SCIENTIFIC RESEARCH PUBLICATIONS

Despite heightened consumer interest in cannabinoids such as cannabidiol (CBD) and tetrahydrocannabinol (THC), little is known about public perceptions regarding their medical use and potential for abuse, particularly relative to commonly used medications. Using data from 1,050 U.S. adult respondents from a national survey conducted in 2019, this study found that more than half of respondents perceived CBD, THC, hemp, and marijuana as having medical use. They also perceived the potential for abuse of CBD, THC, hemp, and marijuana as significantly less than potential for abuse of commonly prescribed anti-anxiety and pain medications. At the nexus of medical use and potential abuse, public perceptions classified CBD and hemp as similar to over-the-counter pain relief medications such as Advil and Tylenol and did not classify marijuana as a Schedule I substance. Slightly more than 20% of respondents reported having consumed CBD and/or THC. CBD was consumed more than THC to reduce pain while THC was consumed more than CBD for recreation. There were no differences in the types of medications they were replacing with CBD and THC.

Marijuana has been used to treat medical disease since well before the 1800s. Recently, increased use of cannabinoids, the chemical components of marijuana, have been seen to treat neurologic illness in children and adults. Unfortunately, data are lacking in treating most neurologic illnesses except in the field of epilepsy and pain from spasticity in multiple sclerosis. Therefore, formal conclusions about the potential efficacy, benefit, and adverse effects for most marijuana based products cannot be made at this time. Further research using gold standard scientific methodology should be performed to help address potential uses and safety for cannabinoids to treat neurologic illnesses.

The therapeutic potential of cannabidiol (CBD) has been explored to treat several pathologies, including those in which pain is prevalent. However, the oral bioavailability of CBD is low owing to its high lipophilicity and extensive first-pass metabolism. Considering the ability of the nasal route to prevent liver metabolism and increase brain bioavailability, we developed nanostructured lipid carriers (NLCs) for the nasal administration of CBD. We prepared particles with a positively charged surface, employing stearic acid, oleic acid, Span 20, and cetylpyridinium chloride to obtain mucoadhesive formulations. Characterisation of the CBD-NLC dispersions showed uniform nano-sized particles with diameters smaller than 200 nm, and high drug encapsulation. The mucoadhesion of cationic particles has been related to interactions with negatively charged mucin. Next, we added in-situ gelling polymers to the CBD-NLC dispersion to obtain a CBD-NLC-gel. A thermo-reversible in-situ forming gel was prepared by the addition of Pluronics. CBD-NLC-gel was characterised by its gelation temperature, rheological behaviour, and mucoadhesion. Both formulations, CBD-NLC and CBD-NLC-gel, showed high mucoadhesion, as assessed by the flow-through method and similar in vitro drug release profiles. The in vivo evaluation showed that CBD-NLC dispersion (without gel), administered intranasally, produced a more significant and lasting antinociceptive effect in animals with neuropathic pain than the oral or nasal administration of CBD solution. However, the nasal administration of CBD-NLC-gel did not lessen mechanical allodynia. These findings demonstrate that in-situ gelling hydrogels are not suitable vehicles for highly lipophilic drugs such as CBD, while cationic CBD-NLC dispersions are promising formulations for the nasal administration of CBD.

Though known as a medicinal herb for centuries, the recent legalization of cannabinoids across many states has ushered in a new era where cannabinoids have become a popular treatment option amongst clinicians and patients alike. Cannabinoids have demonstrated efficacy in wound healing, reducing inflammation, ameliorating pain, and have shown potential as an anti-tumor agent. As a result, cannabinoids have been rapidly woven into the fabric of modern medicine. However, the utility of cannabinoids in dermatologic surgery has not been explored to date. In this paper, we review the current literature to discuss the potential impact of cannabinoid use in dermatologic surgery.

The objective of this study was to provide preliminary data describing the safety and effect of cannabidiol (CBD) for symptom relief of canine osteoarthritis-associated pain in a clinical setting using objective outcome measures. Twenty-three client-owned dogs with naturally occurring osteoarthritis of appendicular joints completed this prospective, double-blinded, crossover, placebo-controlled study. Baseline data were acquired for 4 wk, followed by random allocation to either placebo or CBD treatment for 6 wk, followed by 6 wk with the opposite treatment. Outcome measures included objective gait analysis, activity counts (via accelerometry) and clinical metrology instruments. There were no differences noted between groups at any time point for any of the recorded outcome measures. Adverse events associated with CBD administration included elevation in liver enzymes (n =14) and vomiting (n =2).

Cannabinoids are a group of chemicals that bind to receptors in the human body and, in turn, modulate the endocannabinoid system (ECS). They can be endogenously produced, synthetic, or derived from the plant . Research over the past several decades has shown that the ECS is a cellular communication network essential to maintain multiple biological functions and the homeostasis of the body. Indeed, cannabinoids have been shown to influence a wide variety of biological effects, including memory, pain, reproduction, bone remodeling or immunity, to name a few. Unsurprisingly, given these broad physiological effects, alterations of the ECS have been found in different diseases, including cancer. In recent years, the medical use of cannabis has been approved in different countries for a variety of human conditions. However, the use of these compounds, specifically as anticancer agents, remains controversial. Studies have shown that cannabinoids do have anticancer activity in different tumor types such as breast cancer, melanoma, lymphoma and adult brain cancer. Specifically, phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) has been shown to induce apoptosis and inhibit proliferation of adult cancer cells, as well as modulate angiogenesis and metastasis. Despite increasing evidence that cannabinoids elicit antitumor effects in adult cancers, there is minimal data available on their effects in children or in pediatric cancers despite public and clinical demand for information. Here we describe a comprehensive and critical review of what is known about the effects of cannabinoids on pediatric cancers, highlight current gaps in knowledge and identify the critical issues that need addressing before considering these promising but controversial drugs for use in pediatric oncology.

Vaping has become an increasingly popular alternative to smoking in recent years. We present a rare and unusual case of upper airway bleeding caused by inhalation of a cannabidiol (CBD) oil-based vape due to a chemical burn. There are no case reports of this injury in the literature, and we discuss the clinical presentation, diagnosis and our management of this potentially life-threatening injury. A 27-year-old man presented to the accident and emergency department after using a CBD oil vape. After one inhalation of the CBD oil vape, the patient experienced immediate onset pain in the oropharynx, dyspnoea, expectoration of blood and hoarseness. The patient had used a CBD oil vape four hours earlier that evening for the first time, which was procured from an unregulated online source. The patient was referred to the Ear, Nose and Throat (ENT) team where the examination of oropharynx identified a posterior pharyngeal bleeding point. Flexible nasal endoscopy was undertaken showing profound erythema and inflammation throughout the oropharynx and posterior pharyngeal wall. The mucous membranes had been detached leaving an exposed bleeding submucosa. The patient was commenced on three cycles of back-to-back adrenaline nebulisers (1:1000 adrenaline in 5ml of 0.9% NaCl), 6.6mg dexamethasone intravenously and hydrogen peroxide gargles (5ml of 3% hydrogen peroxide in 10ml of water) three times a day. There were early involvement and review of the airway by the anaesthetic and intensive care teams, which was deemed safe at the time. A plan was made for a definitive airway if bleeding reoccurred. Upper airway bleeding can present as a rare form of vape-induced injury and should be considered part of the differential diagnosis particularly in those using CBD oil vapes. History taking is pertinent and patients should be questioned on the specific vape liquids used. Airway stabilisation is the priority with early involvement of the multi-disciplinary team including anaesthetists, intensive care specialists and ENT surgeons.

Multiple sclerosis (MS) is the most common chronic autoimmune disease of the central nervous system. Efficacy of treatments for MS is associated with risk of adverse effects, and effective and well-tolerated drugs remain a major unmet need. Cannabis (Cannabis sativa L., fam. Cannabaceae) and cannabinoids are popular among MS patients to treat spasticity and pain. Cannabinoids are endowed with remarkable immunomodulating properties, and in particular the non-psychotropic cannabinoid cannabidiol (CBD) is increasingly recognized as anti-inflammatory and immunosuppressive, nevertheless with excellent tolerability even at high doses. In this systematic review, we retrieved and critically evaluated available evidence regarding the immune and disease-modifying effects of CBD in experimental autoimmune encephalomyelitis (EAE) and in MS. Evidence in rodent models of EAE strongly supports CBD as effective, while clinical evidence is still limited and usually negative, due to paucity of studies and possibly to the use of suboptimal dosing regimens. Better characterization of targets acted upon by CBD in MS should be obtained in ex vivo/in vitro studies in human immune cells, and higher doses should be tested in well-designed clinical trials with clinically relevant efficacy endpoints. Graphical Abstract.

