SCIENTIFIC RESEARCH PUBLICATIONS

Cannabinoids are lipophilic substances derived from Cannabis sativa that can exert a variety of effects in the human body. They have been studied in cellular and animal models as well as in human clinical trials for their therapeutic benefits in several human diseases. Some of these include central nervous system (CNS) diseases and dysfunctions such as forms of epilepsy, multiple sclerosis, Parkinson's disease, pain and neuropsychiatric disorders. In addition, the endogenously produced cannabinoid lipids, endocannabinoids, are critical for normal CNS function, and if controlled or modified, may represent an additional therapeutic avenue for CNS diseases. This review discusses in vitro cellular, ex vivo tissue and in vivo animal model studies on cannabinoids and their utility as therapeutics in multiple CNS pathologies. In addition, the review provides an overview on the use of cannabinoids in human clinical trials for a variety of CNS diseases. Cannabinoids and endocannabinoids hold promise for use as disease modifiers and therapeutic agents for the prevention or treatment of neurodegenerative diseases and neurological disorders.

Painful knee osteoarthritis (KOA) is common, pharmacological treatment, however, is often hampered by limited tolerability. Cannabidiol, which preclinically showed anti-inflammatory, analgesic activity, could supplement established analgesics, but robust clinical trials are lacking. The aim of our study was to investigate the effects of oral high-dose CBD administered over 8 weeks on pain, function and patient global assessment as an add-on to continued paracetamol in chronic symptomatic KOA.

Cannabis (delta-9-tetrahydrocannabinol), a nonselective cannabinoid-receptor agonist, relieves nausea and pain. Cannabidiol (CBD), a cannabinoid receptor 2 inverse agonist with central effects, also reduces gut sensation and inflammation. We compared the effects of 4 weeks of treatment with pharmaceutical CBD vs placebo in patients with idiopathic or diabetic (diabetes mellitus) gastroparesis.

This study investigated the antinociceptive potential of cannabidiol (CBD) in male and female Wistar rats. The assessment and analysis included tail withdrawal to thermal stimulation (tail flick test) and mechanical allodynia induced by plantar incision injury (von Frey test). CBD reduced acute thermal sensitivity in uninjured animals and post-operative mechanical allodynia in males and females. In the tail flick test, CBD 30mg/kg i.p. was required to induce antinociception in males. During the proestrus phase, females did not show a statistically significant antinociceptive response to CBD treatment despite a noticeable trend. In contrast, in a separate group of rats tested during the late diestrus phase, antinociception varied with CBD dosage and time. In the post-operative pain model, CBD at 3mg/kg decreased mechanical allodynia in males. Similarly, this dose reduced allodynia in females during proestrus. However, in females during late diestrus, the lower dose of CBD (0.3mg/kg) reduced mechanical allodynia, although the latency to onset of the effect was slower (90minutes). The effectiveness of a 10-fold lower dose of CBD during the late diestrus stage in females suggests that ovarian hormones can influence the action of CBD. While CBD has potential for alleviating pain in humans, personalized dosing regimens may need to be developed to treat pain in women.

variants are associated with rare developmental and epileptic encephalopathies (DEEs). Although -related childhood phenotypes are well characterized, the adult phenotype remains ill-defined. We sought to investigate phenotypes and outcomes in adults with variants and epilepsy.

Cannabinoid CB receptor (CBR) is a class A G protein-coupled receptor (GPCR) involved in a broad spectrum of physiological processes and pathological conditions. For that reason, targeting CBR might provide therapeutic opportunities in neurodegenerative disorders, neuropathic pain, inflammatory diseases, and cancer. The main components from Cannabis sativa, such as Δ-tetrahydrocannabinol (Δ-THC) and cannabidiol (CBD), have been therapeutically exploited and synthetically-derived analogs have been generated. One example is cannabidiol-dimethylheptyl (CBD-DMH), which exhibits anti-inflammatory effects. Nevertheless, its pharmacological mechanism of action is not yet fully understood and is hypothesized for multiple targets, including CBR. The aim of this study was to further investigate the molecular pharmacology of CBD-DMH on CBR while CBD was taken along as control. These compounds were screened in equilibrium and kinetic radioligand binding studies and various functional assays, including G protein activation, inhibition of cAMP production and ß-arrestin-2 recruitment. In dissociation studies, CBD-DMH allosterically modulated the radioligand binding. Furthermore, CBD-DMH negatively modulated the G protein activation of reference agonists CP55,940, AEA and 2-AG, but not the agonist-induced ß-arrestin-2 recruitment. Nevertheless, CBD-DMH also displayed competitive binding to CBR and partial agonism on G protein activation, inhibition of cAMP production and ß-arrestin-2 recruitment. CBD did not exhibit such allosteric behavior and only very weakly bound CBR without activation. This study shows a dual binding mode of CBD-DMH, but not CBD, to CBR with the suggestion of two different binding sites. Altogether, it encourages further research into this dual mechanism which might provide a new class of molecules targeting CBR.

The synthesis and degradation of endocannabinoids, location of cannabinoid (CB) receptors, and cannabinoid mechanisms of action on immune/inflammatory, neuromuscular, and sensory functions in digestive organs are well documented. CB mechanisms are particularly relevant in immune and sensory functions. Increasing use of cannabinoids in the United States is impacted by social determinants of health including racial discrimination, which is associated with tobacco and cannabis co-use, and combined use disorders. Several conditions associated with emesis are related to cannabinoid use, including cannabinoid hyperemesis or withdrawal, cyclic vomiting syndrome, and nausea and vomiting of pregnancy. Cannabinoids generally inhibit gastrointestinal motor function; yet they relieve symptoms in patients with gastroparesis and diverse nausea syndromes. Cannabinoid effects on inflammatory mechanisms have shown promise in relatively small placebo-controlled studies in reducing disease activity and abdominal pain in patients with inflammatory bowel disease. Cannabinoids have been studied in disorders of motility, pain, and disorders of gut-brain interaction. The CB-receptor agonist, cannabidiol, reduced the total Gastroparesis Cardinal Symptom Index and increases the ability to tolerate a meal in patients with gastroparesis appraised over 4 weeks of treatment. In contrast, predominant-pain end points in functional dyspepsia with normal gastric emptying were not improved significantly with cannabidiol. The CB agonist, olorinab, reduced abdominal pain in inflammatory bowel disease in an open-label trial and in constipation-predominant irritable bowel syndrome in a placebo-controlled trial. Cannabinoid mechanisms alter inflammation in pancreatic and liver diseases. In conclusion, cannabinoids, particularly agents affecting CB mechanisms, have potential for inflammatory, gastroparesis, and pain disorders; however, the trials require replication and further understanding of risk-benefit to enhance use of cannabinoids in gastrointestinal diseases.

Bioactive phenolic compounds are commonly found in medications, with examples including apomorphine, estrone, thymol, estradiol, propofol, o-phenylphenol, l-Dopa, doxorubicin, tetrahydrocannabinol (THC), and cannabidiol (CBD). This study is the first to explore the creation and assessment of metal and ammonium phenolate salts using CBD as an example. CBD is used in medicine to treat anxiety, insomnia, chronic pain, and inflammation, but its bioavailability is limited due to poor water solubility. In this study exploit a synthetic route to convert CBD into anionic CBD-salts to enhance water solubility. Various CBD-salts with metal and ammonium counterions such as lithium (Li+), sodium (Na+), potassium (K+), choline hydroxide ([(CH)NCHCHOH]), and tetrabutylammonium ([N(CH)]) have been synthesized and characterized. These salts are obtained in high yields, ranging from 74 % to 88 %, through a straightforward dehydration reaction between CBD and alkali metal hydroxides (LiOH, NaOH, KOH) or ammonium hydroxides (choline hydroxide, tetrabutylammonium hydroxide). These reactions are conducted in either ethanol, methanol, or a methanol:water mixture, maintaining a 1:1 molar ratio between the reactants. Comprehensive characterization using Fourier-Transform Infrared Spectroscopy (FT-IR), Nuclear Magnetic Resonance (NMR) spectroscopy, and elemental (CHN) analysis confirms the formation of CBD-salts, as evidenced by the absence of aromatic hydroxyl resonances or stretching frequencies. The molecular formulas of CBD salts were determined based on CHN analysis, and CBD quantification from acid regeneration experiments. Characterization data confirms that each CBD phenolate in a specific CBD salt was electrostatically stabilized by one of the either alkali metal or ammonium ion. The CBD-salts are highly susceptible to acidic conditions, readily reverting back to the original CBD. The percentage and purity of CBD in the CBD-metal/ammonium salts have been studied using High-Performance Liquid Chromatography (HPLC) analysis. Solubility studies indicate that the conversion of CBD into CBD salts significantly enhances its solubility in water, ranging from 110 to 1606 folds greater than pure CBD. Furthermore, the pharmacokinetic evaluation of oral administration of CBD-salts compared to CBD were determined in rats.

Δ-Tetrahydrocannabinol (Δ-THC) is a principal psychoactive extract of Cannabis sativa and has been traditionally used as palliative medicine for neuropathic pain. Cannabidiol (CBD), an extract of hemp species, has recently attracted increased attention as a cancer treatment, but Δ-THC is also requiring explored pharmacological application.

Cannabinoid-containing products are marketed to athletes as promoting recovery, in spite of a lack of data on their safety and effects. This randomized, double-blind, placebo-controlled, repeated-dose pilot study tested the safety, tolerability, and preliminary effects on recovery of a formulation containing cannabidiol (CBD; 35 mg), cannabigerol (CBG; 50 mg), beta caryophyllene (BCP; 25 mg), branched-chain amino acids (BCAAs; 3.8 g), and magnesium citrate (420 mg).

P2X purinoceptor 4 (P2X4) is an ATP-gated ion channel receptor with diverse neurophysiological functions, and P2X4 modulators hold promise as potential therapeutics for neuropathic pain, neuroinflammation, and neurodegenerative diseases. While several cannabinoids have been reported as modulators of purinoreceptors, their specific purinoreceptor-binding characteristics remain elusive. In this study, we established a comprehensive workflow that included a binding screening platform and a novel surface plasmon resonance (SPR) competitive assay, complemented by computational docking, to identify potential P2X4 binders among a panel of twenty-eight cannabinoids. Through SPR, we determined the binding affinities of cannabinoids ( values ranging from 3.4 × 10 M to 1 × 10 M), along with two known P2X4 antagonists, BX430 ( = 4.5 × 10 M) and 5-BDBD ( = 7.8 × 10 M). The competitive SPR assay validated that BX430 and 5-BDBD acted as non-competitive binders with P2X4. In the following competitive assays, two cannabinoids including cannabidiol (CBD) and cannabivarin (CBV) were identified as competitive P2X4-binders with 5-BDBD, while the remaining cannabinoids exhibited non-competitive binding with either BX430 or 5-BDBD. Our molecular docking experiments further supported these findings, demonstrating that both CBD and CBV shared identical binding sites with residues in the 5-BDBD binding pocket on P2X4. In conclusion, this study provides valuable insights into the P2X4-binding affinity of cannabinoids through SPR and sheds light on the interactions between cannabinoids (CBD and CBV) and P2X4.

