Doses Of Cannabis Research Articles

Cannabis and Cannabinoid Signaling: Research Gaps and Opportunities.

Cannabis and its products have been used for centuries for both medicinal and recreational purposes. The recent widespread legalization of cannabis has vastly expanded its use in the United States across all demographics except for adolescents. Meanwhile, decades of research have advanced our knowledge of cannabis pharmacology and particularly of the endocannabinoid system with which the components of cannabis interact. This research has revealed multiple targets and approaches for manipulating the system for therapeutic use and to ameliorate cannabis toxicity or cannabis use disorder. Research has also led to new questions that underscore the potential risks of its widespread use, particularly the enduring consequences of exposure during critical windows of brain development or for consumption of large daily doses of cannabis with high content Δ 9-tetrahydrocannabinol. This article highlights current neuroscience research on cannabis that has shed light on therapeutic opportunities and potential adverse consequences of misuse and points to gaps in knowledge that can guide future research. SIGNIFICANCE STATEMENT: Cannabis use has escalated with its increased availability. Here, the authors highlight the challenges of cannabis research and the gaps in our knowledge of cannabis pharmacology and of the endocannabinoid system that it targets. Future research that addresses these gaps is needed so that the endocannabinoid system can be leveraged for safe and effective use.

Functional brain connectivity predictors of prospective substance use initiation and their environmental correlates

BackgroundEarly substance use initiation (SUI) places youth at substantially higher risk for later substance use disorders. Furthermore, adolescence is a critical period for the maturation of brain networks, the pace and magnitude of which are susceptible to environmental influences and may shape risk for SUI. MethodsWe examined whether patterns of functional brain connectivity during rest (rsFC), measured longitudinally in pre-and-early adolescence, can predict future SUI. Next, in an independent sub-sample, we tested whether these patterns are associated with earlier environmental exposures, specifically neighborhood pollution and socioeconomic dimensions. We utilized data from the Adolescent Brain Cognitive Development (ABCD) Study®. SUI was defined as first-time use of at least one full dose of alcohol, nicotine, cannabis, or other drugs. We created a control group (N = 228) of participants without SUI who were matched with the SUI group (N = 233) on age, sex, race/ethnicity, and parental income and education. ResultsMultivariate analysis showed that whole-brain rsFC from 9-10 to 11-12 years of age (prior to SUI) prospectively differentiated the SUI and control groups. The SUI-related rsFC pattern was also related to aging in both groups, suggesting a pattern of accelerated maturation in the years prior to SUI. This same pattern of rsFC was predicted by higher pollution, but not neighborhood disadvantage (adjusted for family socioeconomic factors) in an independent sub-sample (N = 2,854). ConclusionBrain functional connectivity patterns in early adolescence that are linked to accelerated maturation can predict SUI in youth and are associated with exposure to pollution.

Medical Cannabis Dosing Trajectories of Patients: Evidence From Sales Data

Medical cannabis use is rising with limited high-quality clinical trial data to guide dosing. This study relies on real-world, longitudinal medical cannabis purchase data to provide information on Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) dosing trends for patients with qualifying medical conditions. A retrospective study of purchases by 16,727 patients obtaining medical cannabis from dispensaries located in New York between 2016 and 2019, recorded in point-of-sale data. Group-based trajectory modeling was used to identify clusters of patients following similar progressions in dosing of THC and CBD over time. χ2 tests were performed to identify which patient characteristics and qualifying medical conditions were associated with membership in each trajectory group. Six trajectory groups were identified that described different patterns in the THC and CBD doses that patients purchased over the whole time period. For THC, the majority of patients (62.6%) purchased a steady amount but at different levels: consistently low (4.1 mg) or moderate (7.4 mg). Three groups, representing 22.0% together, exhibited doses that either fluctuate or constantly increase over time (5-20 mg). A final group of patients (15.8%) exhibited constant decrease in dose from 11 to 5 mg. For CBD, the data show similar trajectories, but at the generally higher values (4-16 mg). Patients with chronic pain, neuropathy, and cancer were overrepresented in groups where higher doses of THC were purchased over time. Patients with epilepsy had a higher representation in groups with higher doses of CBD across time. Results suggest heterogeneous dosing patterns and trajectories in the use of medical cannabis by patients with different medical conditions.