Cannabidiol (CBD) is widely advertised as helpful for chronic pain management but research is limited. Using a cross-sectional, anonymous survey, we examined patterns of naturalistic CBD use among individuals with fibromyalgia (FM) and other chronic pain conditions. Our objective was to better understand rates of CBD use, reasons for use and discontinuation, communication with healthcare professionals about CBD, and perceptions of CBD effectiveness and safety among people with FM. After excluding incomplete surveys, our study population consisted of N = 2,701 participants with fibromyalgia, primarily in the United States. Overall, 38.1% reported never using CBD, 29.4% reported past CBD use, and 32.4% reported current CBD use. Past-year cannabis use was strongly associated with past or current CBD use. Those using CBD typically did so due to inadequate symptom relief, while those not using CBD typically cited safety concerns as their reason for not using CBD. Two-thirds of participants disclosed CBD use to their physician, although only 33% asked for physician advice on using CBD. Participants used CBD for numerous FM-related symptoms (most commonly pain), and generally reported slight to much improvement across symptom domains. Around half of participants reported side effects, which were typically minor. Our findings are limited by selection bias and our cross-sectional design, which prevents causal associations. In conclusion, CBD use is common among individuals with FM and many individuals using CBD report improvements across numerous FM-related symptoms. Our findings highlight the need for additional rigorous studies to better understand CBD's potential for FM management. PERSPECTIVE: This article indicates that CBD use is common among people with fibromyalgia, and the results suggest that many derive benefit from using CBD across multiple symptoms domains. Clinicians should discuss CBD use with fibromyalgia patients, and future studies are needed to rigorously assess CBD's therapeutic value for fibromyalgia symptoms.

Cannabis has been widely used as a medicinal plant for millennia; however, studies related to its main components were first conducted in 1960. Subsequently, laboratories have produced new components and structures related to its active biological properties. Countries that have approved the medicinal use of cannabis impose regulations that govern its clinical and scientific use. One means of administering medicinal cannabis is via a magistral preparation that must have a medical prescription and be prepared in an establishment that meets quality standards to ensure the quantities of its main components, such as tetrahydrocannabinol (THC) and cannabidiol (CBD). Furthermore, suppliers must have a clear indication of its use in the patient before prescription. This review shows the published evidence regarding the clinical use of medicinal cannabis magistral preparations in the management of post-chemotherapy nausea and vomiting, neuropathic pain in multiple sclerosis, and anorexia and cachexia in patients with HIV.

Cannabidiol (CBD) products lacking regulatory approval are being used to self-treat a myriad of conditions and for their unsubstantiated health benefits. The scientific evidence supporting these claims largely arises not from controlled clinical trials, but from the recognition that CBD has numerous biological targets. Yet, CBD is commonly consumed and often in over-the-counter products that are unapproved and of unknown composition. Epidiolex® is the only product that has undergone rigorous pharmacokinetic assessment and testing in clinical trials; it was approved as a non-scheduled drug by the U.S. Food and Drug Administration for the treatment of intractable childhood-onset seizures. However, studies investigating CBD for other medical conditions are limited in number and often lack the scientific rigor, controls, or sample sizes required to draw clinically meaningful conclusions. Although Epidiolex® is safe for human consumption, recent changes in regulation of commercially available CBD products have resulted in limited quality control and products marketed with unknown CBD bioavailability. Even scientifically rigorous studies have used different sources of CBD and different suspension vehicles for administration, making it difficult to compare results among studies and resolve mixed outcomes.

Use of cannabis is increasing in a variety of populations in the United States; however, few investigations about how and for what reasons cannabis is used in older populations exist.

Cannabis has long been used for healing and recreation in several regions of the world. Over 400 bioactive constituents, including more than 100 phytocannabinoids, have been isolated from this plant. The non-psychoactive cannabidiol (CBD) and the psychoactive Δ-tetrahydrocannabinol (Δ-THC) are the major and widely studied constituents from this plant. Cannabinoids exert their effects through the endocannabinoid system (ECS) that comprises cannabinoid receptors (CB1, CB2), endogenous ligands, and metabolizing enzymes. Several preclinical studies have demonstrated the potential of cannabinoids against leukemia, lymphoma, glioblastoma, and cancers of the breast, colorectum, pancreas, cervix and prostate. Cannabis and its constituents can modulate multiple cancer related pathways such as PKB, AMPK, CAMKK-β, mTOR, PDHK, HIF-1α, and PPAR-γ. Cannabinoids can block cell growth, progression of cell cycle and induce apoptosis selectively in tumour cells. Cannabinoids can also enhance the efficacy of cancer therapeutics. These compounds have been used for the management of anorexia, queasiness, and pain in cancer patients. Cannabinoid based products such as dronabinol, nabilone, nabiximols, and epidyolex are now approved for medical use in cancer patients. Cannabinoids are reported to produce a favourable safety profile. However, psychoactive properties and poor bioavailability limit the use of some cannabinoids. The Academic Institutions across the globe are offering training courses on cannabis. How cannabis and its constituents exert anticancer activities is discussed in this article. We also discuss areas that require attention and more extensive research.

This study aimed to assess the quality of online resources pertaining to cannabidiol (CBD) for the nonoperative management of hip and knee arthritis.

In the USA, opioid analgesic use and overdoses have increased dramatically. One rapidly expanding strategy to manage chronic pain in the context of this epidemic is medical cannabis. Cannabis has analgesic effects, but it also has potential adverse effects. Further, its impact on opioid analgesic use is not well studied. Managing pain in people living with HIV is particularly challenging, given the high prevalence of opioid analgesic and cannabis use. This study's overarching goal is to understand how medical cannabis use affects opioid analgesic use, with attention to Δ9-tetrahydrocannabinol and cannabidiol content, HIV outcomes and adverse events.

This systematic review focused on the efficacy of topical products in reducing temporomandibular joint disorder (TMD)-associated pain, in comparison to placebo or control interventions. The EMBASE, Web of Science, Cochrane Library, and MEDLINE via PubMed databases were searched for randomized controlled trials (RCTs) using topical interventions in adults diagnosed with TMD. The pain intensity was the primary outcome, and other clinical findings were the secondary outcomes. The risk of bias was evaluated according to the Cochrane's handbook. The search up to February 7, 2020 identified a total of 496 unduplicated references. Nine RCTs with 355 adult patients diagnosed with TMD were included. The meta-analysis did not show a significant reduction in baseline pain intensity in the nonsteroidal anti-inflammatory drug (NSAIDs) group, when compared to the placebo group (P = 0.288). One study demonstrated a statistically significant pain score decrease for Theraflex-TMJ compared to placebo after 10 d of treatment (P = 0.003) and follow-up, 5 d after the last application (P = 0.027). Ping On reduced pain at 4 weeks of application (P < 0.001) but not after 7 d of application (P = 0.136). In one study, cannabidiol (CBD) significantly improved the pain intensity compared to placebo (P < 0.001). However, no differences were found with capsaicin in the two studies (P = 0.465). Evidence was of low quality because the studies were considered as having an unclear or a high risk of bias and a small number of studies were analyzed. The evidence is not sufficient to support the use of topical NSAIDs and capsaicin, and limited evidence was found for Threraflex-TMJ, bee venom, Ping On, and CBD, with only one study reporting for each. Additional studies are recommended to validate these results.

Cannabis is increasingly being used for medicinal purposes but remains outside Western medical practice. Data on perioperative use and outcomes are scarce. Few surgeons receive training regarding legal endorsement, reported medicinal benefits, and potential risks, making it difficult to advise patients. Guidelines and additional research are needed.

Cannabis sativa is a well-known plant which has been of benefit since ancient times in several medicinal systems, including Chinese, Indian, Greek and Egyptian ones. Although C. sativa is one of the most investigated medicinal plants in the world, it faces the most controversial of issues for its legalization as a medication. C. sativa contains several hundreds of phytoconstituents including the infamous «cannabinoid." It is necessary to properly understand the medicinal importance of these phytochemicals and spread awareness among the countries where it's still facing legal complexities. The current review is focusing on most recent literature pertaining to the various applications of cannabinoids with a special focus on medicinal aspect of the phytochemicals. Peer reviewed articles focusing on the importance of cannabis and cannabinoids were the target of this review. Articles were selected based on the relevance to the general scope of the work i.e. application of cannabinoids. Cannabinoids can truly be regarded as wonder drug keeping their immense diversity of usage but unfortunately, many of the mares never researched biologically or pharmacologically due to their low yield in the plant. However, the approval of some cannabinoids by the FDA (along with other recognized national medical health systems) has opened the horizons for the explicit use of these natural drugs in medicines such as Epidiolex® (cannabidiol used for the treatment of severe forms of epilepsy) and Sativex®('Δ9 -tetrahydrocannabinol and cannabidiol' used for the treatment of spasticity caused by multiple sclerosis, aka: MS.) Many pharmacological properties of C. sativa are attributed to cannabidiol (CBD), a non-psychoactive component, along with Δ9 -tetrahydrocannabinol (Δ9 -THC), a psychoactive component. This review addresses the most important application or current utilization of cannabinoids in a variety of treatments such as: chronic pain, cancer, emesis, anorexia, irritable bowel syndrome, communicative diseases, glaucoma and central nervous system disorders. The biosynthetic pathway of cannabinoids is also discussed. In short, this plant has a myriad of bioactive compounds which have the potential to increase the list of approved cannabinoids suitable for therapy.

Cannabidiol (CBD) is the second most abundant component of the Cannabis plant and is known to have effects distinct from Δ -tetrahydrocannabinol (THC). Many studies that examined the behavioral effects of CBD concluded that it lacks the psychotomimetic effects attributed to THC. However, CBD was shown to have a broad spectrum of effects on several conditions such as anxiety, inflammation, neuropathic pain, and epilepsy. It is currently thought that CBD engages different targets and hence CBD's effects are thought to be due to multiple molecular mechanisms of action. A well-accepted set of targets include GPCRs and ion channels, with the serotonin 5-HT receptor and the transient receptor potential cation channel TRPV1 channel being the two main targets. CBD has also been thought to target G protein-coupled receptors (GPCRs) such as cannabinoid and opioid receptors. Other studies have suggested a role for additional GPCRs and ion channels as targets of CBD. Currently, the clinical efficacy of CBD is not completely understood. Evidence derived from randomized clinical trials, in vitro and in vivo models and real-world observations support the use of CBD as a drug treatment option for anxiety, neuropathy, and many other conditions. Hence an understanding of the current status of the field as it relates to the targets for CBD is of great interest so, in this review, we include findings from recent studies that highlight these main targets.

