Ultra-endurance exercise events result in central fatigue, impacting on mental alertness and decision making. Endocannabinoids are typically elevated during endurance exercise and have been implicated in central processes such as learning and memory, but their role in central fatigue has never been studied. Twenty-four recreational male ultrarunners participated in a 100-km trail run, and 18 of them completed at least 60 km and were included in the analyses. A cognitive test battery to assess median reaction time (MRT) and median movement time during a reaction time task and median response latency during a rapid visual information processing task was completed prior to and immediately after the trail. Blood serum samples pre- and postexercise were analyzed for endocannabinoids and related lipids (anadamide: AEA; 2-arachidonoylglycerol: 2-AG; palmitoylethanolamide: PEA; oleoylethanolamide: OEA; stearoylethanolamine: SEA) via liquid chromatography-mass spectrometry. Ultra-endurance exercise worsened all cognitive parameters and increased abundance of AEA, PEA, OEA, and SEA but not 2-AG. Interestingly, the exercise-induced change in MRT showed moderate, positive correlations with the change in different endocannabinoids, that is, AEA ( = 0.5164, = 0.0338), PEA ( = 0.5466, = 0.0251), and OEA ( = 0.5442, = 0.0239). These results indicate a potential role of endocannabinoids on mental alertness following ultra-endurance exercise.

To examine the acute pharmacokinetics (PK) and pharmacodynamics (PD) of a patented oral cannabinoid product containing a botanical hemp-derived "full-spectrum" extract with an approximate 1:1 ratio of cannabidiol (CBD) to cannabidiolic acid (CBDA) and delta-9-tetrahydrocannabinol (THC) to delta-9-tetrahydrocannabinolic acid (THCA). Healthy adults ( = 15) ingested soft gels containing 0 (placebo), and approximately 1, 2, and 4 mg/kg of total cannabinoids (combination of CBD, CBDA, THC, THCA, and other minor cannabinoids) in an ascending-dose order in four experimental sessions separated by ≥1 week (the placebo condition occurred randomly within the dose sequence). Mean doses (mg) of primary cannabinoids in the active drug conditions were: 1 mg/kg condition (CBD = 41.1, CBDA = 43.7, THC = 2.2, THCA = 1.6), 2 mg/kg condition (CBD = 73.4, CBDA = 77.9, THC = 3.9, THCA = 2.9), and 4 mg/kg condition (CBD = 134.5, CBDA = 142.8, THC = 7.2, THCA = 5.3). PD outcomes (subjective, cognitive, and physiological effects) were measured before and repeatedly for 8 h after dosing. Plasma specimens were collected throughout the 8-h sessions and at 24- and 48-h post-dosing. PK outcomes included peak plasma concentration () and time to maximum concentration (). For PD outcomes, few differences were observed between 1 mg/kg and placebo. However, relative to placebo, 2 mg/kg and 4 mg/kg produced small to moderate increases in subjective drug effects, including abuse liability items (e.g., "like"), and 4 mg/kg also impaired working memory performance. Generally, PD effects peaked 3-5 h post-dosing and returned to baseline by 8 h. Dose-orderly increases in were observed for CBD, CBDA, THC, THCA, and their respective metabolites (e.g., 7-COOH-CBD, THCCOOH), which were often detectable 48 h post-dosing. Across all doses, for CBDA and THCA was 19-25-fold higher and was up to 2-fold earlier compared with CBD and THC, respectively. Acute administration of a "full-spectrum" hemp-derived cannabinoid product produced dose-orderly effects; the highest dose elicited several adverse events and produced moderate cognitive impairment and subjective intoxication, despite containing a relatively low dose of THC (mean: 7.2 mg). Carboxylated cannabinoids (e.g., CBDA) exhibited substantially greater bioavailability and faster absorption compared with decarboxylated cannabinoids (e.g., CBD). Additional systematic research is needed to characterize how constituent profile impacts the effects of cannabinoid products, and more studies directly comparing carboxylated and decarboxylated compounds appear warranted.