Effects of Cannabis sativa on the Neuromuscular System and Cognitive Behavior of Male Wistar Rats

This research investigates the influence of Cannabis sativa on the neuromuscular system and cognitive behavior of male Wistar rats. Twenty rats were randomly allocated into five groups, with Group 5 serving as the control and Groups 1 to 4 receiving oral doses of Cannabis sativa at concentrations of 100 mg/kg, 200 mg/kg, 400 mg/kg, and 800 mg/kg, respectively. The study employs various behavioral tests, including the Beam Walking Test, Morris Water Maze, Tail Suspension Test, Open-Field Test, and Hand Grip Test, to assess the effects of Cannabis on Wistar rats. Results from the Beam walking Test suggest that the control group (Group 5) demonstrated the best neuromuscular performance, with Group 3, (receiving 400 mg/kg), following closely. In the Morris Water Maze, Groups 1 and 5 exhibited superior results, while higher doses had a negative impact. Tail Suspension Test outcomes revealed that Group 5 displayed non-depressive behavior, while Group 4 exhibited signs of depression. The Hand Grip Test demonstrated longer duration for Groups 2 and 4, suggesting a positive impact on muscle strength compared to the control, on Open Field Test, Group 1 spent the most of the time at the center, indicating lower anxiety, whereas other groups displayed increased anxiety with higher Cannabis doses. The study highlights complex and dose-dependent effects of Cannabis on neuromuscular and cognitive parameters. Caution is advised in interpreting these findings, and further research is recommended to elucidate underlying mechanisms and explore a broader range of doses. Keywords: Cannabis sativa, cognitive function neuromuscular function

Functional brain connectivity predictors of prospective substance use initiation and their environmental correlates.

Early substance use initiation (SUI) places youth at substantially higher risk for later substance use disorders. Furthermore, adolescence is a critical period for the maturation of brain networks, the pace and magnitude of which are susceptible to environmental influences and may shape risk for SUI. We examined whether patterns of functional brain connectivity during rest (rsFC), measured longitudinally in pre-and-early adolescence, can predict future SUI. In an independent sub-sample, we also tested whether these patterns are associated with key environmental factors, specifically neighborhood pollution and socioeconomic dimensions. We utilized data from the Adolescent Brain Cognitive Development (ABCD) Study®. SUI was defined as first-time use of at least one full dose of alcohol, nicotine, cannabis, or other drugs. We created a control group (N = 228) of participants without SUI who were matched with the SUI group (N = 233) on age, sex, race/ethnicity, and parental income and education. Multivariate analysis showed that whole-brain rsFC prior to SUI during 9-10 and 11-12 years of age successfully differentiated the prospective SUI and control groups. This rsFC signature was expressed more at older ages in both groups, suggesting a pattern of accelerated maturation in the SUI group in the years prior to SUI. In an independent sub-sample (N = 2,854) and adjusted for family socioeconomic factors, expression of this rsFC pattern was associated with higher pollution, but not neighborhood disadvantage. Brain functional connectivity patterns in early adolescence that are linked to accelerated maturation and environmental exposures can predict future SUI in youth.

Abstract PO4-18-05: Safety and Feasibility of Administration of an Oral Cannabis Preparation in The Preoperative Period in Breast and Oral Cavity Cancer

