Chronic non-cancer pain, defined by the Center for Disease Control and Prevention (CDC) as lasting beyond three months, significantly affects individuals' quality of life and is often linked to various medical conditions or injuries. Its management is complex. Cannabis, containing the key compounds Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), has garnered interest for its potential in pain management, though it remains controversial due to its psychoactive effects and illegal status in many countries. THC provides pain relief by blocking nociceptive stimuli but has psychoactive effects and may potentially induce dependency. CBD has calming and antipsychotic properties. The inhalation of cannabis offers quick relief but poses respiratory risks, while its oral administrations are safer but act more slowly. Short-term cannabis use can impair cognition and motor skills, while long-term use may lead to dependency and cognitive decline, especially if used from an early age. Adverse effects vary by gender and prior use, with addiction mainly linked to THC and influenced by genetics. Despite these risks, patients often report more benefits, such as improved quality of life and reduced opioid use, although the evidence remains inconclusive. The legal landscape for medical cannabis varies globally, with some positive public health outcomes like reduced opioid-related issues in areas where it is legalized. Cannabis shows promise in managing chronic pain, but its psychoactive effects and dependency risks necessitate cautious use. Future research should prioritize long-term clinical trials to establish optimal dosing, efficacy, and safety, aiding in the development of informed guidelines for safe cannabis use in chronic pain management. This review examines the use of cannabis in managing chronic non-cancer pain, focusing on its benefits, drawbacks, mechanisms, delivery methods, and impact on quality of life.

Marijuana is now one of the most widely used substances in the United States that has been rising in prevalence given increasing legalization and recreational and medical usage. Despite its widespread use, there have been increasing concerns regarding the cardiovascular safety of marijuana. Recent studies have found a link between marijuana use and the development of cardiovascular disease. Most notably, marijuana has been found to be associated with various cardiac complications, including atherosclerosis, myocardial infarction, stroke, cardiomyopathy, arrhythmia, and arteritis. Given these growing concerns, this article seeks to examine the effects and significance of marijuana on cardiovascular health.

Cannabinoids exert their effects on body tissues via cannabinoid 1 (CB 1 ) and cannabinoid 2 (CB 2 ) receptors. Receptors are present in brain, myocardium, vascular endothelium, platelets, and adipose tissues. Under normal physiologic conditions, endocannabinoid effects are minimal. The use of exogenous cannabis leads to endothelial dysfunction and increases vascular thrombosis via CB 1 receptor stimulation. On the other hand, CB 2 receptors may have a beneficial anti-inflammatory response.

We reviewed reports of the effects of cannabis on the cardiovascular system utilizing PUBMED from the last 20 years with emphasis on the most recent reports.

Despite a plethora of reviews and some retrospective studies, there is a need for more definitive data regarding the effect of cannabis use on cardiovascular events (CVE). Marijuana does not appear to accelerate atherosclerosis. There is a suggestion that it may induce myocardial infarction in a small percentage of users, especially in male users, particularly during recent use. It has a possibility of increasing cerebrovascular events when combined with other risk factors such as tobacco use. There is an association between cannabis use and increased evidence of peripheral vascular disease. To have a definitive answer to the question of whether cannabis contributes to CVE, there is an urgent need for prospective controlled studies with patients presenting to academically oriented medical facilities with CVE following cannabis use for either medicinal or recreational use.

With recent evolution of cannabis legalization around the world and multiplication of cannabis derived products, identifying and qualifying cannabis consumption has a proven interest. Although blood, plasma, and urine are common matrices widely used in toxicology laboratories, oral fluid presents specific advantages. In the context of doping tests, addiction consultation or roadside checks, where other matrices are impractical to collect or can be adulterated, oral fluid is a promising matrix that allows a non-invasive, rapid, and monitored self-sampling. However, available devices required a consequent volume of oral fluid, more than 250 µL, sometimes difficult to collect. We present here a fully optimized quantitative method for seven cannabinoids, including four metabolites, in oral fluid, Δ9-tetrahydrocannabinol, 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol; cannabidiol, 7-hydroxy and 7-carboxycannabidiol; and cannabinol. After self-collection of 20 µL using an accurate and precise volumetric absorptive microsampling device (VAMS®), cannabinoids were derivatized with 2-fluoro-1-methylpyridinium p-toluenesulfonate to increase sensitivity. The successive steps of the proposed method, including biosampling, 1 h sample preparation with derivatization, and acquisition by ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry, were fully optimized. A limit of quantification of 0.5 ng/mL (≈10 pg per sampling) was thus targeted, adapted to the legal threshold required by the authorities and to clinical monitoring. Applied to six cannabis consumers, the proposed method made it possible to quantify in 20 µL oral fluid samples, Δ9-tetrahydrocannabinol ranging from 0.5 to 6236 ng/mL, cannabidiol from 0.6 to 190 ng/mL and cannabinol from 0.5 to 118 ng/mL.

Determine the association of marijuana use with serious psychological distress (SPD) among adults aged 18 years or older using a large, nationally representative sample of US households.

Cross-sectional analysis.

Data from the National Survey on Drug Use and Health, 2021.

47,247 respondents representing 253.7 million adults (age>18 years) in the US.

Marijuana use was categorized as (1) None, (2) within the past month, (3) within 1 year, and (4) more than a year ago from the interview time. SPD was measured with the Kessler-6 distress scale.

Bivariable and multivariable logistic regression analyses accounting for complex survey designs were conducted.

Among adults in the US, 50.9% never used marijuana, 13.7%, 6.0%, and 29.4% reported marijuana use in the past month, in the past year, and more than a year ago, respectively. Individuals using marijuana within the past month, within a year, and more than a year ago reported higher past month SPD (15.3%, 13.5%, and 6.8%, respectively) than never-users (4.9%). Adjusted logistic regression analysis revealed that marijuana use in the past month, past year (1-12 months), and over a year ago is associated with higher SPD (AOR [95% CI] = 2.06 [1.72, 2.45]; 1.82 [1.50, 2.21]; 1.53 [1.26, 1.87], respectively) compared to no marijuana use.

Adults who used marijuana more recently were more likely to report SPD.

Cannabis use has increased among young individuals in recent years. Although dependent cannabis use disorder (CUD) has been associated with various cardiac events, its effects on young adults without concurrent substance use remain understudied.

To examine trends in hospitalizations for major adverse cardiac and cerebrovascular events (MACCE) in this cohort.

We used the National Inpatient Sample (2016-2019) to identify hospitalized young individuals (18-44 years), excluding those with concurrent substance usage (tobacco, alcohol, and cocaine). They were divided into CUD+ and CUD-. Using International Classification of Diseases-10 codes, we examined the trends in MACCE hospitalizations, including all-cause mortality (ACM), acute myocardial infarction (AMI), cardiac arrest (CA), and acute ischemic stroke (AIS).

Of 27.4 million hospitalizations among young adults without concurrent substance abuse, 4.2% (1.1 million) had co-existent CUD. In CUD+ group, hospitalization rates for MACCE (1.71% vs 1.35%), AMI (0.86% vs 0.54%), CA (0.27% vs 0.24%), and AIS (0.49% vs 0.35%) were higher than in CUD- group (P < 0.001). However, rate of ACM hospitalizations was lower in CUD+ group (0.30% vs 0.44%). From 2016 to 2019, CUD+ group experienced a relative rise of 5% in MACCE and 20% in AMI hospitalizations, compared to 22% and 36% increases in CUD- group (P < 0.05). The CUD+ group had a 13% relative decrease in ACM hospitalizations, compared to a 10% relative rise in CUD- group (P < 0.05). However, when adjusted for confounders, MACCE odds among CUD+ cohort remain comparable between 2016 and 2019.

