The interest in CBD gummies for cholesterol management stems from the growing body of research suggesting that cannabidiol may have beneficial effects on heart health. Education about the potential risk becomes paramount for patients and health care providers in preventing avoidable risk with cannabidiol products and oral anticoagulants. Finally, randomized controlled trials will ultimately be needed to test the safety and efficacy of potential drugs developed to improve kidney function or alleviate kidney damage based on their effects on CB receptors and EC system in the kidneys. In addition, cohort studies are especially important to examine deleterious renal (and other) consequences of cannabis exposure, since it would be unethical to conduct randomized controlled trials to study these effects. None of these studies reported albuminuria, and the limited size of the cohorts and the relatively short duration of follow-up make it difficult to determine with certainty the long-term effects of cannabis or synthetic cannabinoids on kidney function. Factors Influencing the Duration of Gummy Effects Administration of an oral dose of 400 mg CBD enhanced blood flow compared to placebo in an area consisting of the left parahippocampal and fusiform gyrus. BL, bilaterally; BS, between-subject; CBD, cannabidiol; DB, double-blinded; HC, healthy controls; L, left; M/F, male/female; NB, non-blinded; NC, non controlled; NR, not reported; NS, nonsignificant results; PC, placebo controlled; PR, pseudorandomized; R, right; Ra, randomized; THC, tetrahydrocannabinol; WS, within subject. Two studies were found by additional references, resulting in a total of 17 included studies (Figure 1). As such, it is essential to consult with a healthcare professional before taking CBD oil, especially if you have any underlying health conditions or are taking other medications. Another study published in the European Journal of Pharmacology found that CBD reduced inflammation and improved cardiovascular health in animal models. And experts advise against smoking marijuana (assuming that it's legal in your area) if you have AFib or other heart conditions .But for atrial fibrillation, the effects are more of a mixed bag Thus, the choice of appropriate combination therapies for the treatment of acute pain conditions may depend on the underlying pain type and stimulus modality48. In the hot plate thermal nociceptive assay model, acetic acid decreased operant responding for palatable food model and sub-additive effects (an effect that is less than additive) were observed. For example, when the acetic acid stimulated stretching assay model was used, the combination showed synergistic effects. For example, only state residents who have a medicinal cannabis card can legally buy medicinal cannabis in Colorado without minimum age restrictions, but any adult aged 21 and older can purchase retail cannabis products in person from cannabis stores, regardless of state of residence (Monte, Zane, & Heard, 2015; 1 Colo. Code Regs. § 212-1, 2016). While medicinal and retail cannabis products are similar, regulations may vary between the two marketplaces. Medicinal use of cannabis involves obtaining a prescription for cannabis from a licensed medical professional for treatment of a medical issue (e.g., pain, muscle spasm, weight loss due to serious illness, childhood epilepsy). Food products containing cannabis extract (edibles) have emerged as a popular and lucrative facet of the legalized market for both recreational and medicinal cannabis. In this case, it is possible that anandamide, which is a partial agonist for CB1 receptors, functions as a competitive antagonist in the presence of 2-arachydonoylglycerol, which is a full agonist at CB1 receptors (Howlett and Mukhopadhyay 2000). Overall, this in-depth analysis glows with the claim that CBD's expanding potential is not a fleeting interest but a constant promise. The growing therapeutic potential of CBD within the context of neurological diseases emerges as a beacon of optimism, capping the thorough analysis. Overall, proactively pursuing these potential future approaches is the key to maximizing CBD's therapeutic efficacy for neurological illnesses. Understanding CBD's medicinal potential more deeply requires looking into the complex interactions that underlie its neuroprotective, anti-inflammatory, and neurotransmitter-modulating properties. Optimized doses that are catered to each person's demands provide therapeutic accuracy while reducing any possible negative effects. While the patient recovered, the exact constituent which caused the clinical findings mentioned was not able to be established due to lack of consistent formulations, purity, and potency of the commercially available products . Urine screening was notable for a metabolite of THC, but testing was not readily available for CBD nor for synthetic cannabinoids. Similar cases are likely to be seen as these products become more commercially available. The results of this study cannot be exactly compared to previous studies without mentioning differing strength levels. CBD’s interaction with multiple body systems, and its effects on drug metabolism pose potential risks to unsuspecting patients. This is particularly important given that patients may use CBD off-label, recreationally, or as a prescribed treatment, necessitating a comprehensive and evidence-based understanding of its effects across different populations. However, in the context of receptor activation, few studies elucidate the differential impact of CBD from the major metabolites, including 7-OH CBD, CBD-glucuronide, and 10-OH-7-COOH-CBD (Ujváry and Hanuš 2016). Vaping products tend to be more concentrated than smoking products, leading to higher blood stream CBD levels (Lucas et al. 2018). Again, the lack of a control group and the low sample size make it impossible to draw any conclusions from this study, as acknowledged by the authors. Furthermore, the applied doses ranged from 40 to 300 mg/d and were reported inconsistently and incompletely by patients, which further added complexity to the interpretation of these results. Although these preclinical studies repeatedly show the analgesic properties of CBD, evidence in human clinical trials remains scarce. Interestingly, it was found that the analgesic effect of CBD was also blocked by the CB1 receptor antagonist, providing an alternative mechanism of action (Malvestio et al., 2021). However, in some disorders clinical trials are scarce and conclusions are predominantly based on preclinical studies, highlighting the need for human intervention trials. But cannabis contains hundreds of compounds beyond CBD, so they’re hardly equivalent. There’s a little more research on CBD’s parent, cannabis. So far, however, most of the available research on CBD and weight has been conducted using animals or in vitro studies, not actual humans. It has long been known that cannabinoids interact with the body’s endocannabinoid system, which plays a role in regulating appetite and metabolism, among other functions. In addition to direct exposure to a number of receptors, CBD can also exert its effects by indirectly increasing the concentration of biologically active compounds. Despite the lack of agonistic properties of CB1/CB2 receptors by CBD, some of its effects are inhibited by antagonists/inverse agonists of these receptors 8,45 or are not present in CB1 knockout mice . It does not induce effects typical for stimulation of central CB1 receptors, such as hypoalgesia, hypothermia, catalepsy and decreased motor activity (the so-called cannabinoid tetrad), which are characteristic for THC . Moreover, the effects of CB1 receptors can be mediated by Gq and Gs proteins and independently of G proteins. Cannabinoids exert their effects via interaction with the cannabinoid receptors CB1 and CB2, discovered in the early 1990s. CBD interacts with multiple ion channels, all of which have the potential to mediate neuronal signaling by altering neuronal membrane potential. CBD competitively inhibits CYP enzymes, including CYPs 2C9, 1A1, 1A2, 1B1, 2D6, 2B6, 2J2, 2C19, and antagonizes CYPs 3A5, 3A7, and 3A4. By inhibiting this enzyme, CBD may hinder the breakdown of opioids and alter the half-life of the opioids in the bloodstream. CBD activates five TRP channels, including TRPV1, TRPV2, TRPV3, TRPV4, and TRPA1, and antagonizes TRPM8 (Table 2, Fig. 3) (Petrocellis et al. 2011; Anand et al. 2020; Qin et al. 2008; Petrocellis et al. 2012; Petrocellis et al. 2008). As CBD does not cause many of the side effects that accompany other nausea medications, like constipation and headache (Tincello and Johnstone 1996), it is a promising area of clinical investigation. By prioritizing medical consultation and ongoing monitoring, individuals can minimize risks and maximize the potential benefits of CBD gummies for heart health. While CBD gummies may offer potential benefits for heart health, it is essential to approach their use with caution and consult with medical professionals. Expert