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Background: Cannabis-based medicinal products (CBMPs) are increasingly demonstrating effectiveness in treating a wide range of conditions, with a relatively high safety profile in clinical usage compared to other prescription pain medications and few contraindications. Consultation and other prescription-related costs are, at present, higher for CBMPs than for some other treatment options, leading to some concern around wider prescribing. Research design and Methods: An early cost-effectiveness model was developed to estimate the impact of prescribing CBMPs alone and/or in addition to analgesics, physiotherapy, and cognitive behavioral therapy for chronic pain in the UK for 1 year. Results: Due to their comparative effectiveness, CBMPs were found to be cost saving. Various scenarios were model tested; in all scenarios where CBMPs decrease pain-level states, less resource use is required. Increased efficacy of 5% was conservatively assumed based on current Real-World Evidence. In this scenario, CBMPs were significantly more cost-effective, and as costs relating to the prescribing of these continue to fall, relative savings are predicted to increase. Conclusion: These findings highlight the substantial cost saving that CBMPs may represent for the treatment of chronic pain patients, and the benefits for healthcare providers as a treatment for this often hard-to-treat population. [ABSTRACT FROM AUTHOR]

Increased cases of canine tetrahydrocannabinol (THC) toxicosis have been reported in North America in recent years. Cases are often evaluated on an emergency basis and treatment has relied upon supportive care which can be costly and prohibitive for some pet owners. The purpose of this report is to describe the clinical findings and outcomes in dogs with non-medical, presumptive THC toxicosis treated by administration of a cannibidiol (CBD)-infused transmucosal dissolving sheet. Medical records of six cases of non-medical, presumptive THC toxicosis from a private primary care practice and a private after-hours emergency practice were reviewed and summarized. Five of six cases were treated exclusively with transmucosal CBD (0.4–2.6 mg/kg); one case also received injectable anti-emetic therapy. Lethargy and ataxia noticeably improved and all additional clinical signs resolved within 45 min of treatment in five of six cases. No further follow-up measures for THC toxicosis were required in any case; one case required additional follow-up for presumably unrelated gastrointestinal distress. This is the first report of treatment of canine THC toxicosis by administration of CBD. The use of transmucosal CBD-infused dissolving sheets resulted in expedient resolution of clinical signs in a minimally invasive manner that is accessible to both clients and veterinary practitioners. [ABSTRACT FROM AUTHOR]

ObjectivesMethodsResultsConclusionsClinical ImplicationsTo examine older adults’ cannabidiol (CBD) use and its associations with cannabis use and physical/mental health and other substance use problems.Using the 2022 National Survey on Drug Use and Health (N = 10,516 respondents age 50+), we fitted generalized linear models (GLM) with Poisson and log link using CBD as the dependent variable in the 50–64 and the 65+ age groups.In the 50–64 age group, 18.3% and 18.0% reported past-year CBD and cannabis, respectively, use. In the 65+ age group, the percentages were 14.3% and 8.0%. GLM results showed significant positive associations with both medical and non-medical cannabis use in both age groups. CBD use was positively associated with physical/mental health and illicit drug use problems in the 50–64 age group and with disordered psychotherapeutic drug use in the 65+ age group. Minoritized older adults had a lower likelihood of CBD use.CBD use is common, more so than cannabis especially in the 65+ age group and positively correlated with both medical and nonmedical cannabis use.Research is needed to examine therapeutic benefits and negative effects of CBD use in late life. Public health education is needed for growing numbers of older-adult CBD users. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Discussion Conclusion Chronic pain (CP) affects 35.0%–51.3% of the UK population, with 67%–88% reporting sleep disturbances. Cannabis‐based medicinal products (CBMPs) have shown therapeutic potential in managing CP. Evidence suggests poor sleep worsens pain perception; therefore, this study aimed to assess patient‐reported outcome measures (PROMs) following CBMP treatment in CP patients with and without co‐morbid sleep impairment.A prospective cohort study of CP patients from the UK Medical Cannabis Registry was conducted. Participants were separated by baseline single‐item sleep quality scale (SQS) score into sleep impaired (SQS ≤3) and unimpaired (SQS ≥4) cohorts. The primary outcome assessed changes in PROMs from baseline to 1‐, 3‐, 6‐, and 12‐months. Participants completed the following: SQS, General Anxiety Disorder‐7, EQ‐5D‐5L, Brief Pain Inventory (BPI), and Short‐Form McGill Pain Questionnaire‐2. Significance was defined as p < 0.050.1139 participants met the inclusion criteria (sleep impaired: n = 517, 45.4%; sleep unimpaired: n = 622, 54.61%). The sleep impaired cohort showed improvements in all PROMs at each follow‐up (p < 0.010). The sleep unimpaired cohort showed similar results (p < 0.050), except in SQS and ED‐5Q‐5L: self‐care and anxiety/depression scores (p > 0.050). However, the sleep impaired cohort observed greater improvements in BPI pain severity (p < 0.050) and SQS (p < 0.001) than the sleep unimpaired cohort at all follow‐ups. 2817 adverse events were self‐reported between both cohorts (p = 0.197).These findings align with literature that shows associated improvements in pain outcomes following CBMP administration. Sleep impaired individuals were more likely to experience greater pain severity improvements. However, this was not confirmed on multivariate logistic regression analysis and instead may be confounded by baseline pain severity.Whilst these results show promise for the effects of CBMPs on CP, they must be examined within the limitations of the study design. These findings provide further evidence to support the design of subsequent randomized controlled trials to verify causality between CBMPs and pain outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Cannabis, commonly known for both therapeutic and intoxicating effects, is gaining accessibility on legal markets and traction as a potential alternative therapy for pain mediation, particularly in those suffering from chronic low back pain. However, the effectiveness in this population of legal market forms of cannabis, particularly commonly used edibles, is unknown. Methods: Therefore, this study utilized a naturalistic prospective design where participants with chronic low back pain with intentions to initiate cannabis use for treatment were recruited and self-selected edible cannabis products containing varying amounts of delta- 9 tetrahydrocannabinol (THC) and cannabidiol (CBD). Products were categorized as CBD-dominant, THC-dominant, or combined THC and CBD (THC + CBD). Results: 249 participants [140 female (56.62%), mean (SD) age of 46.30 (16.02), 90% White] were tracked over 2 weeks of ad libitum use and assessed during a naturalistic acute cannabis administration session on changes in pain, mood, and subjective drug effects. During acute administration, a significant correlation between THC dose and short-term pain relief was found, suggesting that higher THC doses were associated with greater pain reduction (p <.05). In addition, THC was associated with higher levels of subjective cannabis drug effects (p <.001), regardless of whether CBD was also in the edible product. Acute CBD dose was primarily associated with short-term tension relief (p <.05); however, there were no associations between CBD dose and acute pain. Over the 2-week ad libitum administration period results suggested pain reductions across participants using all forms of cannabis. However, trends suggested that more frequent use of CBD-dominant edible cannabis may be associated with greater reductions in perceived pain over the 2-week observation period (p =.07). Discussion: These findings support the short-term analgesic effects of THC and anxiolytic effects of CBD and further suggest that orally-administered THC and CBD should continue to be evaluated for the potential to provide both acute and extended relief from chronic low back pain. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT03522324?locStr=Boulder,%20CO&country=United%20States&state=Colorado&city=Boulder&cond=chronic%20low%20back%20pain&intr=Cannabis&rank=1, identifier NCT03522324. [ABSTRACT FROM AUTHOR]