Abstract Introduction- Cannabis is world’s oldest cultivated medicinal plant. It has potential applications in oncology, in reducing chronic pain, stimulating appetite, alleviating nausea/vomiting, improving overall well-being as well as its anti-cancer properties. We conducted a phase-1 dose escalation study to determine safety of pre-operative oral cannabis in breast and oral cavity squamous cell carcinoma (OC-SCC) with an intent to explore its anticancer potential in the “pre-operative” window. The primary objective was to determine maximum tolerated dose (MTD) and establish dose limiting toxicity (DLT). Secondary objectives were pharmacokinetic profiling and transcriptomic analysis of tumour tissue. Methodology- Primary objective was to determine maximum tolerated dose (MTD) and establish dose limiting toxicity (DLT). Secondary objectives were pharmacokinetic profiling and transcriptomic analysis of tumour tissue. Non-metastatic breast and OC-SCC patients planned for curative surgery were consented after thorough medical and mini-psychiatric evaluation with Brief Psychiatry Rating Scale (BPRS). The investigational product (IP) comprised of a capsule containing 2.5mg of tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD) in 100 mg monocrotolyn oil extract of dried leaves of C. sativa. The capsules were manufactured in an Ayurvedic GMP facility. The classical 3+3, phase-1 design used modified Fibonacci sequence for dose escalation, starting with 5mg THC+5mg CBD. Patients received IP once a day for 5 days after breakfast with hemodynamic and psychiatric monitoring and underwent the planned surgery on day-6. Pharmacokinetic samples were collected at predefined time-points and plasma levels of THC, 11-OH-THC, 11-COOH-THC and CBD were determined using a validated LC-MS/MS method. Tumour tissue was collected before 1st dose of cannabis and during surgery for biomarker analysis. Results- A total of 12 patients were enrolled (6-breast, 3-buccal mucosa, and 3-tongue cancers). First 3 patients completed the study without DLT at 5+5mg dose. A DLT was observed at dose level-2 (10+10mg) and therefore additional 3 patients were enrolled at the same dose. Two patients out of six at this dose had DLT (anxiety- grade-3 and somnolence- grade-2) necessitating dose de-escalation in the next cohort. At 7.5+7.5mg dose, all 3 patients tolerated the IP(MTD). Ten patients completed the study protocol. Common adverse effects were headache (2/12, grade-1), heavy head (8/12, grade-1), hypotension (2/12, grade-1 and 3), epigastric discomfort (1/12, grade-1), diarrhoea (1/12, grade-1), hyponatremia (1/12, grade-1), hypertension (1/12, grade-2), anxiety (1/12, grade-2). Pharmacokinetics of both CBD and THC was less than dose proportional. At the MTD (7.5+7.5), day-1 and day-5 AUC0-24 [median (range)] for CBD were 21.75 (12.44–41.44) ng/ml−1*h and 24.85 (13.72–35.93) ng/ml−1*h respectively. Similarly, for THC, day 1 and day 5 AUC0-24 were 11.79 (8.06–70.58) ng/ml−1*h and 68.98 (1.78 – 136.17) ng/ml−1*h, respectively. Significant accumulation of both CBD and THC was observed across all doses from day 1 to 5. A high variability in pharmacokinetics was observed for both constituents (CV Cmax = 101.26% and 117.48%; CV AUC0-24 = 102.50% and 112.37% for CBD and THC respectively. The median half-life of CBD and THC was 2.2 (1.6–10.7) and 1.9 (1.6–2.4) h respectively. There was no correlation observed between drug exposure and toxicity. There was no significant change in BPRS score before and after IP. Conclusion- We report the first phase-1 study of cannabis in breast and OC-SCC cancer in pre-operative setting for its anti-cancer potential. Biomarker analysis is awaited. MTD identified will be further explored in phase 2/3 clinical trials in breast, oral cavity, lung and pancreatic cancer with survival endpoints. Citation Format: Rajendra Badwe, Shalaka Joshi, Shiva Thiagarajan, Vikram Gota, Vaibhav Vanmali, Pallavi Daphale, Jayita Deodhar, Rohan Chaubal, Rohini Hawaldar, Jaya Chitra Aadhi, Saurabh Kumar Gupta, Delzaad Deolaliwala, Anil Bhansali, Siddhant Mistry, Satyajeet Singh, Nita Nair, Vani Parmar, Sudeep Gupta. Safety and Feasibility of Administration of an Oral Cannabis Preparation in The Preoperative Period in Breast and Oral Cavity Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-18-05.

Abstract WP271: Marijuana Use and Stroke: A Systematic Review and Meta-Analysis

Introduction: The prevalence of stroke among young adults has been on the rise, along with a similar rising trend in marijuana use. Ischemic strokes, intracerebral hemorrhage (ICH), reversible cerebral vasoconstriction syndrome (RCVS), and subarachnoid hemorrhage (SAH) are among the commonly reported neurovascular events associated with marijuana use. We attempted to systematically review the literature and find an association between marijuana use and stroke. Methods: We searched data from PubMed/Medline, SCOPUS and studies that met the inclusion criteria were selected and Review Manager 5.4.1 was used for statistical analysis of data. Twenty six studies with a total of 13,550 patients were selected of which 11 were included in the meta analysis. Results: The pooled odds of cannabis use in ischemic stroke patients was statistically significant at 1.16 (95% CI: 1.07-1.25). Among patients with undefined stroke, pooled odds of cannabis use were 0.86 (0.43, 1.72). Meta-analysis for the SAH subgroup could not be done due to varying outcome measures. Overall, upon combining all the subgroups, the odds of cannabis use among stroke patients was not significant (OR: 0.96; 0.77,1.20, I2-100%). High heterogeneity might be the pooling of studies with different stroke types and individual study variations. Conclusions: Cannabis use was significantly associated with ischemic stroke although this significance was not maintained among other stroke subgroups and with overall analysis. Further research should be done to assess the association of dose, chronicity and frequency of cannabis on stroke to further delineate the true association.

Anticoagulant drug-drug interactions with cannabinoids: Asystematic review.

