has sparked growing interest in their therapeutic applications. Prohibition laws established in 1937 hindered formal research on cannabis, a plant with cultural and medicinal roots dating back to 2700 BC in Chinese history. Despite regulatory hurdles, published research on cannabis has emerged; yet elite athletes remain an underrepresented population in these studies. Athletes, known for exploring diverse substances to optimize performance, are drawn to the potential benefits of cannabinoid therapy, with anecdotal reports suggesting positive effects on issues ranging from anxiety to brain injuries. This review aims to evaluate empirical published cannabis research with a specific focus on its potential applications in athletics. The changing legal landscape, especially the removal of cannabis from drug testing programs in leagues such as the National Basketball Association (NBA), and endorsements by Major League Baseball (MLB) for cannabinoid products and the National Football League (NFL) for cannabis research, reflects a shift in the acceptability of such substances in sports. However, stigma, confusion, and a lack of education persist, hindering a cohesive understanding among sports organizations, including business professionals, policymakers, coaches, and medical/training staff, in addition to athletes themselves. Adding to the confusion is the lack of consistency with cannabinoid regulations from sport to sport, within or out of competition, and with cannabis bioactive compounds. The need for this review is underscored by the evolving attitudes toward cannabinoids in professional sports and the potential therapeutic benefits or harms they may offer. By synthesizing current cannabis research, this review aims to provide a comprehensive understanding of the applications and implications of cannabinoid use in the realm of athletics.

ObjectiveTo determine the pharmacokinetics (PK) of two oral doses of a Cannabis herbal extract (CHE) containing 1:20 THC:CBD in 12 healthy Domestic Shorthair cats.MethodsSingle-dose PK were assessed after oral administration of CHE at low or high dose (2 mg CBD + 0.1 mg THC, or 5 mg CBD + 0.25 mg THC per kg bw, respectively; n = 6 per group) in fasting cats. Blood samples were drawn up to 48 h following CHE administration. Plasma samples were analyzed for CBD, THC, and metabolites 6-OH-CBD, 7-OH-CBD, 11-OH-THC, and THC-COOH using a previously validated LC–MS/MS method.ResultsCBD and THC were quickly absorbed (mean Tmax of 2.4–2.9 h). Maximum plasma concentrations (Cmax) ranged from 36–511 ng/mL and 6.8–61 ng/mL for CBD and THC, respectively. Elimination was initially rapid for both CBD and THC, though a prolonged elimination phase was noted for CBD in some cats (T1/2 λ up to 26 h). Dose-adjusted Cmax and AUC0-last values were not statistically significantly different (p > 0.05) between dose groups indicating CBD and THC concentrations increased in a manner proportional (linear) to the dose. Dose-adjusted THC Cmax and AUC0-last were significantly higher than the corresponding dose-adjusted CBD parameters (p < 0.01). Low concentrations of the metabolite 6-OH-CBD were quantified but metabolites 7-OH-CBD, 11-OH-THC, and THC-COOH were not detected in any plasma samples. Inter-individual variance was notable. Salivation shortly after dosing was observed in two cats in the high dose group; these animals had substantially lower cannabinoid concentrations than other cats in this group. No adverse clinical signs (including vomiting, change in mentation or other neurological signs) were noted.Clinical significanceAlthough cats did not display adverse effects after administration of a single oral dose of 1:20 THC:CBD CHE formulation at 2 or 5 mg CBD/kg bw, observed plasma concentrations were highly variable but generally lower than in dogs receiving the same dose and formulation. Administration of CHE in the fasting state may not optimize CBD absorption, and oral dosing may be challenging when administering an oil-based CHE in some cats.