Aim: Our objective was to systematically assess the prevalence and clinical features of adverse events related to interactions between cannabinoids and psychotropic drugs through a retrospective chart review. Methodology: 1586 adverse event reports were assessed. Cases included in the analysis showed a high probability of a causal relationships between cannabinoid-psychotropic drug interactions and adverse events. Data extracted included age, sex, psychotropic drug, cannabinoid products, other medications, and the clinical outcomes and mechanisms of these interactions. Results: Cannabinoids were involved in 8% of adverse events associated with the concomitant use of psychotropic drugs and other preparations. We identified 20 reports in which side effects presented a causal relationship with the use of psychotropic drugs and cannabinoids. Preparations containing 18% or more tetrahydrocannabinol (THC), presented significant side effects with the following antidepressants: mianserine (restless legs syndrome, urogenital pain, ventricular tachycardia), mirtazapine (pancreatitis, hyperhidrosis, arthralgia), quetiapine (myocarditis, renal failure, bradycardia, sialorrhea), haloperidol (ventricular arrhythmia, prolonged QTc), aripiprazole (prolonged QTc), ventricular tachycardia) and cariprazine (stomach pain, hepatotoxicity), sertraline (ataxia, hyperactivity, coma, hallucinations, anxiety, agitation, tachycardia, panic attacks, disorientation, headache, dizziness, blurry vision, severe emesis, xerostomia, dry eyes), trazodone (disorientation, memory impairment, sedation), fluvoxamine (tachycardia, tachypnoea, dysarthria, auditory hallucinations). Two out of 20 reports (10%) analyzed in our study was related with the simultaneous use of cannabidiol (CBD) oil and sertraline. Concomitant use of those substances was associated with the adverse events in form of diarrhea, emesis, fever and severe fatigue. Conclusion: Clinicians need to closely monitor adverse events resulting from the combined use of cannabinoids and psychotropic medications. The accumulation of side effects and pharmacokinetic interactions (including CYP and p-glycoprotein inhibition) between these drugs can lead to clinically significant adverse outcomes. [ABSTRACT FROM AUTHOR]

Objective: This study aims to describe patterns, sources, and reasons for cannabis use among cancer patients during active treatment (+CDTX) compared to no‐use during active treatment (−CDTX). Methods: Data are from 385 surveys collected via REDCap during phase I of an ongoing study among adult cancer patients seen at an NCI‐designated comprehensive cancer center within the last 5 years of treatment. A harmonized survey was created with 11 other NCI centers to assess cannabis use patterns, sources, and reasons for use. Sociodemographics and cancer details were also collected via self‐report. Descriptive statistics were calculated and stratified by +/−CDTX. Chi‐squared tests were conducted to compare proportions between groups. Results: Among the sample [49.5 years (SD 15.9); 53.0% male; and 41.6% Hispanic/Latino], 41.0% + CDTX and 59.0% −CDTX. A majority (71.8%) of +CDTX initiated use before diagnosis versus 44.1% in −CDTX (p < 0.0001); patients diagnosed with stage 4 cancer had a statistically significant higher prevalence of +CDTX (60.0%; p = 0.003); 53.3% in radiation reported +CDTX compared to 42.8% in chemotherapy, and 36.4% in immunotherapy. Dispensaries and local dealers were the top sources of cannabis in both groups. Among +CDTX, 44.3% consumed cannabis at least once a day DTX, dominant cannabinoids used were CBD (35.2%), Delta‐8‐THC (18.3%), and CBD + THC ratio (14.1%); 12.7% were unsure what they consumed. Joints were the most common inhalation method (61.5%), and store‐bought candy was the most common edible (39.2%). Depression/mood, pain, and enjoyment were the top three reasons for +CDTX compared to enjoyment, depression/mood, and nausea/upset stomach in −CDTX (p = 0.02). Conclusions: Patterns, sources, and reasons for cannabis use varied between +CDTX and ‐CDTX. Future studies should examine the impacts of cannabis and specific cannabinoids on cancer treatment, drug interactions, survival outcomes, and quality of life. [ABSTRACT FROM AUTHOR]

Background: Limited research considers the quantity and potency of cannabis products along with social context on the subjective effects of real-world cannabis use. Aims: This study examined the subjective effects of acute use as a function of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) doses and social context during cannabis use episodes. Method: Ninety-six participants (43.75% male, M age = 35.73) reporting weekly cannabis use completed a baseline self-report battery assessing cannabis use. Then, THC and CBD potency and quantity of the cannabis product, social context, and subjective experience were assessed through self-initiated surveys after cannabis use episodes during a 14-day ecological momentary assessment (EMA). Results: Greater feeling high and liking were significantly associated with a higher THC dose than one's average (b = 0.03, p < 0.001; b = 0.02, p < 0.001) and social use (b = 0.38, p < 0.001; b = 0.20, p = 0.01). A higher CBD dose than one's average (b = 0.01, p = 0.04) was significantly associated with greater liking. A significant interaction effect of THC dose and social context (b = 0.01, p = 0.02) was observed such that solitary use had a negative association between THC dose and disliking (b = −0.01, p = 0.04), and social use had a null association (b = 0.003, p = 0.25). Individuals with greater cannabis problems reported lower liking (b = −0.18, p = 0.03) and higher disliking (b = 0.08, p = 0.02), but not feeling high, on average, across the EMA protocol. Conclusion: Social context plays an important role in the subjective experience of cannabis use. Interventions targeting cannabis problems could highlight the evidence that individuals with greater cannabis problems might experience less liking but more disliking in general across use episodes to effectively challenge expectancies/motives of use. [ABSTRACT FROM AUTHOR]

Purpose of Review: This document critically examines the role of cannabinoids in cancer care during an era marked by rapid advancements in oncology and changing perceptions on cannabis. It traces the historical context of cannabis in medicinal use, navigating its journey from widespread acceptance, subsequent criminalization, to its resurgence in modern therapeutic applications, particularly within the framework of Evidence-Based Medicine (EBM). Recent Findings: Anchored in EBM principles, this study synthesizes current research from clinical trials, systematic reviews, and meta-analyses to evaluate the efficacy and safety of cannabinoids in oncology. The focus is on their palliative effects, considering the nuances of effectiveness, risk assessment, and challenges inherent in translating these findings into clinical guidelines. Summary: The study seeks to bridge the gap between scientific research and clinical practice, offering insights to inform future oncological therapies and symptom management strategies involving cannabinoids. The potential benefits and risks of cannabinoid use in cancer treatment are assessed to guide clinicians and researchers in developing comprehensive, evidence-based approaches to patient care. [ABSTRACT FROM AUTHOR]

Cannabinoids represent a highly researched group of plant-derived ingredients. The substantial investment of funds from state and commercial sources has facilitated a significant increase in knowledge about these ingredients. Cannabinoids can be classified into three principal categories: plant-derived phytocannabinoids, synthetic cannabinoids and endogenous cannabinoids, along with the enzymes responsible for their synthesis and degradation. All of these compounds interact biologically with type 1 (CB1) and/or type 2 (CB2) cannabinoid receptors. A substantial body of evidence from in vitro and in vivo studies has demonstrated that cannabinoids and inhibitors of endocannabinoid degradation possess anti-inflammatory, antioxidant, antitumour and antifibrotic properties with beneficial effects. This review, which spans the period from 1940 to 2024, offers an overview of the potential therapeutic applications of natural and synthetic cannabinoids. The development of these substances is essential for the global market of do-it-yourself drugs to fully exploit the promising therapeutic properties of cannabinoids. [ABSTRACT FROM AUTHOR]

Recently, the anti-tumor effects of cannabis extract on various cancers have attracted the attention of researchers. Here, we report a nanoemulsion (NE) composition designed to enhance the delivery of two active components in cannabis extracts (∆9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD)) in an animal model of glioblastoma. The efficacy of the NE containing the two drugs (NED) was compared with the bulk drugs and carrier (NE without the drugs) using the C6 tumor model in rats. Hemocompatibility factors (RBC, MCV, MCH, MCHC, RDW, PPP, PT and PTT) were studied to determine the potential in vivo toxicity of NED. The optimized NED with mean ± SD diameter 29 ± 6 nm was obtained. It was shown that by administering the drugs in the form of NED, the hemocompatibility increased. Cytotoxicity studies indicated that the NE without the active components (i.e. mixture of surfactants and oil) was the most cytotoxic group, while the bulk group had no toxicity. From the in vivo MRI and survival studies, the NED group had maximum efficacy (with ~4 times smaller tumor volume on day 7 of treatment, compared with the control. Also, survival time of the control, bulk drug, NE and NED were 9, 4, 12.5 and 51 days, respectively) with no important adverse effects. In conclusion, the NE containing cannabis extract could be introduced as an effective treatment in reducing brain glioblastoma tumor progression. [ABSTRACT FROM AUTHOR]

