Pharmacokinetic of two oral doses of a 1:20 THC:CBD cannabis herbal extract in cats.

Objective: To 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. Methods: Single-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. Results: CBD 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 significance: Although 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.

Removing barriers to accessing medical cannabis for paediatric patients.

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.

Medical cannabis in schools: A qualitative study on the experiences of clinicians.

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.

Medical cannabis in schools: The experiences of caregivers.

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.

Cardiolipin released by microglia can act on neighboring glial cells to facilitate the uptake of amyloid-ß (1-42).

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-ß (Αß) 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 Αß. 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 Aß42. Extracellular cardiolipin upregulated internalization of fluorescently-labeled Aß42 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 Aß42 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 Aß42 augments the release of cardiolipin from microglia into the extracellular space, where it can act on microglia and astrocytes to enhance their endocytosis of Aß42. Our observations suggest that the reduced glial uptake of Aß due to the decreased levels of cardiolipin could be at least partially responsible for the extracellular accumulation of Aß in aging and Alzheimer's disease.

Fundamental Neurochemistry Review: Incorporating a greater diversity of cell types, including microglia, in brain organoid cultures improves clinical translation.

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.

Availability of bioactive flax lignan from foods and supplements.

Hyperlipidemia, high levels of blood lipids including cholesterol and triglycerides, is a major risk factor for cardiovascular disease. Traditional treatments of hyperlipidemia often include lifestyle changes and pharmacotherapy. Recently, flaxseed has been approved as a nutrient that lowers blood lipids. Several metabolites of flaxseed lignan secoisolariciresinol diglucoside (SDG), have been identified that reduce blood lipids. SDG is present in flaxseed hull as an ester-linked copolymer with 3-hydroxy-3-methylglutaric acid (HMGA). However, purification processes involved in hydrolysis of the copolymer and enriching SDG are often expensive. The natural copolymer of SDG with HMGA (SDG polymer) is a source of bioactive compounds useful in prophylaxis of hypercholesterolemia. After consumption of the lignan copolymer, SDG and HMGA are released in the stomach and small intestines. SDG is metabolized to secoisolariciresinol, enterolactone and enterodiol, the bioactive forms of mammalian lignans. These metabolites are then distributed throughout the body where they accumulate in the liver, kidney, skin, other tissues, and organs. Successively, these metabolites reduce blood lipids including cholesterol, triglycerides, low density lipoprotein cholesterol, and lipid peroxidation products. In this review, the metabolism and efficacies of flaxseed-derived enriched SDG and SDG polymer will be discussed.

A Tale of Two Cancers: A Current Concise Overview of Breast and Prostate Cancer.

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.

Pharmacokinetics of apixaban and tacrolimus or cyclosporine in kidney and lung transplant recipients.

Apixaban is frequently used off-label in transplant recipients. However, a potential drug interaction exists with the calcineurin inhibitors. We conducted an open-label drug-drug interaction study to determine the pharmacokinetics of apixaban in lung and kidney transplant recipients who were taking a calcineurin inhibitor. A single dose of apixaban 10 mg was administered orally to kidney and lung transplant recipients maintained on either tacrolimus or cyclosporine, and pharmacokinetic parameters were compared to a reference cohort of 12 healthy subjects who used the same apixaban dose and pharmacokinetic blood sampling. Fourteen participants were enrolled (n = 6 kidney, n = 8 lung), with 10 maintained on tacrolimus and four on cyclosporine. Data from 13 participants was usable. Participants were taking triple therapy immunosuppression and had a mean (SD) of 12 (3) medications. Participants receiving tacrolimus and cyclosporine had area under the plasma concentration-time curve from time zero to infinity (AUC0-inf ) geometric least square means (90% confidence interval [CI]) of 4312 (95% CI 3682, 5049) and 5388 (95% CI 3277, 8858), respectively. Compared to healthy subjects, the associated geometric mean ratios (GMRs) for apixaban maximum plasma concentration (Cmax ), AUC from time zero to the last quantifiable concentration (AUC0-tlast ) and AUC0-inf were 197% (95% CI 153, 295), 244% (95% CI 184, 323), and 224% (95% CI 170, 295) for transplant recipients on tacrolimus. The GMR (90% CI) Cmax , AUC0-tlast , and AUC0-inf of apixaban for patients on cyclosporine were 256% (95% CI 184, 358), 287% (95% CI 198, 415), and 280% (95% CI 195, 401). Kidney and lung transplant recipients receiving tacrolimus had higher apixaban exposure. A similar trend was noted for patients receiving cyclosporine, but additional patients are needed to confirm this interaction. Future studies are needed before apixaban can be safely recommended in this population, and the impact of dose staggering should be investigated. This study highlights the importance of pharmacokinetic studies in actual patient populations.