Although the majority of cannabinoid research has focused on delta-9-tetrahydrocannabinol (Δ-THC) and cannabidiol (CBD), there is increasing interest in the therapeutic effects of other phytocannabinoid compounds (i.e., minor cannabinoids), as there is little known about their effects or interaction with CBD. The current study objective was to determine the concentrations of 15 minor cannabinoids in unregulated, over-the-counter CBD products. A cross-section sample of 80 local and national brands of hemp-derived oil products was purchased both online and in local retail outlets in central Kentucky. Epidiolex® was included as a regulated control. Samples from each product were extracted by solvent extraction and quantified by liquid-chromatography tandem mass-spectrometry. The targeted cannabinoids were: cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabidivarinic acid, Δ-tetrahydrocannabivarin, Δ-tetrahydrocannabivarinic acid, Δ-tetrahydrocannabinolic acid-A, Δ-tetrahydrocannabinol (Δ-THC), cannabigerol (CBG), cannabigerolic acid, cannabinol (CBN), cannabinolic acid, cannabicyclol (CBL), cannabicyclolic acid, cannabichromene (CBC) and cannabichromenic acid. Among the unregulated products included in this analysis, the most frequently detected minor cannabinoids were CBDV (100% of samples tested), CBG (77%), CBC (72%), CBN (67%), CBL (67%), and CBDA (51%). Δ-THC was not detected in any of the products tested. Concentrations of these cannabinoids varied widely from trace concentrations to several mg/mL (e.g., CBDA: 0.006-12.258 mg/mL). These data indicate CBD products often contain minor cannabinoids, although the array and concentrations of these cannabinoids vary widely across products. The concentrations of these minor cannabinoids are largely absent from product labels, leaving consumers uninformed about product contents.

In 2020, the Lebanese parliament legalized cannabis for medical and industrial use, sparking diverse reactions among health care professionals (HCP). Few studies have been conducted to reflect the position of HCP on the topic, and no previous studies targeted all physicians with relevant specialties or had a large sample size. The current study aimed to assess the knowledge, attitude, and practice of the Lebanese medical community toward medicinal cannabis (MC). A cross-sectional study was conducted targeting HCP from different backgrounds and specialties. The survey questionnaire was disseminated through different scientific societies in the Lebanese Order of Physicians and other professional bodies. An online survey was shared with oncologists, rheumatologists, psychiatrists, neurologists, pharmacists, and psychotherapists across different geographic regions. It covered questions about sociodemographic details, knowledge, attitude, and practice related to MC. Descriptive and bivariate analyses were performed. A total of 202 HCP responded to the survey, yielding a response rate of 34%. Eighteen percent of the participants described their level of knowledge about the indications of MC as good. Twenty-five percent of the respondents are willing to prescribe, and 30% "may consider" it. Among those willing to prescribe, the majority may consider MC to treat chronic pain, palliative care, post-traumatic stress disorder, epilepsy, and anxiety. Respondents' knowledge about the side effects of MC is as follows: driving difficulties (82%), addiction (69%), drug interactions (65%), and weight gain (43%). Willingness to prescribe varies by medical specialty, previous clinical experience with MC, and gender. The majority of the participants expressed concerns about the potential harm of using MC and indicated that legalization would negatively impact society. Sixty-nine percent of the respondents reported not receiving any formal education about MC and agreed on the need to expand knowledge about its indications and side effects. The majority agreed that MC should be dispensed based on a prescription from a physician with special training and recognized the importance of establishing a national registry for patients undergoing MC treatment, as well as the necessity of guidelines for approval. The current data indicate that attitudes toward prescribing MC vary by medical specialty, gender, and clinical experience. Implementation of effective educational strategies in Lebanon to enhance HCP knowledge about MC and promote its proper use is crucial.