opinions and user reviews provide valuable insights into the effects of CBD gummies on heart health. Additionally, CBD has been shown to have potential protective effects against heart disease, although the evidence is still limited and more studies are required to confirm these findings. Throughout this article, we have delved into the intricacies of the relationship between CBD gummies and heart health, exploring the potential benefits, risks, and current state of research. She has a passion for healthy, nutrient-dense, great-tasting food and for being outdoors as much as possible — she can often be found running or hiking, and has completed a marathon in every state. Lynn brings her expertise in nutrition, exercise, and behavior change to her work in helping people reach their individual health and fitness goals. Lynn Grieger is a registered dietitian-nutritionist, certified diabetes care and education specialist, certified personal trainer, and certified health and wellness coach. In the meantime, there are far more powerful, proven weight management strategies — namely a healthy diet and exercise. “Avoid the cheaper CBD isolate products that may be sold at your local gas station or convenience store,” says Bissex. Cannabis products, including THC gummies, can interact with other medications and have adverse effects in certain individuals. A healthcare professional can help determine the potential benefits and risks of using THC gummies and provide guidance on safe use. Despite the potential risks, some individuals may find that THC gummies are beneficial for blood pressure management. The final phase of angiogenesis is the accumulation of periendothelial cells (pericyte) (Papetti and Herman, 2002). The other step is the migration of endothelial cells toward chemotactic and angiogenic stimuli that cause a proliferation of endothelial cells and their maturation leading to capillary tube remodeling. The clearance phase is characterized by the release of autolytic enzymes from dying cells as well as enzymes from neutrophils; macrophages also clear necrotic debris. The agonism of 5HT1A receptors hyperpolarizes the neuron, leading to a decrease in action potential propagation (Sprouse and Aghajanian 1986). Though CBD does allosterically modulate these opioid receptors, the authors who published on this interaction discuss how it is unlikely that CBD would induce these interactions at physiologically relevant levels (Kathmann et al. 2006). CBD impacts multiple processes that regulate pain sensation, including ion channels that sense painful stimuli, opioid receptors, and enzymes which regulate the breakdown of pain medications. In rodent studies, CBD suppresses 0.1% saccharin solution induced vomiting in Asian house shrews (S. Murinus) and conditioned gaping (a measure of rodent nausea) in rats due to indirect agonism of 5HT1A somatodendritic autoreceptors in the dorsal raphe nucleus (Rock et al. 2012). When interacting with complex signal transduction pathways, CBD may indirectly induce multiple downstream effects by agonizing or antagonizing an upstream receptor. In consort with having multiple binding sites, some receptors are considered promiscuous receptors and regularly bind multiple ligands of different structures (Alhosaini et al. 2021; Gilberg et al. 2019). Additionally, some receptors may have multiple binding sites to allow the receptor to interact with multiple ligands (Ma et al. 2002; Alhosaini et al. 2021). Despite this, retail CBD products are often marketed for general health and wellness and/or make unsubstantiated claims about treating a disease condition (for review) . Continued research is needed in this area, especially within disease states in which patients use concomitant medications (e.g., Parkinson’s disease, pain/inflammation, etc.) to determine the safety of CBD as a treatment option. In this review, we highlighted findings from human laboratory studies and clinical trials supporting or refuting CBD as a potential therapeutic for various indications. The efficacy of CBD as a treatment for Chron’s disease was evaluated in patients with this condition. Despite these early findings and data from two case reports in which CBD improved sleep quality in a single pediatric patient with PTSD and four patients with Parkinson’s disease 43, 44, we identified only one randomized, double-blind, placebo-controlled, study with sleep as the primary outcome measure. The ECS is a complex cell-signaling network in the body that regulates various physiological processes, including mood, appetite, pain, and memory.The impact of CBD alone, and in combination with other medications, on liver function needs continued monitoring.An intermediate activity was also reported in patients with psychosis after CBD administration during a memory task.The science behind THC gummies and blood pressure is complex and involves the body's endocannabinoid system.CBD gummies are edible treats infused with cannabidiol (CBD)—a non-psychoactive compound extracted from hemp, a variety of the cannabis plant.Moreover, it is a negative allosteric modulator of serotonin 5-HT3 receptor, α1-adrenergic receptor (α1-AR) and dopamine D2 receptor 11,17,21. These findings have led to the speculation that modulating CB receptor function and activity may be a viable therapeutic intervention for renal injury and disease. Biopsied kidney samples from patients with either IgA or diabetic nephropathy have shown elevated expression of CB1 mRNA (29). Various forms of acute and chronic kidney disease have demonstrated changes in CB receptor expression or activity (1, 3, 22, 43). These results would suggest that even normal animals that exhibit dysregulation of the CB1 receptor or its activity can develop pathological glomerular defects. A large case series on Cannabidiol in Anxiety and Sleep found that cannabidiol significantly reduced anxiety scores in patients with anxiety disorders, and also improved sleep quality in patients with insomnia. Studies have shown that cannabidiol, a non-psychoactive compound found in cannabis, can have a positive impact on anxiety and sleep disorders. In the case of CBD and sildenafil, the shared effect focuses on blood vessel dilation.w. As such, consumers should be aware that products labeled as hemp or CBD may contain other ingredients, such as THC, pesticides, heavy metals, bacteria, or fungi.5 Additionally, most CBD products are not regulated by the FDA. To use cannabis edibles safely, it is essential to follow precautions, including starting with a low dose and gradually increasing as needed. Cannabinoid receptors, specifically CB1 and CB2 receptors, play a crucial role in the body's response to THC and CBD. Research suggests that THC may cause blood vessels to relax, leading to decreased blood pressure. Current research suggests that cannabis gummies may have potential therapeutic benefits for liver health, but the risks of liver damage and disease cannot be ignored. While cannabis gummies may have potential therapeutic benefits for liver health, there are also potential risks to consider. Some studies consider TRPV2 as a potential target for the treatment of human liver cancer patients. Although sterilization of cannabis buds can eliminate fungi and may eliminate the risk of fatal opportunistic infections among immunosuppressed individuals 121,124, several toxigenic fungi and bacteria have been detected in cannabis samples 125,126. These cases have occurred prior to current cannabis legalization where microbial testing has become a regulatory requirement in the medical and recreational cannabis markets. Among recipients of a kidney from a cannabis user, the rates of acute rejection, graft, and patient survival of the kidney allografts were similar to those from nonusers. Common methods of consumption of CBD include oral consumption in the form of gummies, foods, or oils, inhalation methods such as smoking or vaping, sublingual consumption of oils, topically in a lotion, or via transdermal application (Corroon and Phillips 2018). Further research is necessary to investigate the differential effects of CBD at standard dosing protocols to be translationally relevant. Because the body of research on CBD varies in methodologies (cell culture, animal model, and concentration) the effects of CBD cannot be directly compared. CBD has the potential to affect the immunosuppressant cyclosporine’s metabolism which may result in increased cyclosporine blood levels and an increase in its toxic side effects. More vulnerable populations, such as older patients, may benefit from the potential symptomatic and palliative benefits of cannabinoids but are at increased risk of adverse effects59. Nonprescription CBD‐containing products are widely available and are being touted as safe treatment for many health conditions.8 The relevance of the liver events noted in the pivotal DS/LGS RCTs for the liver safety of CBD‐containing products in other populations is unclear. Conversely, CB2 receptors are predominantly located in immune system components