Cannabis, a diverse compounded plant with a rich cultural and scientific history, has garnered significant attention due to its therapeutic and medicinal potential. The plant's main active compounds, phytocannabinoids, notably A9-tetrahydrocannabinol (THC) and cannabidiol (CBD), play important roles in its effects. Cannabis formulations range from traditional herbal preparations to modern innovations like edibles, sprays, topicals and vaporizable products. Achieving consistent potency, controlled release, and desirable pharmacokinetics remain a challenge. The article delves into its diverse formulations obtained along with its routes of administration. The article provides an overview of cannabinoids-based formulations, highlighting their significance in the context of emerging therapeutic and commercial opportunities, while acknowledging the need for further research to optimize formulations and maximize benefits. [ABSTRACT FROM AUTHOR]

The public is increasingly reporting using cannabis for anxiety relief. Both cannabis use and the endocannabinoid system have been connected with anxiety relief/anxiolytic properties, but these relationships are complex, and the underlying mechanisms for them are unclear. Background/Objectives: Work is needed to understand how the endocannabinoid system, including the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG), may be impacted by the main constituents of cannabis, Δ9-tetrahydrocannabinol (THC), and cannabidiol (CBD). Methods: The current study examined how the ab libitum use of products differing in THC and CBD affected AEA and 2-AG among 292 individuals randomly assigned to THC-dominant use (N = 92), CBD-dominant use (N = 97), THC + CBD use (N = 74), or non-use (N = 29). Results: The findings suggest that AEA levels do not change differently based on 4 weeks of cannabis use or by cannabinoid content, as AEA similarly increased across all conditions from study weeks 2 to 4. In contrast, AEA decreased at an acute administration session with product conditions containing any THC having greater AEA levels on average than the non-use condition. With regard to 2-AG, its levels appeared to primarily be affected by THC-dominant use, both acutely and over 4 weeks, when controlling for baseline cannabis use and examining study product use frequency among use conditions. Conclusions: Overall, the results continue to shed light on the complicated relationship between cannabinoid content and endocannabinoid production, and highlight the need for continued research on their interplay in human subjects. [ABSTRACT FROM AUTHOR]

As cannabidiol (CBD) is not considered to be a drug and because of its potential health claims, it is an interesting compound that is often found in cosmetics. However, the safety of CBD, as well as the presence of trace amounts of other phytocannabinoids, including the psychoactive substance ∆9‐tetrahydrocannabinol (THC), is still being debated. A robust analytical technique capable of analysing cosmetic products and determining their phytocannabinoid content will be crucial in assessing the safety of these products. This systematic review aims to highlight the current analytical tools that could be used to analyse phytocannabinoids in cosmetics. The ideal method would be able to analyse high levels of CBD in combination with trace levels of THC and their acids. The method should provide good recoveries and accuracies in a variety of matrices while providing information on up‐coming phytocannabinoids such as cannabichromene (CBC), cannabigerol (CBG) and cannabinol (CBN). The systematic review approach was based on the Preferred Reporting Items for Systematic review and Meta‐Analyses method. The research focused on studies published from January 2010 to December 2022 in PubMed and Scopus. A total of 15 datasets met the inclusion and exclusion criteria and were tabulated to allow easy comparison. Although some of the reviewed methods can handle multiple matrices and provide satisfactory recoveries, this review process did not identify an ideal method. The most suitable methods either could not quantify phytocannabinoid acids or were not sensitive enough to quantify trace levels of psychoactive phytocannabinoids. [ABSTRACT FROM AUTHOR]

Increased cases of canine tetrahydrocannabinol (THC) toxicosis have been reported in North America in recent years. Cases are often evaluated on an emergency basis and treatment has relied upon supportive care which can be costly and prohibitive for some pet owners. The purpose of this report is to describe the clinical findings and outcomes in dogs with non-medical, presumptive THC toxicosis treated by administration of a cannibidiol (CBD)-infused transmucosal dissolving sheet. Medical records of six cases of non-medical, presumptive THC toxicosis from a private primary care practice and a private after-hours emergency practice were reviewed and summarized. Five of six cases were treated exclusively with transmucosal CBD (0.4–2.6 mg/kg); one case also received injectable anti-emetic therapy. Lethargy and ataxia noticeably improved and all additional clinical signs resolved within 45 min of treatment in five of six cases. No further follow-up measures for THC toxicosis were required in any case; one case required additional follow-up for presumably unrelated gastrointestinal distress. This is the first report of treatment of canine THC toxicosis by administration of CBD. The use of transmucosal CBD-infused dissolving sheets resulted in expedient resolution of clinical signs in a minimally invasive manner that is accessible to both clients and veterinary practitioners.

The inclusion of spent hemp biomass (SHB), an extracted byproduct from industrial cannabidiol (CBD) production, in the diets of dairy cows and lambs appears to be safe with minor effects on the metabolism, including a decrease in circulating cholesterol and increase bilirubinemia, both associated with liver metabolism. Those effects could be consequence of the presence of cannabinoids, particularly Δ9-tetrahydrocannabinol (THC) and CBD in the SHB. This study aimed to study the transcriptional profile of the liver of dairy cows and lambs fed SHB. Dairy cows received SHB or alfalfa pellet for four weeks of intervention (IP) and four weeks of withdrawal periods (WP). Finishing lambs were fed a control diet (CON), 10% (LH2), or 20% (HH2) SHB for 2 months or 1 month followed by 1-month SHB withdrawal (LH1 and HH1, respectively). RNA sequencing was performed, and the mRNA was annotated using the latest reference genomes. The RNAseq data were filtered, normalized for library size and composition, and statistically analyzed by DESeq2. The bioinformatic analysis was performed by using DAVID, Gene Set Enrichment Analysis (GSEA), and the Dynamic Impact Approach. Using a 0.2 FDR cut-off, we identified only ≤24 differentially expressed genes (DEG) in the liver by feeding SHB in dairy cows and a larger number of DEGs in lambs (from 71 in HH1 vs. CON to 552 in LH1 vs. CON). The KEGG analysis demonstrated that feeding SHB in dairy cows and lambs had relatively minor to moderate metabolic alterations in dairy cows and lambs mainly associated with amino acids and lipid metabolism whereas cholesterol synthesis was overall activated in lambs. GSEA identified activation of the PPAR signaling pathway only in dairy cows. We found an opposite effect on activation of metabolism of drug and xenobiotics by cytochrome P450 enzymes in dairy cows and lambs receiving less SHB but an inhibition in HH2 lambs. Immune system-related pathways were inhibited by feeding SHB in lambs, but the impact was minor. Cumulatively, inclusion of SHB containing cannabinoids in dairy and lambs demonstrate very little effects on the alteration of transcriptomic profile of the liver. [ABSTRACT FROM AUTHOR]

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a shared burden for 68.1% of oncological patients undergoing chemotherapy with Paclitaxel (PTX). The symptoms are intense and troublesome, patients reporting paresthesia, loss of sensation, and dysesthetic pain. While current medications focus on decreasing the symptom intensity, often ineffective, no medication is yet recommended by the guidelines for the prevention of CIPN. Cannabinoids are an attractive option, as their neuroprotective features have already been demonstrated in neuropathies with other etiologies, by offering the peripheral neurons protection against toxic effects, which promotes analgesia. Methods: We aim to screen several new cannabinoids for their potential use as neuroprotective agents for CIPN by investigating the cellular toxicity profile and by assessing the potential neuroprotective features against PTX using a primary dorsal root ganglion neuronal culture. Results: Our study showed that synthetic cannabinoids JWH-007, AM-694 and MAB-CHMINACA and phytocannabinoids Cannabixir® Medium dried flowers (NC1) and Cannabixir® THC full extract (NC2) preserve the viability of fibroblasts and primary cultured neurons, in most of the tested dosages and time-points. The combination between the cannabinoids and PTX conducted to a cell viability of 70%-89% compared to 40% when PTX was administered alone for 48 h. When assessing the efficacy for neuroprotection, the combination between cannabinoids and PTX led to better preservation of neurite length at all tested time-points compared to controls, highly drug and exposure-time dependent. By comparison, the combination of the cannabinoids and PTX administered for 24 h conducted to axonal shortening between 23% and 44%, as opposed to PTX only, which shortened the axons by 63% compared to their baseline values. Discussion and Conclusion: Cannabinoids could be potential new candidates for the treatment of paclitaxel-induced peripheral neuropathy; however, our findings need to be followed by additional tests to understand the exact mechanism of action, which would support the translation of the cannabinoids in the oncological clinical practice. [ABSTRACT FROM AUTHOR]