This systematic review evaluates the extent to which the effect of anticoagulants may be altered in the presence of cannabinoids. The following databases were searched: EMBASE, PubMed, Web of Science, Scopus, PscycINFO, and CINAHL from database inception through May 2023. Search terms included cannabis AND anticoagulant AND drug interactions and related keywords. The major outcome was hemorrhage or thrombosis and if available the relative change in quantitative intensity of anticoagulation after cannabinoid exposure. The search generated 959 citations. After the removal of 440 duplicates, 519 citations were screened. Overall, with the exception of warfarin, evidence supporting an interaction between cannabinoids and anticoagulants is non-existent. Seven case reports evaluating an interaction with warfarin were reported. Cannabis doses involved were either extremely high (e.g., >260 mg/day of delta-9-tetrahydrocannabidiol [THC] or >600 mg/day of cannabidiol [CBD]) or were not known. Hemorrhage was identified in 14.2% (1/7) of reports and thrombosis in 0%. Quantitative anticoagulation levels were increased in patients on warfarin (elevated International Normalized Ratio [INR]) in six of seven cases. A maximum INR change was available in five of seven reports, ranging from +0.4 to +9.61. One report found no change in INR after 4 days of medical cannabis exposure. Another report outlined two separate episodes of INR elevation associated with bleeding requiring hospitalization and reversal after marijuana smoking. Four cases involved reduction in weekly warfarin dose ranging from 22% to 31%. The Drug Information Probability Score was calculated in six cases, with a score of probable for five cases and possible for one. Very low-quality data support a potential drug-drug interaction with warfarin and both THC and CBD. Clinician recognition of this potential interaction is important. Available evidence supports the need to conduct a drug interaction study between cannabinoids and warfarin to clarify the existence of an interaction.

Toxic Tetrahydrocannabinol (THC) Dose in Pediatric Cannabis Edible Ingestions.

The study characterizes cannabis toxicity in relation to tetrahydrocannabinol (THC) dose in pediatric edible cannabis ingestions. This is a retrospective review of children aged <6 years presenting with edible cannabis ingestions of known THC dose within a pediatric hospital network (January 1, 2015-October 25, 2022). Cannabis toxicity was characterized as severe if patients exhibited severe cardiovascular (bradycardia, tachycardia/hypotension requiring vasopressors or intravenous fluids, other dysrhythmias), respiratory (respiratory failure, apnea, requiring oxygen supplementation), or neurologic (seizure, myoclonus, unresponsiveness, responsiveness to painful stimulation only, requiring intubation or sedation) effects. Cannabis toxicity was characterized as prolonged if patients required >6 hours to reach baseline. The relationship between THC dose and severe and prolonged toxicity was explored using multivariable logistic regression and receiver operator characteristic curve analyses. Eighty patients met inclusion. The median age was 2.9 years. The median THC ingestion was 2.1 mg/kg. Severe and prolonged toxicity was present in 46% and 74%, respectively. THC dose was a significant predictor of severe (adjusted odds ratio 2.9, 95% confidence interval: 1.8-4.7) and prolonged toxicity (adjusted odds ratio 3.2, 95% confidence interval: 1.6-6.5), whereas age and sex were not. Area under the curve was 92.9% for severe and 87.3% for prolonged toxicity. THC ingestions of ≥1.7 mg/kg can predict severe (sensitivity 97.3%) and prolonged toxicity (sensitivity 75.4%). The THC dose of edible cannabis correlates to the degree of toxicity in children <6 years old. The threshold of 1.7 mg/kg of THC may guide medical management and preventive regulations.

Cannabis dispensary staff approaches to counseling on potential contraindications to cannabis use: insights from a national self-report survey