The Cannabis sativa plant contains more than 120 cannabinoids. With the exceptions of ∆-tetrahydrocannabinol (∆-THC) and cannabidiol (CBD), comparatively little is known about the pharmacology of the less-abundant plant-derived (phyto) cannabinoids. The best-studied transducers of cannabinoid-dependent effects are type 1 and type 2 cannabinoid receptors (CB1R, CB2R). Partial agonism of CB1R by ∆-THC is known to bring about the 'high' associated with Cannabis use, as well as the pain-, appetite-, and anxiety-modulating effects that are potentially therapeutic. CB2R activation by certain cannabinoids has been associated with anti-inflammatory activities. We assessed the activity of 8 phytocannabinoids at human CB1R, and CB2R in Chinese hamster ovary (CHO) cells stably expressing these receptors and in C57BL/6 mice in an attempt to better understand their pharmacodynamics. Specifically, ∆-THC, ∆-tetrahydrocannabinolic acid (∆-THCa), ∆-tetrahydrocannabivarin (THCV), CBD, cannabidiolic acid (CBDa), cannabidivarin (CBDV), cannabigerol (CBG), and cannabichromene (CBC) were evaluated. Compounds were assessed for their affinity to receptors, ability to inhibit cAMP accumulation, βarrestin2 recruitment, receptor selectivity, and ligand bias in cell culture; and cataleptic, hypothermic, anti-nociceptive, hypolocomotive, and anxiolytic effects in mice. Our data reveal partial agonist activity for many phytocannabinoids tested at CB1R and/or CB2R, as well as in vivo responses often associated with activation of CB1R. These data build on the growing body of literature showing cannabinoid receptor-dependent pharmacology for these less-abundant phytocannabinoids and are critical in understanding the complex and interactive pharmacology of Cannabis-derived molecules.

Cannabis has a long history of medical use. Although there are many cannabinoids present in cannabis, Δ9tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are the two components found in the highest concentrations. CBD itself does not produce typical behavioral cannabimimetic effects and was thought not to be responsible for psychotropic effects of cannabis. Numerous anecdotal findings testify to the therapeutic effects of CBD, which in some cases were further supported by research findings. However, data regarding CBD's mechanism of action and therapeutic potential are abundant and omnifarious. Therefore, we review the basic research regarding molecular mechanism of CBD's action with particular focus on its analgesic potential. Moreover, this article describes the detailed analgesic and anti-inflammatory effects of CBD in various models, including neuropathic pain, inflammatory pain, osteoarthritis and others. The dose and route of the administration-dependent effect of CBD, on the reduction in pain, hyperalgesia or allodynia, as well as the production of pro and anti-inflammatory cytokines, were described depending on the disease model. The clinical applications of CBD-containing drugs are also mentioned. The data presented herein unravel what is known about CBD's pharmacodynamics and analgesic effects to provide the reader with current state-of-art knowledge regarding CBD's action and future perspectives for research.

Opioid misuse and overuse have contributed to a widespread overdose crisis and many patients and physicians are considering medical cannabis to support opioid tapering and chronic pain control. Using a five-step modified Delphi process, we aimed to develop consensus-based recommendations on: 1) when and how to safely initiate and titrate cannabinoids in the presence of opioids, 2) when and how to safely taper opioids in the presence of cannabinoids and 3) how to monitor patients and evaluate outcomes when treating with opioids and cannabinoids.

Chronic pelvic pain (CPP) affects up to 15% of women in the United States. The endocannabinoid system is a potential pharmacological target for pelvic pain as cannabinoid receptors are highly expressed in the uterus and other nonreproductive tissues. We hypothesize that cannabis use is common for self-management of CPP, and our primary objective was to determine the prevalence of cannabis use in this population. A cross-sectional survey of women with pelvic and perineal pain, dyspareunia, or endometriosis was performed between March and August 2019. Subjects were recruited in an outpatient gynecology office. An anonymous, confidential, electronic survey was performed using a tablet. Statistical analysis was performed using JMP (SAS, Cary, NC). A total of 240 patients were approached, with 113 responses (47.1% response rate). There were 26 patients who used cannabis (23%). The majority used at least once per week ( = 18, 72%). Most users ( = 24, 96%) reported improvement in symptoms, including pain, cramping, muscle spasms, anxiety, depression, sleep disturbances, libido, and irritability. Over one-third (35%) stated that cannabis use decreased the number of phone calls or messages sent to their provider, and 39% reported decreased number of clinical visits. Side effects, including dry mouth, sleepiness, and feeling "high," were reported by 84% ( = 21). Almost one-quarter of patients with CPP report regular use of cannabis as an adjunct to their prescribed therapy. Although side effects are common, most users report improvement in symptoms. Our study highlights the potential of cannabis as a therapeutic option for patients with CPP.

In the last decade the use of medical cannabis (MC) for palliative cancer treatment has risen. However, the choice between products is arbitrary and most patients are using Tetrahydrocannabinol (THC)-dominant cannabis products. In this study, we aimed to assess the short-term outcomes of MC treatment prescribed by oncologists in relation to the type of cannabis they receive. A comparative analysis was used to assess the differences in treatment effectiveness and safety between THC-dominant ( = 56, 52%), cannabidiol (CBD)-dominant ( = 19, 18%), and mixed ( = 33, 30%) MC treatments. Oncology patients ( = 108) reported on multiple symptoms in baseline questionnaires, initiated MC treatment, and completed a one-month follow-up. Most parameters improved significantly from baseline, including pain intensity, affective and sensory pain, sleep quality and duration, cancer distress, and both physical and psychological symptom burden. There was no significant difference between the three MC treatments in the MC-related safety profile. Generally, there were no differences between the three MC treatments in pain intensity and in most secondary outcomes. Unexpectedly, CBD-dominant oil treatments were similar to THC-dominant treatments in their beneficial effects for most secondary outcomes. THC-dominant treatments showed significant superiority in their beneficial effect only in sleep duration compared to CBD-dominant treatments. This work provides evidence that, though patients usually consume THC-dominant products, caregivers should also consider CBD-dominant products as a useful treatment for cancer-related symptoms.

Cannabidiol (CBD) serves as a promising medicine, with few known adverse effects apart from the potential of drug interactions with the cytochrome P450 system. It has been hypothesized drug interactions may occur with chemotherapeutic agents, but no supporting evidence has been published to date.

Dronabinol is used to treat a variety of conditions, including loss of appetite in people with AIDS and severe nausea and vomiting caused by cancer chemotherapy. Its therapeutic potential for pain management is now being explored in specific populations. Monitoring dronabinol compliance is challenging because its active ingredient, Δ-9-tetrahydrocannabinol (THC), is also present in cannabis. We developed a rapid LC-MS/MS assay with minimal specimen preparation to quantitate 11 cannabinoids in urine. Using this assay coupled with urine samples from normal controls, cannabis, and dronabinol users, we show the ability to differentiate cannabis from dronabinol use.

Increased public access to cannabis calls for a deeper understanding of cannabis's constituents and how they interact to induce clinical effects. Whereas trans-Δ -tetrahydrocannabinol (THC) is considered the main psychoactive component in cannabis, producing the associated "high" or "euphoria," various findings demonstrate medical potential for cannabidiol (CBD), from anxiolytic to antiepileptic implications. This has translated into a public optimism and given way to the popular opinion that CBD can provide countless other therapeutic benefits, including the potential to mitigate some of the adverse side effects of THC, such as intoxication, psychomotor impairment, anxiety, and psychotic symptoms. This is particularly relevant for patients seeking to garner therapeutic benefits from cannabis without experiencing the burden of a significant subjective high. Thus, this article analyzes the scientific evidence available to support or disprove the idea that presence of CBD is beneficial and can exude a protective effect against THC. A thorough review of relevant literature, a basis from which to interpret such evidence through a critical mechanistic discussion, and the implications for patients are presented in this article.

Cannabidiol (CBD), which is nonintoxicating pharmacologically relevant constituents of Cannabis, demonstrates several beneficial effects. It has been found to have antioxidative, anti-inflammatory, and neuroprotective effects. As the medicinal use of CBD is gaining popularity for treatment of various disorders, the recent flare-up of largely unproven and unregulated cannabis-based preparations on medical therapeutics may have its greatest impact in the field of neurology. Currently, as lot of clinical trials are underway, CBD demonstrates remarkable potential to become a supplemental therapy in various neurological conditions. It has shown promise in the treatment of neurological disorders such as anxiety, chronic pain, trigeminal neuralgia, epilepsy, and essential tremors as well as psychiatric disorders. While recent FDA-approved prescription drugs have demonstrated safety, efficacy, and consistency enough for regulatory approval in spasticity in multiple sclerosis (MS) and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges still remain. In the current review, the authors have shed light on the application of CBD in the management and treatment of various neurological disorders.