Around 2% of the population have intellectual disabilities. Over one-third people with intellectual disabilities (PwID) present with 'challenging behaviour', which nosologically and diagnostically is an abstract concept. Challenging behaviour is influenced by a range of bio-psycho-social factors in a population, which is unable to suitably comprehend and/or communicate concerns. This predisposes to poor health and social outcomes. There is no evidence-based treatments for managing challenging behaviour. Cannabidiol (CBD) and tetrahydrocannabinol (THC) are being trialled for a range of disorders, which are over-represented in PwID and provoke challenging behaviours, such as severe epilepsy, spasticity, post-traumatic stress disorder, social phobia, pain, etc.

Here, we report a dramatic efficacy of cannabidiol in an adolescent with SCD suffering from chronic pain refractory to other analgesics, with complete regression of chronic pain and rapid plasma histamine level normalization after treatment.

Bone fractures are among the most prevalent musculoskeletal injuries, and pain management is an essential part of fracture treatment. Fractures heal through an early inflammatory phase, followed by repair and remodeling. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended for fracture pain control as they potently inhibit the inflammatory phase and, thus, impair the healing. Opioids do not provide a better alternative for several reasons, including abuse potential. Accordingly, there is an unmet clinical need for analgesics that effectively ameliorate postfracture pain without impeding the healing. Here, we investigated the analgesic efficacy of two nonpsychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG), in a mouse model for tibial fracture. Mice with fractured tibiae exhibited increased sensitivity to mechanical, cold, and hot stimuli. Both CBD and CBG normalized pain sensitivity to all tested stimuli, and their analgesic effects were comparable to those of the NSAIDs. Interestingly, CBD and CBG promoted bone healing via multiple mechanisms during the early and late phases. During the early inflammatory phase, both cannabinoids increased the abundance of periosteal bone progenitors in the healing hematoma and promoted the osteogenic commitment of these progenitors. During the later phases of healing, CBD and CBG accelerated the fibrocartilaginous callus mineralization and enhanced the viability and proliferation of bone and bone-marrow cells. These effects culminated in higher bone volume fraction, higher bone mineral density, and improved mechanical quality of the newly formed bone. Together, our data suggest CBD and CBG as therapeutic agents that can replace NSAIDs in managing postfracture pain as both cannabinoids exert potent analgesic effects and, at the same time, promote bone healing. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Cannabidiol (CBD) is one of the most commonly utilised phytocannabinoids due to its non-psychoactive and multiple potential therapeutic properties and its non-selective pharmacology. Recent studies have demonstrated efficacy of CBD in some types of drug resistant epilepsies in combination with other therapies; comparative efficacy to other agents or placebo has been hoped for anxiety, chronic pain, and inflammatory disorders based on animal data. Although CBD products are generally treated as a restricted substance, these are being eased, partially in response to significant growth in CBD product usage and increased production but more due to emerging evidence about its safety and pharmacological properties. Currently, only one CBD product (Epidiolex®) has been approved by the Australian Therapeutic Goods Administration and US Food and Drug Administration. CBD has demonstrated promise in alleviating gut and lung diseases in vitro; however, its physicochemical properties pose a significant barrier to achieving pharmacological effects in in vivo and clinical trials. Improving CBD formulations and delivery methods using technologies including self-emulsifying emulsion, nano and micro particles could overcome these shortfalls and improve its efficacy. This review focuses on the therapeutic potential of CBD in gastrointestinal and lung diseases from the available in vitro, in vivo, and clinical research. We report on identified research gaps and obstacles in the development of CBD-based therapeutics, including novel delivery methods.

Cannabidiol (CBD), a component in Cannabis, is used to treat seizures, anxiety, and pain. Little is known about how effectively CBD works in managing chronic pain, a condition characterized by discomfort that persists beyond 3-6 months or beyond expected normal healing. Therefore, this systematic review aimed to synthesize evidence on the effectiveness of CBD in chronic pain management.

» Cannabinoids, such as D9-tetrahydrocannabinol and cannabidiol, interact with endocannabinoid receptors in the central nervous system and immune system, potentially offering pain relief. The entourage effect, resulting from the interaction of multiple cannabis components, may enhance therapeutic impact and efficacy, making them promising candidates for exploring pain relief in spine operations, known to be among the most painful operative procedures.» The use of cannabinoids in pain management requires careful consideration of safety, including their cognitive and psychomotor effects, potential cardiovascular risks, risk of dependence, mental health implications, and drug interactions.» Few studies have analyzed cannabinoid use in relation to spine surgery, with variable results reported, indicating possible effects on reoperation rates, mortality, complications, postoperative opioid use, and length of hospital stay.» Current knowledge gaps exist in the understanding of cannabinoid effects on spine surgery, including the exploration of different administration routes, timing, dosage, and specific outcomes. In addition, mechanistic explanations for the observed results are lacking.» Ethical considerations related to informed consent, medical expertise, societal impact, and legal compliance must also be thoroughly addressed when considering the utilization of cannabinoids in spinal pathologies and back pain treatment.

Published data on the safety of natural medical cannabis (MC) when used in the real-world clinical practice setting are lacking. This study aimed to describe adverse events (AEs) reported across three years following MC initiation.

Cannabidiol (CBD), a non-intoxicating substance of Cannabis sativa L., is gaining consumer attention. Yet, legal regulations in the EU are complex and questions of potential health risks remain partly unanswered. In Germany, little is known about people who use CBD products. The aim of this cross-sectional study was to gain insight into the user group of CBD, reasons for consumption and risk perception towards CBD-containing products.

Neuropathic pain remains prevalent and challenging to manage and is often comorbid with depression and anxiety. The new approach that simultaneously targets neuropathic pain and the associated comorbidities, such as depression and anxiety, is timely and critical, given the high prevalence and severity of neuropathic pain and the lack of effective analgesics. In this review, we focus on the animal models of neuropathic pain that researchers have used to investigate the analgesic effects of cannabidiol (CBD) and Beta-Caryophyllene (BCP) individually and in combination while addressing the impact of these compounds on the major comorbidity (e.g., depression, anxiety) associated with neuropathic pain. We also addressed the potential targets/mechanisms by which CBD and BCP produce analgesic effects in neuropathic pain models. The preclinical studies examined in this review support CBD and BCP individually and combined as potential alternative analgesics for neuropathic pain while showing beneficial effects on depression and anxiety.

To understand real-world dispensing and utilization patterns of medical cannabis (MC) and its financial impact on patients, we analyzed the database of a cannabis company licensed in New York state. To evaluate the tetrahydrocannabinol (THC)/cannabidiol (CBD) dose ratios, association of various medical conditions to THC/CBD dose, and the cost of products in registered patients receiving MC from four licensed state dispensaries. Retrospective analysis conducted on anonymized data between January 1, 2016 and December 31, 2020 listing 422,201 dispensed products from 32,845 individuals aged 18 years and older. Adult patients with medical certification for cannabis use in New York, USA. The database included patient's age, gender, qualifying medical condition, type and dose of product, medication directions, and amount of product dispensed. Findings showed a median age of 53 years with 52% of patients female. Males were found to use more products than females (1.06:1). Pain (85%) was the most common medical condition and inhalation (57%) the most common route except when used for cancer-directed treatment and neurological conditions. Individuals received a median of six prescriptions costing a median of $50/product. Average THC:CBD ratios were 28:0.5 mg/day and 12:0.25 mg/dose. Neurological conditions demonstrated the highest average cost [mean (95% confidence interval {CI}): $73 ($71-$75)] and average CBD/dose per product [mean (95% CI): 5.89 (5.38-6.40)]. Individuals with a history of substance use disorder utilizing MC as an alternative substance displayed the highest average THC/dose [mean (95% CI): 14.25 (13.36-15.14)]. MC was utilized for various medical conditions with variability in THC:CBD ratio seen depending on the condition. Cost variation was also observed based on the individual's medical condition.

Medical cannabis use is increasing in Australia and other jurisdictions, yet little is known about the effects of medical cannabis on cognitive function. Findings from studies of non-medical ('recreational') cannabis may not be applicable to patients using prescribed medical cannabis to manage a health condition.

Cannabis may have therapeutic benefits to relieve symptoms of amyotrophic lateral sclerosis (ALS) thanks to its pleiotropic pharmacological activity. This study is the first to present a large questionnaire-based survey about the "real-life" situation regarding cannabis use in the medical context in ALS patients in France. There were 129 respondents and 28 reported the use of cannabis (21.7%) to relieve symptoms of ALS. Participants mostly reported the use of cannabidiol (CBD) oil and cannabis weed and declared benefits both on motor (rigidity, cramps, fasciculations) and non-motor (sleep quality, pain, emotional state, quality of life, depression) symptoms and only eight reported minor adverse reactions (drowsiness, euphoria and dry mouth). Even if cannabis is mostly used outside medical pathways and could expose patients to complications (street and uncontrolled drugs, drug-drug interactions, adverse effects…), most of the participants reported "rational" consumption (legal cannabinoids, with only few combustion and adverse reactions). Despite some limitations, this study highlights the need for further research on the potential benefits of cannabis use for the management of ALS motor and non-motor symptoms. Indeed, there is an urgent need and call for and from patients to know more about cannabis and secure its use in a medical context.

Odontogenic pain can be debilitating, and nonopioid analgesic options are limited. This randomized placebo-controlled clinical trial aimed to assess the effectiveness and safety of cannabidiol (CBD) as an analgesic for patients with emergency acute dental pain. Sixty-one patients with moderate to severe toothache were randomized into 3 groups: CBD10 (CBD 10 mg/kg), CBD20 (CBD 20 mg/kg), and placebo. We administered a single dose of respective oral solution and monitored the subjects for 3 h. The primary outcome measure was the numerical pain differences using a visual analog scale (VAS) from baseline within and among the groups. Secondary outcome measures included ordinal pain intensity differences, the onset of significant pain relief, maximum pain relief, changes in bite force within and among the groups, psychoactive effects, mood changes, and other adverse events. Both CBD groups resulted in significant VAS pain reduction compared to their baseline and the placebo group, with a maximum median VAS pain reduction of 73% from baseline pain at the 180-min time point ( < 0.05). CBD20 experienced a faster onset of significant pain relief than CBD10 (15 versus 30 min after drug administration), and both groups reached maximum pain relief at 180-min. Number needed to treat was 3.1 for CBD10 and 2.4 for CBD20. Intragroup comparisons showed a significant increase in bite forces in both CBD groups ( < 0.05) but not in the placebo group ( > 0.05). CBD20 resulted in a significant difference in mean percent bite force change in the 90- and 180-min time points compared to the placebo group ( < 0.05). Compared to placebo, sedation, diarrhea, and abdominal pain were significantly associated with the CBD groups ( < 0.05). There were no other significant psychoactive or mood change effects. This randomized trial provides the first clinical evidence that oral CBD can be an effective and safe analgesic for dental pain.