The CUD+ group had higher rates of MACCE, but the rising trends were more apparent in the CUD- group over time. Interestingly, the CUD+ group had lower ACM rates than the CUD- group.

Background: Cannabis use is associated with an increased risk of coronary heart disease (CHD), including angina pectoris (AP), and myocardial infarction (MI). However, it is not clear whether cannabis use is an independent risk factor of AP and/or MI, because cannabis is often smoked together with tobacco. We investigated whether cannabis is an independent risk factor of MI and whether this risk is similar in cannabis smokers, cannabis vapers, and those who use cannabis edibles. Methods: A systematic review was performed, according to the PRISMA guidelines and using Medline (PubMed), Embase, and Google Scholar as databases. Results: Twenty-two eligible papers were identified. After adjustment for concurrent tobacco use, cannabis smoking remained significantly associated with incidents of MI, with aORs ranging between 1.03 and 5.24, and particularly high aORs in the younger age group. In never-tobacco smokers, frequent cannabis smoking was also associated with a significant MI risk (aOR = 1.88). Frequent and current cannabis use in any form other than smoking (e.g., vaping, but mostly ingestion) was not associated with a significantly increased cardiovascular risk (frequent use: aOR = 1.00 ns; current use: aOR = 1.31 ns). Conclusions: Like tobacco smoking, cannabis smoking may independently provoke MI. Vaping and ingestion of cannabis might be less harmful, probably because absence of combustion prevents exposure to certain toxins in cannabis smoke, including carbon monoxide.

Cannabinoid use, particularly for recreational purposes, is increasing exponentially across all age groups, especially in younger populations, due to its perceived low risk and legalization. While cannabinoids may be largely considered as safe, there is mounting evidence of increased risk of systemic and neurological complications through their interaction with the poorly understood endocannabinoid receptor network within the central nervous system and other organ systems. Acute cannabinoid exposure can cause neuropsychiatric symptoms in addition to altering cerebral blood flow, leading to cerebrovascular complications such as ischemic stroke, subarachnoid hemorrhage, and reversible cerebral vasoconstriction syndrome (RCVS). Chronic use, particularly among adolescents, may be associated with increased risk of long-term cognitive deficits, schizophrenia, and other neuropsychiatric effects. Synthetic cannabinoids have increased potency, with reports of causing profound neurological complications including coma, seizures, posterior reversible encephalopathy syndrome, and RCVS. Despite increasing evidence, the quality of literature describing neurologic complications with cannabinoids remains limited to case series and retrospective cohort studies, with significant confounding factors such as concomitant use of other illicit drugs, limiting interpretation. In this review, we summarize the effect of cannabinoids on the neurologic system and associated neurological complications.

Cannabis has been employed medicinally throughout history, with recent renewed interest for use due to media awareness and medical marijuana legislation. The geriatric population, identified as those 65 years of age and older, is increasingly using cannabis-derived products, has a higher likelihood of having multiple comorbidities, and is subject to polypharmacy. These individuals are at increased risk of psychiatric and other medical adverse events due to their decreased physical and cognitive reserve and changes in their physicality. Recreational use of cannabis in this population has not been well studied, but medical marijuana use has been investigated more frequently. Increased nonmedical use increases the risk of adverse health consequences. Heavy regular use can lead to cannabis use disorder (CUD), which is formerly known as cannabis abuse and dependence, and may also lead to impaired social functioning and psychiatric comorbidity. The pattern of patients admitted to hospitals has dramatically changed recently, with an increased number of elderly patients being frequently admitted. As such, due to the ease of accessing CBD, this vulnerable cohort is seen more frequently in the hospital, and we need to be more vigilant and inquire about cannabis use as we do, asking about routine medications and over-the-counter supplements. In the U.S., marijuana laws have been changing rapidly, and Americans increasingly favor legalizing cannabis for medical and recreational uses. Policymakers should ensure that training on cannabis screening and interventions for CUD are provided to clinicians to equip them better to monitor and treat patients with cannabis-related problems.

Cannabis sativa is known for its therapeutic benefit in various diseases including pain relief by targeting cannabinoid receptors. The primary component of cannabis, Δ9-tetrahydrocannabinol (THC), and other agonists engage the orthosteric site of CB1, activating both Gi and β-arrestin signaling pathways. The activation of diverse pathways could result in on-target side effects and cannabis addiction, which may hinder therapeutic potential. A significant challenge in pharmacology is the design of a ligand that can modulate specific signaling of CB1. By leveraging insights from the structure-function selectivity relationship (SFSR), we have identified Gi signaling-biased agonist-allosteric modulators (ago-BAMs). Further, two cryoelectron microscopy (cryo-EM) structures reveal the binding mode of ago-BAM at the extrahelical allosteric site of CB1. Combining mutagenesis and pharmacological studies, we elucidated the detailed mechanism of ago-BAM-mediated biased signaling. Notably, ago-BAM CB-05 demonstrated analgesic efficacy with fewer side effects, minimal drug toxicity and no cannabis addiction in mouse pain models. In summary, our finding not only suggests that ago-BAMs of CB1 provide a potential nonopioid strategy for pain management but also sheds light on BAM identification for GPCRs.

The association between mortality and cannabis use remains unclear.

To examine sex-stratified associations of cumulative lifetime cannabis use with all-cause, cardiovascular disease (CVD), and cancer mortality in the UK Biobank population.

This cohort study used data from volunteers in the UK Biobank population. Participant monitoring for mortality in the UK Biobank study commenced from the point of their inclusion between 2006 and 2010 and continued until December 19, 2020. Data regarding the causes of death were sourced from the National Health Service Information Centre. Data were analyzed from inception of study inclusion to December 2020.

Cannabis use status was assessed by questionnaire and categorized as heavy, moderate, low, and never.

The main outcomes were all-cause, CVD, and cancer mortality. Sex-stratified associations of cumulative lifetime cannabis use with mortality were estimated using Cox proportional hazards regression with adjustment for demographic and clinical variables.

Among 121 895 participants (54.51% females with mean [SD] age of 55.15 [7.64] years; 45.49% males with mean [SD] age of 56.46 [7.79] years) during an overall median of 11.80 years (IQR, 10.53-13.22 years) of follow-up, 2375 total deaths occurred, including 1411 deaths from CVD and 440 from cancer. In males, after full adjustment, the hazard ratios (HRs) were 1.28 (95% CI, 0.90-1.81) for all-cause mortality, 0.98 (95% CI, 0.43-2.25) for CVD mortality, and 1.09 (95% CI, 0.71-1.67) for cancer mortality among heavy cannabis users compared with never users. In females, after full adjustment, the HRs were 1.49 (95% CI, 0.92-2.40) for all-cause mortality, 2.67 (95% CI, 1.19-4.32) for CVD mortality, and 1.61 (95% CI, 0.91-2.83) for cancer mortality among heavy cannabis users compared with never users. In female current tobacco users, after full adjustment, heavy cannabis use was associated with all-cause mortality (HR, 2.25; 95% CI, 1.12-4.53), CVD mortality (HR, 2.56; 95% CI, 1.43-15.36), and cancer mortality (HR, 3.52; 95% CI, 1.50-8.33) and among never tobacco users was associated with CVD mortality (HR, 2.98; 95% CI, 1.67-6.61). In male current tobacco users, heavy cannabis use was associated with cancer mortality (HR, 2.44; 95% CI, 1.14-5.23).

In this study, a positive association between CVD mortality and heavy lifetime cannabis use was observed among females. Longitudinal studies are needed in general populations to investigate the potential effects of cannabis on mortality.