BackgroundCannabinoids such as cannabidiol (CBD) exhibit anti-inflammatory properties and have the potential to act as a therapeutic following mild traumatic brain injury. There is limited evidence available on the pharmacological, physiological and psychological effects of escalating CBD dosages in a healthy, male, university athlete population. Furthermore, no dosing regimen for CBD is available with implications of improving physiological function. This study will develop an optimal CBD dose based on the pharmacokinetic data in contact-sport athletes. The physiological and psychological data will be correlated to the pharmacokinetic data to understand the mechanism(s) associated with an escalating CBD dose.Methods/designForty participants will receive escalating doses of CBD ranging from 5 mg CBD/kg/day to 30 mg CBD/kg/day. The CBD dose is escalated every two weeks in increments of 5 mg CBD/kg/day. Participants will provide blood for pharmacological assessments at each of the 10 visits. Participants will complete a physiological assessment at each of the visits, including assessments of cerebral hemodynamics, blood pressure, electrocardiogram, seismocardiogram, transcranial magnetic stimulation, and salivary analysis for genomic sequencing. Finally, participants will complete a psychological assessment consisting of sleep, anxiety, and pain-related questionnaires.DiscussionThis study will develop of an optimal CBD dose based on pharmacological, physiological, and psychological properties for future use during contact sport seasons to understand if CBD can help to reduce the frequency of mild traumatic injuries and enhance recovery.Trial registrationClinicaltrials.gov: NCT06204003.

INTRODUCTION:Cannabis products have been used in the management of headaches in adults and may play a role in pediatric chronic pain. Canadian pediatricians report increasing use of cannabis for the management of chronic headaches, despite no well-controlled studies to inform its dosing, safety, and effectiveness. The aim of our clinical trial is to determine the dosing and safety of a Cannabidiol (CBD)-enriched Cannabis Herbal Extract (CHE) for the treatment of chronic headaches in adolescents. METHODS AND ANALYSIS:Youth, parents, and an expert steering committee co-designed this tolerability study. Twenty adolescents (aged 14 to 17 years), with a chronic migraine diagnosis for more than 6 months that has not responded to other therapies will be enrolled into an open label, dose escalation study across three Canadian sites. Study participants will receive escalating doses of a CBD-enriched CHE (MPL-001 with a THC:CBD of 1:25), starting at 0.2-0.4 mg/kg of CBD per day and escalating monthly up to 0.8-1.0 mg/kg of CBD per day. The primary objective of this study is to determine the safety and tolerability of CBD-enriched CHE in adolescents with chronic migraine. Secondary objectives of this study will inform the development of subsequent randomized controlled trials and include investigating the relationship between the dose escalation and change in the frequency of headache, impact and intensity of pain, changes in sleep, mood, function, and quality of life. Exploratory outcomes include investigating steady-state trough plasma levels of bioactive cannabinoids and investigating how pharmacogenetic profiles affect cannabinoid metabolism among adolescents receiving CBD-enriched CHE. DISCUSSION:This protocol was co-designed with youth and describes a tolerability clinical trial of CBD-enriched CHE in adolescents with chronic headaches that have not responded to conventional therapies. This study is the first clinical trial on cannabis products in adolescents with chronic headaches and will inform the development of future comparative effectiveness clinical trials. TRIAL REGISTRATION:CAN-CHA trial is registered with ClinicalTrials.gov with a number of register NCT05337033.

ObjectiveTo quantify and characterize plasma cannabinoid concentrations in cases of suspected cannabis toxicity in dogs, identify potential correlations between clinical signs and plasma concentrations, and assess the specificity of cannabis toxicity diagnosis based on clinical signs alone.DesignObservational study.SettingVeterinary teaching hospital.AnimalsThirty-eight client-owned animals.InterventionsBlood was collected from dogs presenting to the emergency room for suspected cannabinoid intoxication based on history or physical examination findings. Samples were analyzed using a validated liquid chromatography-tandem mass spectrometry method for the cannabinoids Delta 9-tetrahydrocannabinol (THC), cannabidiol (CBD), and their active metabolites.Measurements and Main ResultsThe most common abnormality observed was ataxia (35/38 dogs), with urinary incontinence, lethargy, and hyperesthesia also commonly noted. Cannabinoids were quantifiable in 37 of 38 plasma samples (97.4%), with THC the predominant cannabinoid (range: 1.99-2748 ng/mL). Lower concentrations of CBD (up to 115.3 ng/mL) and cannabinoid metabolites were detected. Of the clinical signs recorded, only abnormal reflexes were statistically correlated with the THC concentration at the time of sampling (P = 0.01).ConclusionsA diagnosis of suspected cannabinoid toxicity based on case history and clinical presentation was confirmed via quantifiable plasma concentrations in nearly all cases. Although the range of plasma cannabinoid concentrations was broad, the clinical signs observed were generally similar. Other than the presence of abnormal reflexes, clinical signs were not associated with plasma THC concentrations. Subsequent confirmation of cannabinoids in plasma indicates that cannabis toxicity in dogs can be diagnosed with high specificity by veterinarians based only on history and clinical abnormalities.