Scientific evidence exists about the association between neurological diseases (i.e., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, depression, and memory loss) and oxidative damage. The increasing worldwide incidence of such diseases is attracting the attention of researchers to find palliative medications to reduce the symptoms and promote quality of life, in particular, in developing countries, e.g., South America and Africa. Among potential alternatives, extracts of L. are suitable for people who have neurological disorders, spasticity, and pain, nausea, resulting from diseases such as cancer and arthritis. In this review, we discuss the latest developments in the use of Cannabis, its subtypes and constituents, extraction methods, and relevant pharmacological effects. Biomedical applications, marketed products, and prospects for the worldwide use of L. extracts are also discussed, providing the bibliometric maps of scientific literature published in representative countries from South America (i.e., Brazil) and Africa (i.e., South Africa). A lack of evidence on the effectiveness and safety of Cannabis, besides the concerns about addiction and other adverse events, has led many countries to act with caution before changing Cannabis-related regulations. Recent findings are expected to increase the social acceptance of Cannabis, while new technologies seem to boost the global cannabis market because the benefits of (-)-trans-delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) use have been proven in several studies in addition to the potential to general new employment.

Cannabidiol (CBD) is on the rise as over-the-counter medication to treat sleep disturbances, anxiety, pain, and epilepsy due to its action on the excitatory/inhibitory balance in the brain. However, it remains unclear if CBD also leads to adverse effects on memory via changes of sleep macro- and microarchitecture. To investigate the effect of CBD on sleep and memory consolidation, we performed two experiments using the object space task testing for both simple and cumulative memory in rats. We show that oral CBD administration extended the sleep period but changed the properties of rest and non-REM sleep oscillations (delta, spindle, ripples). Specifically, CBD also led to less long (>100 ms) ripples and, consequently, worse cumulative memory consolidation. In contrast, simple memories were not affected. In sum, we can confirm the beneficial effect of CBD on sleep; however, this comes with changes in oscillations that negatively impact memory consolidation.

The current study aimed to evaluate anxiety behavior, hippocampal ionized calcium-binding adaptor molecule 1 (Iba1) and cannabinoid receptor 1 (CB1) gene expression, and nociceptive response in adulthood after a combination of fentanyl and cannabidiol (CBD) for nociceptive stimuli induced during the first week of life in rats. Complete Freund's adjuvant-induced inflammatory nociceptive insult on postnatal day (PN) 1 and PN3. Both fentanyl and CBD were used alone or in combination from PN1 to PN7. Behavioral and nociceptive tests were performed at PN60 and PN62. The expression of the microglial calcium-binding proteins Iba1 and CB1 was detected in the hippocampus using reverse Quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Our results suggest that the anxiety behavior response and immune activation in adult life depend on the CBD dose combined with fentanyl for the nociceptive stimuli induced during the first week of life. Treatment of neonatal nociceptive insult with CBD and opioids showed significant dose-dependent and male-female differences. The increased gene expression in the hippocampus of the analyzed cannabinoid gene supports this data. In addition, treatment with fentanyl led to an increase in CB1 protein expression. Moreover, the expression of Iba1 varied according to the administered dose of CBD and may or may not be associated with the opioid. A lower dose of CBD during the inflammatory period was associated with enhanced anxiety in adult life. PERSPECTIVE: The treatment of nociceptive stimuli with CBD and opioids during the first week of life demonstrated significant sex differences in adult life on anxiety behavior and supraspinal pain sensitivity.

Migraine is a disabling disorder characterized by recurrent headaches, accompanied by abnormal sensory sensitivity and anxiety. Despite extensive historical use of cannabis in headache disorders, there is limited research on the nonpsychoactive cannabidiol (CBD) for migraine and there is no scientific evidence to prove that CBD is an effective treatment. The effects of CBD are examined here using a calcitonin gene-related peptide (CGRP)-induced migraine model that provides measures of cephalic allodynia, spontaneous pain, altered light sensitivity (photophobia), and anxiety-like behavior in C57BL/6J mice. A single administration of CGRP induced facial hypersensitivity in both female and male mice. Repeated CGRP treatment produced progressively decreased levels in basal thresholds of allodynia in females, but not in males. A single CBD administration protected both females and males from periorbital allodynia induced by a single CGRP injection. Repeated CBD administration prevented increased levels of basal allodynia induced by repeated CGRP treatment in female mice and did not lead to responses consistent with migraine headache as occurs with triptans. Cannabidiol, injected after CGRP, reversed CGRP-evoked allodynia. Cannabidiol also reduced spontaneous pain traits induced by CGRP administration in female mice. Finally, CBD blocked CGRP-induced anxiety in male mice, but failed in providing protection from CGRP-induced photophobia in females. These results demonstrate the efficacy of CBD in preventing episodic and chronic migraine-like states with reduced risk of causing medication overuse headache. Cannabidiol also shows potential as an abortive agent for treating migraine attacks and headache-related conditions such as spontaneous pain and anxiety.

The underlying pathomechanism of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is the immune response to inflammation or infection within the pulmonary microcirculation. Systemic spread of pathogens, activated immune cells, and inflammatory mediators contributes significantly to mortality in patients with ARDS. The endogenous cannabinoid system is a major modulator of the immune response during inflammation and infection. Phytocannabinoids, such as cannabidiol (CBD), have shown promising anti-inflammatory effects in several pathologies. The overall objective of this study was to evaluate the effects of CBD on local and systemic inflammation in endotoxin-induced ALI in mice. ALI was induced by pulmonary endotoxin challenge. Four groups of male C57BL/6 mice were randomized in this study: control, ALI, ALI with CBD treatment, and control with CBD treatment. Analyses of local and systemic cytokine levels, lung histology, and leukocyte activation as visualized by intravital microscopy of the intestinal and pulmonary microcirculation were performed 6 h following intranasal endotoxin administration. Pulmonary endotoxin challenge induced significant inflammation evidenced by local and systemic cytokine and chemokine release, lung histopathology, and leukocyte adhesion. Intraperitoneal CBD treatment resulted in a significant decrease in systemic inflammation as shown by reduced leukocyte adhesion in the intestinal microcirculation and reduced plasma cytokine and chemokine levels. Pulmonary chemokine levels were decreased, while pulmonary cytokine levels were unchanged. Surprisingly, the ALI score was slightly increased by CBD treatment in a manner driven by enhanced neutrophil infiltration of the alveoli. In this model of experimental ALI, CBD administration was associated with reduced systemic inflammation and heterogeneous effects on pulmonary inflammation. Future studies should explore the mechanisms involved as they relate to neutrophil infiltration and proinflammatory mediator production within the lungs.

Parkinson's disease (PD) is a serious neurodegenerative condition impacting many individuals worldwide. There is a need for new non-invasive treatments of PD. Cannabinoids in the form of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) may offer utility as treatment, and our objective was hence to conduct a systematic review regarding the clinical evidence for the efficacy and safety of cannabinoids in treating PD. Screening, data extraction, and quality assessments were all conducted by multiple reviewers, with discrepancies resolved by consensus. After conducting searches in 4 different databases, 673 articles were screened. Thirteen articles were deemed eligible for inclusion in this review. It was shown that cannabis, CBD, and nabilone (a synthetic form of THC) were capable of consistently improving motor symptoms more than a placebo. All treatments improved various non-motor symptoms, particularly with cannabis improving pain intensity, and CBD improving psychiatric symptoms in a dose-dependent manner. Adverse effects were usually minor, and, in the case of CBD, rare (except at very high doses). Cannabinoids have been shown to safely offer important potential in treating motor symptoms in PD and some non-motor symptoms. More large-scale randomized control trials for specific forms of cannabinoid treatments are required to determine their overall efficacy.

Voltage-gated sodium (Na) channels govern membrane excitability, thus setting the foundation for various physiological and neuronal processes. Na channels serve as the primary targets for several classes of widely used and investigational drugs, including local anesthetics, antiepileptic drugs, antiarrhythmics, and analgesics. In this study, we present cryogenic electron microscopy (cryo-EM) structures of human Na1.7 bound to two clinical drugs, riluzole (RLZ) and lamotrigine (LTG), at resolutions of 2.9 Å and 2.7 Å, respectively. A 3D EM reconstruction of ligand-free Na1.7 was also obtained at 2.1 Å resolution. RLZ resides in the central cavity of the pore domain and is coordinated by residues from repeats III and IV. Whereas one LTG molecule also binds to the central cavity, the other is found beneath the intracellular gate, known as site BIG. Therefore, LTG, similar to lacosamide and cannabidiol, blocks Na channels via a dual-pocket mechanism. These structures, complemented with docking and mutational analyses, also explain the structure-activity relationships of the LTG-related linear 6,6 series that have been developed for improved efficacy and subtype specificity on different Na channels. Our findings reveal the molecular basis for these drugs' mechanism of action and will aid the development of novel antiepileptic and pain-relieving drugs.

Complex regional pain syndrome type I (CRPS-I) is a debilitating neuropathic painful condition associated with allodynia, hyperalgesia, sudomotor and/or vasomotor dysfunctions, turning investigation of its pathophysiology and new therapeutic strategies into an essential topic. We aim to investigate the impact of ischemia/reperfusion injury on the immunocontent of CB1 and CB2 cannabinoid receptor isoforms in the paws of mice submitted to a chronic postischemia pain (CPIP) model and the effects of local administration of cannabidiol (CBD) on mechanical hyperalgesia. Female Swiss mice, 30-35 g, were submitted to the CPIP model on the right hind paw. Skin and muscle samples were removed at different periods for western blot analysis. No changes in the immunocontent of CB1 and CB2 receptors in paw muscle tissues after ischemia-reperfusion were observed. CBD promoted an antihyperalgesic effect in both phases. AM281 reversed the effect of CBD, whereas ruthenium red abolished the late phase. Our results point to the possible beneficial effects of local administration of CBD in modulating CRPS-I in humans. As possible targets for CBD antihyperalgesia in this model, the contribution of cannabinoid receptor CB1, in addition to TRPM8 is suggested.

Cannabis and cannabis products are becoming increasingly popular options for symptom management of inflammatory bowel diseases, particularly abdominal pain. While anecdotal and patient reports suggest efficacy of these compounds for these conditions, clinical research has shown mixed results. To date, clinical research has focused primarily on delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is a ligand of classical cannabinoid receptors (CBRs). CBD is one of a large group of nonintoxicating cannabinoids (niCBs) that mediate their effects on both CBRs and through non-CBR mechanisms of action. Because they are not psychotropic, there is increasing interest and availability of niCBs. The numerous niCBs show potential to rectify abnormal intestinal motility as well as have anti-inflammatory and analgesic effects. The effects of niCBs are frequently not mediated by CBRs, but rather through actions on other targets, including transient receptor potential channels and voltage-gated ion channels. Additionally, evidence suggests that niCBs can be combined to increase their potency through what is termed the entourage effect. This review examines the pre-clinical data available surrounding these niCBs in treatment of abdominal pain with a focus on non-CBR mechanisms.