Although treatable with antiretroviral therapy, HIV infection persists in people living with HIV (PLWH). It is well known that the HIV virus finds refuge in places for which antiretroviral medications do not reach therapeutic levels, mainly the CNS. It is clear that as PLWH age, the likelihood of developing HIV-associated neurological deficits increases. At the biochemical level neurological dysfunction is the manifestation of altered cellular function and ineffective intercellular communication. In this review, we examine how intercellular signaling in the brain is disrupted in the context of HIV. Specifically, the concept of how the blood-brain barrier can be a convergence point for crosstalk, is explored. Crosstalk between the cells of the neurovascular unit (NVU) (endothelium, pericytes, astrocytes, microglia and neurons) is critical for maintaining proper brain function. In fact, the NVU allows for rapid matching of neuronal metabolic needs, regulation of blood-brain barrier (BBB) dynamics for nutrient transport and changes to the level of immunosurveillance. This review invites the reader to conceptually consider the BBB as a router or convergence point for NVU crosstalk, to facilitate a better understanding of the intricate signaling events that underpin the function of the NVU during HIV associated neuropathology.

Cannabis use among youth is increasing; this study aimed to assess college students' knowledge, attitude, and expectancies toward cannabis use.

Cross-sectional survey using standardized tools among undergraduate and postgraduate college students in urban Bangalore, India (N = 405).

Ten percent reported past three-month cannabis use, with 1% reporting daily use. Users were significantly older (median age 21, IQR 22,20 [vs. 20, IQR 21,19], p < .001) and belonged to families with higher monthly incomes (p = .02). Use was significantly higher among males than females (65.9% vs. 34.1%, p = .006) and postgraduate students than undergraduates (51.2% vs. 48%, p = .001). Users were also significantly more favorable toward cannabis use (median score 4, IQR 6,2 [vs. median 3, IQR 4,2], p = .005) and had more positive expectancies from use (median score 2, IQR 3,2 [vs. median 2, IQR 2,0], p = .001). Nearly 30% were unaware that cannabis can affect a person's ability to drive safely or that it can affect executive functions, including academic performance. Over one-third were unaware of the current legal status of cannabis in India. Overall, 36%, 25%, and 17%, respectively, said that cannabis use is safe when used for recreational purposes, cannabis should be legalized as it helps to relieve stress, and cannabis use among youngsters should be acceptable in society as it is "part of college life."

Findings build on existing literature on cannabis use among college youth in India, which can guide preventive interventions and policies for this vulnerable group.

Aim: Knowledge of the cardiovascular and respiratory effects of cannabis use by route of administration is unclear. This evidence is necessary to increase clinical and public health awareness given the recent trend in cannabis legalization, normalization, and surge in the availability and usage of various forms of cannabis products. Methods: Search was conducted in Web of Science, ProQuest, Psych INFO, Scopus, Embase, and Medline databases, and subsequently in the references of retrieved articles. Peer-reviewed articles published between 2009 and 2023, that reported on cardiovascular and respiratory effects of cannabis use by route of administration were included. Studies with no report of the route of administration and combined use of other illicit substances were excluded. The review was guided by Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Results: Of the 1873 articles retrieved, 42 met inclusion criteria encompassing six case reports, 21 reviews, and 15 empirical studies. Four administration routes were identified: smoking, vaping, oral ingestion, and dabbing. Smoking was the most common route of administration and was associated with both respiratory effects, such as bronchitis, dyspnea, and chronic obstructive lung disease, and cardiovascular effects including tachycardia, ventricular arrhythmias, and myocardial infarction. Cannabis edibles were associated with minimal respiratory effects. Tachycardia was the most common cardiovascular effect and was associated with all routes of administration. Conclusion: Cannabis use does cause cardiovascular and respiratory effects, but the conclusion remains tentative of the cardiovascular and respiratory effects by route of administration due to methodological limitations of the studies.

In this review, we discuss the potential role of cannabis and cannabinoids in the management of cancer-related symptoms. There is limited evidence demonstrating the effectiveness of cannabis-based products in treating cancer-related pain and gastrointestinal symptoms such as nausea, vomiting, and loss of appetite. Regarding the role of cannabis-based products in the treatment of insomnia and mood disorders, most studies looked at these symptoms as secondary outcomes with mixed results. Cannabis-based products have adverse effects, ranging from neuropsychiatric to systemic effects to potential drug interactions.

Worldwide, approximately 15 million people per year suffer from stroke. With about 5 million deaths, stroke is the second most common cause of death and a major cause of long-term disability. It is estimated that about 25% of people older than 85 years will develop stroke. Cannabis sativa and derived cannabinoids have been used for recreational and medical purposes for many centuries. However, due to the legal status in the past, research faced restrictions, and cannabis use was stigmatized for potential negative impacts on health. With the changes in legal status in many countries of the world, cannabis and cannabis-derived substances such as cannabinoids and terpenes have gained more interest in medical research. Several medical effects of cannabis have been scientifically proven, and potential risks identified. In the context of stroke, the role of cannabis is controversial. The negative impact of cannabis use on stroke has been reported through case reports and population-based studies. However, potential beneficial effects of specific cannabinoids are described in animal studies under certain conditions. In this narrative review, the existing body of evidence regarding the negative and positive impacts of cannabis use prior to stroke will be critically appraised.

In about a decade, half of the United States has legalized marijuana for recreational use. The drug has been associated with acute myocardial infarction, acute stroke, congestive heart failure, and various cardiac arrythmias. Data have shown that legalization of the drug led to an increase of its use as well as an increase in tetra hydro cannabinoid positive tests in patients admitted to emergency departments. In Colorado, one of the earlier states to implement legalization, there was an increase in traffic accidents, suicide rates, and even total mortality. However, there is a paucity of data on the effect of marijuana legalization on various cardiovascular events. It is prudent to have well-designed studies with enough power to provide consumers and health care providers the information they need to decide whether the risks of marijuana, especially on the cardiovascular front, are worth the "high" or potential benefits that have been described for other medical conditions.

Tobacco use disorder (TUD) adversely impacts older patients with established cardiovascular disease (CVD) risk. However, CVD risk in chronic habitual cannabis users without the confounding impact of TUD hasn't been explored. We aimed to determine the risk of major adverse cardiac and cerebrovascular events (MACCE) in older non-tobacco smokers with established CVD risk with vs. without cannabis use disorder (CUD).

We queried the 2019 National Inpatient Sample for hospitalized non-tobacco smokers with established traditional CVD risk factors aged ≥65 years. Relevant ICD-10 codes were used to identify patients with vs. without CUD. Using multivariable logistic regression, we evaluated the odds of MACCE in CUD cohorts compared to non-CUD cohorts.

Prevalence of CUD in the sample was 0.3% (28,535/10,708,815, median age 69), predominantly male, black, and non-electively admitted from urban teaching hospitals. Of the older patients with CVD risk with CUD, 13.9% reported MACCE. The CUD cohort reported higher odds of MACCE (OR 1.20, 95% CI 1.11-1.29, p < 0.001) compared to the non-CUD cohort. Comorbidities such as hypertension (OR 1.9) and hyperlipidemia (OR 1.3) predicted a higher risk of MACCE in the CUD cohort. The CUD cohort also had higher unadjusted rates of acute myocardial infarction (7.6% vs. 6%) and stroke (5.2% vs. 4.8%).

Among older non tobacco smokers with known CVD risk, chronic cannabis use had a 20% higher likelihood of MACCE compared to those who did not use cannabis.