BackgroundLegal cannabis is available in more than half of the United States. Health care professionals (HCPs) rarely give recommendations on dosing or safety of cannabis due to limits imposed by policy and lack of knowledge. Customer-facing cannabis dispensary staff, including clinicians (pharmacists, nurses, physician’s assistants), communicate these recommendations in the absence of HCP recommendations. Little is known about how dispensary staff approach individuals with complex medical and psychiatric comorbidities. Using responses from a national survey, we describe how cannabis dispensary staff counsel customers with medical and psychiatric comorbidities on cannabis use and examine whether state-specific cannabis policy is associated with advice given to customers.MethodsNational, cross-sectional online survey study from February 13, 2020 to October 2, 2020 of dispensary staff at dispensaries that sell delta-9-tetrahydrocannabinol containing products. Measures include responses to survey questions about how they approach customers with medical and psychiatric comorbidities; state medicalization score (scale 0-100; higher score indicates more similarity to regulation of traditional pharmacies); legalized adult-use cannabis (yes/no). We conducted multiple mixed effects multivariable logistic regression analyses to understand relationships between state medicalization and dispensary employees’ perspectives.ResultsOf 434 eligible respondents, most were budtenders (40%) or managers (32%), and a minority were clinicians (18%). State medicalization score was not associated with responses to most survey questions. It was associated with increased odds of encouraging customers with medical comorbidities to inform their traditional HCP of cannabis use (Odds ratio [OR]=1.2, 95% confidence interval [CI] 1.0-1.4, p=0.03) and reduced odds of recommending cannabis for individuals with cannabis use disorder (CUD) (OR=0.8, 95% CI 0.7-1.0, p=0.04). Working in a state with legalized adult-use cannabis was associated with recommending traditional health care instead of cannabis in those with serious mental illness (OR 2.2, 95% CI 1.1-4.7, p=0.04). Less than half of respondents believed they had encountered CUD (49%), and over a quarter did not believe cannabis is addictive (26%).ConclusionsWhen managing cannabis dosing and safety in customers with medical and psychiatric comorbidity, dispensary staff preferred involving individuals’ traditional HCPs. Dispensary staff were skeptical of cannabis being addictive. While state regulations of dispensaries may impact the products individuals have access to, they were not associated with recommendations that dispensary staff gave to customers. Alternative explanations for dispensary recommendations may include regional or store-level variation not captured in this analysis.

Does medicinal cannabis or cannabis consumption have an influence on the perioperative anesthesiological management?

The greatly increasing use of medicinal cannabis products as well as the upcoming legalization of cannabis not only require ageneral re-evaluation of how these substances might be classified as illegal drugs, but also enforce acritical view on the possible consequences that cannabis consumption might have on the anesthesiological strategies applied for surgical procedures. Although high-quality clinical studies are still lacking, several clinical studies meanwhile indicate that an active preoperative cannabis consumption seems to be associated with relevant pathophysiological aspects. Patients who regularly consume high doses of cannabis show an increased risk of cardiovascular and respiratory complications as well as the postoperative nausea and vomitting (PONV) associated with anesthesia. This also applies to relatively young patients. Moreover, the requirements for general anesthetics and analgesics seem to be increased in the context of cannabis consumption, e.g., these patients may require additional efforts when it comes to monitoring the depth of anesthesia and providing apersonalized multimodal postoperative pain therapy. It therefore appears to be meaningful to carefully assess and document the extent and duration of the preoperative cannabis consumption during the preoperative assessment. Furthermore, the possibility to perform apreoperative dose reduction of cannabis products in cases with high doses should at least be considered. As the consumption of cannabis is not only increasing in Germany but also worldwide, important future insights will offer aguide towards asafe handling of cannabis in perioperative medicine in the coming years.

Dose-dependent Relationships of Same-day and Typical Substance Use to Sleep Duration in College Cannabis and Alcohol Users: A Multilevel Modeling Approach Using Daily Diary Data.

This study characterized how quantities of cannabis and alcohol use affect sleep. Single-day and typical cannabis and alcohol use patterns were considered to assess acute-chronic use interactions. Linear and non-linear associations assessed dose-dependence. College students (n=337; 52% female) provided 11,417 days of data, with up to five time points per day. Daily self-reported sleep duration, cannabis use quantity, and alcohol use quantity were subjected to linear mixed modeling to capture linear and curvilinear associations between single-day and typical use on same-night and typical sleep. Sleep duration (difference between bedtime and waketime) was the outcome. Quantity of cannabis used each day andtypical quantity used across all days were predictors in the cannabis models. Parallel single-day and typical alcohol variables were predictors in the alcohol models. Follow-up analyses excluded days with alcohol-cannabis co-use. Main effects of single-day and typical cannabis quantity on sleep duration were observed when all cannabis-use days were modeled. Higher than typical doses of single-day and typical cannabis were associated with longer sleep durations, but only to a point; at the highest doses, cannabis shortened sleep. A main effect of single-day alcohol quantity and two interactions (single-day use with both linear and curvilinear typical use) on sleep duration were observed when all alcohol-use days were modeled. Greater alcohol consumption on a given day led to shorter same-night sleep, but typically heavier drinkers required higher doses than typically lighter drinkers to experience these adverse effects. Follow-up models suggested alcohol co-use may contribute to the purported sleep-promoting effects of cannabis.