Cannabidiol (CBD) attracts considerable attention for promoting good health and treating various conditions, predominantly pain, often in breach of advertising rules. Examination of available CBD products in North America and Europe demonstrates that CBD content can vary from none to much more than advertised and that potentially harmful other chemicals are often included. Serious harm is associated with chemicals found in CBD products and reported in children, adults, and the elderly. A 2021 International Association for the Study of Pain task force examined the evidence for cannabinoids and pain but found no trials of CBD. Sixteen CBD randomized trials using pharmaceutical-supplied CBD or making preparations from such a source and with pain as an outcome have been published subsequently. The trials were conducted in 12 different pain states, using 3 oral, topical, and buccal/sublingual administration, with CBD doses between 6 and 1,600 mg, and durations of treatment between a single dose and 12 weeks. Fifteen of the 16 showed no benefit of CBD over placebo. Small clinical trials using verified CBD suggest the drug to be largely benign; while large-scale evidence of safety is lacking, there is growing evidence linking CBD to increased rates of serious adverse events and hepatotoxicity. In January 2023, the Food and Drug Administration (FDA) announced that a new regulatory pathway for CBD was needed. Consumers and health care providers should rely on evidence-based sources of information on CBD, not just advertisements. Current evidence is that CBD for pain is expensive, ineffective, and possibly harmful. PERSPECTIVE: There is no good reason for thinking that CBD relieves pain, but there are good reasons for doubting the contents of CBD products in terms of CBD content and purity.

Cannabidiol (CBD) is a multitarget agent possessing anti-inflammatory and antioxidant properties. Unlicensed CBD gained public favor for the care of general health and well-being as well as to get comfort from inflammatory complaints, pain, anxiety, mood, and sleep disorders. Safety profile of unlicensed CBD has been not sufficiently described. For this reason, suspected adverse reactions (SARs) to CBD unlicensed products were analyzed. Serious SARs to unlicensed CBD products in EudraVigilance, a system purchased by the European Medicines Agency, were analyzed for age, sex of the patient, adverse reactions, indication for use, and concomitant drugs. Serious SARs were 18.9% of all adverse events to unlicensed CBD; they were more frequent in men and adult people and, to a less extent, in children (3-11 years). About sex, in EudraVigilance serious Individual Cases Safety Reports of SARs to CBD in men are in the largest number (58.8%) with respect to women. Unlicensed CBD was used in the 38.8% of cases for treatment of epilepsy; more frequent adverse effects were: mental disorders, hepatic disorders, and aggravation of pre-existing epilepsy. Drugs or substances more frequently associated with SARs were the antiepileptics clobazam and valproic acid, followed by cannabis. Results suggest that precautions and appropriate surveillance of adverse effects should be taken when unlicensed CBD is used.

Given the ongoing national opiate crisis, physicians have been challenged with mitigating the risk of opiate dependence in their patients. With current physician efforts to mitigate the risks of treating pain with opioid prescriptions, this study evaluates medical students' and residents' understanding and perceptions regarding cannabidiol (CBD) in current medical care and their future medical practice.

Cannabidiol (CBD) is a known pain modulator that is garnering increased attention in the orthopaedic world. There may be a considerable knowledge gap among orthopaedic sports medicine providers and their perception of its therapeutic value.

Chronic neuropathic pain is a debilitating pain syndrome caused by damage to the nervous system that is poorly served by current medications. Given these problems, clinical studies have pursued extracts of the plant Cannabis sativa as alternative treatments for this condition. The vast majority of these studies have examined cannabinoids which contain the psychoactive constituent delta-9-tetrahydrocannabinol (THC). While there have been some positive findings, meta-analyses of this clinical work indicates that this effectiveness is limited and hampered by side-effects. This review focuses on how recent preclinical studies have predicted the clinical limitations of THC-containing cannabis extracts, and importantly, point to how they might be improved. This work highlights the importance of targeting channels and receptors other than cannabinoid CB1 receptors which mediate many of the side-effects of cannabis.

Low back pain (LBP) is a major cause of disability and the main reason why individual patients need medical attention. Pharmacological treatment options for LBP are limited and are often associated with serious side-effects. This makes it necessary to search for new painkillers. One potential therapeutic agent is cannabidiol (CDB). Cannabidiol and tetrahydrocannabinol are the most researched components of cannabis, the plant more commonly known as marijuana or hemp. To the best of our knowledge, this is the first narrative review of the effects of CBD alone on acute and chronic back pain.

Simple and fast detection of small molecules is critical to health and environmental monitoring. Methods for chemical detection often use mass spectrometers or enzymes; the former relies on expensive equipment and the latter is limited to those that can act as enzyme substrates. Affinity reagents like antibodies can target a variety of small-molecule analytes, but the detection requires successful design of chemically conjugated targets or analogs for competitive binding assays. Here, we developed a generalizable method for highly sensitive and specific in-solution detection of small molecules, using cannabidiol (CBD) as an example. Our sensing platform uses gold nanoparticles (AuNPs) functionalized with a pair of chemically induced dimerization (CID) nanobody binders (nano-binders), where CID triggers AuNPs aggregation and sedimentation in the presence of CBD. Despite moderate binding affinities of the two nano-binders to CBD (s of ~6 and ~56 μM), a scheme consisting of CBD-AuNP pre-analytical incubation, centrifugation, and electronic detection (ICED) was devised to demonstrate a high sensitivity (limit of detection of ~100 picomolar) in urine and saliva, a relatively short assay time (~2 hours), a large dynamic range (5 logs), and a sufficiently high specificity to differentiate CBD from its analog, tetrahydrocannabinol. The high sensing performance was achieved with the multivalency of AuNP sensing, the ICED scheme that increases analyte concentrations in a small assay volume, and a portable electronic detector. This sensing system is readily coupled to other binders for wide molecular diagnostic applications.

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.

Historically, cannabis has been valued for its pain-relieving, anti-inflammatory, and calming properties. Ancient civilizations like the Egyptians, Greeks, and Chinese medicines recognized their therapeutic potential. The discovery of the endocannabinoid system, which interacts with cannabis phytoconstituents, has scientifically explained how cannabis affects the human immune system, including the central nervous system (CNS). This review explores the evolving world of cannabis-based treatments, spotlighting its diverse applications. By researching current research and clinical studies, we probe into how cannabinoids like Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) help to manage conditions ranging from chronic pain, persistent inflammation, cancer, inflammatory bowel disease, and neurological disorders to even viral diseases such as Human Immunodeficiency virus (HIV), SARS-CoV-2. and the emerging monkeypox. The long-term recreational use of cannabis can develop into cannabis use disorder (CUD), and therefore, understanding the factors contributing to the development and maintenance of cannabis addiction, including genetic predisposition, neurobiological mechanisms, and environmental influences, will be timely. Shedding light on the adverse impacts of CUD underscores the importance of early intervention, effective treatment approaches, and public health initiatives to address this complex issue in an evolving landscape of cannabis policies and perceptions.

There is increasing interest in the use of cannabis and cannabinoid therapies (CCT) by the general population and among people with headache disorders, which results in a need for healthcare professionals to be well versed with the efficacy and safety data. In this manuscript, we review cannabis and cannabinoid terminology, the endocannabinoid system and its role in the central nervous system (CNS), the data on efficacy, safety, tolerability, and potential pitfalls associated with use in people with migraine and headache disorders. We also propose possible mechanisms of action in headache disorders and debunk commonly held myths about its use.

Humans have employed cannabis for multiple uses including medicine, recreation, food, and fibre. The various components such as roots, flowers, seeds, and leaves have been utilized to alleviate pain, inflammation, anxiety, and gastrointestinal disorders like nausea, vomiting, diarrhoea, and inflammatory bowel diseases (IBDs). It has occupied a significant space in ethnomedicines across cultures and religions. Despite multi-dimensional uses, the global prohibition of cannabis by the USA through the introduction of the Marijuana Tax Act in 1937 led to prejudice about the perceived risks of cannabis, overshadowing its medicinal potential. Nevertheless, the discovery of tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, and the endocannabinoid system renewed scientific interest in understanding the role of cannabis in modulating different conditions, including gastrointestinal disorders. Preparations combining cannabidiol and THC have shown promise in mitigating gut symptoms through anti-inflammatory and motility-enhancing effects. This review revisits the ethnomedicinal use of cannabis in gastrointestinal diseases and emphasizes the need for further research to determine optimal dosages, formulations, and safety profiles of cannabis-based medicines. It also underscores the future potential of cannabinoid-based therapies by leveraging the role of the expanded endocannabinoid system, an endocannabinoidome, in the modulation of gastrointestinal ailments.

The use of cannabinoids (substances contained specifically in hemp plants) for therapeutic purposes has received increased attention in recent years. Presently, attention is paid to two main cannabinoids: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). With respect to the psychotropic effects and dependence potential of THC (though it is very mild), its use is associated with certain restrictions, and thus the therapeutic properties of CBD are frequently emphasized because there are no limitations associated with the risk of dependence. Therefore, this review covers the main pharmacodynamic and pharmacokinetic features of CBD (including characteristics of endocannabinoidome) with respect to its possible beneficial effects on selected diseases in clinical practice. A substantial part of the text deals with the main effects of CBD on aging, including Alzheimer's disease and related underlying mechanisms.

Symptoms such as pain, nausea, and anxiety are common in individuals with cancer. Treatment of these issues is often challenging. Cannabis products may be helpful in reducing the severity of these symptoms. While some studies include data on the prevalence of cannabis use among patients with cancer, detailed data remain limited, and none have reported the prevalence of cannabidiol (CBD) use in this population. Adult patients with cancer attending eight clinics at a large, NCI-designated Comprehensive Cancer Center completed a detailed, cannabis-focused questionnaire between 2021 and 2022. Eligible participants were diagnosed with invasive cancer and treated in the past 12 months. Summary statistics were calculated to describe the sample regarding cannabis use. Approximately 15% (n = 142) of consented patients (n = 934) reported current cannabis use (defined as use within the past 12 months). Among which, 75% reported cannabis use in the past week. Among current cannabis users, 39% (n = 56; 6% overall) used CBD products. Current users reported using cannabis a median of 4.5 (interquartile range: 0.6–7.0) days/week, 2.0 (1.0–3.0) times per use/day, and for 3 years (0.8–30.0). Use patterns varied by route of administration. Patients reported moderate to high relief of symptoms with cannabis use. This study is the most detailed to date in terms of cannabis measurement and provides information about the current state of cannabis use in active cancer. Future studies should include complete assessments of cannabis product use, multiple recruitment sites, and diverse patient populations.