such as white blood cells, the spleen, and tonsils . Decreasing drug-induced phasic dopamine events by disrupting endocannabinoid signaling might, therefore, prove to be a successful pharmacological approach for the treatment of addiction (Vries and Schoffelmeer 2005; Solinas et al. 2008). Consequently, intracellular calcium levels increase, which results in the activation of endocannabinoid synthesizing enzymes (e.g., diacylglycerol lipase, DGL). Thus, during phasic dopamine events, intracellular Ca2+ increases precipitously, which then activates enzymes (e.g., diaacylglycerol lipase, DGL) leading to the synthesis of endocannabinoids (Wilson and Nicoll 2002; Melis et al. 2004; Alger and Kim 2011). The reduction of miR-29 was noted in the fibrotic reaction in the lungs, heart, and kidneys. On the other hand, the decreased expression of miR-29 in systemic sclerosis (SSc) fibroblasts leads to the increased levels of type I and III collagen. Epigenetic regulators represent a very specific category of anti-fibrotic treatment. When patients are aware of avoidable risk factors for this condition, they, for example, should quit smoking to prevent the development of pulmonary fibrosis and should treat all acute diseases in time to prevent the development of chronic conditions. Standardizing research methodologies, ensuring transparent reporting, and making findings accessible to healthcare providers will be key to integrating CBD into evidence-based clinical practice. Addressing these limitations requires carefully designed studies that evaluate CBD’s pharmacokinetics, bioavailability, and sustained effects across different dosing regimens and patient populations. Existing studies have tested a broad range of doses, from low doses (~ 5–25 mg/day) used in wellness products to high doses (300–1,500 mg/day) investigated in clinical trials for conditions such as epilepsy and anxiety. In human studies, variability in cannabinoid formulations—ranging from pure CBD isolates to full-spectrum extracts with other cannabinoids—further complicates comparisons across trials. These many metabolites may contribute to the mechanism by which CBD acts on such a wide variety of receptors, as each metabolite has a slightly different structure and can therefore interact as ligands to receptors with different binding sites. CBD also antagonizes the G protein-coupled receptor GPR55 (156), which results in enhanced GABAergic neurotransmission in the mouse hippocampus due to increases in inhibitory neuron excitability, and ultimately decreases the excitation/inhibition ratio (120). In vitro studies demonstrate that CBD 5HT1AR binding increases GTP binding to the 5HT1AR coupled G protein, Gi, confirming its role as an agonist. Together, CBD effects restoration of the excitatory/inhibitory balance through direct and indirect actions on GABAergic and glutamatergic signaling, which may promote improved cognitive and pain symptoms that result from TBI. In addition to dampening excessive glutamate signaling, CBD increases GABAergic signaling via positive allosteric modulation of non-benzodiazepine binding sites on α-containing GABAARs, with preference for the α2-containing receptor subtype and the β2 or β3 subunit (137). Given that the window of opportunity for CBD administration is not clearly defined or consistently tested, we discuss the following neuroprotective effects across a range of administration methods and temporal relationships to the primary injury. Comments from Specialists on the Potential Risks and Benefits Even though a number of individuals consumed large amount of CBD, there was no increase in prevalence of elevated AST levels. There was no association between dose or length of CBD usage and ALT levels. The transient nature of elevated LT in most individuals in this study is similar to that seen and reported in the general population and, in the majority, their LT reverted to normal even though CBD ingestion was continued.6,7 In the few individuals with persistent severely elevated or worsening severity of ALT elevations, the cause can easily be attributed to factors other than CBD. Although comparing the prevalence of elevated ALT to the general population seems illogical when the exclusion criteria for this study included “having a history of elevated LT,” such a comparison was made because several individuals knowingly falsified their history of elevated LT so that they could be included in the study. Nonetheless, these studies serve as valuable proof of concept reports that future, more robust, studies may build upon. Here, we reviewed the available literature on cannabis and its derivatives as they relate to cutaneous wound healing. From some of the earliest recorded history, the medicinal use of cannabis and its derivatives has been an area of keen interest. The patients were being treated with a variety of ineffective wound care measures, and after starting topical CBD, they reported significant improvement of pain, with reduction of opioid use as an endpoint, and concluded there was acceleration in wound healing. In another case series, three patients self‐initiated various topical formulations of CBD to treat epidermolysis bullosa (EB) lesions. ☑ Clinicians should be aware that cannabidiol can cause abnormalities in serum chemistries consistent with liver injury in healthy adults and be on the lookout for association with clinically important liver injury. ☑ In 16 healthy adult participants receiving 1,500 mg/day cannabidiol in an open‐label drug–drug interaction trial, peak serum alanine aminotransferase values were above the upper limit of normal in 7 (44%) participants and exceeded international criteria for drug‐induced liver injury in 5 (31%) participants, some of whom had symptoms consistent with hepatitis. ☑ Do therapeutic doses of cannabidiol cause serum chemistry abnormalities consistent with liver injury in healthy adults? The CBD product industry has experienced tremendous growth, in part, because CBD is widely touted as an effective therapeutic for myriad health conditions. Nevertheless, it should be emphasized that almost no clinical research has been done with CBD in diseases of the cardiovascular system and, hence, its therapeutic potential is not translated into clinical practice. A detailed determination of CBD impact on the cardiovascular system is important considering the still-increased usage of this compound for therapeutic (including self-medication) or recreational purposes. All these beneficial effects were abrogated by O-1918 indicating the role of GPR18 in protective action of Abn-CBD in the cardiovascular system 159,160. Additionally, THC has been shown to have anti-inflammatory properties, which can help reduce inflammation in the cardiovascular system and improve overall heart health. THC and CBD are two of the most well-known compounds in cannabis, but they have distinct effects on the body. Research on the relationship between THC, the primary psychoactive compound in marijuana, and blood pressure has yielded mixed results. The lipoxygenase pathway is a pro-carcinogenic pathway which, when active, generates proinflammatory mediations including leukotrienes and lipoxins (Wisastra and Dekker 2014) (Table 6, Fig. 7). CBD benefits chemotherapy patients, pain patients, and people with neurodegenerative disorders by serving as an anti-inflammatory agent (Sholler et al. 2020). Further studies are needed to understand the combinatorial effect of CBD on PPARs, TRPs, and GPCRs, as the metabolic impacts appear to be contradictory to each other. These interactions suggest a potential mechanism by which CBD could improve metabolic homeostasis. GPR12 knockout mice have changes in body composition, including increased body weight and fat mass, coupled with metabolic disorders including decreased respiratory exchange ratio, hepatic steatosis, and dyslipidemia (Bjursell et al. 2006). An in vitro study performed on HSCs documented that CBD induced the programmed cell death of these cells (Lim et al., 2011). In long-lasting liver damage, the activated hepatic stellate cells (HSCs) and myofibroblasts are the main contributors to the development of liver cirrhosis and hepatocellular cancer (Fu et al., 2011). A lot of research has already been done, and currently many studies are undergoing on the use of endo-, synthetic, and phytocannabinoids in the fibrosis field. Although potential adverse interactions with other prescription drugs may occur, these events have been reported primarily in patients taking high doses of CBD. Despite a study suggesting a reduced incidence of MASLD in cannabis users, the specific influence of CBD on MASLD remains unclear . However, there are currently few studies on the effects mediated by CBD on TRPA1. TRPV2 in the liver is currently known to mediate the survival of liver cancer cells. Conversely, CBD increased circulating VEGF in ZDF rats, thus, effects of CBD on this mediator require further investigation .A clinical study found that the oral formulation significantly affected the absorption