Collisions and cannabis: Measuring the effect of recreational marijuana legalization on traffic crashes in Washington State

Objective Washington State was among the first states in the US to legalize recreational consumption and retail sales of marijuana. Recreational use of cannabis was legalized December 6, 2012, following the passage of Initiative 502 30 days prior. Roughly 19 months later the first retail cannabis stores opened their doors for public sales (“commercialization”). I measure the impact of cannabis legalization and commercialization on traffic collisions in Washington State. Methods With county-level vehicle crash data from the Washington State Department of Transportation collected monthly, I utilize an interrupted time-series framework with Poisson estimation to compare traffic collisions with recreational retail cannabis sales revenue from 2011 (three years pre-commercialization) through 2017 (three years post-commercialization). First, I measure the shift in collisions brought about by Washington’s 2012 cannabis legalization. Then, I compare retail cannabis sales—a measure of commercialization—to traffic collisions based on severity of injury (fatal, severe injury, minor injury, non-injury, and all). Results After controlling for confounding factors, evidence suggests that recreational cannabis legalization led to fewer fatal and serious injury collisions. Retail cannabis sales generally correlate with more traffic collisions, particularly for less severe (minor injury) crashes. These findings are robust to the inclusion of additional control variables pertaining to county-level cannabis usage and driving behavior while intoxicated. Conclusions Cannabis legalization led to fewer fatal, serious, and minor injury collisions. Commercialization (cannabis sales) correlated with an increase in less severe crashes. Although cannabis use generally increased in Washington State following legalization/commercialization, survey data suggest that driving behavior while under the influence of cannabis did not change significantly over the post-commercialization period. Future research should focus on measuring the dose-dependent impact of cannabis consumption on traffic collisions. This should include recognition of the importance of cannabis dosing, timing, and route of consumption. Lastly, the dangers of poly-drug driving—particularly cannabis and alcohol—are well established and should be high priority for further research.

Medicinal Cannabis Guidance and Resources for Health Professionals to Inform Clinical Decision Making

PurposeInterest in the use of cannabis as a medicine has markedly increased during the last decade, with an unprecedented number of patients now seeking advice or prescriptions for medicinal cannabis. Unlike other medicines prescribed by physicians, many medicinal cannabis products have not undergone standard clinical trial development required by regulatory authorities. Different formulations with varying strengths and ratios of tetrahydrocannabinol and cannabidiol are available, and this diversity of medicinal cannabis products available for a myriad of therapeutic indications adds to the complexity. Physicians face challenges and barriers in their clinical decision making with medicinal cannabis because of current evidence limitations. Research efforts to address evidence limitations are ongoing; in the interim, educational resources and clinical guidance are being developed to address the gap in clinical information and support the needs of health professionals. MethodsThis article provides an overview of various resources that health professionals may use when seeking information about medicinal cannabis in the absence of high-quality evidence and clinical guidelines. It also identifies examples of international evidence-based resources that support clinical decision making with medicinal cannabis. FindingsSimilarities and differences between international examples of guidance and guideline documents are identified and summarized. ImplicationsGuidance can help guide physicians in the individualized choice and dose of medicinal cannabis. Before quality clinical trials and regulator-approved products with risk management programs, safety data require clinical and academic collaborative pharmacovigilance.

The Effect of Feeding Laying Hens with Nonindustrial Hemp Seed on the Fatty Acid Profile, Cholesterol Level, and Tocopherol Composition of Egg Yolk.

The purpose of this study was to evaluate how cannabis-derived nonindustrial hemp seed (HS) inclusion in laying hen diets, as well as treatment duration, affected the fatty acid (FA) profile, cholesterol level, and tocopherol composition of egg yolks. Ninety-six (n = 96) Lohmann Brown classic laying hens were randomly assigned to one of the four groups: control (standard diet) and HS-containing diets (10% HS, 20% HS, and 30% HS). The study was conducted for a period of 4 months. The findings demonstrated that the FA profile and the tocopherol composition are strongly impacted by the addition of HS to the diet of laying hens (p < 0.05), but the cholesterol content remained unaffected. The increase in the dose of cannabis incorporated into the hen's diet (HS-30% group) led to a significant increase in the amounts of the polyunsaturated fatty acids n-3 and n-6 content of egg yolk. This enrichment was accompanied by a considerable decrease in the n-6/n-3 ratio (p < 0.001) from 8.19 to 4.88, on day 84 of the experiment. The total tocopherol content significantly increased (p < 0.05) from 281.44 (control) to 327.02 μg/g yolk (HS-30%) on day 84. Finally, in the context of warfare, these seeds might be used as a feed additive for laying hens to produce higher nutritive value eggs with affordable prices.

An Individuality of Response to Cannabinoids: Challenges in Safety and Efficacy of Cannabis Products.