Delta 9 tetrahydrocannabinol (THC), the main component of cannabis, has adverse effects on the cardiovascular system, but whether concomitant ethanol (EtOH) and aging modulate its toxicity is unknown. We investigated dose responses of THC and its vehicle, EtOH, on mitochondrial respiration and reactive oxygen production in both young and old rat cardiac mitochondria (12 and 90 weeks). THC dose-dependently impaired mitochondrial respiration in both groups, and such impairment was enhanced in aged rats (-97.5 ± 1.4% vs. -75.6 ± 4.0% at 2 × 10-5 M, and IC50: 0.7 ± 0.05 vs. 1.3 ± 0.1 × 10-5 M, p < 0.01, for old and young rats, respectively). The EtOH-induced decrease in mitochondrial respiration was greater in old rats (-50.1 ± 2.4% vs. -19.8 ± 4.4% at 0.9 × 10-5 M, p < 0.0001). Further, mitochondrial hydrogen peroxide (H2O2) production was enhanced in old rats after THC injection (+46.6 ± 5.3 vs. + 17.9 ± 7.8%, p < 0.01, at 2 × 10-5 M). In conclusion, the deleterious cardiac effects of THC were enhanced with concomitant EtOH, particularly in old cardiac mitochondria, showing greater mitochondrial respiration impairment and ROS production. These data improve our knowledge of the mechanisms potentially involved in cannabis toxicity, and likely support additional caution when THC is used by elderly people who consume alcohol.

Marijuana is the most commonly used federally illegal drug in the United States. Acute marijuana use is associated with several cardiovascular and neuropsychological adverse effects. Ocular complications of marijuana abuse are very rare. Herein, we present the first report of bilateral optic neuropathy following smoking marijuana. A 28-year-old man presented to the emergency room with sudden onset of bilateral blurring of the inferior visual field 8 h after smoking marijuana. His best-corrected visual acuity was 20/30 in the right eye and 20/20 in the left eye. Fundus examination revealed blurring of the optic disc margins in both eyes and a splinter haemorrhage in the right eye. Bilateral inferior visual field defects were detected with greater severity on the right side. Optical coherence tomography confirmed the diagnosis of bilateral optic neuropathy. A urine drug screen test was positive for tetrahydrocannabinol, which is the primary active ingredient in cannabinoids. The rest of the neurological examination and imaging were normal. The patient was treated with intravenous corticosteroids and an anti-platelet drug. His vision recovered to 20/20 in both eyes, with complete resolution of the field defect over a follow-up of 6 months. Optic neuropathy following marijuana abuse is unusual. The results of our report emphasise the need for awareness of marijuana-associated optic neuropathy as part of ocular adverse effects of marijuana intoxication.

There is limited information regarding the perioperative effects of marijuana in breast reconstructive surgeries.

The objective of this study was to explore the association between a history of cannabis use and postoperative complications in the setting of implant-based breast reconstruction.

Two databases, TriNetX and PearlDiver, were queried for patients undergoing implant-based breast reconstruction. Patients were divided into 4 groups based on active ICD-10 diagnostic codes: (1) cannabis use only, (2) tobacco use only, (3) cannabis and tobacco use, and (4) neither cannabis nor tobacco use. Associations with postoperative complications were analyzed with a logistic regression test.

TriNetX search revealed that 327 patients had an active diagnosis of cannabis use only and 1118 had an active diagnosis of tobacco use only. Patients in the cannabis only cohort had a significantly increased risk of developing surgical site infection. Patients in the tobacco only cohort had significantly increased risk of developing wound dehiscence, need for debridement, and surgical site infection. The PearlDiver search included 472 patients who had an active diagnosis of both cannabis and tobacco use and 17,361 patients with a diagnosis of tobacco use only. Patients with a diagnosis of cannabis and tobacco use had a significantly increased risk of developing postoperative complications including surgical site infection, wound dehiscence, need for incision and drainage, and debridement.

Patients undergoing implant-based breast reconstruction with an active diagnosis of cannabis with or without tobacco use were at increased risk of developing postoperative complications, and the risk was even higher in patients using both tobacco and cannabis.

Cannabis plants have been used in medicine since ancient times. They are well known for their anti-diabetic, anti-inflammatory, neuroprotective, anti-cancer, anti-oxidative, anti-microbial, anti-viral, and anti-fungal activities. A growing body of evidence indicates that targeting the endocannabinoid system and various other receptors with cannabinoid compounds holds great promise for addressing multiple medical conditions. There are two distinct avenues in the development of cannabinoid-based drugs. The first involves creating treatments directly based on the components of the cannabis plant. The second involves a singular molecule strategy, in which specific phytocannabinoids or newly discovered cannabinoids with therapeutic promise are pinpointed and synthesized for future pharmaceutical development and validation. Although the therapeutic potential of cannabis is enormous, few cannabis-related approved drugs exist, and this avenue warrants further investigation. With this in mind, we review here the medicinal properties of cannabis, its phytochemicals, approved drugs of natural and synthetic origin, pitfalls on the way to the widespread clinical use of cannabis, and additional applications of cannabis-related products.

Rheumatoid diseases, including rheumatoid arthritis, osteoarthritis, and fibromyalgia, are characterized by progressive inflammation in the musculoskeletal system, predominantly affecting the joints and leading to cartilage and bone damage. The resulting pain and ongoing degradation of the musculoskeletal system contribute to reduced physical activity, ultimately impacting quality of life and imposing a substantial socioeconomic burden. Unfortunately, current therapeutics have limited efficacy in slowing disease progression and managing pain. Thus, the development of novel and alternative therapies is imperative. Cannabinoids possess beneficial properties as potential treatments for rheumatoid diseases due to their anti-inflammatory and analgesic properties. Preclinical studies have demonstrated promising results in halting disease progression and relieving pain. However, there is a scarcity of patient clinical studies, and the available data show mixed results. Consequently, there are currently no established clinical recommendations regarding the utilization of cannabis for treating rheumatoid diseases. In this review, we aim to explore the concept of cannabis use for rheumatoid diseases, including potential adverse effects. We will provide an overview of the data obtained from preclinical and clinical trials and from retrospective studies on the efficacy and safety of cannabis in the treatment of rheumatoid diseases.

Rationale: Cannabis use is increasing worldwide, especially among older individuals at risk for chronic ischemic heart disease (IHD). However, little is known about the arrhythmic effects of cannabis use in IHD. Accordingly, we prospectively assessed the relationship between cannabis use, heart rate (HR), and arrhythmias in healthy age-matched controls and subjects with IHD. Methods: Healthy controls (n=37, 57% men) and subjects with IHD (myocardial infarction ≥3 months ago; n=24, 58% men) who used cannabis wore a Zio® (iRhythm Technologies) monitor for 14 days. Noncannabis using ischemic subjects (n=35, 51% males) wore Zio monitors for standard clinical indications. Baseline HR was compared with average HR measured for 4 h following consumption and changes in HR and frequency of arrhythmias were correlated with cannabis use. Results: In controls, HR increased 20 min (4.99±6.7 bpm, p=0.08) after use, then declined 4 h following use (-7.4±7.7, p<0.001). Conversely, subjects with IHD showed minimal HR increase (1.6±3.9 bpm) and blunted HR decline (-3.4±5.6 bpm, p<0.001). Supraventricular tachycardia (SVT) (29.7% vs. 58.3%; p=0.04) and nonsustained ventricular tachycardia (NSVT) (5.6% vs. 47.8%, p=0.01) were the most frequently occurring arrhythmias in controls and IHD subjects, respectively. Incidence of SVT decreased as cannabis use increased in both groups. Conversely, NSVT tended to increase with increased use in controls, and was significantly more prevalent in IHD. However, overall arrhythmia burden did not differ between cannabis users and nonusers with IHD. Conclusion: Our findings demonstrate that chronic cannabis use is associated with only mild HR changes, which are blunted in IHD. In addition, our data suggest that among cannabis users, arrhythmias are more frequent in IHD subjects that in healthy subjects.