The administration of cannabinoids for disease and symptom management such as pain continues to elicit significant interest, albeit limited information that is available regarding their pharmacokinetics and pharmacodynamics to guide clinical practice. Cannabis-based medicines contain a wide variety of chemical compounds, of which the most common include the cannabinoids delta-9-tetrahydrocannabinol (Δ9THC), and the nonpsychomimetic cannabidiol (CBD). The pharmacokinetics of cannabis-based medicines and the effects observed depend on the formulation and route of administration. THC and CBD are subject to extensive first-pass hepatic metabolism and pharmacokinetic drug interactions, the latter via inhibition or induction of enzymes and transporters. This study was conducted to describe the pharmacokinetics of CBD, THC, and its metabolites following orobuccal administration, providing pivotal information to guide the clinical development program of a self-assembled micellized nanoparticle formulation containing 1:1 Δ9THC and CBD. Pharmacokinetic data was obtained from a phase 1, two-stage study in patients with advanced cancer, and modelled using a population pharmacokinetic approach. To provide an indication of predicted exposure with multiple dosing, the final population pharmacokinetic models were used to simulate concentration-time profiles for each of the active compounds. The developed population pharmacokinetic models provided important information on the bioavailability of CBD and THC, with estimated values of 10% and 27%, respectively. These values were approximately two-fold greater than that which has been previously described for oromucosal formulations. This enhanced bioavailability can most likely be attributed to the NanoCelle® technology. This technology provides evidence to support the application of this innovative drug delivery platform to overcome limitations associated with cannabinoid administration for therapeutic use.

Medicinal cannabis (MC) has potential therapeutic effects in Tourette Syndrome (TS), however there has been limited research in adolescent patients. This pilot study aimed to investigate the feasibility of conducting a randomized placebo-controlled crossover trial of MC in adolescents with TS. This was a phase I/II double-blind, cross-over pilot study comparing MC with matched placebo in adolescents aged 12-18 years with TS. The active medication was Δ9-tetrahydrocannabinol (THC) 10 mg/mL and CBD 15 mg/mL in peppermint-flavored medium-chain triglyceride oil. The dose titration schedule was stratified into two participant weight bands: below 50 kg (max THC 10 mg/day) or ≥50 kg (max THC 20 mg/day). Each treatment phase lasted 10 weeks, with a 4-week washout period. Ten adolescents were randomized (mean age 14.8 years, 50% male) and seven completed the full study protocol. Two adolescents discontinued due to adverse events (one on MC, one placebo) and one was lost to follow-up. The most common adverse event was dizziness (67%). There were no serious adverse events. Among actively enrolled participants, protocol adherence was excellent: study visits 100%, blood test completions 100%, and online questionnaire completion 97.6%. Medication adherence was acceptable in 63.6%. Parents reported a high degree of study design acceptability. On the Clinical Global Impression-Improvement scale, three participants were rated as much improved on MC compared with one on placebo at 10 weeks. The findings suggest that the study protocol is feasible and acceptable to patients with TS and their families. A fully powered study is needed to evaluate the efficacy of MC in adolescent TS.