Cannabinoids are compounds found in the cannabis sativa plant. Cannabinoids, such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have potential therapeutic benefits in various medical conditions. Some can activate the cannabinoid receptors type-1 and -2 (CB1 and CB2), that are part of the endocannabinoid system (ECS), alongside the endocannabinoids and their metabolic enzymes. The ECS regulates physiological and cognitive processes and is a potential therapeutic target for a wide range of health conditions like chronic pain, anxiety, and neurodegenerative diseases. Synthetic cannabinoids, are associated with serious health risks, including addiction, psychosis, and death. Nonetheless, some of these molecules are also being explored for pharmacological applications. Angiogenesis is the process of forming new blood vessels from existing ones, crucial for growth, repair, and tissue maintenance. Dysregulation of this process is associated with several diseases, including cancer, diabetic retinopathy and reproductive pathologies, such as preeclampsia. Recent data suggests that cannabinoids may affect angiogenesis. Here, we reviewed their impact on pro-angiogenic factors, extracellular matrix enzymes and inhibitors, immune-inflammatory responses, angiogenic pathways and functional assays, focusing on the main compounds for each cannabinoid class: THC and CBD for phytocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG) for endocannabinoids and WIN-55, JWH-133, XLR-11, LYR-7 and LYR-8, for the synthetic cannabinoids. Despite conflicting reports about the actions of phytocannabinoids and endocannabinoids on angiogenesis, the ability to modulate the angiogenic process is undoubtedly confirmed. This may open a new therapeutical route for angiogenesis-related pathologies. In addition, synthetic cannabinoids present anti-angiogenic actions in several cell models, hinting their potential as anti-angiogenic drugs.

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

To assess cannabinoid dosing that could be associated with a reduction in opioid use.

For many chemotherapy patients peripheral neuropathy is a debilitating side effect. Mitragyna speciosa (kratom) contains the alkaloid mitragynine (MG), which produces analgesia in multiple preclinical pain models. In humans, anecdotal reports suggest cannabidiol (CBD) may enhance kratom-related analgesia. We examined the interactive activity of MG and CBD in a mouse chemotherapy-induced peripheral neuropathy (CIPN) model. We also examined MG + CBD in acute antinociception and schedule-controlled responding assays, as well as examined underlying receptor mechanisms.

Cannabis, more commonly known as marijuana or hemp, has been used for centuries to treat various conditions. Cannabis contains two main components cannabidiol (CBD) and tetrahydrocannabinol (THC). CBD, unlike THC, is devoid of psychoactive effects and is well tolerated by the human body but has no direct effect on the receptors of the endocannabid system, despite the lack of action on the receptors of the endocannabid system.

Cannabidiol (CBD) is a phytocannabinoid with great potential in clinical applications. The mechanism(s) of action of CBD require further investigation. Previous studies suggested that adenosine A receptors (ARs) could play a role in CBD-induced effects. Here, we evaluated the ability of CBD to modify the function of AR.

Microfluidic technology is applied across various research areas including organ-on-chip (OOC) systems. The main material used for microfluidics is polydimethylsiloxane (PDMS), a silicone elastomer material that is biocompatible, transparent, and easy to use for OOC systems with well-defined microstructures. However, PDMS-based OOC systems can absorb hydrophobic and small molecules, making it difficult and erroneous to make quantitative analytical assessments for such compounds. In this paper, we explore the use of a synthetic fluoropolymer, poly(4,5-difluoro-2,2-bis(trifluoromethyl)-1,3-dioxole--tetrafluoroethylene) (Teflon™ AF 2400), with excellent "non-stick" properties to functionalize OOC systems. Cannabinoids, including cannabidiol (CBD), are classes of hydrophobic compounds with a great potential for the treatment of anxiety, depression, pain, and cancer. By using CBD as a testing compound, we examined and systematically quantified CBD absorption into PDMS by means of an LC-MS/MS analysis. In comparison to the unmodified PDMS microchannels, an increase of approximately 30× in the CBD signal was detected with the fluoropolymer surface modification after 3 h of static incubation. Under perfusion conditions, we observed an increase of nearly 15× in the CBD signals from the surface-modified microchannels than from the unmodified microchannels. Furthermore, we also demonstrated that fluoropolymer-modified microchannels are compatible for culturing hCMEC/D3 endothelial cells and for CBD perfusion experiments.

To systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational studies and randomised controlled trials (RCTs).

A placebo-controlled study evaluated the clinical efficacy and safety of a commercially available cannabidiol (CBD) oral formulation as an adjunctive treatment for pain management for feline chronic gingivostomatitis (FCGS). CBD was included in a multimodal treatment routinely performed on client-owned cats with FCGS that were submitted to dental extractions. Twenty-two cats were consecutively included in the study. The first group was treated using a fixed dosage of 4 mg per cat every 12 h for 15 consecutive days, and the second received a placebo of similar features. Treatments began 2 h before dental extractions. Pain and disease severity were assessed at days 0 and 15 using the Composite Oral Pain Scale (COPS-C/F) and the Stomatitis Disease Activity Index score (SDAI). Weight, vital and biochemistry parameters, and analgesic reinforcement needs were also registered at the same time points. In the treated cats, blood was collected after 4, 8, and 12 h to determine CBD serum concentrations using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS). After data analysis using mixed models, a significant improvement in the SDAI scores of cats medicated with CBD was found. The protocol is safe since severe adverse effects and biochemical changes were not observed during the treatment period. This study suggests that the cats benefited from this treatment.

Thousands of people suffer from nausea with pregnancy each year. Nausea can be alleviated with cannabidiol (CBD), a primary component of cannabis that is widely available. However, it is unknown how fetal CBD exposure affects embryonic development and postnatal outcomes. CBD binds and activates receptors that are expressed in the fetal brain and are important for brain development, including serotonin receptors (5HT), voltage-gated potassium (Kv)7 receptors, and the transient potential vanilloid 1 receptor (TRPV1). Excessive activation of each of these receptors can disrupt neurodevelopment. Here, we test the hypothesis that fetal CBD exposure in mice alters offspring neurodevelopment and postnatal behavior. We administered 50 mg/kg CBD in sunflower oil or sunflower oil alone to pregnant mice from embryonic day 5 through birth. We show that fetal CBD exposure sensitizes adult male offspring to thermal pain through TRPV1. We show that fetal CBD exposure decreases problem-solving behaviors in female CBD-exposed offspring. We demonstrate that fetal CBD exposure increases the minimum current required to elicit action potentials and decreases the number of action potentials in female offspring layer 2/3 prefrontal cortex (PFC) pyramidal neurons. Fetal CBD exposure reduces the amplitude of glutamate uncaging-evoked excitatory post-synaptic currents, consistent with CBD-exposed female problem-solving behavior deficits. Combined, these data show that fetal CBD exposure disrupts neurodevelopment and postnatal behavior in a sex specific manner.

In recent years, the therapeutic use of cannabis products, especially cannabis oils, has increased significantly, due to the pharmacological potential of their cannabinoids, for the treatment of conditions, such as pain management, cancer, and epilepsy. In Argentina, patients with medical prescriptions can access to cannabis oil, through self-cultivation, a third-person (grower or importer), or a civil organization authorized for that purpose. However, these products remain largely unregulated in Argentina, and information available regarding labeling accuracy, especially cannabidiol (CBD)/ Δ-tetrahydrocannabinol (Δ-THC) concentrations are inconsistent or nonexistent, nor long-term product stability, and lot to lot variability. Understanding these properties is fundamental if these products are to be used in patients with a determinate pathology. Therefore, we analyzed commercially available cannabis oils (n: 500) in Argentina for qualitative and quantitative cannabinoids content. In order to provide a detailed overview of their cannabinoids profiles, and determine Δ-THC, CBD, and cannabinol (CBN) concentrations, samples were diluted and analyzed by gas chromatography- mass spectrometry (GC/MS). Most of the samples tested positive for cannabinoids (n: 469) with Δ-THC and CBD as the predominant cannabinoids. Among products tested, only 29.8% (n: 149) gave specific CBD label claims, and testing indicated a CBD tested positive of 70.5% (n: 105). For products (n: 17) with a THC-free label claim, testing indicated 76.5% (n: 13) of Δ-THC positive, and cannabinoids were not detected in four products. Δ-THC concentrations ranged from 0.1 to 143.0 mg/mL, CBD concentrations from 0.1 to 125.3 mg/mL, and CBN concentrations from 0.04 to 60.10 mg/mL; CBN/ Δ-THC ratios ranged from 0.0012 to 2.31, and CBD/ Δ-THC ratios from 0.0008 to 178.87. Furthermore, the (Δ-THC + CBN)/CBD ratio of most samples was greater than one. In summary, our results indicate that cannabis oil products show wide variability in cannabinoids content, purity, and labeling.

Cannabidiol (CBD) is the primary non-psychoactive chemical from Cannabis Sativa, a plant used for centuries for both recreational and medicinal purposes. CBD lacks the psychotropic effects of Δ9-tetrahydrocannabinol (Δ9-THC) and has shown great therapeutic potential. CBD exerts a wide spectrum of effects at a molecular, cellular, and organ level, affecting inflammation, oxidative damage, cell survival, pain, vasodilation, and excitability, among others, modifying many physiological and pathophysiological processes. There is evidence that CBD may be effective in treating several human disorders, like anxiety, chronic pain, psychiatric pathologies, cardiovascular diseases, and even cancer. Multiple cellular and pre-clinical studies using animal models of disease and several human trials have shown that CBD has an overall safe profile. In this review article, we summarize the pharmacokinetics data, the putative mechanisms of action of CBD, and the physiological effects reported in pre-clinical studies to give a comprehensive list of the findings and major effects attributed to this compound.

Chronic neuropathic pain (CNP) is a vast world health problem often associated with the somatosensory domain. This conceptualization is problematic because, unlike most other sensations that are usually affectively neutral and may present emotional, affective, and cognitive impairments. Neuronal circuits that modulate pain can increase or decrease painful sensitivity based on several factors, including context and expectation. The objective of this study was to evaluate whether subchronic treatment with Cannabidiol (CBD; 0.3, 3, and 10 mg/kg intraperitoneal route - i.p., once a day for 3 days) could promote pain-conditioned reversal, in the conditioned place preference (CPP) test, in male Wistar rats submitted to chronic constriction injury (CCI) of the sciatic nerve. Then, we evaluated the expression of astrocytes and microglia in animals treated with CBD through the immunofluorescence technique. Our results demonstrated that CBD promoted the reversal of CPP at 3 and 10 mg/kg. In CCI animals, CBD was able to attenuate the increase in neuronal hyperactivity, measured by FosB protein expression, in the regions of the corticolimbic circuit: anterior cingulate cortex (ACC), complex basolateral amygdala (BLA), granular layer of the dentate gyrus (GrDG), and dorsal hippocampus (DH) - adjacent to subiculum (CA1). CBD also prevented the increased expression of GFAP and IBA-1 in CCI animals. We concluded that CBD effects on CNP are linked to the modulation of the aversive component of pain. These effects decrease chronic neuronal activation and inflammatory markers in regions of the corticolimbic circuit.