Little is known about the patients' view on treatment with medical cannabis (MC) for Parkinson's disease (PD).

Cannabidiol (CBD), a major non-psychoactive cannabinoid, has received a lot of attention due to its potential anti-inflammatory, pain-relieving, and anti-anxiety properties. This has led to a recent boom in CBD-rich commercial products, which are sold without prescription in the form of oils, candies, and cosmetics. Since these products are derived from cannabis, the presence of the psychoactive tetrahydrocannabinol (THC) has to be tested before they enter the market. Here, we present a high-throughput approach based on liquid chromatography coupled to UV and tandem mass spectrometric detection for the determination of CBD, THC, and six other minor cannabinoids (cannabigerolic acid, cannabidivarin, cannabinol, cannabigerol, cannabidiolic acid, and tetrahydrocannabinolic acid) in a wide range of concentrations and in a variety of matrices, including oils, hydrophobic ointments, water-soluble liquids, plant material and gelatinous gummies. Each product was dissolved in a suitable solvent and further diluted to avoid matrix interference. The diluted samples were analyzed by reversed-phase chromatography, coupled to a UV detector followed by a triple quadrupole mass spectrometer, used in the multiple reaction monitoring mode. The UV signal was utilized for the quantification of samples containing high levels of CBD, while the mass spectrometer was used for low levels of THC and other minor cannabinoids. This allowed us to meet the required sensitivity for THC while significantly expanding the range of analyzed CBD, all within an 8-min long chromatographic run. The samples were further quantified using calibration in solvent, the approach was validated, and the validation criteria were met for all matrices except for two (i.e., emulsions and gels). The lower limit of quantification for THC was 0.5 μg/g in gummies, 1.0 μg/g in oils, ointments and liquids, and 5.0 μg/g in plant material. CBD was analyzed in the range of 0.5-60,000 μg/g in gummies, 1-120,000 μg/g in oils, ointments and liquids, and 5-300,000 μg/g in plant material. The developed method was used for the analysis of thirteen real products with a wide range of CBD content, with positive THC findings in twelve of them.

Recently, several countries authorized the use of cannabis flowering tops (dried inflorescences) with a standardized amount of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD) and their acidic precursors [Δ-9-tetrahydrocannabinolic acid A (THCA-A) and cannabidiolic acid (CBDA)] to treat neurogenic pain. We studied the acute pharmacological effects and disposition of cannabinoids and their metabolites in serum, oral fluid, sweat patch and urine of 13 healthy individuals treated with medical cannabis decoction and oil. Cannabinoids and their metabolites were quantified by ultrahigh performance tandem mass spectrometry. Even if the oil contained a significantly higher amount of THC, the absorption of THC and its metabolites were similar in both herbal preparations. Conversely, whereas oil contained a significantly higher amount of CBD and a lower amount of CBDA, absorption was significantly higher after decoction intake. Only cannabinoids present in both herbal preparations (THC, CBD, THCA-A and CBDA) were found in oral fluid, due to the higher acidity compared with that of serum. THC metabolites urinary excretion was always higher after decoction administration. Decoction induced greater feeling of hunger and drowsiness than oil preparation. Pharmacokinetics of cannabinoids, their precursors and their metabolites in biological fluids of individuals treated with cannabis decoction and oil showed a high interindividual variability. The aqueous preparation was generally better absorbed than the oil, even if it contained a minor amount of THC, THCA-A and CBD.

To compile and synthesize the available literature describing medical cannabis use across various disease states.

Cannabis use has been increasing in the United States and throughout the world. It is derived from one of the earliest plants cultivated by humans - Cannabis sativa. Cannabis (also called marijuana) is the most commonly used psychoactive substance worldwide. The cannabis plant has more than 400 chemicals, of which more than 100 cannabinoids (such as cannabigerol, cannabidiol, and cannabinol) have been identified. The endocannabinoid system (ECS) plays an essential role in the effects of cannabis on end organs. Although cannabis use has been reported for many decades, some of its unique adverse effects of nausea, vomiting, and abdominal pain, termed as cannabis hyperemesis syndrome (CHS), were noted recently. The legal status of cannabis in the United States has been rapidly changing from state to state. The incidence of CHS is expected to rise with rising access to cannabis in the United States. Furthermore, CHS is frequently underdiagnosed due to a lack of uniform criteria, subjective nature of symptoms, and overlap with cyclical vomiting syndrome (CVS). Understanding the ECS and its role in biphasic response (proemetic and antiemetic) of CHS is critical to explain its pathophysiology. As the use of cannabis increases globally, awareness of CHS is warranted for early recognition and prompt treatment to avoid complications. We describe the putative mechanism of CHS with an overview of the clinical features in these patients. Furthermore, we highlight the differences between CHS and CVS with important differentials to consider. We provide a narrative update on the current evidence on CHS pathophysiology, diagnosis, treatment, and identifying research gaps.

Cannabis has been used as a medicine for millennia. Prohibition in the mid-20th century precluded early scientific investigation. 'Cannabis' describes three separate forms - herbal cannabis, 'hemp' products, pharmaceutical-grade regulated cannabinoid-based medical products (CBMP). In Australia, CBMP became available for prescription in November 2016. Herbal cannabis with Δ9-tetrahydrocannabinol (THC), which is illegal, and cannabidiol (CBD) in herbal extracts, are both unregulated and unreliable sources of cannabinoids. The endocannabinoid system (ECS), delineated in the late 1990s, has increased the understanding and interest in research for appropriate clinical indications. The ubiquitous ECS has homeostatic and anti-inflammatory effects and comprises cannabinoid receptors, endocannabinoids and degrading enzymes. Phytocannabinoids are partial agonists of the ECS. In pre-clinical studies, THC and CBD produce beneficial effects in chronic pain, anxiety, sleep and inflammation. Systematic reviews often conflate herbal cannabis and CBMP, confusing the evidence. Currently large randomised controlled trials are unlikely to be achieved. Other methodologies with quality end-points are required. Rich, valuable high-quality real-world evidence for the safe and effective use of CBMP provides an opportunity to examine benefits and potential harms. Evidence demonstrates benefit of CBMP in multiple sclerosis, chronic neuropathic pain, chemotherapy induced nausea and vomiting, resistant paediatric epilepsy, anxiety and insomnia. CBMP are well tolerated with few serious adverse events. Additional clinical benefits are promising in many other resistant chronic conditions. Pharmaceutical grade prescribed CBMP has proven clinical benefits and provides another clinical option in the physician's pharmacopeia.

Cannabidiol (CBD) and Δ -tetrahydrocannabinol (THC) are the two best known and most extensively studied phytocannabinoids within Cannabis Sativa. An increasing number of pre-clinical studies and clinical trials have been conducted with one or both compounds, often probing their therapeutic effects in conditions such as paediatric epilepsy, anxiety disorders or chronic pain. Accurate monitoring of THC and CBD and their metabolites is essential for tracking treatment adherence and pharmacokinetics. However, fully validated methods for the comprehensive analysis of major phase I CBD metabolites are yet to be developed due to a historical lack of commercially available reference material. In the present study, we developed, optimized, and validated a method for the simultaneous quantification of CBD, THC, and their major phase I metabolites 6-hydroxy-cannabidiol (6-OH-CBD), 7-hydroxy-cannabidiol (7-OH-CBD), 7-carboxy-cannabidiol (7-COOH-CBD), 11-hydroxy-tetrahydrocannabinol (11-OH-THC), and 11-carboxy-tetrahydrocannabinol (11-COOH-THC) as per Food and Drug Administration (FDA) guidelines for bioanalytical method validation. The method is accurate, reproducible, sensitive, and can be carried out in high-throughput 96 well formats, ideal for larger-scale clinical trials. Deuterated internal standards for each analyte were crucial to account for variable matrix effects between plasma lots. Application of the method to plasma samples, taken from people who had been administered oral CBD as part of an open label trial of CBD effects in anxiety disorders, demonstrated its immediate utility in ongoing and upcoming clinical trials. The method will prove useful for future studies involving CBD and/or THC and can likely accommodate the inclusion of additional metabolites as analytical reference materials become commercially available.

Many people with MS (pwMS) use unregulated cannabis or cannabis products to treat the symptoms associated with the disease. In line with this, Sativex, a synthetic combination of cannabidiol (CBD) and Δ-tetrahydrocannabinol (Δ-THC) has been approved to treat symptoms of spasticity. In animals, CBD is effective in reducing the amounts of T-cell infiltrates in the spinal cord, suggesting CBD has anti-inflammatory properties. By doing this, CBD has shown to delay symptom onset in animal models of multiple sclerosis and slow disease progression. Importantly, combinations of CBD and Δ-THC appear more effective in treating animal models of multiple sclerosis. While CBD reduces the amounts of cell infiltrates in the spinal cord, Δ-THC reduces scores of spasticity. In human studies, the results are less encouraging and conflict with the findings in animals. Drugs which deliver a combination of Δ-THC and CBD in a 1:1 ratio appear to be only moderately effective in reducing spasticity scores, but appear to be almost as effective as current front-line treatments and cause less severe side effects than other treatments, such as baclofen (a GABA-B receptor agonist) and tizanidine (an α2 adrenergic receptor agonist). The findings of the studies reviewed suggest that cannabinoids may help treat neuropathic pain in pwMS as an add-on therapy to already established pain treatments. It is important to note that treatment with cannabinoid compounds may cause significant cognitive dysfunction. Long term double-blind placebo studies are greatly needed to further our understanding of the role of cannabinoids in multiple sclerosis treatment.