Cardiolipin is a mitochondrial phospholipid that is also detected in serum inferring its extracellular release; however, this process has not been directly demonstrated for any of the brain cell types. Nevertheless, extracellular cardiolipin has been shown to modulate several neuroimmune functions of microglia and astrocytes, including upregulation of their endocytic activity. Low cardiolipin levels are associated with brain aging, and may thus hinder uptake of amyloid-β (Αβ) in Alzheimer's disease. We hypothesized that glial cells are one of the sources of extracellular cardiolipin in the brain parenchyma where this phospholipid interacts with neighboring cells to upregulate the endocytosis of Αβ. Liquid chromatography-mass spectrophotometry identified 31 different species of cardiolipin released from murine BV-2 microglial cells and revealed this process was accelerated by exposure to Aβ42. Extracellular cardiolipin upregulated internalization of fluorescently-labeled Aβ42 by primary murine astrocytes, human U118 MG astrocytic cells, and murine BV-2 microglia. Increased endocytic activity in the presence of extracellular cardiolipin was also demonstrated by studying uptake of Aβ42 and pHrodo™ Bioparticles™ by human induced pluripotent stem cells (iPSCs)-derived microglia, as well as iPSC-derived human brain organoids containing microglia, astrocytes, oligodendrocytes and neurons. Our observations indicate that Aβ42 augments the release of cardiolipin from microglia into the extracellular space, where it can act on microglia and astrocytes to enhance their endocytosis of Aβ42. Our observations suggest that the reduced glial uptake of Aβ due to the decreased levels of cardiolipin could be at least partially responsible for the extracellular accumulation of Aβ in aging and Alzheimer's disease.

Brain organoids have the potential to improve clinical translation, with the added benefit of reducing any extraneous use of experimental animals. As brain organoids are three-dimensional in vitro constructs that emulate the human brain, they bridge in vitro and in vivo studies more appropriately than monocultures. Although many factors contribute to the failure of extrapolating monoculture-based information to animal-based experiments and clinical trials, for the purpose of this review, we will focus on glia (non-neuronal brain cells), whose functions and transcriptome are particularly abnormal in monocultures. As discussed herein, glia require signals from-and contact with-other cell types to exist in their homeostatic state, which likely contributes to some of the differences between data derived from monocultures and data derived from brain organoids and even two-dimensional co-cultures. Furthermore, we highlight transcriptomic differences between humans and mice in regard to aging and Alzheimer's disease, emphasizing need for a model using the human genome-again, a benefit of brain organoids-to complement data derived from animals. We also identify an urgency for guidelines to improve the reporting and transparency of research using organoids. The lack of reporting standards creates challenges for the comparison and discussion of data from different articles. Importantly, brain organoids mark the first human model enabling the study of brain cytoarchitecture and development.

Medical cannabis (MC) may offer therapeutic benefits for children with complex neurological conditions and chronic diseases. In Canada, parents, and caregivers frequently report encountering barriers when accessing MC for their children. These include negative preconceived notions about risks and benefits, challenges connecting with a knowledgeable healthcare provider (HCP), the high cost of MC products, and navigating MC product shortages. In this manuscript, we explore several of these barriers and provide recommendations to decision-makers to enable a family-centered and evidence-based approach to MC medicine and research for children.