Pain is common in Parkinson's disease (PD), but effective therapies are limited.

Studies have shown high comorbidity of anxiety disorder and chronic pain; generalized anxiety disorder (GAD) and neuropathic pain are among these pathologies. Cannabidiol (CBD) has been considered a promising treatment for these conditions. This study investigated whether chronic systemic treatment with CBD alters pain in high- (CHF) and low-freezing (CLF) Carioca rats (GAD model) and control rats (CTL) submitted to chronic neuropathic pain. The rats were evaluated in the sensory aspects (von Frey, acetone, and hot plate tests) before the chronic constriction injury of the ischiatic nerve (CCI) or not (SHAM) and on days 13 and 23 after surgery. Chronic treatment with CBD (5 mg/kg daily) was used for ten days, starting the 14th day after surgery. The open field test on the 22nd also evaluated locomotion and anxiety-like behavior. CBD treatment had an anti-allodynic effect on the mechanical and thermal threshold in all lineages; however, these effects were lower in the CHF and CLF lineages. Considering emotional evaluation, we observed an anxiolytic effect in CTL+CCI and CHF+CCI after CBD treatment and increased mobility in CLF+SHAM rats. These results suggest that the CBD mechanical anti-allodynic and emotional effects can depend on anxiety level.

There is a need for more research examining the use of cannabis, tetrahydrocannabinol (THC), and cannabidiol (CBD) products in people with Parkinson's disease (PD), especially given the recent increase in the use of these products.

While cannabidiol (CBD) and 4',7-isoflavandiol (Equol) have been examined individually in various skin studies, the present investigation tested whether topically applied CBD with Equol may yield enhanced effects on human skin biomarkers.

Patients with multiple sclerosis (MS) and spinal cord injury (SCI) commonly sustain central neuropathic pain (NP) and spasticity. Despite a lack of consistent evidence, cannabis-based medicine (CBM) has been suggested as a supplement treatment. We aimed to investigate the effect of CBM on NP and spasticity in patients with MS or SCI. We performed a randomized, double-blinded, placebo-controlled trial in Denmark. Patients aged ≥18 years with NP (intensity >3, ≤9 on a numerical rating scale (NRS0-10) and/or spasticity (>3 on NRS0-10) were randomized to treatment consisting of either delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), a combination of THC&CBD in maximum doses of 22.5 mg, 45 mg and 22.5/45 mg per day, respectively, or placebo. A baseline registration was performed before randomization. Treatment duration was six weeks followed by a one-week phaseout. Primary endpoints were the intensity of patient-reported NP and/or spasticity. Between February 2019 and December 2021, 134 patients were randomized (MS = 119, SCI = 15), where 32 were assigned to THC, 31 to CBD, 31 to THC&CBD, and 40 to placebo. No significant difference was found for: mean pain intensity (THC 0.42 (-0.54-1.38), CBD 0.45 (-0.47-1.38) and THC&CBD 0.16 (-0.75-1.08)), mean spasticity intensity (THC 0.24 (-0.67-1.45), CBD 0.46 (-0.74-1.65), and THC&CBD 0.10 (-1.18-1.39), secondary outcomes (patient global impression of change and quality of life), or any tertiary outcomes. We aimed to include 448 patients in the trial; however, due to COVID-19 and recruitment challenges, fewer were included. Nevertheless, in this four-arm parallel trial, no effect was found between placebo and active treatment with THC or CBD alone or in combination on NP or spasticity in patients with either MS or SCI. The trial was registered with the EU Clinical Trials Register EudraCT (2018-002315-98).

Pain-relief is a long-term research hotspot with huge demand in clinical treatment. The analgesics currently used have several side effects, such as being addictive and causing gastrointestinal bleeding. Therefore, new drugs and targets in analgesic field are both desirable. Transient Receptor Potential Vanilloid 1 (TRPV1) plays an essential role in pain perception and regulation, providing a new strategy for the development of antinociceptive agents. Here, a series of novel TRPV1 agonists were designed and synthesized based on Cannabidiol (CBD), a widely used pain-relieving agent with weak agonistic activity on TRPV1. According to the results of systematic in vitro and in vivo biological assays, compound 10f was finally identified as a promising TRPV1 agonist, with higher target affinity, stronger analgesic activity, and weak side effect of hyperthermia. Molecular docking simulations revealed a significant hydrogen bond interaction between 10f and Arg557, an amino acid residue key to the activity of TRPV1 protein. Taken together, compound 10f can be used as a lead compound for further optimization.

Exosomes are extracellular vesicles (EVs) originating from endosomes that play a role in cellular communication. These vesicles which mimic the parental cells that release them are promising candidates for targeted drug delivery and therapeutic applications against cancer because of their favorable biocompatibility, specific targeting, low toxicity, and immunogenicity. Currently, Delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD) and other cannabinoids (e.g., CBG, THCV, CBC), are being explored for their anticancer and anti-proliferative properties. Several mechanisms, including cell cycle arrest, proliferation inhibition, activation of autophagy and apoptosis, inhibition of adhesion, metastasis, and angiogenesis have been proposed for their anticancer activity. EVs could be engineered as cannabinoid delivery systems for tumor-specificity leading to superior anticancer effects. This review discusses current techniques for EV isolation from various sources, characterization and strategies to load them with cannabinoids. More extensively, we culminate information available on different sources of EVs that have anticancer activity, mechanism of action of cannabinoids against various wild type and resistant tumors and role of CBD in histone modifications and cancer epigenetics. We have also enumerated the role of EVs containing cannabinoids against various tumors and in chemotherapy induced neuropathic pain.

The use of cannabidiol (CBD) for therapeutic purposes is receiving considerable attention, with speculation that CBD can be useful in a wide range of conditions. Only one product, a purified form of plant-derived CBD in solution (Epidiolex), is approved for the treatment of seizures in patients with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex. Appraisal of the therapeutic evidence base for CBD is complicated by the fact that CBD products sometimes have additional phytochemicals (like tetrahydrocannabinol (THC)) present, which can make the identification of the active pharmaceutical ingredient (API) in positive studies difficult. The aim of the present review is to critically review clinical studies using purified CBD products only, in order to establish the upcoming indications for which purified CBD might be beneficial. The areas in which there is the most clinical evidence to support the use of CBD are in the treatment of anxiety (positive data in 7 uncontrolled studies and 17 randomised controlled trials (RCTs)), psychosis and schizophrenia (positive data in 1 uncontrolled study and 8 RCTs), PTSD (positive data in 2 uncontrolled studies and 4 RCTs) and substance abuse (positive data in 2 uncontrolled studies and 3 RCTs). Seven uncontrolled studies support the use of CBD to improve sleep quality, but this has only been verified in one small RCT. Limited evidence supports the use of CBD for the treatment of Parkinson's (3 positive uncontrolled studies and 2 positive RCTs), autism (3 positive RCTs), smoking cessation (2 positive RCTs), graft-versus-host disease and intestinal permeability (1 positive RCT each). Current RCT evidence does not support the use of purified oral CBD in pain (at least as an acute analgesic) or for the treatment of COVID symptoms, cancer, Huntington's or type 2 diabetes. In conclusion, published clinical evidence does support the use of purified CBD in multiple indications beyond epilepsy. However, the evidence base is limited by the number of trials only investigating the acute effects of CBD, testing CBD in healthy volunteers, or in very small patient numbers. Large confirmatory phase 3 trials are required in all indications.

Neuropathic pain is a debilitating condition characterized by abnormal signaling within the nervous system, resulting in persistent and often intense sensations of pain. It can arise from various causes, including traumatic nerve injury, neuropathy, and certain diseases. We present an overview of current and emerging pharmacotherapies for neuropathic pain, focusing on novel drug targets and potential therapeutic agents. Current pharmacotherapies, including tricyclic antidepressants, gabapentinoids, and serotonin norepinephrine re-uptake inhibitors, are discussed, as are emerging treatments, such as ambroxol, cannabidiol, and N-acetyl-L-cysteine. Additionally, the article highlights the need for further research in this field to identify new targets and develop more effective and targeted therapies for neuropathic pain management.

Cannabis use during pregnancy is increasing, with 19-22% of patients testing positive at delivery in Colorado and California. Patients report using cannabis to alleviate their nausea and vomiting, anxiety, and pain. However, preclinical and clinical data highlight harmful effects to offspring physiology and behavior following fetal cannabis exposure. This narrative review identifies potential areas for intervention to decrease cannabis consumption during pregnancy.

Dementia affects individuals older than 65 years. Currently, residential aged care facilities (RACF) use psychotropic medications to manage behavioural and neuropsychiatric symptoms of dementia (BPSD), which are recommended for short-term use and have substantial side effects, including increased mortality. Cannabinoid-based medicines (CBM) have some benefits that inhibit BPSD and cause minimal adverse effects (AEs), yet limited research has been considered with this population. The study aimed to determine a tolerable CBM dose (3:2 delta-9-tetrahydrocannabinol:cannabidiol), and assessed its effect on BPSD, quality of life (QoL) and perceived pain.

Patients suffering from arthritis have limited treatment options for nonoperative management. In search of pain relief, patients have been taking over-the-counter cannabinoids. Cannabidiol (CBD) and cannabichromene (CBC) are minor cannabinoids with reported analgesic and anti-inflammatory properties and have been implicated as potential therapeutics for arthritis-related pain. To this end, we utilized a murine model to investigate the effectiveness of and mechanism by which CBC alone, CBD alone, or CBD and CBC in combination may provide a reduction in arthritis-associated inflammation.

Pain is a common symptom in people with cancer; 30% to 50% of people with cancer will experience moderate-to-severe pain. This can have a major negative impact on their quality of life. Opioid (morphine-like) medications are commonly used to treat moderate or severe cancer pain, and are recommended for this purpose in the World Health Organization (WHO) pain treatment ladder. Pain is not sufficiently relieved by opioid medications in 10% to 15% of people with cancer. In people with insufficient relief of cancer pain, new analgesics are needed to effectively and safely supplement or replace opioids.

Cannabidiol (CBD), a major non-psychoactive phytocannabinoid in cannabis, is an effective treatment for some forms of epilepsy and pain. At high concentrations, CBD interacts with a huge variety of proteins, but which targets are most relevant for clinical actions is still unclear. Here we show that CBD interacts with Na1.7 channels at sub-micromolar concentrations in a state-dependent manner. Electrophysiological experiments show that CBD binds to the inactivated state of Na1.7 channels with a dissociation constant of about 50 nM. The cryo-EM structure of CBD bound to Na1.7 channels reveals two distinct binding sites. One is in the IV-I fenestration near the upper pore. The other binding site is directly next to the inactivated "wedged" position of the Ile/Phe/Met (IFM) motif on the short linker between repeats III and IV, which mediates fast inactivation. Consistent with producing a direct stabilization of the inactivated state, mutating residues in this binding site greatly reduced state-dependent binding of CBD. The identification of this binding site may enable design of compounds with improved properties compared to CBD itself.