Background: The recent exponential increase in legalized medical and recreational cannabis, development of medical cannabis programs, and production of unregulated over-the-counter products (e.g., cannabidiol (CBD) oil, and delta-8-tetrahydrocannabinol (delta-8-THC)), has the potential to create unintended health consequences. The major cannabinoids (delta-9- tetrahydrocannabinol and cannabidiol) are metabolized by the same cytochrome P450 (CYP) enzymes that metabolize most prescription medications and xenobiotics (CYP3A4, CYP2C9, CYP2C19). As a result, we predict that there will be instances of drug-drug interactions and the potential for adverse outcomes, especially for prescription medications with a narrow therapeutic index. Methods: We conducted a systematic review of all years to 2023 to identify real world reports of documented cannabinoid interactions with prescription medications. We limited our search to a set list of medications with predicted narrow therapeutic indices that may produce unintended adverse drug reactions (ADRs). Our team screened 4,600 reports and selected 151 full-text articles to assess for inclusion and exclusion criteria. Results: Our investigation revealed 31 reports for which cannabinoids altered pharmacokinetics and/or produced adverse events. These reports involved 16 different Narrow Therapeutic Index (NTI) medications, under six drug classes, 889 individual subjects and 603 cannabis/cannabinoid users. Interactions between cannabis/cannabinoids and warfarin, valproate, tacrolimus, and sirolimus were the most widely reported and may pose the greatest risk to patients. Common ADRs included bleeding risk, altered mental status, difficulty inducing anesthesia, and gastrointestinal distress. Additionally, we identified 18 instances (58%) in which clinicians uncovered an unexpected serum level of the prescribed drug. The quality of pharmacokinetic evidence for each report was assessed using an internally developed ten-point scale. Conclusion: Drug-drug interactions with cannabinoids are likely amongst prescription medications that use common CYP450 systems. Our findings highlight the need for healthcare providers and patients/care-givers to openly communicate about cannabis/cannabinoid use to prevent unintended adverse events. To that end, we have developed a free online tool (www.CANN-DIR.psu. edu) to help identify potential cannabinoid drug-drug interactions with prescription medications. [ABSTRACT FROM AUTHOR]

Rationale: Attentional bias to drug-related stimuli is hypothesised to contribute towards addiction. However, the acute effects of Δ9-tetrahydrocannabinol (THC) on attentional bias to cannabis cues, the differential response in adults and adolescents, and the moderating effect of cannabidiol (CBD) are unknown. Objectives: Our study investigated (1) the acute effects of vaporised cannabis on attentional bias to cannabis-related images in adults and adolescents and (2) the moderating influences of age and CBD. Methods: We conducted a randomised, double-blind, placebo-controlled, cross-over study where three weight-adjusted vaporised cannabis preparations: 'THC' (8 mg THC for a 75-kg person), 'THC + CBD' (8 mg THC and 24 mg CBD for a 75-kg person) and PLA (matched placebo). Cannabis was administered on 3 separate days to 48 participants, who used cannabis 0.5–3 days/week: 24 adolescents (12 females, aged 16–17) and 24 adults (12 females, aged 26–29). Participants completed a visual probe task with cannabis cues. Our primary outcome was attentional bias to cannabis stimuli, measured using the differential reaction time to a cannabis vs. neutral probe, on 200-ms trials. Results: In contrast to hypotheses, attention was directed away from cannabis cues on placebo, and there was a main effect of the drug (F(2,92) = 3.865, p = 0.024, η2p = 0.077), indicating THC administration eliminated this bias. There was no significant impact of CBD nor an age-by-drug interaction. Conclusions: Acute THC intoxication eliminated attentional bias away from cannabis cues. There was no evidence of differential response in adolescents compared to adults and no evidence that a moderate vaporised dose of CBD altered the impact of cannabis on attentional bias. Trial registration: This study was listed with the US National Library of Medicine and registered on ClinicalTrials.gov, URL: Do Adolescents and Adults Differ in Their Acute Response to Cannabis?—Full Text View—ClinicalTrials.gov, registration number: NCT04851392. [ABSTRACT FROM AUTHOR]

Although an increasing number of patients suffering from mental illnesses self-medicate with cannabis , current knowledge about the efficacy and safety of cannabis -based medicine in psychiatry is still extremely limited. So far, no cannabis -based finished product has been approved for the treatment of a mental illness. There is increasing evidence that cannabinoids may improve symptoms in autism spectrum disorder (ASD), Tourette syndrome (TS), anxiety disorders, and post-traumatic stress disorder (PTSD). According to surveys, patients often use cannabinoids to improve mood, sleep, and symptoms of attention deficit/hyperactivity disorder (ADHD). There is evidence suggesting that tetrahydrocannabinol (THC) and THC-containing cannabis extracts, such as nabiximols, can be used as substitutes in patients with cannabis use disorder. Preliminary evidence also suggests an involvement of the endocannabinoid system (ECS) in the pathophysiology of TS, ADHD, and PTSD. Since the ECS is the most important neuromodulatory system in the brain, it possibly induces beneficial effects of cannabinoids by alterations in other neurotransmitter systems. Finally, the ECS is an important stress management system. Thus, cannabinoids may improve symptoms in patients with mental illnesses by reducing stress. Practically, cannabis -based treatment in patients with psychiatric disorders does not differ from other indications. The starting dose of THC-containing products should be low (1–2.5 mg THC/day), and the dose should be up-titrated slowly (by 1–2.5 mg every 3–5 days). The average daily dose is 10–20 mg THC. In contrast, cannabidiol (CBD) is mainly used in high doses>400 mg/day. [ABSTRACT FROM AUTHOR]

There is an ongoing debate in the literature about the place of cannabinoid therapy in everyday clinical practice. This overview examined systematic reviews and meta-analyses on the use of medical marijuana (MM) for specific symptoms or diseases, such as epilepsy, multiple sclerosis, pain, nausea and vomiting during chemotherapy, cachexia, and sleep disorders. We analyzed different cannabinoids like CBD, THC, dronabinol, nabilone, and THC:CBD combinations (nabiximols) to understand their effects on various medical conditions, dose effectiveness, and side effects. CBD showed promise for epilepsy. Nabilone showed a significant reduction in pain and insomnia. Nabiximols have been effective in reducing spasticity, pain, and sleep disturbances in multiple sclerosis patients. Nabilone and dronabinol improved nausea and vomiting due to chemotherapy, but the evidence is weak. The results on the effectiveness of MM in the treatment of cachexia and cancer pain are inconclusive. Outcomes suggest that side effects typically were mild to moderate in severity. The type of cannabinoid (including CBD and THC content) and dosage were found to potentially influence the results obtained in the trials, affecting both the effectiveness and the side effects experienced by patients. Young people, elderly, and children are particularly vulnerable and, despite ongoing research in these age groups, we still know too little about whether and for which clinical conditions the use of medical cannabis is justified. The analyzed studies faced limitations due to heterogeneity in methodology, dosages, and outcome measures and highlighting potential controversies in interpreting the results, thus further research is needed. [ABSTRACT FROM AUTHOR]

AimOur objective was to systematically assess the prevalence and clinical features of adverse events related to interactions between cannabinoids and psychotropic drugs through a retrospective chart review.Methodology1586 adverse event reports were assessed. Cases included in the analysis showed a high probability of a causal relationships between cannabinoid-psychotropic drug interactions and adverse events. Data extracted included age, sex, psychotropic drug, cannabinoid products, other medications, and the clinical outcomes and mechanisms of these interactions.ResultsCannabinoids were involved in 8% of adverse events associated with the concomitant use of psychotropic drugs and other preparations. We identified 20 reports in which side effects presented a causal relationship with the use of psychotropic drugs and cannabinoids. Preparations containing 18% or more tetrahydrocannabinol (THC), presented significant side effects with the following antidepressants: mianserine (restless legs syndrome, urogenital pain, ventricular tachycardia), mirtazapine (pancreatitis, hyperhidrosis, arthralgia), quetiapine (myocarditis, renal failure, bradycardia, sialorrhea), haloperidol (ventricular arrhythmia, prolonged QTc), aripiprazole (prolonged QTc), ventricular tachycardia) and cariprazine (stomach pain, hepatotoxicity), sertraline (ataxia, hyperactivity, coma, hallucinations, anxiety, agitation, tachycardia, panic attacks, disorientation, headache, dizziness, blurry vision, severe emesis, xerostomia, dry eyes), trazodone (disorientation, memory impairment, sedation), fluvoxamine (tachycardia, tachypnoea, dysarthria, auditory hallucinations). Two out of 20 reports (10%) analyzed in our study was related with the simultaneous use of cannabidiol (CBD) oil and sertraline. Concomitant use of those substances was associated with the adverse events in form of diarrhea, emesis, fever and severe fatigue.ConclusionClinicians need to closely monitor adverse events resulting from the combined use of cannabinoids and psychotropic medications. The accumulation of side effects and pharmacokinetic interactions (including CYP and p-glycoprotein inhibition) between these drugs can lead to clinically significant adverse outcomes.