There has been an increased interest of the scientific community in cannabis and its constituents for therapeutic purposes. Although it is believed that cannabinoids can be effective for a few different conditions and syndromes, there are little objective data that clearly support the use of cannabis, cannabis extracts or even cannabidiol (CBD) oil. This review aims to explore the therapeutic potential of phytocannabinoids and synthetic cannabinoids for the treatment of several diseases. A broad search covering the past five years, was performed in PubMed and ClinicalTrial.gov databases, to identify papers focusing on the use of medical phytocannabinoids in terms of tolerability, efficacy and safety. Accordingly, there are preclinical data supporting the use of phytocannabinoids and synthetic cannabinoids for the management of neurological pathologies, acute and chronical pain, cancer, psychiatric disorders and chemotherapy-induced emetic symptoms. However, regarding the clinical trials, most of the collected data do not fully support the use of cannabinoids in the treatment of such conditions. Consequently, more studies are still needed to clarify ascertain if the use of these compounds is useful in the management of different pathologies.

Cannabis enjoyed a "golden age" as a medicinal product in the late 19th, early 20th century, but the increased risk of overdose and abuse led to its criminalization. However, the 21st century have witnessed a resurgence of interest and a large body of literature regarding the benefits of cannabinoids have emerged. As legalization and decriminalization have spread around the world, cancer patients are increasingly interested in the potential utility of cannabinoids. Although eager to discuss cannabis use with their oncologist, patients often find them to be reluctant, mainly because clinicians are still not convinced by the existing evidence-based data to guide their treatment plans. Physicians should prescribe cannabis only if a careful explanation can be provided and follow up response evaluation ensured, making it mandatory for them to be up to date with the positive and also negative aspects of the cannabis in the case of cancer patients. Consequently, this article aims to bring some clarifications to clinicians regarding the sometimes-confusing various nomenclature under which this plant is mentioned, current legislation and the existing evidence (both preclinical and clinical) for the utility of cannabinoids in cancer patients, for either palliation of the associated symptoms or even the potential antitumor effects that cannabinoids may have.

This article seeks to determine dental students' knowledge, attitudes, and perceptions toward patients' marijuana use and whether dental students would like additional marijuana education.

Predoctoral dental students were invited in 2021 to complete a questionnaire regarding marijuana's oral health effects, their comfort discussing marijuana with patients and their interest in additional training.

Among participants (n = 206, 32.7% response rate), most were familiar with smoked, smokeless and edible methods, but only 39.3% were familiar with topical applications. Only 29.6% of preclinical and 32.2% of clinical Doctor of Dental Medicine students agreed that smoking marijuana was detrimental to one's health, compared to 64.6% of internationally trained Advanced Standing students. Significantly more clinical students (70.6%) could identify how often they treat patients having used marijuana compared to the estimates of preclinical students (36.7%), although 44.2% of all students indicated they were unsure. Not surprisingly, more preclinical students were uncomfortable treating patients during routine dental procedures (45.6% preclinical vs. 32.8% clinical) and when administering local anesthesia (45.6% preclinical vs. 38.8% clinical) due to not yet providing direct patient care. A majority of both preclinical (92.2%) and clinical (89.7%) students agreed they would benefit from more marijuana education. Clinical students preferred adding a brief introductory seminar while preclinical students preferred multiple lectures throughout the curriculum.

As states legalize medical and recreational marijuana use, dental schools need to evaluate marijuana education in their curriculum and develop resources so students can feel comfortable and confident in their ability to identify and safely treat patients who use marijuana.

The association between cardiovascular (CV) risk and cannabis use remains inconsistent. The purpose of this study was to examine sex stratified associations of the different lifetime aspects of cannabis use and estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk levels among the general UK Biobank population.

Among 104,092 volunteers of the UK Biobank population, cannabis use status was assessed by questionnaire and range as heavy, moderate, low, and never users. Associations between cannabis use and ASCVD risk were estimated using multiple regressions.

Males presented a higher estimated 10-year ASCVD risk compared to females (7.96% vs. 2.24%, p < 0.001) and a higher proportion of heavy lifetime cannabis users (4.00% vs 2.01%, p < 0.001). In all covariate adjusted models, lifetime heavy cannabis use was associated with an increase in estimated 10-year ASCVD risk in both males and females, but with a higher effect among males (in males, B = 0.51 (0.34; 068), in females, B = 0.14 (0.05; 0.23)). When considering high estimated 10-year ASCVD risk (superior to 7.5%), similar results were observed, in males, OR=2.14 [1.82-2.51] and in females: OR=2.07 [1.35-3.17]). The current consumption of cannabis was associated with increased ASCVD risk in both males and females (p < 0.001). When considering the overall population, a significant interaction was observed between sex and cannabis use (p < 0.001).

A positive association between estimated 10-year ASCVD risk and heavy lifetime cannabis use was observed but this was higher in males. Longitudinal studies are needed in general populations to highlight the causal effects of cannabis on the atherosclerosis process.

Thromboangiitis obliterans (TAO), or Buerger's disease, is a non-atherosclerotic inflammatory disease of the small and medium-sized arteries, veins, and nerves of the legs and arms, strongly associated with the use of tobacco products in young adults. Cannabis arteritis (CA), an entity with similar clinical and pathological features, has been described in marijuana users as a subtype of TAO. Distinction between TAO and CA is challenging, given that most patients use tobacco and marijuana products concomitantly. Herein, we report the case of a male in his late forties who was referred to rheumatology with a 2-month history of hand swelling and bilateral painful digital ulcers with blue discoloration on his fingers and toes. The patient reported daily use of marijuana in blunt wraps and denied tobacco use. His laboratory work-up was negative for scleroderma and other connective tissue diseases. His angiogram confirmed the diagnosis of thromboangiitis obliterans, which was attributed to cannabis arteritis. The patient was started on aspirin and nifedipine daily and discontinued marijuana use. His symptoms resolved within 6 months and have not recurred for more than a year with continued avoidance of marijuana. Our case is one of the few that features primarily marijuana-driven CA and highlights the importance of not only considering marijuana use but also blunt wrap use in patients presenting with Raynaud's phenomenon and ulcerations as cannabis use rises globally.

No studies have investigated the association between arterial stiffness index (ASI) and cannabis use. The purpose of this study is to examine sex-stratified associations of cannabis use and ASI levels in a middle-aged general population.

Cannabis use of 46 219 volunteers of the middle-aged UK Biobank population was assessed by questionnaire and investigates several aspects of cannabis use (lifetime, frequency and current status). Associations between cannabis use and ASI were estimated using sex multiple linear regressions. Covariates were tobacco status, diabetes dyslipidaemia, alcohol status, BMI categories, hypertension, mean blood pressure and heart rate.

Men presented higher ASI levels compared with women (respectively, 9.826 vs. 8.578 m/s, P < 0.001), a higher heavy lifetime cannabis users (4.0 vs. 1.9%, P < 0.001), higher current cannabis users (3.1 vs. 1.7%, P < 0.001), higher current smokers (8.4 vs. 5.8%, P < 0.001) and higher alcohol users (95.6 vs. 93.4%, P < 0.001). After adjustment for all covariates in sex models, heavy lifetime cannabis users were associated with higher ASI levels in men [b = 0.19, 95% confidence interval (0.02; 0.35)] but not in women [b = -0.02 (-0.23; 0.19)]. Current cannabis users were associated with higher ASI levels in men [b = 0.17 (0.01; 0.32)] but not in women [b = -0.01 (-0.20; 0.18)] and among cannabis users, every day frequency was associated with increased ASI levels in men [b = 0.29 (0.07; 0.51)] but not in women [b = 0.10 (-0.17; 0.37)].

The observed association between cannabis use and ASI could participate in accurate and appropriate cardiovascular risk reduction strategies among cannabis users.