To determine the benefit of a tetrahydrocannabinol (THC)-rich cannabis oil on symptoms and quality of life of fibromyalgia patients.

Background A substantial and unmet clinical need exists for pharmacological treatment of cannabis use disorders. Cannabidiol could offer a novel treatment, but it is unclear which doses might be efficacious or safe. Therefore, we aimed to identify efficacious doses and eliminate inefficacious doses in a phase 2a trial using an adaptive Bayesian design.

To review pharmacology, available dosage forms, efficacy, and safety of cannabis and cannabinoids in cancer patients.

To investigate the action of cannabinoids on spasticity and pain in secondary progressive multiple sclerosis, by means of neurophysiological indexes.

To use crowdfunding campaigns to better understand how cannabidiol (CBD) is represented (and misrepresented) as cancer-related care. We analyzed CBD-related crowdfunding campaigns (n = 155) created between January 2017 and May 2019 in multiple countries on GoFundme.com. More than 81.9% of campaigns fundraised CBD for curative or life-prolonging reasons, and 25.2% fundraised for pain management. Most campaigns seeking funds for CBD for cancer-related care on GoFundMe are for curative or life-prolonging purposes and present CBD definitively as an effective treatment option. In general, campaigners supported their funding requests with anecdotal claims of efficacy and referenced sources of information that were either not evidence-based or that misrepresented existing evidence. Misinformation around CBD for cancer is widespread on medical crowdfunding campaigns. Given the potential adverse impact, crowdfunding platforms, like GoFundMe, must take steps to address their role in enabling and spreading this misinformation.

Chronic pelvic pain affects women across all demographics. Its management is complex and requires a multimodal approach. Cannabis has been legal for medical purposes for many years; however, its pharmacokinetics are just beginning to be understood, as are its analgesic effects and other benefits, such as improved sleep quality and reduced nausea and vomiting. Given the recent Canada-wide legalization of cannabis for non-medical use, patients may be more willing to disclose cannabis use and use it for pain management. Given the complexity of chronic pain management, physicians must be open to cannabis as an analgesic option. Cannabis use may decrease the need for opioids, a phenomenon that could reduce opioid dependency. Now is the ideal time to study patients' use of and perspectives on cannabis for pain relief in order to establish its effectiveness and safety. Cannabis shows potential to be a key player in a multimodal approach to chronic pelvic pain.

Hemp ( L.) seed contains high contents of various nutrients, including fatty acids and proteins. Cannabidiol (CBD) is a non-psychoactive compound that can be extracted from and used for treating epilepsy and pain. Industrial hemp products, including CBD and hemp seed oils, have become increasingly popular. Some products are marketed without a clear distinction between CBD and hemp seed oils. Herein, the CBD content and biological activities of commercial CBD and hemp seed oils were examined. CBD content was measured by high-performance liquid chromatography. For in vitro antioxidant activity determination, 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) radical-scavenging assays were performed. The CBD concentrations in the two CBD oil samples were 18.9 ± 0.5 and 9.2 ± 0.4 mg/mL. Of the seven hemp seed oil samples, six samples contained CBD in concentrations ranging from 2.0 ± 0.1 to 20.5 ± 0.5 µg/mL, but it was not detected in one sample. Antioxidant activity was observed in both CBD oil samples. The results indicate that (1) CBD content varied by hemp seed oil sample and that (2) antioxidant activity could be a useful landmark for discriminating CBD oils from hemp seed oils.

Mast cells are key actors in inflammatory reactions. Upon activation, they release histamine, heparin and nerve growth factor, among many other mediators that modulate immune response and neuron sensitization. One important feature of mast cells is that their population is usually increased in animal models and biopsies from patients with irritable bowel syndrome (IBS). Therefore, mast cells and mast cell mediators are regarded as key components in IBS pathophysiology. IBS is a common functional gastrointestinal disorder affecting the quality of life of up to 20% of the population worldwide. It is characterized by abdominal pain and altered bowel habits, with heterogeneous phenotypes ranging from constipation to diarrhea, with a mixed subtype and even an unclassified form. Nutrient intake is one of the triggering factors of IBS. In this respect, certain components of the daily food, such as fatty acids, amino acids or plant-derived substances like flavonoids, have been described to modulate mast cells' activity. In this review, we will focus on the effect of these molecules, either stimulatory or inhibitory, on mast cell degranulation, looking for a nutraceutical capable of decreasing IBS symptoms.

Cannabidiol (CBD), a non-psychotropic constituent of Cannabis sativa, has shown therapeutic promises by modulating several pathological conditions, including pain, epilepsy autism, among others. However, the molecular mechanism of action of CBD remains unknown and recent data suggest the engagement on CBD´s effects of nuclear elements, such as histone activity.

Cannabis is an annual plant with a long history of use as food, feed, fiber, oil, medicine, and narcotics. Despite realizing its true value, it has not yet found its true place. Cannabis has had a long history with many ups and downs, and now it is our turn to promote it. Cannabis contains approximately 600 identified and many yet unidentified potentially useful compounds. Cannabinoids, phenolic compounds, terpenoids, and alkaloids are some of the secondary metabolites present in cannabis. However, among a plethora of unique chemical compounds found in this plant, the most important ones are phytocannabinoids (PCs). Over hundreds of 21-22-carbon compounds exclusively produce in cannabis glandular hairs through either polyketide and or deoxyxylulose phosphate/methylerythritol phosphate (DOXP/MEP) pathways. Trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are those that first come to mind while talking about cannabis. Nevertheless, despite the low concentration, cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabinodiol (CBND), and cannabinidiol (CBDL) may have potentially some medical effects. PCs and endocannabinoids (ECs) mediate their effects mainly through CB1 and CB2 receptors. Despite all concerns regarding cannabis, nobody can ignore the use of cannabinoids as promising tonic, analgesic, antipyretic, antiemetic, anti-inflammatory, anti-epileptic, anticancer agents, which are effective for pain relief, depression, anxiety, sleep disorders, nausea and vomiting, multiple sclerosis, cardiovascular disorders, and appetite stimulation. The scientific community and public society have now increasingly accepted cannabis specifically hemp as much more than a recreational drug. There are growing demands for cannabinoids, mainly CBD, with many diverse therapeutic and nutritional properties in veterinary or human medicine. The main objective of this review article is to historically summarize findings concerning cannabinoids, mainly THC and CBD, towards putting these valuable compounds into food, feed and health baskets and current and future trends in the consumption of products derived from cannabis.

Pancreatic cancer (PC) is related to lifestyle risks, chronic inflammation, and germline mutations in , , , , or . Surgical resection and adjuvant chemotherapy are the main therapeutic strategies but are less effective in patients with high-grade tumors. Oxygen-ozone (O/O) therapy is an emerging alternative tool for the treatment of several clinical disorders. O/O therapy has been found to ameliorate mechanisms promoting chronic pain and inflammation, including hypoxia, inflammatory mediators, and infection. The advantages of using cannabinoids have been evaluated in vitro and in vivo models of several human cancers. Regarding PDAC, activation of cannabinoid receptors was found to induce pancreatic cancer cell apoptosis without affecting the normal pancreas cells. In a murine model of PDAC, a combination of cannabidiol (CBD) and gemcitabine increased survival length by nearly three times. Herein, we evaluate the anticancer effect of CBD and O/O, alone or in combination, on two human PDAC cell lines, PANC-1 and MiaPaCa-2, examining expression profiles of 92 pancreatic adenocarcinoma associated genes, cytotoxicity, migration properties, and cell death. Finally, we assess the combination effects with gemcitabine and paclitaxel. Summarizing, for the first time the antitumoral effect of combined therapy with CBD and oxygen-ozone therapy in PDAC is evidenced.

Chronic pain can be recurrent or constant pain that lasts for longer than 3 months and can result in disability, suffering, and a physical disturbance. Related to the complex nature of chronic pain, treatments have a pharmacological and non-pharmacological approach. Due to the opioid epidemic, alternative therapies have been introduced, and components of the plant Cannabis Sativa, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have gained recent interest as a choice of treatment. The exact mechanism for CBD is currently unknown, but unlike the CBD's psychoactive counterpart, THC, the side effects of CBD itself have been shown to be overall much more benign. The current pharmaceutical products for the treatment of chronic pain are known as nabiximols, and they contain a ratio of THC combined with CBD, which has been promising. This review focuses on the treatment efficacy of CBD, THC: CBD-based treatments for chronic pain and adverse events with each.