Abstract Background While the use of orally consumed Cannabis, cannabidiol (CBD) and tetrahydrocannabinol (THC) containing products, i.e. “edibles”, has expanded, the health consequences are still largely unknown. This study examines the effects of oral consumption of whole Cannabis and a complex Cannabis extract on neurochemicals, endocannabinoids (eCB), and physiological parameters (body temperature, heart rate) in mice. Methods In this pilot study, C57BL/6 J mice were treated with one of the following every other day for 2 weeks: a complex Cannabis extract by gavage, whole Cannabis mixed with nutritional gel through free feeding, or purified THC/CBD by intraperitoneal (i.p.) injection. Treatments were conducted at 4 doses ranging from 0–100 mg/kg/day of CBD with THC levels of ≤ 1.2 mg/kg/day for free feeding and gavage and 10 mg/kg/day for i.p. Body temperature and heart rate were monitored using surgically implanted telemetry devices. Levels of neurochemicals, eCB, THC, CBD, and 11-OH-THC were measured using mass spectrometry 48 h after the final treatment. Statistical comparisons were conducted using ANOVA and t-tests. Results Differences were found between neurochemicals in the brains and plasma of mice treated by i.p. (e.g. dopamine, p

Opioids are commonly prescribed for the treatment of chronic pain. Approximately 50% of adults who are prescribed opioids for pain co-use cannabis with their opioid treatment. Morphine is primarily metabolized by UDP-glucuronosyltransferase (UGT) 2B7 to an inactive metabolite, morphine-3-glucuronide (M3G), and an active metabolite, morphine-6-glucuronide (M6G). Previous studies have shown that major cannabis constituents including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) inhibit major UGT enzymes. To examine whether cannabinoids or their major metabolites inhibit morphine glucuronidation by UGT2B7, in vitro assays and mechanistic static modeling were performed with these cannabinoids and their major metabolites including 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC), 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (11-COOH-THC), 7-hydroxy-cannabidiol (7-OH-CBD), and 7-carboxy-cannabidiol (7-COOH-CBD). In vitro assays with rUGT-overexpressing microsomes and human liver microsomes showed that THC and CBD and their metabolites inhibited UGT2B7-mediated morphine metabolism, with CBD and THC exhibiting the most potent Ki,u values (0.16 µM and 0.37 µM, respectively). Only 7-COOH-CBD exhibited no inhibitory activity against UGT2B7-mediated morphine metabolism. Static mechanistic modeling predicted an in vivo drug–drug interaction between morphine and THC after inhaled cannabis, and between THC, CBD, and 7-OH-CBD after oral consumption of cannabis. These data suggest that the co-use of these agents may lead to adverse drug events in humans. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting approximately 3% of school-age children. The core symptoms are deficits in social communication and restricted and repetitive patterns of behavior. Associated problems in cognition, language, behavior, sleep and mood are prevalent. Currently, no established pharmacological treatment exists for core ASD symptoms. Risperidone and aripiprazole are used to manage associated irritability, but their effectiveness is limited and adverse events are common. This mini-review summarizes existing scientific literature and ongoing clinical trials concerning cannabinoid treatment for ASD. Uncontrolled case series have documented improvements in both core ASD symptoms and related behavioral challenges in children treated with cannabis extracts rich in cannabidiol (CBD). Placebo-controlled studies involving CBD-rich cannabis extracts and/or pure CBD in children with ASD have demonstrated mixed efficacy results. A similar outcome was observed in a placebo-controlled study of pure CBD addressing social avoidance in Fragile X syndrome. Importantly, these studies have shown relatively high safety and tolerability. While current clinical data suggest the potential of CBD and CBD-rich cannabis extract in managing core and behavioral deficits in ASD, it is prudent to await the results of ongoing placebo-controlled trials before considering CBD treatment for ASD. [ABSTRACT FROM AUTHOR]

Discoid lupus erythematosus (DLE) is a common autoimmune skin disease in dogs. Conventional treatments, such as corticosteroids, can be effective but often have side effects. This case report presents a successful use of cannabinoid therapy (CT) in a dog with DLE resistant to conventional treatment. A 2-year-old mixed-breed dog with a history of DLE presented with worsening lesions despite treatment with corticosteroids and other medications. Liver enzymes levels were elevated, indicating corticosteroid-induced side effects. CT with a CBD-rich full spectrum Cannabis oil was initiated. The dosage was gradually adjusted until the minimum effective dose was found. Within a few weeks of starting CT, the dog showed significant improvement in skin lesions and in liver enzymes levels. After 1 year, the dog remains clinically stable on a low dose of full-spectrum CBD-rich oil. No evidence of DLE recurrence was observed. This case suggests that CT may be a viable alternative or complementary therapy for DLE in dogs, particularly for those experiencing adverse effects from conventional treatments. Further research is warranted to confirm the efficacy and safety of CT for DLE management in dogs. [ABSTRACT FROM AUTHOR]

AbstractBackgroundResultsLow-THC cannabis products have become popular worldwide and are used as self-treatment for a variety of medical conditions despite limited high-quality evidence on efficacy or long-term side-effects.Method: We compare the experiences of CBD-oil-only users to that of users, who indicated use of cannabis products conventionally higher in THC (high-THC cannabis) with respect to number of symptoms relieved, overall perceived effect on symptoms, effect on pain level and sleep duration, and perceived side-effects. A self-selected convenience sample of Danish cannabis users were recruited to an anonymous online survey. Inclusion criteria were 18 years or older and use of cannabis as medicine (CaM) (prescribed or non-prescribed).The final sample included 2.642 users of CaM, of which 992 were CBD-oil-only users and 1650 used high-THC products. Compared to respondents who used high-THC cannabis, CBD-oil-only users reported fewer symptoms relieved by cannabis, a slightly lower overall symptom reduction, as well as comparable pain reduction and sleep improvement. CBD-oil-only users reported fewer side-effects and were more likely to report no side-effects of cannabis.Conclusion: CBD-oils may produce less intense effects compared to high-THC cannabis products, while also producing fewer side-effects. Regulation of the legal low-THC cannabis market is needed. [ABSTRACT FROM AUTHOR]

Aims: To test how attentional bias and explicit liking are influenced by delta‐9‐tetrahydrocannabinol (THC) and whether these effects are moderated by cannabidiol (CBD). Design: Double‐blind, randomised, within‐subjects cross‐over study. Setting NIHR Wellcome Trust Clinical Research Facility at King's College Hospital, London, United Kingdom. Participants/Cases: Forty‐six infrequent cannabis users (cannabis use <1 per week). Intervention(s): Across four sessions, participants inhaled vaporised cannabis containing 10 mg of THC and either 0 mg (0:1 CBD:THC), 10 mg (1:1), 20 mg (2:1) or 30 mg (3:1) of CBD, administered in a randomised order and counter‐balanced across participants (a total of 24 order groups). Measurements Participants completed two tasks: (1) Attentional Bias (AB), comparing reaction times toward visual probes presented behind 28 target stimuli (cannabis/food) compared with probes behind corresponding non‐target (neutral) stimuli. Participants responding more quickly to probes behind target than non‐target stimuli would indicate greater attentional bias to cannabis/food; (2) Picture Rating (PR), where all AB stimuli were rated on a 7‐point pleasantness scale, measuring explicit liking. Findings During the AB task, participants were more biased toward cannabis stimuli in the 0:1 condition compared with baseline (mean difference = 12.2, 95% confidence intervals [CIs] = 1.20–23.3, d = 0.41, P = 0.03). No other significant AB or PR differences were found between cannabis and food stimuli between baseline and 0:1 condition (P > 0.05). No significant CBD effect was found on AB or PR task performance at any dose (P > 0.05). There was additionally no cumulative effect of THC exposure on AB or PR outcomes (P > 0.05). Conclusions: A double‐blind, randomised, cross‐over study among infrequent cannabis users found that inhaled delta‐9‐tetrahydrocannabinol increased attentional bias toward cannabis in the absence of explicit liking, a marker of liability toward cannabis use disorder. At the concentrations normally found in legal and illegal cannabis, cannabidiol had no influence on this effect. [ABSTRACT FROM AUTHOR]