Cannabinoids in the management of behavioral, psychological, and motor symptoms of neurocognitive disorders: a mixed studies systematic review.

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.

Cannabis for the Treatment of Attention Deficit Hyperactivity Disorder: A Report of 3 Cases.

Attention deficit hyperactivity disorder (ADHD) is a chronic neurobehavioral disorder that is highly prevalent in children and adults. An increasing number of patients with ADHD are self-medicating with cannabis, despite a lack of evidence on efficacy and safety. This case report describes 3 males (ages 18, 22, and 23) who have integrated cannabis into their treatment regimen with positive results. Semistructured interviews conducted with the patients describe subjective improvements in symptoms and on quality of life. Improvements on validated rating scales conducted post-cannabis initiation, compared to pre-cannabis initiation obtained from the medical chart, corroborated their personal accounts. Scores on the PHQ-9 (measuring depression) improved by 8-22 points (30-81%), and the SCARED (measuring anxiety) ranged from 0 to 27 points (up to 33%). Improvements on the CEER-9 scale (measuring regulation) ranged from 2 to 7 points (22-78%), and the 9-item SNAP scale (measuring inattention) showed improvements of 2-8 points (7-30%). Mild adverse events including short-term memory problems, dry mouth, and sleepiness were reported. Blood samples were also collected from the patients to determine the plasma concentrations of the cannabinoids and relevant metabolites before and after a cannabis administration. After cannabis use, the plasma levels for CBD and THC ranged from 0 to 15.29 ng/mL and 1.32 to 13.76 ng/mL, respectively. Cannabinoids, however, were not detected prior to dosing, suggesting that cannabis played a complimentary role in the therapeutic regimen of these 3 patients. Clinical trials are recommended to confirm the efficacy of cannabis in the treatment of ADHD.

A series acceleration algorithm for the gamma-Pareto (type I) convolution and related functions of interest for pharmacokinetics.

The gamma-Pareto type I convolution (GPC type I) distribution, which has a power function tail, was recently shown to describe the disposition kinetics of metformin in dogs precisely and better than sums of exponentials. However, this had very long run times and lost precision for its functional values at long times following intravenous injection. An accelerated algorithm and its computer code is now presented comprising two separate routines for short and long times and which, when applied to the dog data, completes in approximately 3 min per case. The new algorithm is a more practical research tool. Potential pharmacokinetic applications are discussed.

Pharmacokinetics and Perceptions of Children and Young Adults Using Cannabis for Attention-Deficit/Hyperactivity Disorder and Oppositional Defiant Disorder: Protocol for a Mixed Methods Proof-of-Concept Study.

BACKGROUND: Despite the lack of evidence on the use of cannabis for the treatment of attention-deficit/hyperactivity disorder (ADHD), the growing perception that cannabis is safe has led more patients and caregivers to self-medicate. Some psychiatrists now authorize medicinal cannabis for patients with ADHD with features of oppositional defiant disorder (ODD) to curtail the unregulated (ie, self-medicated) use of recreational cannabis or to offer a therapeutic option to those who continue to experience symptoms after exhausting all other treatment options. OBJECTIVE: This protocol aims to explore the perceived effectiveness and pharmacokinetics of cannabis in youth and young adults, who are currently taking it as part of their treatment plan for ADHD with features of ODD, under the supervision of a psychiatrist. METHODS: Patients between the ages of 12 and 25 years with a diagnosis of ADHD and features of ODD, who are currently taking cannabis herbal extract (at a Δ9-tetrahydrocannabinol [THC]:cannabidiol [CBD] ratio of 1:20) as a treatment adjunct to stimulant pharmacotherapy will be recruited. A sample size of 10-20 individuals is estimated. The study interview will consist of (1) validated symptom rating scales (Swanson, Nolan, and Pelham-IV Questionnaire [SNAP-IV], 90-item; Patient Health Questionnaire, 9-item [PHQ-9]; and Screen for Child Anxiety Related Emotional Disorders [SCARED] tool to measure symptoms of ADHD and ODD, depression, and anxiety, respectively); (2) a semistructured interview to probe the experiences of using cannabis; and (3) a cannabis side effects survey. A cannabis product sample as well as 2 blood samples (a trough level and 2-hour postdose level) will be collected to measure plasma concentrations of cannabinoids and relevant metabolites (THC, CBD, 11-hydroxy-THC, 7-hydroxy-CBD, cannabichromene, and 11-nor-9-carboxy-THB) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Self-report rating scales (SNAP-IV, SCARED, and PHQ-9) will be scored in accordance with standard protocols and compared to retrospective scores obtained from the participant's chart. Demographic variables (age, weight, and race), symptom scores, and blood levels (peaks and troughs) of THC, CBD, cannabichromene (CBC), and metabolites will be summarized using descriptive statistics. Relationships between plasma concentrations and symptom scores will be determined using analysis of variance, and multiple regression analysis will be performed to determine associations between plasma concentrations and demographic variables (age, weight, and ethnicity). The qualitative data will be audio-recorded and transcribed and organized into themes. RESULTS: The protocol was approved by the Biomedical Research Ethics Board at the University of Saskatchewan (protocol #1726), and recruitment began in May 2021. CONCLUSIONS: This proof-of-concept study will explore the potential treatment effectiveness of medical cannabis in participants with ADHD and ODD through a mixed methods approach to inform future research in this area. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31281.