Fibromyalgia is a complex disease process that is as prevalent as it is poorly understood. Research into the pathophysiology is ongoing, and findings will likely assist in identifying new therapeutic options to augment those in existence today that are still insufficient for the care of a large population of patients. Recent evidence describes the use of cannabinoids in the treatment of fibromyalgia. This study provides a systematic, thorough review of the evidence alongside a review of the seminal data regarding the pathophysiology, diagnosis, and current treatment options. Fibromyalgia is characterized by widespread chronic pain, fatigue, and depressive episodes without an organic diagnosis, which may be prevalent in up to 10% of the population and carries a significant cost in healthcare utilization, morbidity, a reduced quality of life, and productivity. It is frequently associated with psychiatric comorbidities. The diagnosis is clinical and usually prolonged, and diagnostic criteria continue to evolve. Some therapies have been previously described, including neuropathic medications, milnacipran, and antidepressants. Despite some level of efficacy, only physical exercise has strong evidence to support it. Cannabis has been used historically to treat different pain conditions since ancient times. Recent advances allowed for the isolation of the active substances in cannabis and the production of cannabinoid products that are nearly devoid of psychoactive influence and provide pain relief and alleviation of other symptoms. Many of these, as well as cannabis itself, are approved for use in chronic pain conditions. Evidence supporting cannabis in chronic pain conditions is plentiful; however, in fibromyalgia, they are mostly limited. Only a handful of randomized trials exists, and their objectivity has been questioned. However, many retrospective trials and patient surveys suggest the significant alleviation of pain, improvement in sleep, and abatement of associated symptoms. Evidence supporting the use of cannabis in chronic pain and specifically in fibromyalgia is being gathered as the use of cannabis increases with current global trends. While the current evidence is still limited, emerging data do suggest a positive effect of cannabis in fibromyalgia. Cannabis use is not without risks, including psychiatric, cognitive, and developmental as well as the risks of addiction. As such, clinical judgment is warranted to weigh these risks and prescribe to patients who are more likely to benefit from this treatment. Further research is required to define appropriate patient selection and treatment regimens.

Microscopic colitis (MC) is a chronic inflammation condition of the colon characterized by watery diarrhea and normal appearing mucosa. A 75-year-old female presented with one-year history of chronic diarrhea while taking cannabidiol (CBD) for pain. Colonoscopy with random colon biopsies revealed collagenous colitis. She started budesonide and stopped CBD. At six-week follow-up, her diarrhea improved, and the budesonide dose was decreased. She restarted CBD oil twice but had diarrhea both times. Her diarrhea resolved after taking budesonide and stopping CBD. We report a case of CBD-associated MC to make clinicians aware of this potential adverse effect in patients who chronically use CBD.

While cannabis has been consumed for thousands of years, the medical-legal landscape surrounding its use has dramatically evolved over the past decades. Patients are turning to cannabis as a therapeutic option for several medical conditions. Given the surge in interest over the past decades there exists a major gap in the literature with respect to understanding the products that are currently being consumed by patients. The current perspective highlights the lack of relevance within the current literature towards understanding the medical chemistry of the products being consumed. The cannabis industry must rigorously invest into understanding what people are consuming from a chemical composition standpoint. This will inform what compounds in addition to Δ-tetrahydrocannabinol and cannabidiol may be producing physiologic/therapeutic effects from plant based extracts. Only through real-world evidence and a formalized, granular data collection process within which we know the chemical inputs for patients already using or beginning to use medical cannabis, we can come closer to the ability to provide targeted clinical decision making and design future appropriate randomized controlled trials.

The major phytocannabinoid cannabidiol (CBD) has anxiolytic properties and lacks tetrahydrocannabinol-like psychoactivity. Cannabidiolic acid (CBDA) is the acidic precursor to CBD, and this compound appears more potent than CBD in animal models of emesis, pain and epilepsy. In this short report, we aimed to examine whether CBDA is more potent than CBD in disrupting expression of conditioned fear and generalised anxiety-related behaviour induced by Pavlovian fear conditioning. Mice underwent fear conditioning and 24 h later were administered CBD and CBDA before testing for fear expression and generalized anxiety-like behaviour. We found that CBD and CBDA had dissociable effects; while CBD but not CBDA disrupted cued fear memory expression, CBDA but not CBD normalized trauma-induced generalized anxiety-related behaviour. Neither phytocannabinoid affected contextual fear expression. Our findings form the basis for future experiments examining whether phytocannabinoids, alone and in combination, are effective in these mouse models of fear and anxiety.

Cannabinoids hold promise for treating health problems related to inflammation and chronic pain in dogs, in particular cannabidiol (CBD), and its native acid derivative cannabidiolic acid (CBDA). Information regarding systemic delivery of cannabinoids through transdermal routes is sparse. The purpose of this study was to determine pharmacokinetics of transdermal administration of a low-THC Cannabis sativa extract in healthy dogs. Six purpose-bred research beagles were treated with a transdermal CBD-CBDA-rich extract, and serum concentrations of CBD, CBDA, tetrahydrocannabinol (THC), and its acid derivative tetrahydrocannabinolic acid (THCA) were examined prior to and at the end of weeks 1 and 2. A 4 mg/kg dose of total cannabinoids twice daily resulted in appx 10 ng/ml of CBD, 21-32 ng/ml of CBDA, trace amounts of THCA, and unquantifiable amounts of THC in serum at the end of weeks 1 and 2 of treatment. Results showed that CBDA and THCA were absorbed better systemically than CBD or THC.

Over the last 2 decades, affirmative diagnoses of osteoarthritis (OA) in the United States have tripled due to increasing rates of obesity and an aging population. Hemp-derived cannabidiol (CBD) is the major nontetrahydrocannabinol component of cannabis and has been promoted as a potential treatment for a wide variety of disparate inflammatory conditions. Here, we evaluated CBD for its ability to modulate the production of proinflammatory cytokines in vitro and in murine models of induced inflammation and further validated the ability of a liposomal formulation to increase bioavailability in mice and in humans. Subsequently, the therapeutic potential of both naked and liposomally encapsulated CBD was explored in a 4-week, randomized placebo-controlled, double-blinded study in a spontaneous canine model of OA. In vitro and in mouse models, CBD significantly attenuated the production of proinflammatory cytokines IL-6 and TNF-α while elevating levels of anti-inflammatory IL-10. In the veterinary study, CBD significantly decreased pain and increased mobility in a dose-dependent fashion among animals with an affirmative diagnosis of OA. Liposomal CBD (20 mg/day) was as effective as the highest dose of nonliposomal CBD (50 mg/day) in improving clinical outcomes. Hematocrit, comprehensive metabolic profile, and clinical chemistry indicated no significant detrimental impact of CBD administration over the 4-week analysis period. This study supports the safety and therapeutic potential of hemp-derived CBD for relieving arthritic pain and suggests follow-up investigations in humans are warranted.

To assess the efficacy, safety, and tolerability of oromucosal nabiximols cannabinoid medicine as adjunct therapy for children with spasticity due to cerebral palsy/traumatic central nervous system injury with inadequate response to existing treatment.

Moderate to severe spasticity is commonly reported in Multiple Sclerosis (MS) and its management is still a challenge. Cannabinoids were recently suggested as add-on therapy for the treatment of spasticity and chronic pain in MS but there is no conclusive scientific evidence on their safety, especially on cognition and over long periods. The aim of this prospective pilot study was to assess the long-term effects of a tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray (Sativex®) on cognition, mood and anxiety.

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, affecting ambulation even in people with only mild neurological signs. Patients with MS frequently experience spasticity, which contributes significantly to impair their motor functions, including ambulation, owing to muscle stiffness, spasms, and pain.

The aim of this study was to evaluate the efficacy of oral transmucosal (OTM) cannabidiol (CBD), in addition to a multimodal pharmacological treatment for chronic osteoarthritis-related pain in dogs. Twenty-one dogs were randomly divided into two groups: in group CBD ( = 9), OTM CBD (2 mg kg every 12 h) was included in the therapeutic protocol (anti-inflammatory drug, gabapentin, amitriptyline), while in group C ( = 12), CBD was not administered. Dogs were evaluated by owners based on the Canine Brief Pain Inventory scoring system before treatment initiation (T0), and one (T1), two (T2), four (T3) and twelve (T4) weeks thereafter. Pain Severity Score was significantly lower in CBD than in C group at T1 ( = 0.0002), T2 ( = 0.0043) and T3 ( = 0.016). Pain Interference Score was significantly lower in CBD than in C group at T1 ( = 0.0002), T2 ( = 0.0007) and T4 ( = 0.004). Quality of Life Index was significantly higher in CBD group at T1 ( = 0.003). The addition of OTM CBD showed promising results. Further pharmacokinetics and long-term studies in larger populations are needed to encourage its inclusion into a multimodal pharmacological approach for canine osteoarthritis-related pain.

The pathophysiological relevance of the endocannabinoid system has been widely demonstrated in a variety of diseases including cancer, neurological disorders, and metabolic issues. Therefore, targeting the receptors and the endogenous machinery involved in this system can provide a successful therapeutic outcome. Ligands targeting the canonical cannabinoid receptors, CB and CB, along with inhibitors of the endocannabinoid enzymes have been thoroughly studied in diverse disease models. In fact, phytocannabinoids such as cannabidiol or Δ-tetrahydrocannabinol are currently on the market for the management of neuropathic pain due to spasticity in multiple sclerosis or seizures in children epilepsy amongst others.

The cannabis plant has been widely researched for many therapeutic indications and found to be effective in many chronic conditions such as epilepsy, neuropathic or chronic pain and more. However, biased opinion against compounds of the plant, regulatory as well as compounding challenges have led to very few approved cannabinoid medicinal products. Those formulations which are approved are dosed several times a day, creating an unmet need for controlled release (CR) formulations of cannabinoids. Conventional CR formulations rely on prolonged absorption of the drug, including absorption from the colon. The purpose of this work is to investigate regional absorption of major cannabinoids THC and CBD from the colon and develop a suitable CR formulation. As hypothesized by researchers, THC and CBD have poor absorption from the colon compared to small intestine, suggesting that these compounds have a narrow absorption window. The suggested CR formulation examined in-vitro was a floating gastro retentive tablet based on egg albumin matrix, gas generating agents and surfactants. In-vivo investigation of CBD containing formulation in the freely moving rat model proved a prolonged absorption phase with a substantial increase in bioavailability compared to CBD solution. The findings of this paper answer a crucial question regarding potential application of CR dosage forms for cannabinoids and shed light on the regional intestinal absorption of these compounds. Ultimately, these results cement the way for future development of cannabinoid gastro retentive dosage forms.