The availability of recreational cannabis in the United States has increased dramatically. Neighborhood cannabis dispensary availability may increase problematic use. State and local studies suggest that cannabis dispensary availability may be correlated with neighborhood sociodemographic characteristics. We provide a national-level examination of census tract (CT) sociodemographic characteristic correlates with the availability of cannabis dispensaries in 18 U.S. states that have legalized adult recreational cannabis use. We downloaded the locations of cannabis dispensaries ( = 3,167) from Weedmaps in November 2021. We downloaded ethnic, racial, and socioeconomic estimates from the U.S. Census and categorized CTs into quintiles (Q), where Q1 represents the CTs with the lowest percentage of a variable and Q5 represents CTs with the highest. We fit unadjusted generalized linear mixed models to examine associations between quintiles of each sociodemographic characteristic and the presence of at least one dispensary (vs. none). CTs with a greater percentage of Black residents had a higher odds of having at least one cannabis dispensary (vs. none) across all quintiles. For example, compared to CTs with the lowest percentage of Black residents (Q1), CTs with the greatest percentage of Black residents (Q5) had 2.07 (95% CI: 1.70-2.52) times the odds of having at least one dispensary versus none. We observed a similar pattern of a greater likelihood of a CT having a dispensary (vs. none) as the percentage of Hispanic/Latine residents and percentage of individuals living below the federal poverty line increased across all quintiles. In contrast, as the percentage of homeowner-occupied housing increased across all quintiles, there were lower odds of having at least one dispensary (vs. none). For example, CTs with the highest percentage of homeowner-occupied housing (vs. lowest) had 0.21 (95% CI: 0.17-0.26) times the odds of having at least one dispensary vs. none. Differences in cannabis dispensary availability exist by neighborhood sociodemographic composition. The growing acceptance of cannabis, concern about public health and safety, and the proliferation of adult recreational use laws offer local and state policymakers an opportunity to engage local communities in shared decision-making about the location of dispensaries.

Following the spread of recreational cannabis legalization and commercialization, cannabis has become increasingly available at lower prices. As policies regulating prices are common tools to control the demand for commercialized drugs, it is crucial to understand how cannabis use responds to price changes. In this study, we assessed the association between wholesale prices for legal cannabis flower and adults' self-reported current cannabis use in ten states with recreational cannabis commercialization in the U.S. We conducted a secondary data analysis using individual-level data on cannabis use from the longitudinal Population Assessment of Tobacco and Health Study, during 2015 and 2021. Our analysis included 19,812 U.S. adults from ten states that legalized recreational cannabis sales during the study period. We first conducted logistic regressions to estimate the association between state-level cannabis prices and individual current cannabis use. To address potential endogeneity of cannabis prices, we then employed generalized method of moment (GMM) estimator, using cannabis taxes as an instrumental variable (IV). IV-based GMM regressions suggested that cannabis taxes were a significant predictor of cannabis prices. However, the association between legal cannabis flower prices and adults' current cannabis use was negative but statistically insignificant (coefficient = -0.18, = 0.086). Price elasticity estimates for current cannabis use ranged from -0.66 to -0.59 across different model specifications. In the initial years of recreational cannabis commercialization in the U.S., the price elasticity of cannabis use among adults was negative but statistically insignificant. Given the rapid progression of commercialization, further research utilizing longer-term data is needed.

Cannabinoids are increasingly being explored as a potential treatment for neurodegenerative diseases. This article aims to provide a narrative review of available data on the treatment of neurological disorders with cannabis constituents, focusing on ischemic stroke. Selected articles are summarized to describe design, results, limitations, conclusions, and implications about this theme. The growing understanding of the endocannabinoid system and the cannabinoid receptors distribution in all human body systems and organs and particularly in brain structures importantly involved in myelination processes, suggests potential benefits for stroke symptoms and overall patient improvement. However, the variety of studied compounds, the different administration routes, dosages, and timing complicates data comparison, especially due to limited studies about these compounds, peculiarly in stroke patients. Thereat, this review to showcase disparities in findings and to summarize current advancements in cannabinoid use for potential future treatments. This article offers a review of the current literature in the field and discuss a pragmatic approach to the clinical use of cannabinoids in patients with ischemic stroke.