Chronic pain constitutes one of the most common chronic complaints that people experience. According to the International Association for the Study of Pain, chronic pain is defined as pain that persists or recurs longer than 3 months. Chronic pain has a significant impact on individuals' well-being and psychosocial health and the economy of healthcare systems as well. Despite the availability of numerous therapeutic modalities, treatment of chronic pain can be challenging. Only about 30% of individuals with non-cancer chronic pain achieve improvement from standard pharmacological treatment. Therefore, numerous therapeutic approaches were proposed as a potential treatment for chronic pain including non-opioid pharmacological agents, nerve blocks, acupuncture, cannabidiol, stem cells, exosomes, and neurostimulation techniques. Although some neurostimulation methods such as spinal cord stimulation were successfully introduced into clinical practice as a therapy for chronic pain, the current evidence for brain stimulation efficacy in the treatment of chronic pain remains unclear. Hence, this narrative literature review aimed to give an up-to-date overview of brain stimulation methods, including deep brain stimulation, motor cortex stimulation, transcranial direct current stimulation, repetitive transcranial magnetic stimulation, cranial electrotherapy stimulation, and reduced impedance non-invasive cortical electrostimulation as a potential treatment for chronic pain.

The conundrum of 's applications for therapeutical purposes is set apart by the hundreds of known and commercially available strains, the social, cultural and historical context, and the legalization of its use for medical purposes in various jurisdictions around the globe. In an era where targeted therapies are continuously being developed and have become the norm, it is imperative to conduct standardized, controlled studies on strains currently cultivated under Good Manufacturing Practices (GMP) certification, a standard that guarantees the quality requirements for modern medical and therapeutic use. Thus, the aim of our study is to evaluate the acute toxicity of a 15.6% THC: <1% CBD, EU-GMP certified, L. in rodents, following the OECD acute oral toxicity guidelines, and to provide an overview of its pharmacokinetic profile. Groups of healthy female Sprague-Dawley rats were treated orally with a stepwise incremental dose, each step using three animals. The absence or presence of plant-induced mortality in rats dosed at one step determined the next step. For the EU GMP-certified L. investigated, we determined an oral LD50 value of over 5000 mg/kg in rats and a human equivalent oral dose of ≈806.45 mg/kg. Additionally, no significant clinical signs of toxicity or gross pathological findings were observed. According to our data, the toxicology, safety and pharmacokinetic profile of the tested EU-GMP-certified L. support further investigations through efficacy and chronic toxicity studies in preparation for potential future clinical applications and especially for the treatment of chronic pain.

Despite advancements in dental pain management, one of the most common reasons for emergency dental care is orofacial pain. Our study aimed to determine the effects of non-psychoactive constituents in the treatment of dental pain and related inflammation. We tested the therapeutic potential of two non-psychoactive constituents, cannabidiol (CBD) and β-caryophyllene (β-CP), in a rodent model of orofacial pain associated with pulp exposure. Sham or left mandibular molar pulp exposures were performed on Sprague Dawley rats treated with either vehicle, the phytocannabinoid CBD (5 mg/kg i.p.) or the sesquiterpene β-CP (30 mg/kg i.p.) administered 1 h pre-exposure and on days 1, 3, 7, and 10 post-exposure. Orofacial mechanical allodynia was evaluated at baseline and post-pulp exposure. Trigeminal ganglia were harvested for histological evaluation at day 15. Pulp exposure was associated with significant orofacial sensitivity and neuroinflammation in the ipsilateral orofacial region and trigeminal ganglion. β-CP but not CBD produced a significant reduction in orofacial sensitivity. β-CP also significantly reduced the expression of the inflammatory markers AIF and CCL2, while CBD only decreased AIF expression. These data represent the first preclinical evidence that non-psychoactive cannabinoid-based pharmacotherapy may provide a therapeutic benefit for the treatment of orofacial pain associated with pulp exposure.

Currently, cannabis is considered an attractive option for the treatment of various diseases, including pain management. Thus, developing new analgesics is paramount for improving the health of people suffering from chronic pain. Safer natural derivatives such as cannabidiol (CBD) have shown excellent potential for the treatment of these diseases. This study aimed to evaluate the analgesic effect of a CBD-rich cannabis extract (CE) encapsulated in polymeric micelles (CBD/PMs) using different pain models. The PEG-PCL polymers were characterized by gel permeation chromatography and H-NMR spectroscopy. PMs were prepared by solvent evaporation and characterized by dynamic light scattering (DLS) and transmission electron microscopy. The analgesic activity of CBD/PMs and nonencapsulated CE rich in CBD (CE/CBD) was evaluated using mouse thermal, chemical, and mechanical pain models. The acute toxicity of the encapsulated CE was determined by oral administration in mice at a dose of 20 mg/kg for 14 days. The release of CBD from the nanoparticles was assessed in vitro using a dialysis experiment. CBD/PMs with an average hydrodynamic diameter of 63.8 nm obtained from a biocompatible polyethylene glycol-block-polycaprolactone copolymer were used as nanocarriers for the extract formulations with 9.2% CBD content, which corresponded with a high encapsulation efficiency of 99.9%. The results of the pharmacological assays indicated that orally administered CBD/PMs were safe and exerted a better analgesic effect than CE/CBD. The micelle formulation had a significant analgesic effect in a chemical pain model, reaching a percentage of analgesia of 42%. CE was successfully encapsulated in a nanocarrier, providing better stability. Moreover, it proved to be more efficient as a carrier for CBD release. The analgesic activity of CBD/PMs was higher than that of free CE, implying that encapsulation is an efficient strategy for improving stability and functionality. In conclusion, CBD/PMs could be promising therapeutics for pain management in the future.

In the United States, cannabis use is rising, including among older adults, as is unintentional ingestion. We describe the case of a 94-year-old woman admitted with altered mental status, diarrhea, and hallucinations. She lived with her family, who had noticed recent confusion with weakness, poor oral intake, and loose bowel movements. In the emergency room, her vital signs revealed mild tachycardia and hypotension. She was lethargic, disoriented, confused, and anxious but could answer simple questions. The attending hospitalist administered the Mini-Cog dementia screening and found that the patient was oriented to herself only and was unable to perform word recall tests or complete a clock drawing. The rest of her physical exam was within normal limits for her age. Despite a workup including urine culture, chest X-ray, and computed tomography scan of her head, no organic source for her mental change was found. After five days of admission, a close relative confessed that they had given the patient cannabis oil (marketed as "pure CBD," i.e., cannabidiol, a nonpsychoactive cannabis derivative widely touted as a remedy for pain, anxiety, and anorexia) in the form of edible brownies to help her with her persistent back pain and poor appetite. We performed a urine drug screen for tetrahydrocannabinol (THC), the psychoactive component of cannabis, which verified cannabis use, as well as exposure to THC. The patient recovered to baseline with supportive care. Currently, there is no governing body or framework for the regulation of cannabis products in the United States. Nonprescription CBD products are not regulated by the US Food and Drug Administration, and these products are not tested for safety, efficacy, or quality. Some producers voluntarily conduct such testing, but there is no regulatory oversight, and consumers may be unaware of the need for testing and/or which testing bodies are credible. Given the rapidly increasing proportion of older adults who are cannabis users, physicians should inquire about outpatient use of cannabis in general and CBD in particular during discussions with patients, even the most elderly.

The phytocannabinoid cannabidiol (CBD) is receiving increasing attention due to its pharmacological properties. Although CBD is extracted from , it lacks the psychoactive effects of Δ9-tetrahydrocannabinol (THC) and has become an attractive compound for pharmacological uses due to its anti-inflammatory, antioxidant, anticonvulsant, and anxiolytic potential. The molecular mechanisms involved in CBD's biological effects are not limited to its interaction with classical cannabinoid receptors, exerting anti-inflammatory or pain-relief effects. Several pieces of evidence demonstrate that CBD interacts with other receptors and cellular signaling cascades, which further support CBD's therapeutic potential beyond pain management. In this review, we take a closer look at the molecular mechanisms of CBD and its potential therapeutic application in the context of cancer, neurodegeneration, and autoimmune diseases.

Cannabidiol (CBD) is the second most abundant component of the plant Cannabis sativa. Currently, CBD is approved for Lennox-Gastaut and Dravet syndrome and newly for tuberous sclerosis complex. However, based on the available data, CBD migth have a broad spectrum of potential therapeutic uses. Therefore, the aim of this review was to summarize the evidence on the effects of CBD on pain and inflammation of various causes. PubMed and Web of Science databases were searched until January 2023. The medical keyword term "cannabidiol" was combined with "pain", "arthritis", and "inflammation". Based on the initial search for these terms, 9, 5, and 5 relevant publications have been selected. Based on the available data, it is not possible to draw a clear conclusion about the effect of CBD to releave pain, because each study used a different route of administration or treatment regimen. The studies also differed in etiopathogenesis of pain (chronic, neuropathic, and possibly inflammatory pain), and in general included only small number of subjects. In case of anti-inflammatory qualities of CBD, its effect on the intestinal system is negligible. On the other hand, positive treatment results were observed in all publications dealing with the effect of CBD on arthritis.

Cannabidiol (CBD) has several potential benefits and therapeutic uses, especially in pain, inflammation, and anxiety. CBD has high hydrophobicity and very low solubility in water. CBD has also shown exceptionally low oral-gastrointestinal (oral-GI) bioavailability. In this study, we aimed to examine the oral gastrointestinal absorption and subsequent bioavailability of CBD in a nanoemulsion formulation prepared by Pressure BioSciences' UltraShear technology.

Nabiximols is a commercially available cannabinoid buccal spray containing 2.7 mg Δ9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD) per spray. It is approved by Health Canada for adults with cancer pain or spasticity/neuropathic pain related to multiple sclerosis. Despite a lack of published studies regarding the use of nabiximols in children, it is being used in clinical practice for indications of pain, nausea/vomiting, and spasticity.

Estimated rates of past-month cannabidiol (CBD) use in the general public are 13-26% and emerging research examines CBD as a potential adjunct treatment for several medical conditions, including stress-related disorders (e.g., depression, anxiety, and chronic pain). However, little is known about the effects of different CBD products on self-reported stress. The present study compared the effects of two delta-9-tetrahydrocannabinol (THC)-free CBD tincture products - (1) an isolate CBD oil and (2) a broad spectrum CBD oil - on self-ratings of effectiveness of the product and ability to manage stress.

Little is known about the distribution of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) to patients participating in state medical cannabis programs. The Minnesota cannabis program requires third-party testing of products with limited formulations of cannabis for distribution to patients.

The aim was to demonstrate the safety and tolerability of cannabidiol (CBD) with Δ9-THC in patients with moderate to severe chronic back or neck pain unresponsive to over-the-counter non-opioid analgesics.