Cancer cachexia is a multifactorial disorder characterized by weight loss and muscle wasting, and there are currently no FDA-approved medications. In the present study, upregulation of six cytokines was observed in serum samples from patients with colorectal cancer (CRC) and in mouse models. A negative correlation between the levels of the six cytokines and body mass index in CRC patients was seen. Gene Ontology analysis revealed that these cytokines were involved in regulating T cell proliferation. The infiltration of CD8⁺ T cells was found to be associated with muscle atrophy in mice with CRC. Adoptive transfer of CD8⁺ T cells isolated from CRC mice resulted in muscle wasting in recipients. The Genotype-Tissue Expression database showed that negative correlations between the expression of cachexia markers and cannabinoid receptor 2 (CB2) in human skeletal muscle tissues. Pharmacological treatment with Δ⁹-tetrahydrocannabinol (Δ⁹-THC), a selective CB2 agonist or overexpression of CB2 attenuated CRC-associated muscle atrophy. In contrast, knockout of CB2 with a CRISPR/Cas9-based strategy or depletion of CD8⁺ T cells in CRC mice abolished the Δ⁹-THC-mediated effects. This study demonstrates that cannabinoids ameliorate CD8⁺ T cell infiltration in CRC-associated skeletal muscle atrophy via a CB2-mediated pathway. Serum levels of the six-cytokine signature might serve as a potential biomarker to detect the therapeutic effects of cannabinoids in CRC-associated cachexia.

The use of cannabis has massively increased among younger patients due to increasing legalization and availability.

We performed a retrospective nationwide study using the Nationwide inpatient sample (NIS) database to analyze the trends of acute myocardial infarction (AMI) in young cannabis users and related outcomes among patients aged 18-49 years from 2007 to 2018, using ICD-9 and ICD-10 codes.

Out of 819,175 hospitalizations, 230,497 (28%) admissions reported using cannabis. There was a significantly higher number of males (78.08% vs. 71.58%, p < 0.0001) and African Americans (32.22% vs. 14.06%, p < 0.0001) admitted with AMI and reported cannabis use. The incidence of AMI among cannabis users consistently increased from 2.36% in 2007 to 6.55% in 2018. Similarly, the risk of AMI in cannabis users among all races increased, with the biggest increase in African Americans from 5.69% to 12.25%. In addition, the rate of AMI in cannabis users among both sexes showed an upward trend, from 2.63% to 7.17% in males and 1.62%-5.12% in females.

The incidence of AMI in young cannabis users has increased in recent years. The risk is higher among males and African Americans.

There is paucity of data regarding prevalence and key harms of non-medical cannabis use in surgical patients. We investigated whether cannabis use in patients undergoing surgery or interventional procedures patients was associated with a higher degree of post-procedural healthcare utilisation.

210,639 adults undergoing non-cardiac surgery between January 2008 and June 2020 at an academic healthcare network in Massachusetts, USA, were included. The primary exposure was use of cannabis, differentiated by reported ongoing non-medical use, self-identified during structured, preoperative nursing/physician interviews, or diagnosis of cannabis use disorder based on International Classification of Diseases, 9th/10th Revision, diagnostic codes. The main outcome measure was the requirement of advanced post-procedural healthcare utilisation (unplanned intensive care unit admission, hospital re-admission or non-home discharge).

16,211 patients (7.7%) were identified as cannabis users. The prevalence of cannabis use increased from 4.9% in 2008 to 14.3% by 2020 (p < 0.001). Patients who consumed cannabis had higher rates of psychiatric comorbidities (25.3 versus 16.8%; p < 0.001) and concomitant non-tobacco substance abuse (30.2 versus 7.0%; p < 0.001). Compared to non-users, patients with a diagnosis of cannabis use disorder had higher odds of requiring advanced post-procedural healthcare utilisation after adjusting for patient characteristics, concomitant substance use and socioeconomic factors (aOR [adjusted odds ratio] 1.16; 95% CI 1.02-1.32). By contrast, patients with ongoing non-medical cannabis use had lower odds of advanced post-procedural healthcare utilisation (aOR 0.87; 95% CI 0.81-0.92, compared to non-users).

One in seven patients undergoing surgery or interventional procedures in 2020 reported cannabis consumption. Differential effects on post-procedural healthcare utilisation were observed between patients with non-medical cannabis use and cannabis use disorder.

This work was supported by an unrestricted philantropic grant from Jeff and Judy Buzen to Maximilian S. Schaefer.

G protein-coupled receptors (GPCRs), the largest family of transmembrane proteins, regulate a wide array of physiological processes in response to extracellular signals. Although these receptors have proven to be the most successful class of drug targets, their complicated signal transduction pathways (including different effector G proteins and β-arrestins) and mediation by orthosteric ligands often cause difficulties for drug development, such as on- or off-target effects. Interestingly, identification of ligands that engage allosteric binding sites, which are different from classic orthosteric sites, can promote pathway-specific effects in cooperation with orthosteric ligands. Such pharmacological properties of allosteric modulators offer new strategies to design safer GPCR-targeted therapeutics for various diseases. Here, we explore recent structural studies of GPCRs bound to allosteric modulators. Our inspection of all GPCR families reveals recognition mechanisms of allosteric regulation. More importantly, this review highlights the diversity of allosteric sites and presents how allosteric modulators control specific GPCR pathways to provide opportunities for the development of new valuable agents.

The associations between blood pressure and cannabis use remain inconsistent. The purpose of our study was to examine gender stratified associations of cannabis use and blood pressure [systolic, diastolic blood pressure (BP), pulse pressure (PP)] levels among the general UK Biobank population based study. Among 91,161 volunteers of the UK Biobank population, cannabis use status was assessed by questionnaire and range as heavy, moderate, low and never users. Associations between cannabis use and BP were estimated using multiple gender linear regressions. In adjusted covariates models, lifetime heavy cannabis use was associated with decrease in both SBP, DBP and PP in both genders, but with a higher effect among women (for SBP in men, b = - 1.09 (0.27), p < 0.001; in women, b = - 1.85 (0.36), p < 0.001; for DBP in men, b = - 0.50 (0.15), p < 0.001; in women, b = - 0.87 (0.17), p < 0.001; and for PP in men, b = - 0.60 (0.20), p < 0.001; in women, b = - 0.97 (0.27), p < 0.001. Among men, lower SBP and DBP levels were observed with participants without dyslipidemia and lower PP in participants with high income levels. Among women, lower SBP, DBP and PP were observed with current smokers, moderate/low alcohol levels and participants without dyslipidemia. Current cannabis use was associated with lower SBP levels in men (b = - 0.63 (0.25), p = 0.012) and in women (b = - 1.17 (0.31), p < 0.001). Same results were observed for DBP and PP. Negative association between BP in men was found but not in women. The small association in BP differences between heavy users and never users remains too small to adopt cannabis-blood pressure public policy in clinical practice.

Many states have legalized medical cannabis with various reported therapeutic benefits. However, there is little data assessing the effects of cannabis on surgical outcomes. We sought to compare post-operative pancreatic resection complications between cannabis users and non-users.

This is a single-center, retrospective review of patients who underwent Whipple or distal pancreatectomy from 1/2017-12/2020. The primary outcome was any in-hospital complication, using Clavien-Dindo. Multivariable regression analysis was performed.

There were 486 patients who underwent Whipple (n=346, 71.2%) or distal pancreatectomy (n=140, 28.8%). Overall, 21.4% (n=104) reported cannabis use, of whom 80.8% were current users. Cannabis users were younger (60 vs. 66 years, p < 0.001), and more likely to have smoked tobacco (p=0.04), but otherwise had similar demographics as non-users. There were 288 (59.3%) patients who developed an in-hospital complication (grade 1-2, 75.3%; grade 3-5, 24.7%). A trend towards increased complications was observed with tobacco smoking (OR 1.33, 95% CI 0.91-1.94, p=0.14), but no association of cannabis use with complications was observed (OR 0.93, 95% CI 0.58-1.47, p=0.74).