Hypocholesterolemic Efficacy of Secoisolariciresinol Diglucoside and Its Polymer in Rat.

Hypercholesterolemia is a risk factor for cardiovascular disease. Conventional treatment methods include lifestyle changes and pharmaceutical interventions, but recently Health Canada approved a health claim for whole ground flaxseed as an alternative treatment for hypercholesterolemia. The literature suggests flaxseed lignans are responsible for the cholesterol-reducing effects of flaxseed. In this study, 96.1% secoisolariciresinol diglucoside (SDG) and a 50% SDG enriched polymer (SDG polymer) were investigated as treatments for hypercholesterolemia in rats. Wistar female rats were fed a 1% high-cholesterol diet for a one-week acclimatization prior to a 23-day intervention with enriched SDG or SDG polymer. A reduction in body weight normalized liver weight was observed in rats treated with enriched SDG when compared to the controls. Both enriched SDG (96.1%) and SDG polymer reduced serum triacylglycerol (19% and 15%, respectively) and increased high-density lipoprotein cholesterol (15% and 24%, respectively). Histopathologic analyses revealed lipid-lowering effects of either enriched SDG or SDG polymer along with lower steatosis scores and nonalcoholic fatty liver disease activity. Furthermore, the lack of statistical significance between SDG and SDG polymer treatment groups suggests that SDG polymer may be a potential alternative to enriched SDG for hypercholesterolemia with similar efficacy but lower cost.

Oral Pharmacokinetics of Enriched Secoisolariciresinol Diglucoside and Its Polymer in Rats.

Secoisolariciresinol diglucoside (SDG) is the principal lignan of flaxseed and precursor of its aglycone, secoisolariciresinol (SECO), and the mammalian lignans enterolactone (EL) and enterodiol (ED), the putative bioactive forms of oral administration of SDG. SDG is present in the seed hull as an ester-linked polymer. Although extraction and purification of SDG monomer is costly, the use of naturally occurring SDG in polymer form may offer a more economical approach for delivery of this precursor. The extent of SDG release from the polymer and subsequent bioavailability of SDG metabolites are unknown. To understand the relative bioavailability of SDG polymer, this study examined the comparative bioavailability of enriched SDG and SDG polymer in rats after a single oral SDG equivalent dose (40 mg/kg). A validated LC-MS/MS method quantified SDG and its metabolites in rat plasma following serial blood collections. SDG remained undetectable in rat plasma samples. Unconjugated SECO was detected in plasma after 0.25 h. Unconjugated ED was observed after 8 h (3.4 ± 3.3 ng/mL) and 12 h (6.2 ± 3.3 ng/mL) for enriched SDG and SDG polymer, respectively. Total (conjugated and unconjugated) ED and EL resulting from enriched SDG and SDG polymer reached similar maximal concentrations between 11 and 12 h and demonstrated similar total body exposures (AUC values). These data suggest a similar pharmacokinetic profile between the enriched and polymer form of SDG, providing support for the use of SDG polymer as a more economical precursor for SECO, ED, and EL in applications of chronic disease management.