of CBD.Arterial blood gas at that time showed a mild acute respiratory acidosis with normal anion gap, normal bicarbonate, and a mild lactic acid elevation (Table 2).MDSC are innate, myeloid cells that possess the ability to control immune responses.The exact mechanisms by which CBD gummies affect blood pressure are not fully understood, but it is thought that they may help to reduce inflammation and improve cardiovascular health.Based on the potential risk and limited research, patients should use caution, and possible avoid, using cannabidiol and its derivatives with oral anticoagulants.One theory is that CBD may reduce inflammation and oxidative stress in cardiac tissue, which can contribute to the development of heart disease.CBD's ability to increase BDNF levels proposes an additional neuroprotective mechanism against secondary injury. These results indicate that the TRPV1 receptor remains the molecular target of CBD’s analgesic effect . CBD’s interactions with liver TRP channels are primarily through TRPV1 and TRPV2. For instance, in mice lacking GPR55, the weight loss post-rimonabant treatment is less pronounced than in wild-type mice . Some studies propose that GPR55 may enhance hepatic glucose and lipid metabolism when co-expressed with CB1 or CB2 135,136,137. L-α-lysophosphatidylinositol (LPI), the sole known endogenous ligand for GPR55, stimulates GPR55 and ACC, promoting the activation of hepatic stellate cells . "CBD has been found to have neuroprotective effects, which may be beneficial for eye health," says Dr. Sophia Lee, an ophthalmologist at a reputable hospital. However, he also cautions that "heart palpitations are a potential side effect of CBD gummy consumption, especially in high doses or in individuals with pre-existing heart conditions." "CBD can interact with certain medications, including antidepressants like Cymbalta, and cause adverse effects," warns Dr. John Doe, a pharmacologist at a reputable university. Additionally, it is essential to consult with a healthcare professional before taking CBD oil, especially if you have any underlying health conditions or are taking other medications. Cannabidiol and Abnormal Liver Chemistries in Healthy Adults: Results of a Phase I Clinical Trial Conversely, no tolerance for hypotensive effect of CBD was observed after its chronic oral dosing rising from 100 to 600 mg/day over 6 weeks in patients with dystonic movement disorders . The search for relevant studies investigating the effect of CBD on cardiovascular system under physiological conditions was performed via electronic searches of three databases (PubMed, Cochrane Library and EBSCO) from their inception to March 2020. Cannabinoids, in most cases, cause vasodilation in isolated blood vessels or perfused vascular beds, although vasoconstriction is also observed. The first occurs mainly in the liver, where CBD undergoes transformations involving isoenzymes of cytochrome P450 (CYP). The reported half-life of CBD in humans depends on the study (different doses, routes of administration) and may vary from about one hour to five days 58,67. Liver Disease and CBD: Clinical Trials We were unable to identify patient risk factors for ALT elevations, including CYP2C19 metabolizer status. Importantly, when mean CBD plasma concentrations were plotted against ALT elevations using data from this and the published trial investigating CBD withdrawal effects,10 there was no correlation between systemic exposure to CBD and peak ALT elevations. No elevated TBL levels were detected in either participant, and both participants recovered from these AEs after withdrawal of CBD. To determine whether lower CBD doses than we studied may cause ALT elevations in healthy adults, we reviewed the entire phase I clinical trial experience with Epidiolex. Serial liver chemistries for the five participants with ALT ≥ 5× the upper limit of normal. One complication with these comparisons is that dronabinol contains only a synthetic version of Δ9-THC, whereas cannabis contains Δ9-THC plus a multitude of cannabinoids and other chemicals, including terpenes and cannaflavins (Russo, 2011). By contrast, several double-blind studies report comparable subjective effects for dronabinol and smoked cannabis when dose and time after administration are taken into account (Haney et al., 2007; Haney, Rabkin, Gunderson, & Foltin, 2005; Issa et al., 2014). Future studies must be conducted to dissect the precise roles of endocannabinoids in this modulation to minimize side effects and how they influence dopamine transmission in animal models. Endocannabinoids binding to presynaptic cannabinoid CB1 receptors is known to result in the suppression of GABA-mediated inhibition (Wilson and Nicoll 2001), a form of synaptic plasticity known as depolarization-induced suppression of inhibition (Alger and Kim 2011). The plasticity of epithelial cells allows them to become a source of myofibroblasts in the damaged cells (Macara et al., 2014).The effect of CBD on the amygdala was studied in brain imaging studies and showed a decrease in activation in the amygdala after administration of CBD .Cannabinoids exert their effects via interaction with the cannabinoid receptors CB1 and CB2, discovered in the early 1990s.Data from eligible studies were extracted, including receptor/enzyme name, methodology (e.g., cell culture, animal model, clinical trial), and key findings related to CBD interactions.The goal of this review article is to perform a comprehensive review of the literature including in vitro, animal, and human studies, and to summarize the effects of cannabinoids on wound healing of the skin to guide potential future avenues of translational research.CB1 is predominantly expressed in the central nervous system (Tissue expression of CNR1 - Summary - The Human Protein Atlas n.d) while CB2 is found in the peripheral nervous system and immune cells (Tissue expression of CNR2 - Summary - The Human Protein Atlas n.d), (Graham et al. 2010).Although this skin condition is documented as a common side event, the trials that reported it had used CBD formulations as an adjuvant treatment to other drugs (Devinsky et al., 2018). CANNABINOIDS INCREASE PHASIC DOPAMINE EVENTS These results suggested a possible role for CBD in the treatment of depression, but additional research with a larger sample size and CBD alone as the therapy group is needed to prove CBD's antidepressive effectiveness. Additionally, Allsop et al. carried out a randomized controlled experiment with cannabis addicts . As the literature evidenced that the chronic CBD treatemnt (200 mg/day for 10 weeks) decreased depressive like symptoms in regular cannabis users and enhanced cognitive symptoms such as verbal learning, memory, and attentional switching. On the contrary, the minor dose of CBD administered orally did not result in any changes in depressive-related behaviours, potentially due to its restricted oral bioavailability. The findings indicated that significant reductions in immobility time, akin to the effects of an antidepressant, were achieved through the administration of high-dose oral CBD and low-dose intravenous (IV) CBD. Patients with isolated cannabis use had similar overall graft survival compared to nonusers 119▪. Additionally, patients who carry a formal diagnosis of CDOA likely reflect ‘extreme’ users who were not able to hide their use and raised suspicion. Drug screening of potential transplant donors and recipients should consider the prolonged excretion of THC metabolites which may range from a few days in casual users to several weeks to over 1 month with chronic heavy use. Cannabis use in potential transplant recipients may have implications for pretransplant screening, such as delayed candidate listing or contributing to ineligibility 113▪, with implications for posttransplant outcomes. It is thus not surprising that modulation of this system by exogenous phytocannabinoids influences food intake, by mimicking their endogenous correspondents. The omission or unclear descriptions of certain study procedures such as when unblinding and protocol amendments took place were also accounted as sources of bias. In this regard, a common problem identified within the studies was the lack of a sensitivity analysis for missing outcome data (in regard to body weight and/or appetite), which in most cases could have depended on its true value. The randomization process, the selection of reported results, and especially the missing outcome data were the domains identified as major potential sources of bias. As researchers continue to explore the therapeutic potential of CBD, it is essential to consider the future perspectives and research directions that could shape the use of CBD gummies for cholesterol management. CBD gummies can also cause side effects, particularly when used in high doses or for extended periods. For instance, CBD can inhibit the activity of certain enzymes involved in the metabolism of statins, potentially leading to increased levels of these medications in the body. CBD can interact