Pulmonary arterial hypertension occurs as a result of vascular remodeling and dysregulation of endothelial cells that narrows small pulmonary arteries and raises precapillary pressures. Pulmonary arterial hypertension is a rare and progressive disease characterized by dyspnea, chest pain, and syncope. Parenteral treprostinil is indicated for the treatment of pulmonary arterial hypertension to diminish symptoms associated with exercise. Up to 92% of patients treated with treprostinil via subcutaneous delivery experienced infusion site pain and approximately 23% discontinued treatment due to site pain. Cannabidiol salve may have analgesic and anti-inflammatory properties and could be an additional option for patients with infusion site pain.

Cannabis extracts are being increasingly used to mitigate chronic pain. Current guidelines for their prescription rely on Δ-tetrahydrocannabinol (THC) and cannabidiol (CBD) content as well as the ratio of these major cannabinoids present in the blend. Here we assessed whether these descriptors were representative of product effectiveness to produce a desired outcome such as analgesia. In this study, we used a rat model of diabetic neuropathy and assessed the reduction in mechanical allodynia following intrathecal injection of pure THC, pure CBD, a 1:1 mix of these compounds and a "balanced" chemotype II cannabis extract. Engagement of endocannabinoid targets by different treatments was investigated using CB1 (AM251) and CB2 (AM630) receptor antagonists as well as a TRPV1 channel blocker (capsazepine). Antinociceptive responses induced by an equivalent amount of THC administered in its pure form, as a THC:CBD mix or as a "balanced" extract were distinct. Furthermore, the 1:1 THC:CBD mix and the balanced extract had not only different response profiles but their relative engagement of CB1, CB2 receptors and TRPV1 channels was distinct. These findings indicate that antinociceptive responses and targets engaged by blended cannabinoids are composition-specific, and cannot be simply inferred from THC and CBD contents. This information may have implications in relation to the way medicinal cannabis products are prescribed.

Neuropathic pain is experienced due to injury to the nerves, underlying disease conditions or toxicity induced by chemotherapeutics. Multiple factors can contribute to neuropathic pain such as central nervous system (CNS)-related autoimmune and metabolic disorders, nerve injury, multiple sclerosis and diabetes. Hence, development of pharmacological interventions to reduce the drawbacks of existing chemotherapeutics and counter neuropathic pain is an urgent unmet clinical need. Cannabinoid treatment has been reported to be beneficial for several disease conditions including neuropathic pain. Cannabinoids act by inhibiting the release of neurotransmitters from presynaptic nerve endings, modulating the excitation of postsynaptic neurons, activating descending inhibitory pain pathways, reducing neural inflammation and oxidative stress and also correcting autophagy defects. This review provides insights on the various preclinical and clinical therapeutic applications of cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN) in various diseases and the ongoing clinical trials for the treatment of chronic and acute pain with cannabinoids. Pharmacological and genetic experimental strategies have well demonstrated the potential neuroprotective effects of cannabinoids and also elaborated their mechanism of action for the therapy of neuropathic pain.

Self-dosing of off-the-shelf cannabidiol (CBD) for a myriad of health conditions is common in the USA. These CBD products are often mislabeled, suggesting that much less or much more CBD is being consumed than indicated on the label. This study examined the relationship between long-term self-dosing of CBD and (a) indications and, when a verified concentration of CBD is being consumed, (b) the daily CBD dosage, (c) the impact on general health and symptoms, and (d) over-the-counter (OTC) and prescription (Rx) drug usage.

We measure for the first time the associations between subjective patient experiences of feeling "high" and treatment outcomes during real-time flower consumption sessions. Our study uses data from the mobile health app, Releaf App™, through which 1,882 people tracked the effects of flower on a multitude of health conditions during 16,480 medical cannabis self-administration sessions recorded between 6/5/2016 and 3/11/2021. Session-level reported information included plant phenotypes, modes of administration, potencies, baseline and post-administration symptom intensity levels, total dose used, and real-time side effect experiences. Patients reported feeling high in 49% of cannabis treatment sessions. Using individual patient-level fixed effects regression models and controlling for plant phenotype, consumption mode, tetrahydrocannabinol (THC) and cannabidiol (CBD) potencies, dose, and starting symptom level, our results show that, as compared to sessions in which individuals did not report feeling high, reporting feeling high was associated with a 7.7% decrease in symptom severity from a mean reduction of -3.82 on a 0 to 10 analog scale (coefficient = -0.295, < 0.001) with evidence of a 14.4 percentage point increase ( < 0.001) in negative side effect reporting and a 4.4 percentage point ( < 0.01) increase in positive side effect reporting. Tetrahydrocannabinol (THC) levels and dose were the strongest statistical predictors of reporting feeling high, while the use of a vaporizer was the strongest inhibitor of feeling high. In symptom-specific models, the association between feeling high and symptom relief remained for people treating pain ( < 0.001), anxiety ( < 0.001), depression ( < 0.01) and fatigue ( < 0.01), but was insignificant, though still negative, for people treating insomnia. Although gender and pre-app cannabis experience did not appear to affect the relationship between high and symptom relief, the relationship was larger in magnitude and more statistically significant among patients aged 40 or less. The study results suggest clinicians and policymakers should be aware that feeling high is associated with improved symptom relief but increased negative side effects, and factors such as mode of consumption, product potency, and dose can be used to adjust treatment outcomes for the individual patient.

While cannabis-based medicine is being commonly used in patients with movement disorders, there is a scarcity of publications regarding the effect of cannabis on dystonia. We aimed to describe medical cannabis use in patients with dystonia and related pain.

Canine osteoarthritis (OA) is a degenerative disease with chronic inflammation of internal and external joint structures in dogs. spp. contains cannabidiol (CBD), a substance known for various potential indications, such as pain relief and anti-inflammatory in various types of animals, including dogs with OA. As CBD is increasingly in the spotlight for medical use, we aimed to perform a systematic review and meta-analysis to evaluate the efficacy and safety of CBD in treating canine OA.

Osteoarthritis is a common disease in dogs resulting in chronic pain and decreased wellbeing. Common analgesics such as non-steroidal anti-inflammatories may fail to control pain and can produce major adverse effects. Study objectives were to evaluate pharmacokinetics, therapeutic efficacy, and safety of subcutaneous liposomal-cannabidiol (CBD) as an additional analgesic therapy in dogs suffering from naturally-occurring osteoarthritis.

Cannabidiol (CBD) is a non-intoxicating phytochemical from that is increasingly used to manage pain. The potential for CBD to ameliorate dimensional behavior symptoms occurring in multiple psychiatric disorders was suggested, including social interaction impairments. To test this hypothesis, adult male BTBRT+Itpr3tf/J (BTBR) mice, a model of idiopathic autism exhibiting social preference deficits and restrictive repetitive behaviors, were acutely treated with vehicle or 0.1, 1, or 10 mg/kg CBD. Social interaction preference was assessed 50 min after treatment, followed by social novelty preference at 60 min, marble burying at 75 min and social dominance at 120 min. CBD (10 mg/kg) enhanced BTBR social interaction but not social novelty preference, marble burying or dominance, with serum levels = 29 ± 11 ng/mg at 3 h post-injection. Next, acute 10 mg/kg CBD was compared to vehicle treatment in male serotonin transporter (SERT) knock-out mice, since SERT deficiency is an autism risk factor, and in their wildtype background strain controls C57BL/6J mice. CBD treatment generally enhanced social interaction preference and attenuated social novelty preference, yet neither marble burying nor dominance was affected. These findings show acute treatment with as little as 10 mg/kg purified CBD can enhance social interaction preference in male mice that are otherwise socially deficient.

In the last 5 years, interest has grown in using phytocannabinoids, particularly cannabidiol (CBD), in veterinary medicine to treat several pathologies, including pain, epilepsy, anxiety, nausea, anorexia, skin lesions, and even some types of cancer, among others. Indeed, due to a positive perception of CBD use, many pet owners are increasingly requesting this option to relieve their pets, and many veterinarians are exploring this possibility for their patients. Besides the widespread empiric use of CBD in pets, the research is trying to obtain proof of its efficacy and lack of adverse effects and to know its pharmacokinetics to define an appropriate posology. This review summarizes all data published so far about the canine pharmacokinetics, efficacy, and tolerability of CBD and cannabidiolic acid (CBDA). Despite a certain number of available pharmacokinetic studies, the kinetic profile of CBD has yet to be fully known, probably because of the very different experimental conditions. In terms of efficacy, most studies have tested CBD' ability to relieve osteoarthritic pain. In contrast, few studies have evaluated its role in epilepsy, behavioral disorders, and skin lesions. From obtained results, some evidence exists supporting the beneficial role of CBD. Nevertheless, the limited number of published studies and the occurrence of bias in almost all require caution in interpreting findings. From tolerability studies, CBD' side effects can be classified as mild or unremarkable. However, studies were prevalently focused on short- to medium-term treatment, while CBD is usually employed for long-term treatment. Further studies are warranted to define better whether CBD could be a valid adjunct in canine treatment.

Cannabidiol (CBD) products gain increasing popularity amongst animal owners and veterinarians as an alternative remedy for treatment of stress, inflammation or pain in horses. Whilst the use of cannabinoids is banned in equine sports, there is limited information available concerning CBD detection times in blood or urine. The aim of this study was to determine the pharmacokinetic properties of CBD following oral administration in the horse to assist doping control laboratories with interpreting CBD analytical results. Part 1: dose escalation study: Single oral administration of three escalating doses of CBD paste (0.2 mg/kg,  = 3 horses; 1 mg/kg,  = 3; 3 mg/kg,  = 5) with >7 days wash-out periods in between. Part 2: multiple dose study: oral administration of CBD paste (3 mg/kg,  = 6) twice daily for 15 days. Multiple blood and urine samples were collected daily throughout both studies. Following study part 2, blood and urine samples were collected for 2 weeks to observe the elimination phase. Concentrations of CBD, its metabolites and further cannabinoids were evaluated using gas-chromatography/tandem-mass-spectrometry. Pharmacokinetic parameters were assessed via two approaches: population pharmacokinetic analysis using a nonlinear mixed-effects model and non-compartmental analysis. AUC and were tested for dose proportionality. During the elimination phase, the CBD steady-state urine to serum concentration ratio (Rss) was calculated. Oral CBD medication was well-tolerated in horses. Based on population pharmacokinetics, a three-compartment model with zero-order absorption most accurately described the pharmacokinetic properties of CBD. High volumes of distribution into peripheral compartments and high concentrations of 7-carboxy-CBD were observed in serum. Non-compartmental analysis identified a of 12.17 ± 2.08 ng/mL after single administration of CBD (dose: 3 mg/kg). AUC showed dose proportionality, increase for leveled off at higher doses. Following multiple doses, the CBD terminal half-life was 161.29 ± 43.65 h in serum. Rss was 4.45 ± 1.04. CBD is extensively metabolized and shows high volumes of tissue distribution with a resulting extended elimination phase. Further investigation of the potential calming and anti-inflammatory effects of CBD are required to determine cut-off values for medication control using the calculated Rss.