The endocannabinoid system plays a crucial role in gastrointestinal homeostasis; although some gastrointestinal adverse events have been reported with therapeutic cannabinoids in children, the complete profile of gastrointestinal adverse events in the pediatric population remains unknown. Through a systematic review and meta-analysis, we aimed to identify the prevalence of gastrointestinal adverse events from therapeutic cannabinoids in children. A literature search of OVID MEDLINE, EMBASE, CINAHL, Web of Science, and The Cochrane Library was performed from inception to May 19, 2023. Selected studies included randomized controlled trials, retrospective cohort studies, uncontrolled before-after studies, and observational retrospective studies in English, French, or Spanish that reported gastrointestinal adverse events in the pediatric population under therapeutic cannabinoid interventions. The study was registered with PROSPERO and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. A random-effects model was used to pool and analyze the extracted data. Extracted data included the presence of adverse gastrointestinal events by analyzing the type of cannabinoid, duration of treatment, dosage, and type of study. A subgroup meta-analysis was also performed, focusing on patients' conditions. Twenty-five studies were included, comprising 1,201 pediatric patients receiving therapeutic cannabinoids, of whom 451 experienced gastrointestinal adverse events, representing a cumulative prevalence of 33.91% (95% confidence interval [CI]: 21.49% to 49.04%). Interventional studies reported a higher prevalence of GI adverse events (47.36%; 95% CI: 31% to 64%) compared with observational studies (17.6%; 95% CI: 8.5% to 32.7%). As most studies focused on patients with epilepsy, a subanalysis was performed within this population, revealing that patients with Dravet syndrome had a higher prevalence of diarrhea compared with other types of epilepsy (21.75%; 95% CI: 8.52% to 45.34% vs. 5.95%; 95% CI: 3.11% to 11.1%). This systematic review and meta-analysis showed a high prevalence of gastrointestinal adverse events in children receiving therapeutic cannabinoids, with some populations, such as those with Dravet syndrome, being at higher risk than others. With the increased public discourse of cannabinoids being "natural" and mistakenly equating them as "risk-free," this information can help clinicians educate patients and the broader public on the adverse effects profile of these treatments.

The COVID-19 pandemic has impacted billions of people worldwide, particularly those with chronic health conditions, and has been associated with increases in substance use, including cannabis. The purpose of this study was to estimate the prevalence of cannabis use for symptom management of chronic health conditions during the COVID-19 pandemic. The COVID-19 Cannabis Health Study is an ongoing study among adults ≥18 who self-report cannabis use. Analyses included 1,466 responses received between March 21, 2020, and March 23, 2022, from participants who self-reported cannabis use and a chronic health condition. We examined comorbidities, symptoms managed with cannabis during the COVID-19 pandemic, and fear regarding COVID-19 diagnosis and transmission using the COVID-19 Cannabis Health Questionnaire. Descriptive statistics, Chi-squared, and T-tests were conducted. Results were stratified by those who reported using cannabis to manage a chronic health condition (medicinal cannabis user, = 1,333) and those who did not use cannabis to manage chronic health condition (non-medicinal cannabis user, = 133). Most (90.9%, = 1,333) of the total sample (mean age: 47.1 years [standard deviations {SD} = 15.0]) reported using cannabis to manage a chronic health condition, of which 46.1% ( = 615) reported having a medical card/recommendation, and 4.6% received recommendations to use cannabis to manage COVID-19 from health professionals. There were significant differences in age, gender, race/ethnicity, and education by medicinal cannabis use status. Comorbidities prevalent among medicinal cannabis consumers were mental health-related (66.1%), pain (58.5%), cardiometabolic-related (30.5%), immune-related (21.9%), and respiratory-related (20.8%). The most reported symptoms self-managed with cannabis during the pandemic were sleep (69.2%), chronic noncancer pain (49.7%), acute pain (46.5%), headaches/migraines (39.0%), muscle spasms (33.6%), nausea/vomiting (30.6%), and appetite stimulant (29.9%). There were no statistical differences in COVID-19 testing, fear of diagnosis, fear of transmission, or isolation due to COVID-19 between medicinal and nonmedicinal cannabis consumers in this sample. The perceived therapeutic benefit of cannabis during the COVID-19 pandemic is evident by the high prevalence of adults who reported using cannabis for medicinal reasons despite no recommendation from their health provider. Research is necessary to understand the prospective impact of cannabis use for self-management of chronic disease, especially within the context of COVID-19.