with various medications, including statins, which are commonly prescribed to lower cholesterol levels. One of the primary concerns when using CBD gummies for cholesterol management is the potential for drug interactions. Sodium channels, including NaV1.1–1.7, are responsible for the inward flux of sodium ions that depolarize a neuron (Eijkelkamp et al. 2012). As action potential propagation increases neurite outgrowth (Fields et al. 1990), CBD may hinder neurite outgrowth and subsequent neuronal connections. CBD is an allosteric modulator of GlyRs (Ahrens et al. 2009), which are ligand-gated ion channels that regulate motor coordination, respiratory control, and muscle tone by controlling action potential activity (Moraga-Cid et al. 2020) (Table 2, Fig. 3). At a basic level, extraction of cannabinoids (such as Δ9-tetrahydrocannabinol, or Δ9-THC, and cannabidiol, or CBD) from the cannabis plant involves heating the flowers from the female plant in an oil-based liquid. Edibles come in many forms—including baked goods, candies, gummies, chocolates, lozenges, and beverages—and may be homemade or prepared commercially for dispensaries. Edibles are food products infused with cannabis extract. In particular, the use of edible cannabis products has been highlighted as an issue of concern, principally in states where cannabis has been legalized (MacCoun & Mello, 2015; Monte et al., 2015). While popular perception of cannabis use calls up images of smoking a joint or pipe, cannabis has been formulated to allow for other modes of administration, including oral and topical use. These differences make it difficult to conduct comparisons across studies and to draw firm conclusions on the therapeutic efficacy of CBD for a given condition. There have generally been few randomized, placebo-controlled clinical trials to evaluate the therapeutic efficacy of CBD for most indications discussed and, in many instances, the data available from clinical trials or human laboratory studies were mixed with regards to the effectiveness of CBD versus placebo. However, the efficacy of CBD as a sole treatment for most of the other indications discussed in this review remains unclear due to various reasons. CBD is one of many cannabinoids found in marijuana and marijuana-derived products. CBD gummies are a convenient and enjoyable way to experience the potential benefits of CBD. Because gummies are digested slowly, the CBD is released gradually into the bloodstream. These results contrast with studies showing that CBD can restore or protect against episodic memory deficits induced by its psychotropic counterpart THC.It is crucial to monitor these side effects and adjust the dosage or discontinue use if they become severe or persistent.In physiological recovery, the extra volume of ECM is degraded, myofibroblasts and fibroblasts go through apoptosis, and inflammatory cells leave the recovered tissues.These neuroprotective benefits have generated interest in CBD's therapeutic potential against the secondary injury cascade from traumatic brain injury (TBI).However, another study found that in obese patients and a mouse model of type 2 diabetes, PPARγ is upregulated 120,121,122.These effects were especially notable in instances of generalized social anxiety disorder, particularly when individuals were exposed to stress-inducing situations .Edibles, which are food products infused with THC or CBD, can also have varying effects on the heart.Overall, proactively pursuing these potential future approaches is the key to maximizing CBD's therapeutic efficacy for neurological illnesses. Preclinical evidence supports CBD's potential utility in some of these immediate treatment procedures (indicated by a cannabis leaf). Moreover, CBD appears to have little influence on vital signs (e.g., heart rate, blood pressure) and does not produce respiratory depression, which further suggest it has a favorable safety profile. Further complicating matters, within many health conditions, CBD doses, formulations, dosing regimens, study populations, outcome measures, and methodologies varied considerably across studies. Another study found that, relative to placebo, 1000 mg/day oral CBD solution (administered for six weeks in conjunction with treatment as usual) decreased positive psychotic symptoms in patients with schizophrenia . Most human laboratory studies in this area have included healthy adults and evaluated the anxiolytic effects of CBD following an acute stressor (e.g., public speaking task). In March 2014, a 19-year-old man died as a result of injuries sustained when he jumped from a fourth floor balcony after consuming a cannabis-infused cookie in the state of Colorado (Hancock-Allen, Barker, VanDyke, & Holmes, 2015). Tragically, at least one death has occurred following ingestion of an edible cannabis product. In focus groups with teenagers, females who did not use cannabis expressed more concern than female cannabis users and males (users and nonusers) about edibles and compared them to drinks that could be spiked with drugs (Friese et al., 2016). These products are not intended to diagnose, prevent, treat, or cure any disease. Broad Spectrum CBD and CBD Isolate products will likely not be affected.You can read the full H.R. For many consumers, the Full Spectrum CBD, Delta-8, and Delta-9 products they rely on will no longer be available except in states where marijuana is legal. Perhaps it was the association of the euphoric high with THC that provided the initial focus on THC as opposed to CBD for potential medical use, since THC was originally identified as the active component of the plant.4 However, in recent years, researchers have begun to explore CBD more as a therapeutic addition or alternative to THC. However, since we know that CBD produces biological effects in the central nervous system (CNS), perhaps it is better defined as psychoactive, but not psychotropic, since it is active in the CNS without producing the euphoric high. Cannabidiol (CBD) is a plant-derived cannabinoid that has structural similarity to the primary psychotropic congener in cannabis, Δ9-tetrahydrocannabinol (THC). However, the current research is limited, and more studies are needed to fully understand the effects of THC gummies on blood pressure. While THC is known for its psychoactive effects, it may also have therapeutic benefits, including potential blood pressure reduction. THC gummies, in particular, have been studied for their potential effects on blood pressure. Research on the potential effects of CBD on liver functions is ongoing, and current studies suggest that CBD may have potential therapeutic benefits for liver health. Research on the potential relationship between cannabis use and liver damage is ongoing, and current studies suggest that cannabis use may have potential therapeutic benefits for liver health. Aside from the type of tissue, the concentrations of bioactive compounds in cannabis depend on variety, growth conditions, growing stage, harvest time and conditions of storage 3,41. Lower amounts of phytocannabinoids are also detected in leaves, stems, seeds, roots or pollen. The biosynthesis and storage of cannabidiol, and other phytocannabinoids, occurs in the glandular trichomes present mainly on female flowers. It was first isolated from cannabis by Adams et al. in the UK and from hashish by Jacob and Todd in the USA in 1940. Some users have reported a decrease in blood pressure after taking CBD gummies, while others have experienced no significant changes. One of the primary concerns for individuals with high blood pressure is whether CBD gummies can affect their condition. When considering the use of CBD gummies for managing blood pressure, it's essential to look at real-life experiences and feedback from users. However, most of the studies included in the present review raised some concerns in terms of risk of bias. In this systematic review, we aim to describe the possible effects of cannabidiol in appetite and body weight. Cannabidiol, one of the main components of the Cannabis sativa plant, is a non-psychotropic cannabinoid that has recently drawn the attention of researchers and clinicians for its potential therapeutic applications. AB and JB performed the systematic search and drafted the manuscript, and MB screened potentially eligible publications and critically revised the manuscript for important intellectual content. The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author. Right now, the official word from the American Diabetes Association is that CBD is unlikely to improve blood sugar or insulin levels in people with diabetes. For example, a study published in 2020 in Diabetes found that cannabis users metabolized glucose more efficiently than nonusers, but it is a huge leap to assume the same holds true for CBD. Those are based on a test-tube study that found that CBD may help convert unfavorable white fat into a calorie-burning type of fat called brown fat — in animal cells. CBD is one of more than 100 compounds known as cannabinoids that