Rugby is characterized by frequent high-intensity collisions, resulting in muscle soreness. Players consequently seek strategies to reduce soreness and accelerate recovery, with an emerging method being cannabidiol (CBD), despite anti-doping risks. The prevalence and rationale for CBD use in rugby has not been explored; therefore, we recruited professional male players to complete a survey on CBD. Goodness of fit chi-square (χ2) was used to assess CBD use between codes and player position. Effects of age on use were determined using χ2 tests of independence. Twenty-five teams provided 517 player responses. While the majority of players had never used CBD (p < .001, V = 0.24), 26% had either used it (18%) or were still using it (8%). Significantly more CBD use was observed in rugby union compared with rugby league (p = .004, V = 0.13), but player position was not a factor (p = .760, V = 0.013). CBD use increased with players' age (p < .001, V = 0.28), with mean use reaching 41% in the players aged 28 years and older category (p < .0001). The players using CBD primarily used the Internet (73%) or another teammate (61%) to obtain information, with only 16% consulting a nutritionist. The main reasons for CBD use were improving recovery/pain (80%) and sleep (78%), with 68% of players reporting a perceived benefit. These data highlight the need for immediate education on the risks of CBD, as well as the need to explore the claims regarding pain and sleep.

Cannabis is widely used as a therapeutic drug, especially by patients suffering from psychiatric and neurodegenerative diseases. However, the complex interplay between phytocannabinoids and their targets in the human receptome remains largely a mystery, and there have been few investigations into the relationship between the chemical composition of medical cannabis and the corresponding biological activity. In this study, we investigated 59 cannabis samples used by patients for medical reasons. The samples were subjected to extraction (microwave and supercritical carbon dioxide) and chemical analyses, and the resulting extracts were assayed in vitro using the CB and CB receptors. Using a partial least squares regression analysis, the chemical compositions of the extracts were then correlated to their corresponding cannabinoid receptor activities, thus generating predictive models that describe the receptor potency as a function of major phytocannabinoid content. Using the current dataset, meaningful models for CB and CB receptor agonism were obtained, and these reveal the insignificant relationships between the major phytocannabinoid content and receptor affinity for CB but good correlations between the two at CB receptors. These results also explain the anomalies between the receptor activities of pure phytocannabinoids and cannabis extracts. Furthermore, the models for CB and CB agonism in cannabis extracts predict the cannabinoid receptor activities of individual phytocannabinoids with reasonable accuracy. Here for the first time, we disclose a method to predict the relationship between the chemical composition, including phytocannabinoids, of cannabis extracts and cannabinoid receptor responses.

Epilepsy contributes to approximately 1% of the global disease burden. By affecting especially young children as well as older persons of all social and racial variety, epilepsy is a present disorder worldwide. Currently, only 65% of epileptic patients can be successfully treated with antiepileptic drugs. For this reason, alternative medicine receives more attention. Cannabis has been cultivated for over 6000 years to treat pain and insomnia and used since the 19th century to suppress epileptic seizures. The two best described phytocannabinoids, (-)--Δ-tetrahydrocannabinol (THC) and cannabidiol (CBD) are claimed to have positive effects on different neurological as well as neurodegenerative diseases, including epilepsy. There are different cannabinoids which act through different types of receptors and channels, including the cannabinoid receptor 1 and 2 (CB, CB), G protein-coupled receptor 55 (GPR55) and 18 (GPR18), opioid receptor µ and δ, transient receptor potential vanilloid type 1 (TRPV1) and 2 (TRPV2), type A γ-aminobutyric acid receptor (GABAR) and voltage-gated sodium channels (VGSC). The mechanisms and importance of the interaction between phytocannabinoids and their different sites of action regarding epileptic seizures and their clinical value are described in this review.

Cannabis is the most used illicit drug worldwide and its medicinal use is under discussion, being regulated in several countries. However, the psychotropic effects of Δ-tetrahydrocannabinol (THC), the main psychoactive compound of Cannabis sativa, are of concern. Thus, the interest in the isolated constituents without psychotropic activity, such as cannabidiol (CBD) and cannabidivarin (CBDV) is growing. CBD and CBDV are lipophilic molecules with poor oral bioavailability and are mainly metabolized by cytochrome P450 (CYP450) enzymes. The pharmacodynamics of CBD is the best explored, being able to interact with diverse molecular targets, like cannabinoid receptors, G protein-coupled receptor-55, transient receptor potential vanilloid 1 channel and peroxisome proliferator-activated receptor-γ. Considering the therapeutic potential, several clinical trials are underway to study the efficacy of CBD and CBDV in different pathologies, such as neurodegenerative diseases, epilepsy, autism spectrum disorders and pain conditions. The anti-cancer properties of CBD have also been demonstrated by several pre-clinical studies in different types of tumour cells. Although less studied, CBDV, a structural analogue of CBD, is receiving attention in the last years. CBDV exhibits anticonvulsant properties and, currently, clinical trials are underway for the treatment of autism spectrum disorders. Despite the benefits of these phytocannabinoids, it is important to highlight their potential interference with relevant physiologic mechanisms. In fact, CBD interactions with CYP450 enzymes and with drug efflux transporters may have serious consequences when co-administered with other drugs. This review summarizes the therapeutic advances of CBD and CBDV and explores some aspects of their pharmacokinetics, pharmacodynamics and possible interactions. Moreover, it also highlights the therapeutic potential of CBD and CBDV in several medical conditions and clinical applications.

Cannabis and cannabinoids (such as tetrahydrocannabinol and cannabidiol) are frequently used to relieve gastrointestinal symptoms. Cannabinoids have effects on the immune system and inflammatory responses, as well as neuromuscular and sensory functions of digestive organs, including pancreas and liver. Cannabinoids can cause hyperemesis and cyclic vomiting syndrome, but they might also be used to reduce gastrointestinal, pancreatic, or hepatic inflammation, as well as to treat motility, pain, and functional disorders. Cannabinoids activate cannabinoid receptors, which inhibit release of transmitters from presynaptic neurons and also inhibit diacylglycerol lipase alpha, to prevent synthesis of the endocannabinoid 2-arachidonoyl glycerol. However, randomized trials are needed to clarify their effects in patients; these compounds can have adverse effects on the central nervous system (such as somnolence and psychosis) or the developing fetus, when used for nausea and vomiting during pregnancy. Cannabinoid-based therapies can also hide symptoms and disease processes, such as in patients with inflammatory bowel diseases. It is important for gastroenterologists and hepatologists to understand cannabinoid mechanisms, effects, and risks.

Sickle cell disease (SCD) is characterized by chronic pain and episodic acute pain caused by vasoocclusive crises, often requiring high doses of opioids for prolonged periods. In humanized mouse models of SCD, a synthetic cannabinoid has been found to attenuate both chronic and acute hyperalgesia. The effect of cannabis on chronic pain in adults with SCD is unknown.

Cannabinoid analyses generally included, until recently, the primary psychoactive cannabis compound, Δ9-tetrahydrocannabinol (THC), and/or its inactive metabolite, 11-nor-9-carboxy-THC, in blood, plasma, and urine. Technological advances revolutionized the analyses of major and minor phytocannabinoids in diverse biological fluids and tissues. An extensive literature search was conducted in PubMed for articles on cannabinoid analyses from 2000 through 2019. References in acquired manuscripts were also searched for additional articles.

Cannabidiol (CBD) is a substance chemically derived from Cannabis sativa and discussed to be non-psychoactive. According to the FDA, marijuana is classified as a schedule I substance; however, hemp which is defined as extracts from marijuana including cannabinoids containing less than 0.3% tetrahydrocannabinol (THC), is excluded from that controlled substance act and available at local convenience stores in the US as it is seen as an herbal supplement. CBD is purported to be used for various medical and psychiatric conditions: depression, anxiety, post-traumatic stress disorder, Alzheimer's or other cognitive illnesses as well as pain. There is also a new trend to use CBD for the treatment of opioid use disorder. The one CBD product on the market that is FDA approved for the treatment of childhood epilepsy forms Dravet and Lennox-Gastaut syndromes is available under the name Epidiolex. There is a significant difference between this medication and the over-the-counter CBD products that contain very inconsistent strengths of CBD, if they contain it at all, and vary in percentage even from sample to sample. Frequently the so-called CBD products are not containing any CBD at all, but mostly containing THC. This article is a systematic review of literature reviewing the available clinical data on CBD, for use in various medical and psychiatric conditions with focus on a review of the pharmacology and toxicity. Resources used were ORVID, PubMed, MEDLINE, PsychINFO, EMBASE with keywords CBD, cannabidiol, hemp and cannabinoids.

To evaluate safety and pharmacokinetic parameters (PK) of medical cannabis in add-on for children and young adults with drug-resistant epilepsy.

Cannabis is a naturally occurring plant that is composed of over sixty phytocannabinoids, of which cannabidiol (CBD) has been recently identified as having therapeutic potential.