Benzodiazepines (BZDs) such as oxazepam are commonly prescribed depressant drugs known for their anxiolytic, hypnotic, muscle relaxant, and anticonvulsant effects and are frequently used in conjunction with other illicit drugs including cannabis. Oxazepam is metabolized in an enantiomeric-specific manner by glucuronidation, with S-oxazepam metabolized primarily by UGT2B15 and R-oxazepam glucuronidation mediated by both UGT 1A9 and 2B7. The goal of the present study was to evaluate the potential inhibitory effects of major cannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), and major THC metabolites, 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (11-COOH-THC), on the UGT-mediated metabolism of R- and S-oxazepam. The cannabinoids and metabolites were screened as inhibitors of R- and S-oxazepam glucuronidation in microsomes isolated from HEK293 cells overexpressing individual UGT enzymes (rUGTs). The IC50 values were determined in human liver microsomes (HLM), human kidney microsomes (HKM), and rUGTs and utilized to estimate the nonspecific, binding-corrected Ki (Ki,u) values and predict the area under the concentration–time curve ratio (AUCR). The estimated Ki,u values observed in HLM for S- and R-oxazepam glucuronidation by CBD, 11-OH-THC, and THC were in the micromolar range (0.82 to 3.7 µM), with the Ki,u values observed for R-oxazepam glucuronidation approximately 2- to 5-fold lower as compared to those observed for S-oxazepam glucuronidation. The mechanistic static modeling predicted a potential clinically significant interaction between oral THC and CBD with oxazepam, with the AUCR values ranging from 1.25 to 3.45. These data suggest a pharmacokinetic drug–drug interaction when major cannabinoids like CBD or THC and oxazepam are concurrently administered. [ABSTRACT FROM AUTHOR]

Context: Cannabis has become more prevalent in society and requires greater knowledge on the part of the athletic trainer. Objective. The purpose of this paper is to provide a framework for recognizing how cannabis education can be integrated into the athletic training curriculum utilizing the existing accreditation standards. Background. For decades the use of cannabis has been illegal. Athletes who were caught with cannabis in their system were penalized by their respective e sport organization body. During the past decade in the United States the federal government has moved toward decriminalization and expungement for those found with and arrested for cannabis possession and/or use. Furthermore, many states have maneuvered toward the legalization of marijuana for both medicinal and adult-use (recreational). The United States is not alone in this movement as other countries such as Canada, Israel, United Kingdom, and Australia have made changes toward their cannabis laws. Professional leagues such as Major League Baseball (MLB), the National Football League (NFL), and the NBA have shifted away from a punitive approach toward cannabis use and toward a health and wellness understanding. Additionally, the National Collegiate Athletic Association's (NCAA) Competitive Safeguards and Medical Aspects of Sports Committee has recently announced its intentions to support removing cannabis from the banned drug list. While both acceptance and accessibility of cannabis products has increased, there remains a need to formally educate stakeholders. The cannabis plant is complex and has been associated with numerous proposed therapeutic benefits. There are also known risks and side effects that have been reported with cannabis use that range from cannabinoid hyperemesis syndrome to psychosis. Description. Example plans of action for cannabis curricular integration are provided and associated with respective CAATE standards. Educational Advantage. Athletic trainers must be at the forefront of cannabis knowledge to provide comprehensive and holistic patient care. [ABSTRACT FROM AUTHOR]

The utility of cannabinoids as agents used to treat diseases is a popular topic of discussion these days. The approval of medical marijuana continues to stir up controversy. As far back as ancient times, hemp was used for medicinal purposes. These plants have the ability to produce phytochemicals and other compounds such as flavonoids and terpenes. Respective species of hemp differ in the content of particular chemical compounds and therefore have different possible uses. Among the best-known phytocannabinoids found in hemp are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). They have partially opposing effects and interact with the corresponding receptors of the endocannabinoid system in the body's tissues. We also distinguish between cannabinoids of endogenous origin - endocannabinoids (EC) and synthetic cannabinoids (SC). The effects of THC and CBD on the human body are still being studied. Information about them that appears in the media, is often reported inaccurately or incompletely. There is now a growing body of research into the use of cannabinoids to treat and alleviate the symptoms of many diseases. Due to the neuroprotective effects of THC and CBD, researchers' work has focused on using them to treat neurodegenerative diseases, which include Parkinson's disease (PD).

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a shared burden for 68.1% of oncological patients undergoing chemotherapy with Paclitaxel (PTX). The symptoms are intense and troublesome, patients reporting paresthesia, loss of sensation, and dysesthetic pain. While current medications focus on decreasing the symptom intensity, often ineffective, no medication is yet recommended by the guidelines for the prevention of CIPN. Cannabinoids are an attractive option, as their neuroprotective features have already been demonstrated in neuropathies with other etiologies, by offering the peripheral neurons protection against toxic effects, which promotes analgesia.Methods: We aim to screen several new cannabinoids for their potential use as neuroprotective agents for CIPN by investigating the cellular toxicity profile and by assessing the potential neuroprotective features against PTX using a primary dorsal root ganglion neuronal culture.Results: Our study showed that synthetic cannabinoids JWH-007, AM-694 and MAB-CHMINACA and phytocannabinoids Cannabixir® Medium dried flowers (NC1) and Cannabixir® THC full extract (NC2) preserve the viability of fibroblasts and primary cultured neurons, in most of the tested dosages and time-points. The combination between the cannabinoids and PTX conducted to a cell viability of 70%–89% compared to 40% when PTX was administered alone for 48 h. When assessing the efficacy for neuroprotection, the combination between cannabinoids and PTX led to better preservation of neurite length at all tested time-points compared to controls, highly drug and exposure-time dependent. By comparison, the combination of the cannabinoids and PTX administered for 24 h conducted to axonal shortening between 23% and 44%, as opposed to PTX only, which shortened the axons by 63% compared to their baseline values.Discussion and Conclusion: Cannabinoids could be potential new candidates for the treatment of paclitaxel-induced peripheral neuropathy; however, our findings need to be followed by additional tests to understand the exact mechanism of action, which would support the translation of the cannabinoids in the oncological clinical practice.

BackgroundThe recent exponential increase in legalized medical and recreational cannabis, development of medical cannabis programs, and production of unregulated over-the-counter products (e.g., cannabidiol (CBD) oil, and delta-8-tetrahydrocannabinol (delta-8-THC)), has the potential to create unintended health consequences. The major cannabinoids (delta-9-tetrahydrocannabinol and cannabidiol) are metabolized by the same cytochrome P450 (CYP) enzymes that metabolize most prescription medications and xenobiotics (CYP3A4, CYP2C9, CYP2C19). As a result, we predict that there will be instances of drug-drug interactions and the potential for adverse outcomes, especially for prescription medications with a narrow therapeutic index.MethodsWe conducted a systematic review of all years to 2023 to identify real world reports of documented cannabinoid interactions with prescription medications. We limited our search to a set list of medications with predicted narrow therapeutic indices that may produce unintended adverse drug reactions (ADRs). Our team screened 4,600 reports and selected 151 full-text articles to assess for inclusion and exclusion criteria.ResultsOur investigation revealed 31 reports for which cannabinoids altered pharmacokinetics and/or produced adverse events. These reports involved 16 different Narrow Therapeutic Index (NTI) medications, under six drug classes, 889 individual subjects and 603 cannabis/cannabinoid users. Interactions between cannabis/cannabinoids and warfarin, valproate, tacrolimus, and sirolimus were the most widely reported and may pose the greatest risk to patients. Common ADRs included bleeding risk, altered mental status, difficulty inducing anesthesia, and gastrointestinal distress. Additionally, we identified 18 instances (58%) in which clinicians uncovered an unexpected serum level of the prescribed drug. The quality of pharmacokinetic evidence for each report was assessed using an internally developed ten-point scale.ConclusionDrug-drug interactions with cannabinoids are likely amongst prescription medications that use common CYP450 systems. Our findings highlight the need for healthcare providers and patients/care-givers to openly communicate about cannabis/cannabinoid use to prevent unintended adverse events. To that end, we have developed a free online tool (www.CANN-DIR.psu.edu) to help identify potential cannabinoid drug-drug interactions with prescription medications.