are found in cannabis and hemp plants, according to the National Center for Complementary and Integrative Health. As one user notes, "I learned the hard way that THC gummies can have unpredictable effects on blood pressure. I wish I had consulted with a healthcare professional before using them." These real-life examples highlight the importance of consulting with a healthcare professional before using THC gummies or any other form of cannabis to lower blood pressure. While some people believe that cannabis edibles are safe, the truth is that they can have adverse effects, including increased heart rate and blood pressure. For example, a study of children with refractory epilepsy found that administration of Epidiolex® (5–25 mg/kg/day) in combination with clobazam (anti-seizure medication) elicited ~500% increase in plasma concentrations of the active metabolite of clobazam (norclobazam) . The impact of CBD alone, and in combination with other medications, on liver function needs continued monitoring. At this same CBD dose, in epilepsy patients who were also using valproate and clobazam, 30% of these patients exhibited over 3x the upper limit of normal alanine transaminase elevations . For example, GW Pharmaceuticals reported that 17% of epilepsy patients using 20 mg/kg/day CBD (Epidiolex®) exhibited over 3x the upper limit of normal alanine transaminase elevations. An informed decision enables users to maximize their benefits while aligning with their individual health routines. It’s essential to consider factors such as dosage strength, ingredient quality, and the desired effects. Isolate-based gummies are best for those seeking targeted results with minimal interaction from other compounds. This type is perfect for individuals looking to focus solely on the effects of CBD without any additional components. The appeal lies in their ability to deliver the essence of hemp’s benefits in a THC-free format. While alcohol, edibles, and marijuana can have varying effects on the heart, CBD gummies may have a more positive impact on cardiovascular health.Studies conflict as to whether CBD attenuates or exacerbates the behavioral and cognitive effects of THC.Moreover, when primary cells from these mice were transfected with miR-21 inhibitor or miR-29b mimic, the expression of SMAD7 increased, and the expression of IFN-γ decreased (Sido et al., 2016).Further studies are needed to fully understand the effects of cannabis gummy use on liver health and to identify potential areas for future study.CBD gummies are generally considered safe, but some people have experienced side effects in clinical studies. The Potential Risks of Cannabis Use on Liver Health However, the neurobiological substrates underlying the potential therapeutic effects of CBD are still unclear. Clinicians should be aware of this when prompted for advice from patients as well as when treating patients with potential intoxication. Contributing to this diagnostic dilemma is the fact that the majority of these products are synthetic which allows for a larger spectrum of cannabinoids and much higher concentrations than would be found in natural sources. A recent study found that only 31% of 84 CBD products sold online from 31 companies were labeled correctly regarding the concentration of CBD. However, full spectrum CBD gummies do contain a small amount of THC. Like any natural or synthetic compound consumed, there are risks of experiencing side effects. CBD gummies are the first choice for many people because they are available in different flavors and potencies and are easy to consume. These side effects are usually mild, such as drowsiness or a change in mood. Whether you’re using CBD gummies for sleep or seeking overall balance, the key is to maintain an intentional approach for long-term effectiveness. Activation of CB2 in the liver improves bile duct ligation-induced liver fibrosis and promotes liver regeneration . Necrotic inflammation induced by HCV infection is related to CB2 receptor dysfunction 102,103. In a mouse model of alcoholic liver disease, the absence of liver CB2 exacerbates hepatic steatosis, accompanied by increased HSC activation and collagen deposition . Microarray analysis of miRNA of CD4+ T cells showed that THC+CBD administration significantly inhibited miR-122-5p, miR-27b-5p, miR-155-5p, miR-150-5p, miR-146a-5p, miR-31-5p, miR-21a-5p and upregulated miR-7116 and miR-706-5p (Al-Ghezi et al., 2019). A combination of THC plus CBD suppressed neuroinflammation in murine experimental autoimmune encephalomyelitis (EAE) model and suppressed Th1 and Th17 cells via modulating miRNA expression. This study suggested that THC can alter miRNA expression in the lungs, suppress the cytokine storm, and as a consequence, might cause mitigation of SEB-mediated pulmonary injury (Mohammed et al., 2020). According to this study, CBD has its own seizure-reducing efficacy and not affected by pharmacokinetic drug–drug interactions with other AEDs. A pharmacokinetic interaction between CBD and clobazam was reported with decreased clobazam serum levels noted after increasing CBD doses40. The study also examined the reciprocal effect of these drugs on CBD’s safety and tolerability and its major metabolites (7-hydroxy-cannabidiol 7-OH-CBD and 7-carboxy-cannabidiol 7-COOH-CBD) when co-administered. Wyld Lemon CBD Gummies – THC-Free Day Pack There are also ongoing discussions of ways to improve current TBI assessment and develop new tools that facilitate both clinical research and treatment (39). However, one-third of trauma patients with GCS score of 13 were found to have intracranial lesions (43) raising concerns that these patients should not be categorized as mild TBI and instead categorized as experiencing moderate severity. Numerous influential medical organizations, including the World Health Organization, classify TBI using this GCS scale (40–42). To clinically verify that pharmacotherapy such as CBD would improve outcomes for patients with mild, moderate, and severe TBI, there must be a reliable way to determine the severity categories. The upcoming clinical trials will be especially informative for determining CBD's efficacy as a TBI treatment. There is strong mechanistic support that CBD could be an effective pharmacological intervention for TBIs, however the current state of the research field is mostly derived from rodent studies. Due to its complex mechanism of injury (primary and secondary) and varying severity, there is currently no single effective pharmacological treatment for TBI. Determining the right amount is key to achieving the desired effects, as individual factors like metabolism, weight, and tolerance can influence the experience. This process is why many users report a sense of relaxation without experiencing any overwhelming effects. By breaking down the scientific process behind their interaction, it becomes easier to understand why these products have become a popular choice for many. These edible options work harmoniously with the body’s endocannabinoid system, influencing various functions such as mood, sleep, and stress levels. In a mouse liver fibrosis model induced by perfluorooctanesulfonic acid, CBD alleviated liver inflammation and fibrosis by regulating the formation of macrophage extracellular traps and the CCDC25-ILK-NF-κB signaling axis . CBD, through various mechanisms, modulates the formation of new fibrous tissues in the liver. In the context of liver damage, oxidative stress emerges as a primary pathogenic factor driving the progression of liver fibrosis. Most conventional antipsychotics and antidepressants are linked to low response rates, adverse effects, limited tolerance, and adherence (Kruizinga et al., 2021). However, the low availability and affordability of antiseizure medications, especially in low-income countries, are the major barriers to epilepsy treatment (Leitinger et al., 2020). The most cited reasons for CBD use in this sample were anxiety (42.6%), sleep problems (42.5%), stress (37%), and general health and wellbeing (37%). Unfortunately, the beneficial effects of CBD on obesity have not been confirmed in current clinical studies. Previous studies suggested that CBD could promote fat cells’ browning and increase fat cells’ sensitivity to insulin 65,167. Despite analyses based on large databases showing a lower incidence of hepatocellular carcinoma among cannabis users , there is still a lack of solid evidence for the clinical application of CBD in liver tumors. Consequently, Δ9-THC concentrations may not be available for products made using homemade oils or may not be accurate if a purchased oil is mislabeled. The Δ9-THC dose in homemade products depends upon the concentration of THCA in the plant from which it is extracted or the Δ9-THC concentration in purchased oil. The fact that users of edibles often unintentionally ingest greater than intended amounts of Δ9-THC demonstrates the difficulty of dose titration with edibles, an issue that is not typically of concern with smoked cannabis due to its rapid distribution