Post-surgical pain arises following a clinical operation, often persisting throughout recovery. While current treatments reduce pain, repeated use increases the probability of adverse events. monoacylglycerol lipase (MAGL) inhibition has previously been shown to produce analgesia, either through CB or CB mechanisms, dependent on the underlying pain phenotype. Thus, this study investigated the analgesic potential of inhibiting MAGL, alone and in combination with the analgesic non-steroidal anti-inflammatory drug (NSAID) diclofenac sodium in a model of post-surgical pain. Male and female C57BL/6J mice were subjected to hindpaw incision (HPI) surgery. Mechanical allodynia, climbing, grip strength, and thermal preference were measured 24 h following HPI. The dose-dependent anti-allodynic effects of the MAGL inhibitors (irreversible MAGL inhibitor [JZL184] and selective MAGL inhibitor [MJN110]) and the NSAID diclofenac, as well as the additive potential of combined MAGL and cyclooxygenase (COX) inhibition, were assessed. Selective antagonists of CB and CB receptors were used to challenge the cannabinoid-receptor mechanism of JZL184. Similarly, the anti-allodynic effects of the CB-selective agonist (LY2828360) were tested. JZL184 was administered repeatedly to determine tolerance. Finally, hindpaw cytokines were quantified multiplex ELISA 24 h after HPI surgery. Approximately 24 h post-surgery, the MAGL inhibitors JZL184 (≥4 mg/kg) or MJN110 (≥5 mg/kg), as well as the NSAID diclofenac sodium (≥16.67 mg/kg), attenuated HPI-induced mechanical allodynia, as assessed with von Frey filaments. The anti-allodynic effects of JZL184 (40 mg/kg) were blocked by pre-treatment of the CB antagonist SR144528 (3 mg/kg) but not the CB-selective antagonist rimonabant (SR141716A; 3 mg/kg), suggesting a CB-mediated mechanism of anti-allodynia MAGL inhibition. Similarly, LY2828360 (3 mg/kg) reduced HPI-induced allodynia. Moreover, when administered repeatedly, the anti-allodynic effects of JZL184 (8 mg/kg) persisted and did not undergo tolerance. A separate cohort was administered a sub-analgesic dose of JZL184 (1 mg/kg), diclofenac sodium (1.85 mg/kg), or both compounds concurrently. This subthreshold JZL184 and diclofenac sodium combination attenuated HPI-induced allodynia, suggesting an additive drug interaction. Finally, HPI increased pro-inflammatory cytokine levels, which were unaltered by MAGL inhibition despite the anti-allodynia assessed behaviorally. These data support simultaneously targeting endocannabinoids and COX enzymes as a potential post-operative pain management approach.

Cannabis use is highly prevalent in people with psychotic disorders and is associated with adverse outcomes. We updated our 2020 systematic review related to the efficacy of technology-based psychological interventions (TBPIs) to decrease cannabis use in individuals with psychosis, the design of TBPIs, and their acceptability. We searched Medline, PubMed, Embase, CINAHL, PsycINFO, and EMB Reviews for references indexed between November 27, 2019, and July 27, 2023, and used the PRISMA guidelines to report the results. We screened 5083 unique records and retained three studies for the narrative synthesis. Two quantitative studies showed promising results of internet or virtual reality-based psychological interventions that incorporate cognitive behavioral therapy, motivational interviewing, and psychoeducation principles on the frequency and quantity of cannabis use. A qualitative exploratory study provided an integrative synthesis of patient and clinician opinions pertaining to the use of psychological approaches and technology to tackle cannabis misuse in individuals with psychosis. In contradiction with the rapidly expanding mobile-health solutions in the field of mental health, there is a dearth of research related to the use of internet and app-based psychological interventions for cannabis use in individuals with psychosis. The use of qualitative research is pivotal in the development of TBPIs. Our initial review and its update show that only 11 peer-reviewed journal articles that met our inclusion criteria have been published so far.