A significant proportion of patients undergoing pancreatic resection report cannabis use. These results suggest that there was no association between cannabis use and post-operative complications, future prospective evaluation is warranted.

The endocannabinoid system (ECS) is involved in various processes, including brain plasticity, learning and memory, neuronal development, nociception, inflammation, appetite regulation, digestion, metabolism, energy balance, motility, and regulation of stress and emotions. Physical exercise (PE) is considered a valuable non-pharmacological therapy that is an immediately available and cost-effective method with a lot of health benefits, one of them being the activation of the endogenous cannabinoids. Endocannabinoids (eCBs) are generated as a response to high-intensity activities and can act as short-term circuit breakers, generating antinociceptive responses for a short and variable period of time. A runner's high is an ephemeral feeling some sport practitioners experience during endurance activities, such as running. The release of eCBs during sustained physical exercise appears to be involved in triggering this phenomenon. The last decades have been characterized by an increased interest in this emotional state induced by exercise, as it is believed to alleviate pain, induce mild sedation, increase euphoric levels, and have anxiolytic effects. This review provides information about the current state of knowledge about endocannabinoids and physical effort and also an overview of the studies published in the specialized literature about this subject.

Cardiovascular disease (CVD) causes millions of deaths worldwide each year. Despite the great progress in therapies available for patients with CVD, some limitations, including drug complications, still exist. Hence, the endocannabinoid system (ECS) was proposed as a new avenue for CVDs treatment. The ECS components are widely distributed through the body, including the heart and blood vessels, thus the action of its endogenous and exogenous ligands, in particular, phytocannabinoids play a key role in various pathological states. The cardiovascular action of cannabinoids is complex as they affect vasculature and myocardium directly via specific receptors and exert indirect effects through the central and peripheral nervous system. The growing interest in phytocannabinoid studies, however, has extended the knowledge about their molecular targets as well as therapeutical properties; nonetheless, some areas of their actions are not yet fully recognized. Researchers have reported various cannabinoids, especially cannabidiol, as a promising approach to CVDs; hence, the purpose of this review is to summarize and update the cardiovascular actions of the most potent phytocannabinoids and the potential therapeutic role of ECS in CVDs, including ischemic reperfusion injury, arrhythmia, heart failure as well as hypertension.

Marijuana, also known as cannabis, is the second most widely used illegal psychoactive substance smoked worldwide after tobacco, mainly due to the psychoactive effects induced by D-9-tetrahydrocannabinol (9-THC). Cannabidiol (CBD) is extracted from cannabis and may be used as an anti-inflammatory agent. Some patents on cannabidiol are discussed in this review. The cannabinoid is a non-psychoactive isomer of the more infamous tetrahydrocannabinol (THC); and is available in several administration modes, most known as CBD oil.

This study aims to provide an enhanced review of cannabidiol properties used in treating inflammation. This review also emphasises the current safety profile of cannabidiol.

Cannabis is also called Marijuana. It is the second most commonly used illegal psychoactive substance in the universe after tobacco. D-9-tetrahydrocannabinol (9-THC) present in cannabis produces psychoactive effects. Cannabidiol (CBD) extracted from cannabis is used for antiinflammatory purposes. Cannabis smoking causes various types of cancer, such as lung, tongue, and jaw. The current review took literature from Google Scholar, PubMed, and Google Patents. Many clinical investigations are included in this review.

After analysing the literature on cannabis, it has been suggested that although cannabis is banned in some countries, it may be included in the treatment and mitigation of some diseases and symptoms like pain management, epilepsy, cancer, and anxiety disorder. Mild side effects were frequently observed in cannabis medications, which included infertility in females, liver damage, etc. Conclusion: Cannabis contains chemical compounds such as the cannabinoids delta-9- tetrahydrocannabinol (THC), a psychoactive substance, and non-psychoactive cannabidiol (CBD). Cannabidiol has been confirmed as an efficient treatment of epilepsy in several clinical trials, with one pure CBD product named Epidiolex. It is also used in treating anxiety and acne, as a pain reliever, and has anti-inflammatory properties.

Current research is starting to focus on the medical value of marijuana and the possible health problems it can cause. Previous studies have shown that marijuana can relieve lower urinary tract symptoms, which can pose a significant public health burden. In this study, we assessed the association between regular marijuana use and overactive bladder as part of low urinary tract symptoms.

Data from the National Health and Nutrition Examination Survey 2005-2018 were obtained for analysis. The Overactive Bladder Symptom Score scale was used to define the presence of overactive bladder for each participant. Multivariate logistic regression and ordinal logistic regression were used to analyze the association of marijuana use with the onset and severity of overactive bladder, respectively.

We found that approximately 24% of the US population reported regular marijuana use. Compared with nonregular users, regular marijuana users were younger, thinner, more likely to be male, smokers, low-income, less educated, unmarried, and non-Hispanic White/Black. Multivariate logistic regression revealed that marijuana exposure may be an independent risk factor for overactive bladder (odds ratio 1.39; 95% confidence interval, 1.16-1.66). Ordinal logistic regression results showed that marijuana exposure was associated with the severity of overactive bladder (odds ratio 1.45; 95% confidence interval, 1.30-1.60). Moreover, all frequencies of regular use showed almost consistent effects on the onset and severity of overactive bladder.

Regular marijuana use may increase the risk of overactive bladder. Our data do not support the evidence for the use of cannabinoids in the medical treatment of patients with overactive bladder, especially given the thorny health problems caused by marijuana.

Cannabinoids may be useful to treat pain, epilepsy and spasticity, although they may bear an increased risk of cardiovascular events. This study aims to evaluate the cardiovascular safety of nabiximols, a cannabis-based drug, in patients with spasticity following stroke, thus presenting an increased cardiovascular risk.

This is an ancillary study stemming from the SativexStroke trial: a randomized double-blind, placebo-controlled, crossover study aimed at assessing the effect of nabiximols on post-stroke spasticity. Patients were treated with nabiximols oromucosal spray or placebo and assessed before and after two phases of 1-month duration each. Only the phase with the active treatment was considered for each patient who completed the study. The average values of blood pressure (diastolic, systolic, differential) and heart rate from the first 5 days of the phase (lowest nabiximols dosage) were compared to the average values recorded during the last 5 days at the end of the phase (highest nabiximols dosage). Baseline comparisons between gender, stroke type and affected side and correlation between age and blood pressure and heart rate were performed. The study was registered with the EudraCT number 2016-001034-10.

Thirty-four patients completed the study and were included in the analysis. Thirty-one were taking antihypertensive drugs and, among these, 12 were taking beta-blockers. During the study, no arrhythmic events were recorded, blood pressure and heart rate did not show pathological fluctuations, and no cardiovascular or cerebrovascular events occurred. At baseline blood pressure and heart rate were comparable concerning gender, stroke type and affected side. A significant direct correlation emerged between differential blood pressure and age and an inverse correlation between diastolic blood pressure and age. No correlation emerged between systolic blood pressure or heart rate and age. Blood pressure and heart rate did not change during nabiximols treatment compared to the baseline condition.

This ancillary study adds evidence that, in patients who already underwent a cerebrovascular accident, nabiximols does not determine significant blood pressure and heart rate variation or cardiovascular complications. These data support the cardiovascular safety of nabiximols, encouraging more extensive studies involving cannabinoids characterized by slow absorption rates.