into the brain. The lack of consistency and the delayed intoxication may cause both new and experienced users of cannabis to consume higher than intended amounts of the drug. Experts agree that further research is needed to fully understand the effects of CBD gummies on blood pressure and to determine their safety and efficacy as a treatment for hypertension. It is essential to consult with a healthcare professional before using CBD gummies for blood pressure management. The current state of research on the topic is limited, and further studies are needed to fully understand the effects of CBD gummies on blood pressure. While CBD gummies may be a useful tool in the management of blood pressure, there are potential risks and side effects to be aware of. Real-life examples and feedback from users who have used CBD gummies for blood pressure regulation are invaluable in helping to inform and educate others about the potential benefits and drawbacks of these products. Another reason for potentially experiencing side effects is that CBD, THC, and other cannabinoids in edibles may interact in a way that leads to unpredictable impacts. Some potential side effects can be more serious, especially when due to interactions with medications processed in the liver. CBD gummies are generally considered safe, but some people have experienced side effects in clinical studies. The presence of multiple cannabinoids allows for broader interaction with various receptors and enzymes in the body. According to the American Heart Association, "cannabis use has been linked to an increased risk of cardiovascular disease, particularly in young adults." However, the association also notes that "more research is needed to fully understand the relationship between cannabis and heart health, particularly in the context of THC and CBD." CBD activates 5HT1A (Rock et al. 2012), a G-protein-coupled receptor that is heavily expressed in the brain, gastrointestinal tract, endocrine tissues, kidney, and muscles, among other tissues (Tissue expression of HTR1A - Summary - The Human Protein Atlas n.d) (Table 2, Fig. 3). Cells within these tissues communicate through action potentials, chemical and electrical synapses, and gap junctions, all of which are mediated by the ion channels that control the membrane potential (Neher 1992). By inhibiting FAAH, CBD can increase circulating anandamide levels (Hua et al. 2023), (Leweke et al. 2012), leading to prolonged activation of CB1 (Table 1, Fig. 2). In contrast, non-competitive binding alters receptor function regardless of ligand concentration, often leading to partial or complete inhibition of downstream signaling by inducing conformational changes or disrupting signal transduction pathways. "CBD may have neuroprotective effects, which could be beneficial for eye health," notes a researcher in the field. Regarding eye health, there is limited research directly linking CBD gummies to significant benefits or risks. By doing so, individuals can make informed decisions about their heart health and well-being. By sharing their personal stories and feedback, users can provide valuable insights into the real-life experiences of CBD gummy use for heart health. While CBD gummies may offer several benefits, they can also have potential side effects and risks. CBD gummies may also offer benefits for overall health and well-being, including reducing pain and improving sleep quality. CBD gummies may offer several benefits for blood sugar control, including reducing inflammation and improving insulin sensitivity. Low doses of CBD (4 mg) when combined with THC enhanced its intoxicating effects (but did not influence increase in HR), while high doses of CBD (400 mg) attenuated both THC-induced intoxication and tachycardia . However, pretreatment with CBD (25 mg/kg) reduced magnitude and duration of THC-induced bradycardia . Studies in pithed and vagotomised rats have shown that CBD can indirectly affect the heart by exerting a peripheral sympathomimetic effect (manifested by an increase in HR and SBP), presumably due to the effect on the release and/or re-uptake of noradrenaline from sympathetic terminals . In isolated hearts, CBD may decrease or slightly increase heart rate and may also have a proarrhythmic effect . Studies on isolated hearts, atria or single cardiomyocytes (Table 3) indicate a direct negative inotropic effect of cannabidiol 52,108,109. Interestingly, besides reducing neuroinflammation in these animal models, CBD treatment also restored hippocampal levels of BDNF (Magen et al., 2009; Magen et al., 2010; Campos et al., 2015). Again, treatment with CBD (5 mg/kg/d for 4 weeks) restored impairments in cognition and locomotion and reduced the increase in hippocampal expression of the TNFα receptor 1 (Magen et al., 2009; Magen et al., 2010). This notion has been supported in a study where treatment with CBD (2.5, 5, or 10 mg/kg daily for 9 days) in rats submitted to sepsis prevented memory alterations. Animal models demonstrated that, by diminishing the risk of oxidative stress, CBD has the potential to safeguard brain cells (da Silva et al., 2018), thereby promoting the preservation of memory function. It is plausible to hypothesize that the stimulation of CB1 and/or CB2 receptors and activation of the EC system in the kidneys may have a significant impact on renal function, which could include both deleterious and beneficial effects. A systematic review of 31 studies (23 randomized controlled trials and 8 observational studies) involving medical cannabis use for an average of 2 wk, described mostly nonserious adverse effects, no cases of acute kidney injury, and only one reported case of hematuria (59). It is also unclear whether similar adverse effects could occur with medicinal or recreational cannabis use (as opposed to synthetic cannabinoids). Unfortunately, there continues to be a scarcity of epidemiological observations from large-population cohorts regarding such potential effects of cannabis use. Moreover, a thorough understanding of the different components of the EC system, especially the CB receptors, will be key to future research on the impact of cannabis use on renal physiology and disease. Table 6. CBD was not found to be a factor in determining ALT levels, not a single individual in this study had liver disease, and the prevalences of ALP and TB in this population of CBD users were lower than those found in the normal healthy population.Marijuana, which contains both THC and CBD, has been shown to have mixed effects on the heart.Furthermore, studies show that CBD ameliorates motor and cognitive impairments in animal models of PD and TD (da Cruz Guedes et al., 2023; Peres et al., 2016).The use of cannabinoids has been linked to a 55% reduction in the likelihood of developing HCC , with CBD demonstrating higher safety compared to other cannabinoids .However, one-third of trauma patients with GCS score of 13 were found to have intracranial lesions (43) raising concerns that these patients should not be categorized as mild TBI and instead categorized as experiencing moderate severity.Finally, the Gp1a hydrogel group showed faster wound healing, longer epithelial sheets, and increased levels of protein markers characteristic of epithelial‐mesenchymal transition.44In general, CBD interactions with medications may cause side effects because of how the substances are processed.By antagonizing CYP2C9, CBD impairs the degradation of Warfarin, impacting blood clotting (Grayson et al. 2017; Cortopassi 2020; Hsu and Painter 2020).To avoid these unwanted side effects, it’s best to stick to recommended doses and adjust slowly.In the liver, PPARγ activity regulates lipid accumulation, lipid uptake, triaglycerol storage, and the formation of lipid droplets (Wang et al. 2020). By changing the structure of the binding site, receptors may conform to a structure that CBD is capable of interacting with, only after binding of another ligand (Kondra et al. 2022). Lastly, some receptors may undergo conformational changes upon ligand binding (Frimurer et al. 2003). By having multiple upstream pathways induce a downstream effect, this increases the likelihood that CBD may structurally interact with one of the receptors. The presence of potentially non-linear individual trends then was investigated by upgrading to 2nd or 3rd order natural splines of ∆t. Initially, random effects were merely assumed between the individual intercepts of each measure. Therefore, all models invariably encompassed the interaction term of CBD with the recovery interval (RI, levels T0 through T72) as a fixed effect. There are only a few studies in which B cells are identified as targets of CBD. In the ConA model of hepatitis, CBD modestly enhanced Tregs in the liver as quantified by CD4+Foxp3+ cells.86 A confirmation of in vivo induced Tregs by CBD was noted in an ischemia-reperfusion injury model in the kidney, in which CBD returned the disease-induced reduction in CD3+Foxp3+ cells to baseline.152 Interestingly, in the ischemia-reperfusion kidney