Since legalization, cannabis/marijuana has been gaining considerable attention as a functional ingredient in food. ∆-9 tetrahydrocannabinol (THC), cannabidiol (CBD), and other cannabinoids are key bioactive compounds with health benefits. The oral consumption of cannabis transports much less hazardous chemicals than smoking. Nevertheless, the response to cannabis is biphasically dose-dependent (hormesis; a low-dose stimulation and a high-dose inhibition) with wide individuality in responses. Thus, the exact same dose and preparation of cannabis may be beneficial for some but toxic to others. The purpose of this review is to highlight the concept of individual variations in response to cannabinoids, which leads to the challenge of establishing standard safe doses of cannabis products for the general population. The mechanisms of actions, acute and chronic toxicities, and factors affecting responses to cannabis products are updated. Based on the literature review, we found that the response to cannabis products depends on exposure factors (delivery route, duration, frequency, and interactions with food and drugs), individual factors (age, sex), and susceptibility factors (genetic polymorphisms of cannabinoid receptor gene, N-acylethanolamine-hydrolyzing enzymes, THC-metabolizing enzymes, and epigenetic regulations). Owing to the individuality of responses, the safest way to use cannabis-containing food products is to start low, go slow, and stay low.

State Variation in U.S. Medical Cannabis Limits, Restrictions, and Therapeutic Cannabis Dosing.

Wide variation exists in the possession limits of cannabis products sold for medical use in the U.S. as well as the tetrahydrocannabinol (THC) content of cannabis products. Prior work has found that legal limits on recreational cannabis sold per transaction may promote moderate use and diversion. This paper finds similar results for monthly medical cannabis limits. In the present analyses, state limits on medical cannabis were aggregated and converted into 30-day limits and 5 milligram (mg) THC doses. Grams of pure THC were calculated using plant weight limits and medical cannabis median THC potency aggregated from Colorado and Washington state medical cannabis retail sales data. Weight in pure THC was then broken down into 5 mg doses. Weight-based possession limits of cannabis for medical use varied widely across states (range: 1.5-762.05 grams pure THC per 30 days), with three states lacking a quantifiable weight limit (in which limits are not by weight but by physician's recommendation). States generally do not impose limits on the potency of cannabis products, therefore small differences in weight limits can result in large differences in the amount of total THC allowed to be sold. Assuming a typical medical dose of 5 mg and the median THC potency of 21%, current laws allow for sales of 300 (Iowa) to 152,410 (Maine) doses per month. Current state statutes and methods of cannabis recommendation allow patients to increase therapeutic THC doses independently, and perhaps unknowingly. High THC content products combined with the higher purchase or possession limits allowed by medical cannabis laws may lead to an increased potential for overconsumption or diversion.

Prevalence, Perceptions, and Patterns of Cannabis Use Among Cardiac Inpatients at a Tertiary-Care Hospital: A Cross-Sectional Survey

BackgroundCannabis use may adversely affect cardiovascular health. Patterns of use by cardiac patients are unknown. We evaluated the prevalence, perceptions, and patterns of cannabis use among cardiac inpatients. MethodsA consecutive cross-section of cardiac inpatients, hospitalized between November 2019 and May 2020, were surveyed in-person or via telephone. Descriptive statistics and logistic regression were used to examine the characteristics of cannabis use. ResultsThe prevalence of past-12-month cannabis use was 13.8% (95% confidence interval [CI]: 11.8%-16.0%). Characteristics independently associated with cannabis use were as follows: age < 64 years (< 44 years, odds ratio [OR] = 3.96 [95% CI: 1.65-9.53]; age 45-64 years, OR = 2.72 [95% CI: 1.65-4.47]); tobacco use in the previous 6 months (OR = 1.91 [95% CI: 1.18-3.07]); having a cannabis smoker in one’s primary social group (OR = 4.17 [95% CI: 2.73-6.38]); and a history of a mental health diagnosis (OR = 1.82 [95% CI: 1.19-2.79]). Among those using cannabis, 70.5% reported smoking or vaping it; 47.2% reported daily use. Most did not know the tetrahydrocannabinol (THC; 71.6%) or cannabidiol (CBD; 83.3%) content of their cannabis, or the dose of cannabis in their edibles (66.7%). As defined by Canada’s Lower Risk Cannabis Use Guidelines, 96.7% of cannabis users reported ≥ 1 higher-risk use behaviour (mean = 2.3, standard deviation = 1.2). Over 60% of patients expressed no intention to quit or reduce cannabis use in the next 6 months. ConclusionsCannabis use appears prevalent among cardiac patients. Most users demonstrated higher-risk use behaviours and low intentions to quit. Further work is needed to understand the impacts of cannabis use on the cardiovascular system and to develop guidelines and educational tools relating to lower-risk use, for cardiac patients and providers.