Few studies have directly compared the bioavailability of different cannabinoid formulations. Our goal was to assess the pharmacokinetic parameters and relative bioavailability of two Δ9-tetrahydrocannabinol:cannabidiol (THC:CBD) formulations: orally administered THC:CBD extract and oromucosally administered nabiximols. This pilot crossover study counterbalanced (1) 1 mL of orally administered THC:CBD extract (10 mg/mL each of THC and CBD in grapeseed oil) and (2) oromucosally administered nabiximols (four sprays of 2.7 mg THC and 2.5 mg CBD per spray, for a total dose of 10.8 mg THC and 10 mg CBD). Blood samples were obtained pre-dose and at 16 post-dose timepoints over 24 h. Pharmacokinetic parameters were calculated for THC, 11-hydroxy-tetrahydrocannabinol (11-OH-THC), and CBD. Twelve occasional cannabis users (6 male, 6 female) were tested under fasting conditions. for THC and CBD was significantly higher with significantly shorter half-lives for THC:CBD extract versus nabiximols. for nabiximols was significantly higher in males compared with females. Under both treatment conditions, THC and CBD were undetectable by 24 h post-dose, and 11-OH-THC was markedly reduced from its peak. No serious adverse events were reported. Little is known about the comparative pharmacokinetics of commercially available cannabis products. This pilot study shows that the extract formulation achieved higher THC and CBD concentrations within a shorter time frame than nabiximols. These findings may have implications for clinical populations using these formulations therapeutically. Future studies should examine multiple doses in the context of therapeutic outcomes to characterize the relative clinical utility of these formulations.

Cannabidiol (CBD) exhibits multiple therapeutic properties, but its use in advanced cancer patients raises concerns about potential drug-drug interactions (DDIs) due to polypharmacy. This study aims to look for evidence of DDIs between concomitant medications and CBD oil in a randomized placebo-controlled trial of CBD oil for symptom control (MedCan-1 parent study). Surrogate measures were used to identify possible drug interactions: (1) the maximum mL of oil self-selected by patients in CBD or placebo groups in relation to opioids, specific drug groups, or individual agents; (2) the occurrence of any new or worse adverse effect in relation to the study arm and the concomitant medication classes/medications of interest. The dose of CBD self-selected by participants was not related to opioid use or medications, including benzodiazepines and antipsychotics. The likelihood of developing an adverse effect while on study or when taking specific medications was not increased by CBD. Participants on paracetamol tolerated a higher dose of CBD. Concerns regarding the development of clinically significant drug interactions when taking CBD in the context of anti-cancer and other concomitant medications at least in the short term may be unfounded.

Veterans use cannabis as a chronic pain treatment due to a combination of the easing of restrictions and dissatisfaction with care standards. The segregation of medical cannabis from conventional health systems may translate to opportunities and disadvantages that are not well defined. Our study aimed to characterize how Veterans with chronic pain approach using cannabis for symptom management, including product access, developing a treatment plan, and its integration into daily life. We used an interpretive description design and conducted semi-structured interviews with U.S. Veterans in Michigan who had chronic pain; were aged 21 years or older; and (a) used cannabis, (b) were planning to use cannabis, or (c) interested in learning about how cannabis could help with pain. We analyzed deidentified interview transcripts to develop themes that focused on how Veterans approached new and continued use of cannabis for chronic pain management. Participants were Veterans with chronic pain, median age = 50 years ( = 32). Participants described how factors at the individual, relationship, community, and societal levels influenced their interest in and use of cannabis for chronic pain. We identified five main themes: (1) cannabis supports holistic wellness, but there are also undesired effects; (2) medical cannabis requires a personalized treatment approach; (3) Veterans seek expanded access to medical cannabis and more assurance regarding product safety and efficacy; (4) sociopolitical attitudes and advocacy shape medical cannabis acceptability; and (5) the interest in research to inform treatment approaches and facilitate access. This article illustrates how Veterans approached using cannabis for chronic pain management. Findings illuminate the potential value of cannabis for Veterans with chronic pain while also highlighting numerous obstacles and limitations related to its use. There are opportunities for health care providers to support Veterans who are interested in cannabis while research regarding efficacy and safety continues. Future efforts should engage Veterans to collectively work toward a better understanding of cannabis as a pain treatment option.