Background: Cannabis has been used medicinally for centuries. Historically, cannabis-based medicines have been used to treat many conditions. In the 20th century, their use was criminalized worldwide. Nowadays, many countries decriminalize their use. The complexity of the subject and the qualitative variability of the active factors of individual varieties of this species determine new areas that require research and analysis. Attention is drawn to legal issues, quality control issues, and shortages of randomized and controlled clinical trials. The article is addressed to health care professionals and people interested in legal and medical aspects and the potential benefits and challenges related to medical cannabis. Aim of the study: The aim of article analyzed the legal and practical aspects of access to marijuana and its use for medical application in Poland. Materials and method: Comparing legal solutions and analyzing differences in the regulations of marijuana used for medical purposes in selected countries will also make it possible to indicate the directions of development in this area in Poland. Results: This article discusses the legal framework for access to medical cannabis and its use for medical purposes. There are at least twenty-one types of raw materials on the market in Poland, which, while maintaining the same levels of THC and CBD, differ in their terpene profile and, therefore, in detailed therapeutic properties. Understanding the differences can enable pharmacists to support and monitor patient drug therapy in this area. The area of medical use of cannabis was also presented in terms of the possibility of cooperation between physicians and pharmacists in providing services to patients in order to achieve therapeutic effectiveness and develop risk management tools for pharmacotherapy using medical marijuana. Conclusions: As limitations in research and use are eliminated, new therapeutic options will be explored. Despite numerous challenges and limitations related to the use of Cannabis, such as the problems of raw material selection, quality control, stability, safety and effectiveness, the achievements so far in this area should be considered encouraging and important for the health care system in Poland.

Cannabinoids represent a highly researched group of plant-derived ingredients. The substantial investment of funds from state and commercial sources has facilitated a significant increase in knowledge about these ingredients. Cannabinoids can be classified into three principal categories: plant-derived phytocannabinoids, synthetic cannabinoids and endogenous cannabinoids, along with the enzymes responsible for their synthesis and degradation. All of these compounds interact biologically with type 1 (CB1) and/or type 2 (CB2) cannabinoid receptors. A substantial body of evidence from in vitro and in vivo studies has demonstrated that cannabinoids and inhibitors of endocannabinoid degradation possess anti-inflammatory, antioxidant, antitumour and antifibrotic properties with beneficial effects. This review, which spans the period from 1940 to 2024, offers an overview of the potential therapeutic applications of natural and synthetic cannabinoids. The development of these substances is essential for the global market of do-it-yourself drugs to fully exploit the promising therapeutic properties of cannabinoids.

The public is increasingly reporting using cannabis for anxiety relief. Both cannabis use and the endocannabinoid system have been connected with anxiety relief/anxiolytic properties, but these relationships are complex, and the underlying mechanisms for them are unclear. Background/Objectives: Work is needed to understand how the endocannabinoid system, including the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG), may be impacted by the main constituents of cannabis, Δ9-tetrahydrocannabinol (THC), and cannabidiol (CBD). Methods: The current study examined how the ab libitum use of products differing in THC and CBD affected AEA and 2-AG among 292 individuals randomly assigned to THC-dominant use (N = 92), CBD-dominant use (N = 97), THC + CBD use (N = 74), or non-use (N = 29). Results: The findings suggest that AEA levels do not change differently based on 4 weeks of cannabis use or by cannabinoid content, as AEA similarly increased across all conditions from study weeks 2 to 4. In contrast, AEA decreased at an acute administration session with product conditions containing any THC having greater AEA levels on average than the non-use condition. With regard to 2-AG, its levels appeared to primarily be affected by THC-dominant use, both acutely and over 4 weeks, when controlling for baseline cannabis use and examining study product use frequency among use conditions. Conclusions: Overall, the results continue to shed light on the complicated relationship between cannabinoid content and endocannabinoid production, and highlight the need for continued research on their interplay in human subjects.

BackgroundHIV-associated neurocognitive disorder (HAND) is commonly observed in persons living with HIV (PWH) and is characterized by cognitive deficits implicating disruptions of fronto-striatal neurocircuitry. Such circuitry is also susceptible to alteration by cannabis and other drugs of abuse. PWH use cannabis at much higher rates than the general population, thus prioritizing the characterization of any interactions between HIV and cannabinoids on cognitively relevant systems. Prepulse inhibition (PPI) of the startle response, the process by which the motor response to a startling stimulus is attenuated by perception of a preceding non-startling stimulus, is an operational assay of fronto-striatal circuit integrity that is translatable across species. PPI is reduced in PWH. The HIV transgenic (HIVtg) rat model of HIV infection mimics numerous aspects of HAND, although to date the PPI deficit observed in PWH has yet to be fully recreated in animals.MethodsPPI was measured in male and female HIVtg rats and wild-type controls following acute, nonconcurrent treatment with the primary constituents of cannabis: Δ 9-tetrahydrocannabinol (THC; 1 and 3 mg/kg, s.c.) and cannabidiol (1, 10, and 30 mg/kg, i.p.).ResultsHIVtg rats exhibited a significant PPI deficit relative to wild-type controls. THC reduced PPI in controls but not HIVtg rats. Cannabidiol exerted only minor, genotype-independent effects on PPI.ConclusionsHIVtg rats exhibit a relative insensitivity to the deleterious effects of THC on the fronto-striatal function reflected by PPI, which may partially explain the higher rates of cannabis use among PWH.

Abstract Road safety is an important concern amidst expanding worldwide access to legal cannabis. The present study reports on the driving-related subsection of the Cannabis as Medicine Survey 2020 (CAMS-20) which surveyed driving-related behaviors, attitudes, and perceptions among Australian medical cannabis (MC) users. Of the 1063 respondents who reported driving a motor vehicle in the past 12 months, 28% (297/1063) reported driving under the influence of cannabis (DUIC). Overall, 49–56% of respondents said they typically drive within 6 h of MC use, depending on the route of administration (oral or inhaled). Non-medical cannabis (NMC) was perceived to be more impairing for driving than MC. Binary logistic regression revealed associations between likelihood of DUIC and (1) inhaled routes of cannabis administration, (2) THC-dominant products, (3) illicit rather than prescribed use, (4) believing NMC does not impair driving, and (5) not being deterred by roadside drug testing. Overall, these findings suggest there is a relatively low perception of driving-related risk among MC users. Targeted education programs may be needed to highlight the potential risks associated with DUIC, and further research is needed to determine whether driving performance is differentially affected by MC and NMC.