An Advanced Pharmacy Practice Experience for Community Pharmacies Based on a Clinical Intervention Targeting Patients With Inflammatory Bowel Disease.

Experiential education is a critical component of any pharmacy undergraduate curriculum. Establishing new, high-quality practice sites can be challenging. We designed a new advanced pharmacy practice experiential rotation suitable for implementation in most community pharmacy settings. The aim of this article is to describe the design of this rotation entitled the Targeted Pharmacy Intervention in Inflammatory Bowel Disease (TPI-IBD) and to determine its impact on student knowledge and confidence using a before-after survey design. The TPI-IBD utilizes a student-delivered intervention as a platform for experiential learning in community pharmacy practice. The TPI was focused on patients with IBD, and implementation was guided by a co-preceptor from the university in collaboration with onsite-preceptors at each pharmacy. The TPI-IBD rotation was delivered from 6 community pharmacies during 5 weeks in 2018. Students conducted standardized monitoring on patients with IBD and met weekly with the university preceptor for case presentations and therapeutic discussions. Electronic charts were maintained by students who were responsible for ensuring detailed documentation on each patient. Knowledge, confidence, and overall satisfaction were assessed by a survey given to students before and after the rotation. Students were highly satisfied with the learning experience and improvements in knowledge and confidence were clearly demonstrated. The TPI strategy was an effective way to expand rotation options in community pharmacy sites with minimal burden on local preceptors.

Doxorubicin Cytotoxicity in Differentiated H9c2 Cardiomyocytes: Evidence for Acute Mitochondrial Superoxide Generation.

Although a mitochondrial redox-cycling superoxide-generating mechanism for the cardiotoxicity of doxorubicin was suggested from experiments with isolated mitochondria, its occurrence and contribution to cytotoxicity in intact cardiomyocytes is not fully established. Therefore, we determined the immediate and delayed effects of doxorubicin on the generation of reactive oxygen species (ROS) and cytotoxicity in differentiated H9c2 cardiomyocytes. Although relatively short incubations (3 or 6 h) with 1 or 5 µM doxorubicin did not acutely decrease cell survival, exposure to 5 µM doxorubicin for 3 h was sufficient to cause a significant delayed decrease in cell survival after an additional 24 h without doxorubicin. Mitochondrial superoxide generation was observed to increase within 30 min of incubation with 5 µM doxorubicin. Increased intracellular ROS generation, decreased mitochondrial metabolic activity, and decreased mitochondrial membrane potential (MMP) were observed after more extended periods (6-12 h). Overall, these observations support that the toxicity of doxorubicin to differentiated cardiomyocytes involves acute mitochondrial superoxide generation with subsequent intracellular ROS generation, mitochondrial dysfunction, and cell death.

Stretching is Superior to Brisk Walking for Reducing Blood Pressure in People With High-Normal Blood Pressure or Stage I Hypertension.

BACKGROUND: Aerobic exercise is recommended for reducing blood pressure; however, recent studies indicate that stretching may also be effective. The authors compared 8 weeks of stretching versus walking exercise in men and women with high-normal blood pressure or stage 1 hypertension (ie, 130/85-159/99 mm Hg). METHODS: Forty men and women (61.6 y) were randomized to a stretching or brisk walking exercise program (30 min/d, 5 d/wk for 8 wk). Blood pressure was assessed during sitting and supine positions and for 24 hours using a portable monitor before and after the training programs. RESULTS: The stretching program elicited greater reductions than the walking program (P < .05) for sitting systolic (146 [9] to 140 [12] vs 139 [9] to 142 [12] mm Hg), supine diastolic (85 [7] to 78 [8] vs 81 [7] to 82 [7] mm Hg), and nighttime diastolic (67 [8] to 65 [10] vs 68 [8] to 73 [12] mm Hg) blood pressures. The stretching program elicited greater reductions than the walking program (P < .05) for mean arterial pressure assessed in sitting (108 [7] to 103 [6] vs 105 [6] vs 105 [8] mm Hg), supine (102 [9] to 96 [9] vs 99 [6] to 99 [7] mm Hg), and at night (86 [9] to 83 [10] vs 88 [9] to 93 [12] mm Hg). CONCLUSIONS: An 8-week stretching program was superior to brisk walking for reducing blood pressure in individuals with high-normal blood pressure or stage 1 hypertension.