Objectives Implementing medical cannabis (MC) into a child's daily routine can be challenging and there is a lack of guidance for its therapeutic use in schools in Canada. Our objective was to learn about the experiences of caregivers of school-aged children who require MC. Methods Qualitative description was used and caregivers were interviewed about MC in schools and in general. The transcripts were entered into Dedoose software for qualitative analysis and content analysis was performed. Sentences and statements were ascribed line by line into meaning units and labelled with codes, and organized according to categories and subcategories. Results Twelve caregivers of school-aged children who take MC participated. The most common reasons for treatment were drug-resistant epilepsy (DRE), autism, or other developmental disorders. Approximately half of the participants' children (n = 6) took MC during the school day and most (5/6) perceived their experiences to be positive or neutral but reported a lack of knowledge about MC. While data saturation was not reached regarding MC in schools, rich dialogues were garnered about MC in general and three categories were identified: challenges (subcategories stigma, finding an authorizer, cost, dosing, and supply); parents as advocates (subcategories required knowledge, attitudes, skills, and sources of information); and caregiver relief for positive outcomes. Conclusions Caregivers demonstrate remarkable tenacity despite the many challenges associated with MC use. Education and practice change are needed to ensure that children using MC can benefit from or continue to experience its positive outcomes within the school environment and beyond.

Objectives Guidance is lacking for medical cannabis use in Canadian schools in both legislation and approach; the impact of ambiguous policy on patient care is unknown. A qualitative study was undertaken to explore the experiences of clinicians who care for school-aged children who take medical cannabis. Methods Semi-structured interviews were recorded and transcribed verbatim. Qualitative content analysis performed using the Dedoose qualitative software ascribed meaning units and codes, which were further consolidated into categories and subcategories. Results Thirteen physicians were interviewed virtually, representing seven provinces in Canada. The physicians provided care for between five and hundreds of school-aged children who took medical cannabis. The most common indications were refractory seizure disorders and autism. The interviews provided rich descriptions on perceptions of medical cannabis in schools, and in general. Five overarching categories were identified across both domains including variability, challenges (subcategories: lack of knowledge, stigma, lack of policy, and pragmatic challenges), potential solutions (subcategories: treat it like other medications, communication, education, and family support), positive experiences and improvements over time. Conclusion In Canada, cannabis-based medicine use in schools still faces important challenges. Effective education, communication, family support and policy refinements that allow cannabis to be treated like other prescription medications are recommended to improve the status quo. These findings will guide the C4T Medical Cannabis in Schools Working Group's future priorities and initiatives.

Aim We undertook this systematic review to determine the efficacy and safety of cannabis-based medicine as a treatment for behavioral, psychological, and motor symptoms associated with neurocognitive disorders. Methods We conducted a PRISMA-guided systematic review to identify studies using cannabis-based medicine to treat behavioral, psychological, and motor symptoms among individuals with Alzheimer's disease (AD) dementia, Parkinson’s disease (PD), and Huntington’s disease (HD). We considered English-language articles providing original data on three or more participants, regardless of design. Findings We identified 25 studies spanning 1991 to 2021 comprised of 14 controlled trials, 5 pilot studies, 5 observational studies, and 1 case series. In most cases, the cannabinoids tested were dronabinol, whole cannabis, and cannabidiol, and the diagnoses included AD ( n = 11), PD ( n = 11), and HD ( n = 3). Primary outcomes were motor symptoms (e.g., dyskinesia), sleep disturbance, cognition, balance, body weight, and the occurrence of treatment-emergent adverse events. Conclusions A narrative summary of the findings from the limited number of studies in the area highlights an apparent association between cannabidiol-based products and relief from motor symptoms in HD and PD and an apparent association between synthetic cannabinoids and relief from behavioral and psychological symptoms of dementia across AD, PD, and HD. These preliminary conclusions could guide using plant-based versus synthetic cannabinoids as safe, alternative treatments for managing neuropsychiatric symptoms in neurocognitive vulnerable patient populations.

Cancer is a global issue, and it is expected to have a major impact on our continuing global health crisis. As populations age, we see an increased incidence in cancer rates, but considerable variation is observed in survival rates across different geographical regions and cancer types. Both breast and prostate cancer are leading causes of morbidity and mortality worldwide. Although cancer statistics indicate improvements in some areas of breast and prostate cancer prevention, diagnosis, and treatment, such statistics clearly convey the need for improvements in our understanding of the disease, risk factors, and interventions to improve life span and quality of life for all patients, and hopefully to effect a cure for people living in developed and developing countries. This concise review compiles the current information on statistics, pathophysiology, risk factors, and treatments associated with breast and prostate cancer.