Apichaya Sukpiriyagul,1 Ratiporn Chartchaiyarerk,1 Paluekpon Tabtipwon,1 Buppa Smanchat,1 Sinart Prommas,1 Kornkarn Bhamarapravatana,2 Komsun Suwannarurk3 1Department of Obstetrics and Gynecology, Bhumibol Adulyadej Hospital, Royal Thai Air Force Bangkok Thailand; 2Department of Preclinical Science, Faculty of Medicine, Thammasat University Hospital, Pathum Thani, Thailand; 3Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, Thammasat University Hospital, Pathum Thani, ThailandCorrespondence: Ratiporn Chartchaiyarerk, Department of Obstetrics and Gynecology, Bhumibol Adulyadej Hospital, Pathum Thani, Thailand, Tel +66814092569, Email ratiporn_c@rtaf.mi.thObjective: To evaluate the effects of tetrahydrocannabinol (THC):cannabinoid (CBD) (1:1) oil in reducing chemotherapy-induced nausea and vomiting (CINV) in gynecologic cancer patients who received moderate-to-high emetogenic chemotherapy.Material and Method: This was a randomized, double-blinded, crossover and placebo-controlled trial. The study was conducted at the Gynecologic Oncology Units, Bhumibol Adulyadej Hospital (BAH), Royal Thai Air Force, Bangkok, Thailand, between August and November 2022. Participants had gynecologic cancer and received moderate-to-high emetogenic chemotherapy. Subjects were randomized and divided into two groups (A and B) based on the block of four randomization method. In the first cycle, groups A and B received THC:CBD extract oil 1:1 (TCEO) and placebo before chemotherapy administration. In the second cycle, groups A and B received placebo and TCEO before chemotherapy administration. Both groups received per protocol antiemetic medication during chemotherapy. Nausea score and side effects were recorded.Results: A total of 60 cases were recruited. After exclusion, 54 cases were included in the study. The mean age of participants was 54.4 years. The mean body mass index (BMI) was 26.5 kg/m2. Fifty-nine (21/54) percent cases were the advanced stages of cancer. The nausea score of TCEO and placebo groups were 2.11 and 2.99, respectively (P < 0.05). More than half of the participants (36/54) reported dizziness and sedation side effects. Dry mouth, confusion, anxiety, and palpitation of both groups were comparable.Conclusion: The cannabinoid extract (THC:CBD) was an appropriate adjuvant agent to reduce CINV in patients with gynecologic cancer who received high-emetogenic chemotherapy. Dizziness and sedation were the major side effects.Keywords: CINV, THC, CBD, cannabis

Discoid lupus erythematosus (DLE) is a common autoimmune skin disease in dogs. Conventional treatments, such as corticosteroids, can be effective but often have side effects. This case report presents a successful use of cannabinoid therapy (CT) in a dog with DLE resistant to conventional treatment. A 2-year-old mixed-breed dog with a history of DLE presented with worsening lesions despite treatment with corticosteroids and other medications. Liver enzymes levels were elevated, indicating corticosteroid-induced side effects. CT with a CBD-rich full spectrum Cannabis oil was initiated. The dosage was gradually adjusted until the minimum effective dose was found. Within a few weeks of starting CT, the dog showed significant improvement in skin lesions and in liver enzymes levels. After 1 year, the dog remains clinically stable on a low dose of full-spectrum CBD-rich oil. No evidence of DLE recurrence was observed. This case suggests that CT may be a viable alternative or complementary therapy for DLE in dogs, particularly for those experiencing adverse effects from conventional treatments. Further research is warranted to confirm the efficacy and safety of CT for DLE management in dogs.

Emerging research has revealed a complex bidirectional interaction between the gut microbiome and cannabis. Preclinical studies have demonstrated that the gut microbiota can significantly influence the pharmacological effects of cannabinoids. One notable finding is the ability of the gut microbiota to metabolise cannabinoids, including Δ9-tetrahydrocannabinol (THC). This metabolic transformation can alter the potency and duration of cannabinoid effects, potentially impacting their efficacy in cancer treatment. Additionally, the capacity of gut microbiota to activate cannabinoid receptors through the production of secondary bile acids underscores its role in directly influencing the pharmacological activity of cannabinoids. While the literature reveals promising avenues for leveraging the gut microbiome–cannabis axis in cancer therapy, several critical considerations must be accounted for. Firstly, the variability in gut microbiota composition among individuals presents a challenge in developing universal treatment strategies. The diversity in gut microbiota may lead to variations in cannabinoid metabolism and treatment responses, emphasising the need for personalised medicine approaches. The growing interest in understanding how the gut microbiome and cannabis may impact cancer has created a demand for up-to-date, comprehensive reviews to inform researchers and healthcare practitioners. This review provides a timely and invaluable resource by synthesizing the most recent research findings and spotlighting emerging trends. A thorough examination of the literature on the interplay between the gut microbiome and cannabis, specifically focusing on their potential implications for cancer, is presented in this review to devise innovative and effective therapeutic strategies for managing cancer. [ABSTRACT FROM AUTHOR]

Background: While cannabis is the most widely used recreational drug in the world, the effects of phytocannabinoids on semen parameters and reproductive hormones remain controversial. Cannabinoid receptors are activated by these compounds at each level of the hypothalamus–pituitary–gonadotropic axis. Objectives: To assess the impact of the consumption of Δ‐9‐tetrahydrocannabinol and cannabidiol on semen parameters, as well as on male reproductive hormone and endocannabinoid levels, in a cohort of young Swiss men. Materials and methods: The individuals in a Swiss cohort were divided according to their cannabis consumption. In the cannabis user group, we determined the delay between the last intake of cannabis and sample collection, the chronicity of use and the presence of cannabidiol in the consumed product. Urinary Δ‐9‐tetrahydrocannabinol metabolites were quantified via gas chromatography–mass spectrometry. Blood phytocannabinoids, endocannabinoids and male steroids were determined via liquid chromatography–mass spectrometry/mass spectrometry, and other hypothalamus–pituitary–gonadotropic axis hormones were determined via immunoassays. Semen parameters such as sperm concentration and motility were recorded using computer‐assisted sperm analysis. Results: Anandamide, N‐palmitoyl ethanolamide, androgens, estradiol and sex hormone binding globulin levels were all higher in cannabis users, particularly in chronic, recent and cannabidiol‐positive consumers. Gonadotropin levels were not significantly different in these user subpopulations, whereas prolactin and albumin concentrations were lower. In addition, cannabis users had a more basic semen pH and a higher percentage of spermatozoa with progressive motility. However, the two latter observations seem to be related to a shorter period of sexual abstinence in this group rather than to the use of cannabis. Conclusions: Because both cannabidiol and Δ‐9‐tetrahydrocannabinol are frequently used by men of reproductive age, it is highly relevant to elucidate the potential effects they may have on human reproductive health. This study demonstrates that the mode of cannabis consumption must be considered when evaluating the effect of cannabis on semen quality. [ABSTRACT FROM AUTHOR]

An influential cannabis lobby and its allies are engaged in an aggressive initiative to mandate health and worker's compensation insurance coverage for non-standardized, non-FDA-regulated cannabis products. If successful, mandated reimbursement would present a severe public health risk and force taxpayers to fund a risky and under-regulated industry. Leaders in psychiatry and other medical specialties have sounded the alarm about the marketing and sale of cannabis products for medical uses without prior review by the FDA. We echo their strong opposition to bills requiring workers' compensation carriers and health insurance plans to cover the cost of dispensary-purchased "medical" cannabis. Mandated insurance reimbursement of dispensary products is "a recipe for a public health disaster, as lowering or eliminating out-of-pocket costs will encourage more consumers to become certified under a state's medical cannabis program, and result in more frequent use of higher-potency cannabinoids (e.g., THC and CBD) that are associated with serious adverse events." Until there are thorough studies into these products, including adverse events, side effects and long-term concerns, these products should not be considered appropriate alternatives to FDA-approved medications. Their use should not be encouraged nor paid for through mandated reimbursement by public or private third-party payers. [ABSTRACT FROM AUTHOR]

Among all complaints, pain is one of the most frequently reported symptoms and reasons for using cannabinoids. Adding them to the ongoing treatment of chronic pain is usually a step when standard treatment with analgesics and coanalgesics does not provide satisfactory clinical results or drugs cause unacceptable side effects. Sometimes patients themselves take such a suggestion into consideration. When initiating therapy with cannabinoids, particularly with THC-containing preparations, basic and simple principles should be followed each time. The article presents recommendations developed and based on expert consensus using a modified Delphi process on how to dose and administer cannabinoids in the treatment of patients with chronic pain. CBD and/or THC should be introduced into therapy according to the well-known "start low, go slow" principle. Proper education regarding the use of THC in the form of extracts, as well as communication with the patient, can be of key importance in the attitude towards such therapy, which often translates into its success. Adequate follow-up during titration and continuation of the therapy will ensure patient comfort and safety. [ABSTRACT FROM AUTHOR]