Even as prescription opioid dispensing rates have begun to decrease, the use of illicit opioids such as heroin and fentanyl has increased. Thus, the end of the opioid epidemic is not in sight, and treating patients that are addicted to opioids remains of utmost importance. Currently, the primary pharmacotherapies used to treat opioid addiction over the long term are the opioid antagonist naltrexone, the partial-agonist buprenorphine, and the full agonist methadone. Naloxone is an antagonist used to rapidly reverse opioid overdose. While these treatments are well-established and used regularly, the gravity of the opioid epidemic necessitates that all possible avenues of treatment be explored. Therefore, in this narrative review, we analyze current literature regarding use of the alternative medications ketamine, noribogaine, and cannabinoids in treating patients suffering from opioid use disorder. Beyond its use as an anesthetic, ketamine has been shown to have many applications in several medical specialties. Of particular interest to the subject at hand, ketamine is promising in treating individuals addicted to opioids, alcohol, and cocaine. Therapeutically administered cannabinoids have been proposed for the treatment of multiple illnesses. These include, but are not limited to epilepsy, Parkinson's disease, multiple sclerosis, chronic pain conditions, anxiety disorders, and addiction. The cannabinoid dronabinol has been seen to have varying effects. High doses appear to reduce withdrawal symptoms but this comes at the expense of increased adverse side effects such as sedation and tachycardia. Noribogaine is a weak MOR antagonist and relatively potent KOR agonist, which may explain the clinical anti-addictive effects. More research should be done to assess the viability of these medications for the treatment of OUD and withdrawal.

Combination tetrahydrocannabinol (THC)/cannabidiol (CBD) medicines or CBD-only medicines are prospective treatments for chronic pain, stress, anxiety, depression, and insomnia. THC and CBD increase signaling from cannabinoid receptors, which reduces synaptic transmission in parts of the central and peripheral nervous systems and reduces the secretion of inflammatory factors from immune and glial cells. The overall effect of adding CBD to THC medicines is to enhance the analgesic effect but counteract some of the adverse effects. There is substantial evidence for the effectiveness of THC/CBD combination medicines for chronic pain, especially neuropathic and nociplastic pain or pain with an inflammatory component. For CBD-only medication, there is substantial evidence for stress, moderate evidence for anxiety and insomnia, and minimal evidence for depression and pain. THC/CBD combination medicines have a good tolerability and safety profile relative to opioid analgesics and have negligible dependence and abuse potential; however, should be avoided in patients predisposed to depression, psychosis and suicide as these conditions appear to be exacerbated. Non-serious adverse events are usually dose-proportional, subject to tachyphylaxis and are rarely dose limiting when patients are commenced on a low dose with gradual up-titration. THC and CBD inhibit several Phase I and II metabolism enzymes, which increases the exposure to a wide range of drugs and appropriate care needs to be taken. Low-dose CBD that appears effective for chronic pain and mental health has good tolerability and safety, with few adverse effects and is appropriate as an initial treatment.

The recreatinal use of nitrous oxide has become more common in recent years, especially in adolescents and young adults. It has been mainly associated with medical conditions like megaloblastic anemia and (myelo)neuropathy. We report on the thromboembolic complications, a less known side effect, associated with recreational inhalation of nitrous oxide. An extensive literature search was performed for publications reporting on the thromboembolic complications associated with recreational nitrous oxide abuse. Data about sex, age, location of thrombosis, laboratory findings, therapy and outcome were collected. A total of 13 case reports or case series were identified comprising a total of 14 patients. The reported thromboembolic side effects included deep venous thrombosis, pulmonary embolism, mesenterial-, portal and splenic vein thrombosis, cerebral sinus thrombosis, cortical vein thrombosis, stroke, acute myocardial infarction and peripheral artery thromboembolism. These side effects are possibly mediated by the interaction of nitrous oxide with vitamin B12, a cofactor of the methionine synthase complex, which eventually results in elevation of plasma levels of homocysteine. Despite being a known risk factor for cardiovascular disease, the exact pathophysiological mechanism remains unclear. Cessation of nitrous oxide inhalation is necessary to prevent recurrent thrombosis. Nitrous oxide abuse may thus result in a wide spectrum of thromboembolic complications. One should be aware of this etiology, especially in a young person with no obvious risk factors for cardiovascular disease. Spreading awareness is important to inform people about the potentially serious side effects associated with nitrous oxide inhalation.

Marijuana has vasoconstrictive properties and its use has been associated with increased blood pressure in the general population. Yet, there are limited data on marijuana use and adverse outcomes among women with hypertension in pregnancy, even though these disorders are associated with severe maternal and fetal morbidity and mortality. Since marijuana is currently the most commonly used illicit drug in pregnancy, there is an urgent need to better understand the potential association between marijuana use and hypertension in pregnancy.

To determine the adverse prenatal effects of marijuana use in women with hypertension in pregnancy.

We conducted a retrospective cohort study among individuals with hypertension in pregnancy that delivered ≥23 weeks' gestation at Oregon Health & Science University (October 2013-September 2018). The primary exposure assessed was marijuana use, identified by chart review of documented patient self-report or positive urine toxicology screen. Individuals were stratified into two groups by marijuana use: use during pregnancy versus never used. Primary outcomes included composite adverse maternal and neonatal outcomes. Secondary outcomes included individual maternal outcomes, rarer neonatal outcomes and severe features of preeclampsia. Differences were analyzed by Fisher's exact, t-test, and logistic regression. Significance was determined by alpha = 0.05 for primary outcomes and alpha = 0.01 for secondary outcomes.

From 11,825 deliveries, 1,613 (13.6%) were classified with hypertension in pregnancy. A total of 117 individuals (7.3%) used marijuana during pregnancy, 1,110 (68.2%) had never used marijuana and 396 (24.6%) had unknown marijuana use and were excluded, leaving 1,217 individuals in this analysis. Women using marijuana in pregnancy were more likely to be younger, non-Hispanic White, publicly insured and using other substances compared to women who did not use marijuana. There were no differences in the overall distribution of hypertensive disorders, including preeclampsia with severe features, in women who used marijuana versus those who did not (p = .80). In multivariable analyses, after adjusting for maternal factors and other substance use, marijuana use was not associated with adverse maternal (aOR 1.23, 95% CI 0.43-3.50, p = .69) or neonatal (aOR 0.90, 95% CI 0.28-2.89, p = .86) outcomes.

Marijuana use in pregnancy was not associated with maternal or neonatal outcomes or worsened hypertensive disease among women with hypertension in pregnancy after adjusting for maternal characteristics, including use of other substances. Our data highlight the need to consider use of other substances when evaluating the association between marijuana use in pregnancy and adverse pregnancy outcomes.

Epidemiological studies reveal that marijuana increases the risk of cardiovascular disease (CVD); however, little is known about the mechanism. Δ⁹-tetrahydrocannabinol (Δ⁹-THC), the psychoactive component of marijuana, binds to cannabinoid receptor 1 (CB1/CNR1) in the vasculature and is implicated in CVD. A UK Biobank analysis found that cannabis was an risk factor for CVD. We found that marijuana smoking activated inflammatory cytokines implicated in CVD. In silico virtual screening identified genistein, a soybean isoflavone, as a putative CB1 antagonist. Human-induced pluripotent stem cell-derived endothelial cells were used to model Δ⁹-THC-induced inflammation and oxidative stress via NF-κB signaling. Knockdown of the CB1 receptor with siRNA, CRISPR interference, and genistein attenuated the effects of Δ⁹-THC. In mice, genistein blocked Δ⁹-THC-induced endothelial dysfunction in wire myograph, reduced atherosclerotic plaque, and had minimal penetration of the central nervous system. Genistein is a CB1 antagonist that attenuates Δ⁹-THC-induced atherosclerosis.