The conscientious prescribing of antiemetics by chemotherapy-induced nausea and vomiting (CINV) risk was highlighted in the American Society of Clinical Oncology (ASCO) "Choosing Wisely" recommendations. The pharmacologic properties of medical marijuana (MMJ) may allow for decreased incidence of CINV; however, little is known about the effects of MMJ on the use of antiemetics. This study aimed to determine if MMJ cardholder status, which enables access to MMJ, is associated with antiemetic overuse among patients with cancer. This population-based secondary data analysis examined a retrospective cohort derived from the linked Arkansas All Payers Claims Database (2013-2020) and MMJ cardholder registry (2013-2019). The cohort consisted of 20,558 patients with cancer aged 18 and older with a chemotherapy claim in an outpatient setting within 12 months of a cancer diagnosis. Exposure was a registration to receive an MMJ card that permitted access to MMJ. The primary outcome of interest was antiemetic overuse, as characterized by the ASCO recommendation. Antiemetic use associated with chemotherapy was identified through filled prescriptions and medical claims. Multivariable logistic regression, adjusted for baseline demographic and prescription characteristics, was used to calculate the adjusted odds ratios (aOR) of antiemetic overuse among MMJ cardholders compared with non-MMJ cardholders. Among 20,558 eligible patients, 436 (2.1%) had an MMJ card at some point in the study period. Antiemetic overuse was identified in 7.5% of chemotherapy cycles. Compared with non-MMJ cardholders, MMJ cardholders were less likely to experience antiemetics overuse (aOR: 0.76, < 0.001). Patients with fewer chemotherapy cycles and younger in age had higher odds of antiemetic overuse compared with those with more chemotherapy cycles. The risk of antiemetic overuse did not differ based on gender and rurality of residency. Route of chemotherapy administration, CINV risk category, and type of cancer also impacted the odds of antiemetic overuse. The findings indicate that MMJ cardholders are significantly less likely to experience antiemetic overuse than non-MMJ cardholders. Further investigation into the use, effectiveness, and safety of cannabis for CINV mitigation is needed to inform patient and provider decision-making.

Cannabidiol (CBD), a phytocannabinoid of increasing interest for its purported therapeutic effects, is primarily consumed ingestion and inhalation. While the toxicology of orally administered CBD has been reported, little is known about the effects of CBD inhalation. Doses selected for the present analysis allowed for evaluation of dose-response at concentrations >100-fold higher than typical human consumption levels. CBD (98.89% pure) was formulated in propylene glycol (PG) and aerosolized by nebulization to evaluate biological response after nose-only inhalation. Sprague Dawley rats ( = 35 males, 30 females) were exposed to 1.0 and 1.3 mg/L nominal concentrations of CBD and PG, respectively, for 12-180 min. Resulting average daily presented dose ranges were 8.9-138.5 mg/kg CBD and 11.3-176.0 mg/kg PG. Aerosols of 1.4 µm median diameter were achieved. Biological response indicators included clinical signs, clinical chemistry, hematology, body/organ weights, and pulmonary/systemic histopathology. Inflammatory and necrotic responses were observed in the nose at the highest doses of CBD. Limited findings in the larynx and lung were mainly observed at higher doses. There were no histological findings in extrapulmonary organs. Dosimetry modeling differentiated the no observable adverse effect level between the nasal region and lungs to be 2.8 and 10.6 mg/kg CBD, respectively. Dose-depending findings of histological changes in the respiratory tract are observed at high doses. At lower doses consistent with typical over-the-counter vape products there appears to be substantial safety margin in the present study (93- and 353-fold lower for nose and lung, respectively).