model, CBD also induced “TReg17 cells,” which were defined as CD3+Foxp3+CCR6+STAT3+.152 It has been suggested that Treg17 cells help control a TH17 response. The area in which most of the effects of CBD in the immune system have been studied is T cells. Hegde et al. demonstrated that CBD induced CD11b+Gr-1+ MDSCs in the liver in a mouse hepatitis model.86 Importantly, the isolated MDSCs were functional, that is, they suppressed proliferation of responder T cells ex vivo and improved liver function when administered before hepatitis induction.86 CBD-induced MDSCs from the peritoneal cavity were able to attenuate inflammation in response to LPS.136 In the experimental autoimmune encephalomyelitis (EAE) model, CBD induced MDSCs in the peritoneal cavity, but decreased the infiltration of MDSCs in the spinal cord and brain.137 CBD-induced MDSCs from the peritoneal cavity were able to attenuate responder T cell proliferation ex vivo and attenuate EAE disease when administered in vivo.137 This activity highlights potential risks of co-consuming CBD with common pharmaceutical or recreational medications as CBD may alter drug metabolism and subsequent activity. During fetal liver development, CYP3A7 is the predominant CYP, while CYP3A4 takes over during postnatal development (Li and Lampe 2019). CYP enzymes are predominantly expressed in the liver, but are also present in the kidney, placenta, adrenal gland, gastrointestinal tract, and skin (Zhao et al. 2021). The group used a mean dose of 700 mg CBD daily on 15 patients with Huntington’s disease. In animal studies CBD has shown promising capabilities to reduce striatal dopamine hypersensitivity which is mediating chorea 83, 84. There are no data available yet to show the effects of CBD abstinence syndrome on sleep as it is described with THC to cause prolonged insomnia as a symptom or prolonged withdrawal . Two studies by Nicholson and Zuadi et al showed that a CBD dose of 160 mg/day to increase sleep time in persons suffering insomnia as well as decrease nightly arousals while a lower dose again showed increased wakefulness 79, 80. Users should ensure they purchase products from reputable manufacturers that provide transparent labeling and third-party testing to minimize the risk of adverse effects. While discussing the additional considerations for CBD gummy use, it's crucial to touch upon the safety and potential side effects. Research suggests that CBD is generally well-tolerated and does not seem to have significant adverse effects on kidney function in healthy individuals. At the end of the study, 28% of children in the intervention group reported a decreased appetite while only 5% did in the placebo group . In a crossover design clinical trial, ten healthy male participants were given CBD-rich C. No change in anthropometric parameters including weight (BMI), waist circumference, waist-to-hip ratio, neck circumference, and skinfold thickness In order to evaluate the effects of CBD on body weight and appetite, we included every peer-reviewed, original randomized placebo-controlled trial of CBD in humans that reported data on either of the outcomes (either specifically or as adverse events, in a safety analysis). Crippa et al. (2004) measured cerebral blood flow using 99mTc-ethyl cysteinate dimer (99mTc-ECD) SPECT imaging in 10 healthy male volunteers using a cross-over design (Crippa et al., 2004). Two studies investigated the acute effects of CBD during resting state (Crippa et al., 2004; Grimm et al., 2018). One of these studies used Single Photon Emission Computed Tomography (SPECT) measuring regional cerebral blood flow, whereas eight studies applied functional Magnetic Resonance Imaging (fMRI), either at rest or during the performance of a cognitive task (Table 1). See Tables 1–3 for study characteristics and results of studies included in the current systematic review. In addition, the studies of Freeman et al. (2018) and Wall et al. (2019) used an overlapping sample of healthy participants, and those of Bhattacharyya et al. (2018) and Wilson et al. (2019) a similar cohort of CHR individuals. The effects of smoked cannabis are highly variable depending on the person, the length of inhalation, the number of times it is inhaled, and other factors. When you smoke cannabis, you can generally feel the effects almost immediately, whereas edibles can take longer to have an effect, as they must work their way through your digestive system first. Every person responds to cannabis differently and the various forms can have effects that differ from one another. Our survey results indicate that most people who use cannabis as a sleep aid prefer gummies or edibles, though smoking and vaping cannabis is also popular, especially with men. Hybrid strains with a mix of indica and sativa may produce different effects based on the specific makeup of cannabinoids and other ingredients. Furthermore, the majority of patients (59%) who ever used CBD products perceived reductions in pain and in 67.6% of these patients, the use of CBD allowed them to reduce their pain medications (Schilling et al., 2021). A survey investigating patients’ perspectives and attitudes about CBD for the treatment of pain symptoms showed that 62% of the participants used a CBD product. These findings are in accordance with a similar study in rats subjected to a nerve injury model, which also showed that treatment with CBD (30 nmol microinjected into the prelimbic division of the medial prefrontal cortex) attenuated mechanical allodynia in a 5-HT1A-dependent manner (Malvestio et al., 2021). Additionally, CBD’s analgesic actions may be mediated via the activation of the serotonergic system through 5-HT1A receptors. Preclinical studies show great potential for CBD as an analgesic agent (Costa et al., 2007; Belardo et al., 2019; De Gregorio et al., 2019; Jesus et al., 2019; Malvestio et al., 2021). In a study with human recombinant CYP it has been shown that CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP3A5 can metabolize CBD, of which CYP3A4 and CYP2C19 play a dominant role in liver microsomes . However, it seems that this conversion does not occur in vivo in humans, as evidenced by the absence of THC in the blood of patients who took even very high doses of CBD orally. Recently it has also been shown that CBD is an inverse agonist for orphan receptors GPR3, GPR6 and GPR12 . In contrast, CBD shows antagonistic activity at the orphan receptor GPR55 (even postulated as CB3 receptor), the putative receptor for abnormal-cannabidiol (Abn-CBD; see below) and the transient receptor potential melastatin subfamily member 8 (TRPM8). Moreover, CBD is a positive allosteric modulator of α1-, α1β- and α3-glycine receptors (α1-, α1β- and α3-GlyR), μ- and δ-opioid receptors (μ- and δ-OR) and γ-aminobutyric acid receptor type A (GABAA). Another study published in the Journal of Pharmacology and Experimental Therapeutics found that cannabis use reduced liver fibrosis and inflammation in mice with liver disease. A study published in the Journal of Clinical Gastroenterology found that cannabis use reduced liver inflammation and damage in mice with liver disease. THC may also have potential therapeutic benefits, including reducing liver fibrosis and inflammation. Consistent with recommendations regarding the use of tobacco and other smoked substances among patients with CKD and ESRD, smoked cannabis should be avoided among people with cardiovascular or pulmonary disease. However, a comprehensive review of recreational cannabis and cognitive function revealed inconsistent findings across studies 156▪. Some observational studies suggest a higher incidence of cardiovascular events with cannabis exposure, 143–145 while other studies do not 146,147. However, it is essential to continue to educate and inform others about the potential benefits and drawbacks of using CBD gummies for blood pressure regulation. As more research becomes available, it is likely that CBD gummies will become a widely accepted treatment for blood pressure regulation. The future of research on CBD and blood pressure is promising, with ongoing studies and trials aimed at fully understanding the effects of CBD on blood pressure. Beyond the plant-derived cannabinoids, there are also cannabinoids endogenously produced in humans or animals (so-called endocannabinoids) and synthetic cannabinoids 1,2. Cannabis contains over 700 different chemicals, among which a group of compounds called cannabinoids stands out. Nevertheless, further clinical research is needed to recommend the use of CBD in the treatment of cardiovascular diseases. Administration of CBD to healthy volunteers or animals usually does not markedly affect hemodynamic parameters. CBD can interact with other medications, including blood thinners, and may have adverse effects in certain individuals. The safety of using CBD gummies for high blood pressure is a topic of ongoing debate. Full-spectrum CBD products may contain other compounds found in cannabis, including THC, while isolate CBD products contain only CBD.