Medical Cannabis Use and Inflammatory Cytokines and Chemokines Among Adult Chronic Pain Patients.

Background: Utilizing cannabis as a therapeutic option for chronic pain (CP) has increased significantly. However, data regarding the potential immunomodulatory effects of cannabis in CP patients remain scarce. We aimed at exploring the relationship between cannabis use and inflammatory cytokines and chemokines among a cohort of CP patients. Methods: Adult patients with a CP diagnosis and medical authorization of cannabis were enrolled. Patients completed validated clinical questionnaires and self-reported the effectiveness of cannabis for symptom management. Patients' blood and cannabis samples were analyzed for the presence of four major cannabinoids, two major cannabinoid metabolites, 29 different cytokines/chemokines, and cortisol. The multivariable linear regression model was used to identify cannabis and patient factors associated with immune markers. Results: Fifty-six patients (48±15 years; 64% females) were included, with dried cannabis (53%) being the most common type of cannabis consumed. Seventy percent of products were considered delta-9-tetrahydrocannabinol (Δ9-THC)-dominant. The majority of patients (96%) self-reported effective pain management, and 76% reported a significant decrease in analgesic medication usage (p≤0.001). Compared with males, female patients had higher plasma levels of cannabidiol (CBD), cannabidiolic acid, Δ9-THC, and 11-hydroxy-Δ9-tetrahydrocannabinol but lower concentrations of delta-9-tetrahydrocannabinolic acid and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH). Females had significantly lower eotaxin levels (p=0.04) in comparison to male patients. The regression analysis indicated that high cannabis doses were related to increased levels of interleukin (IL)-12p40 (p=0.02) and IL-6 (p=0.01), whereas female sex was associated with decreased eotaxin (p≤0.01) concentrations. Blood CBD levels were associated with lower vascular endothelial growth factor (p=0.04) concentrations, and THC-COOH was a factor related to decreased tumor necrosis factor alpha (p=0.02) and IL-12p70 (p=0.03). Conclusion: This study provides further support for the patient-perceived effectiveness of cannabis in managing CP symptoms and reducing analgesic medication consumption. The results suggest a potential sex difference in metabolizing cannabinoids, and the varying immune marker concentrations may support a possible immunomodulatory effect associated with patient sex and cannabis product type. These preliminary findings provide grounds for further validation using larger, well-designed studies with longer follow-up periods.

A novel cannabis education clinic for patients with cancer: Patient characteristics from initial visit.

298 Background: Patients with cancer express growing interest in using cannabis to alleviate symptoms and want information from their oncology care teams. However, most oncology clinicians report insufficient knowledge to discuss potential benefits and risks of cannabis with patients. Methods: We created the Cannabis and Cancer Research and Education Clinic (CanCaRE) to educate patients interested in cannabis use through 1:1 video consultations with an oncology advanced practice clinician. We also developed an electronic registry built in REDCap that tracks outcomes including NCI PRO-CTCAE symptom questionnaires. All patients receive an intake survey with questions about their diagnosis, cancer treatments, current symptom burden, cannabis use history, and current medications. Results: During the first 18 months of the CanCaRE clinic, 103 of the 130 patients seen for consultation completed the intake survey. All 16 of our clinic’s medical oncologists had at least one patient receive a consultation. Patients had diverse cancer diagnoses (breast (19%), gynecologic (15%), lung (11%), pancreas (11%)) and were more often white (84%), not currently using cannabis (74%), and female (60%), with a median age of 64 (range 26-92). Most respondents (41%) had stage IV disease with the remaining 32% stage I-III (28% unknown). Table outlines symptom burden at time of initial CanCaRE consultation. The percentage of patients using medications for symptoms was high; non-opioid analgesics (81%), antiemetics (52%), anxiety/depression meds (52%), sleep meds (39%), and opioids (30%). The most common initial cannabis product recommendation included an oral tablet/solution (2.5mg THC/2.5mg CBD) twice daily as well as a THC-dominant vaporizer (3-5mg THC per puff) as needed. Conclusions: The development of a cannabis clinic to provide patients with cancer personalized education and dosing guidance is novel and helps serve an unmet need. Patients have diverse cancer histories and express a high level of symptom burden. Patients and oncology care teams report high satisfaction with our clinic model. Initial cannabis dosing recommendations used a “start low, go slow” titration plan. Analysis has begun on cannabis use patterns and changes in symptoms/concomitant medications to further tailor recommendations that are safe, effective, and cost-efficient. Exploring ways to expand this clinic model to other cancer centers is underway.[Table: see text]