Hemp () has been used to treat pain as far back as 2900 B.C. Its pharmacological effects originate from a large variety of cannabinols. Although more than 100 different cannabinoids have been isolated from plants, clear physiological effects of only a few of them have been determined, including delta-9 tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabigerol (CBG). While THC is an illicit drug, CBD and CBG are legal substances that have a variety of unique pharmacological properties such as the reduction of chronic pain, inflammation, anxiety, and depression. Over the past decade, substantial efforts have been made to develop Cannabis varieties that would produce large amounts of CBD and CBG. Ideally, such plant varieties should produce very little (below 0.3%) if any THC to make their cultivation legal. The amount of cannabinoids in the plant material can be determined using high performance liquid chromatography (HPLC). This analysis, however, is nonportable, destructive, and time and labor consuming. Our group recently proposed to use Raman spectroscopy (RS) for confirmatory, noninvasive, and nondestructive differentiation between hemp and cannabis. The question to ask is whether RS can be used to detect CBD and CBG in hemp, as well as enable confirmatory differentiation between hemp, cannabis, and CBD-rich hemp. In this manuscript, we show that RS can be used to differentiate between cannabis, CBD-rich plants, and regular hemp. We also report spectroscopic signatures of CBG, cannabigerolic acid (CBGA), THC, delta-9-tetrahydrocannabinolic acid (THCA), CBD, and cannabidiolic acid (CBDA) that can be used for Raman-based quantitative diagnostics of these cannabinoids in plant material.

Indications of cannabis use are numerous although the indication to relief pain remains a major research interest and clinical application. Studies investigating the effect of herbal cannabis and cannabis-based medicine on neuropathic, non-neuropathic pain, acute pain and experimentally induced pain were reviewed. A search was performed in PubMed and Cochrane library for articles published in English between January 1, 2000 and May 8, 2020. The search terms used were related to cannabis and pain in adults. We identified 34 studies, of which 30 were randomized controlled clinical trials (RCTs). Varying effects were identified from the RCTs, and as expected more promising effects from non-RCTs. Cannabis-based medications were found most effective as an adjuvant therapy in refractory multiple sclerosis, and weak evidence was found to support the treatment of cancer pain especially in advanced stages. Chronic rheumatic pain showed promising results. Adverse events of cannabis-based treatment were found to be more frequent with tetrahydrocannabinol herbal strains compared to other cannabis-derived products.

The use of cannabidiol products in pediatric patients is becoming more frequent because of the increased ease of accessibility. This case report illustrates the potential for cannabidiol to interact with stable medication regimens. A 13-year-old girl with metastatic cancer and chronic pain presented with increased sleepiness and fatigue. She had been started on 7.5 mg of methadone by mouth twice daily 4 months earlier. Unbeknownst to her physicians, her parents had commenced her on cannabidiol and subsequently increased the dose leading up to her presentation, thinking it would result in tumor shrinkage. The initial serum methadone level was 271 ng/mL, which decreased to 125 ng/mL 14 days after discontinuing cannabidiol. The reduced serum methadone level coincided with improved sleepiness and fatigue. Cannabidiol inhibits CYP3A4 and CYP2C19, both of which are involved in the metabolism of methadone. Pediatricians should be aware of this potential interaction and inquire if their patients are receiving cannabidiol.

Regulatory approvals for Epidiolex (purified cannabidiol) in the treatment of childhood drug resistant epilepsy have set a precedent for the use of cannabinoids as a prescribed medicine. Two common reasons cited for the use and prescription of cannabis-based products are pain and insomnia. Unlike drug resistant epilepsy, the level of evidence of efficacy in pain is poorly developed. The lowest quality trials with the greatest methodological shortcomings suggest some benefit, a level of evidence that is inconsistent with widespread prescribing. The evidence in insomnia is scant. Ongoing trial development and critical review of the literature should not be overshadowed by increasing permissiveness towards cannabis use and anecdotal reports of efficacy.

The use of -based preparations for medicinal use has waxed and waned in the multi-millennial history of human co-existence with the plant and its cultivation. Recorded use of preparations from is effectively as old as recorded history with examples from China, India and Ancient Egypt. Prohibition and restriction of availability allowed a number of alternatives to take the place of preparations. However, there has been a worldwide resurgence in medicinal advocacy from the public. Media interest has been piqued by particular evocative cases. Altogether, therefore, there is pressure on healthcare professionals to prescribe and dispense -based preparations. This review enunciates some of the barriers which are slowing the wider adoption of medicinal .

Few models exist that can control for placebo and expectancy effects commonly observed in clinical trials measuring '' pharmacodynamics. We used the Foramen Rotundum Inflammatory Constriction Trigeminal Infraorbital Nerve injury (FRICT-ION) model to measure the effect of "full-spectrum" whole plant extracted hemp oil on chronic neuropathic pain sensitivity in mice.

Medical cannabis (MC) is becoming more and more popular among patients with chronic pain syndromes. In this study we evaluated the characteristics of MC use among patients with fibromyalgia.

Use of medical marijuana is increasing in the United States and older adults are the fastest growing user group. There is little information about the characteristics and outcomes related to medical marijuana use. This study is a descriptive analysis of older adults (aged ≥50 years old) who were early adopters of a medical marijuana program in the U.S. state of Florida. Per state legislation, initial and follow-up treatment plans were submitted to the University of Florida College of Pharmacy. Data collection included demographics, clinical history, medical conditions, substance use history, prescription history, and health status. Follow-up treatment plans noted changes in the chief complaint and actions taken since the initial visit. Of the state's 7548 registered users between August 2016 and July 2017, = 4447 (58.9%) were older adults. Patients utilized cannabidiol (CBD)-only preparations (45%), preparations that had both tetrahydrocannabinol (THC) and CBD (33.3%) or were recorded to use both CBD-only and THC + CBD products (21.7%). The chief complaints indicating medical cannabis treatment were musculoskeletal disorders and spasms (48.4%) and chronic pain (45.4%). Among other prescription medications, patients utilized antidepressants (23.8%), anxiolytics and benzodiazepines (23.5%), opioids (28.6%), and cardiovascular agents (27.9%). Among all drug classes with potential sedating effects, 44.8% of the cohort were exposed to at least one. Patients with follow-up visits (27.5%) exhibited marked improvement as assessed by the authorizing physicians. However, the patient registry lacked detailed records and linkable information to other data resources to achieve complete follow up in order to assess safety or efficacy. Future improvements to registries are needed to more adequately capture patient information to fill knowledge gaps related to the safety and effectiveness of medical marijuana, particularly in the older adult population.

Cannabis has been used to relieve the symptoms of disease for thousands of years. However, social and political biases have limited effective interrogation of the potential benefits of cannabis and polarised public opinion. Further, the medicinal and clinical utility of cannabis is limited by the psychotropic side effects of ∆-tetrahydrocannabinol (∆-THC). Evidence is emerging for the therapeutic benefits of cannabis in the treatment of neurological and neurodegenerative diseases, with potential efficacy as an analgesic and antiemetic for the management of cancer-related pain and treatment-related nausea and vomiting, respectively. An increasing number of preclinical studies have established that ∆-THC can inhibit the growth and proliferation of cancerous cells through the modulation of cannabinoid receptors (CB1R and CB2R), but clinical confirmation remains lacking. In parallel, the anti-cancer properties of non-THC cannabinoids, such as cannabidiol (CBD), are linked to the modulation of non-CB1R/CB2R G-protein-coupled receptors, neurotransmitter receptors, and ligand-regulated transcription factors, which together modulate oncogenic signalling and redox homeostasis. Additional evidence has also demonstrated the anti-inflammatory properties of cannabinoids, and this may prove relevant in the context of peritumoural oedema and the tumour immune microenvironment. This review aims to document the emerging mechanisms of anti-cancer actions of non-THC cannabinoids.

A 56-year-old male with no known history of substance abuse and no known prior medical conditions presented via ambulance to the emergency department after being found by coworkers with bizarre behavior, vomiting, and slurred speech. He had legally purchased cannabidiol (CBD) gummies marketed for pain and anxiety relief at a gas station several hours prior. Vitals upon arrival were temperature 36.8 Celsius, heart rate (HR) 79, respiratory rate (RR) 12, blood pressure (BP) 113/60, and oxygen saturation (O) of 84% on room air that improved upon arousal. Physical exam showed an obese man in no acute distress with a depressed level of consciousness but who awoke to painful stimuli. Neuro exam was significant for dysarthric, hypophonic speech. Labs were significant for a primary respiratory acidosis with concomitant mild lactic acid elevation, normal bicarbonate, and normal anion gap. A comprehensive urine toxicology screen including cannabis was negative. Vital signs three hours after presentation deteriorated, showing: HR 47, RR 8-12, BP 88/52, O 78%. Electrocardiogram (EKG) revealed sinus bradycardia. The patient progressively became more obtunded and required constant stimuli in order to maintain a patent airway. Non-invasive positive pressure ventilation was not administered due to persistent emesis. The patient underwent supportive care with intravenous fluids, oxygen, anti-emetics, continuous stimulation, and close neurologic monitoring with full recovery by the following morning. Further, patient history revealed that he had consumed two packages of CBD gummies, totaling 370 mg total of CBD (serving size on the package was 30 mg). He felt the products were healthy and safe based on packaging and therefore did not believe they would have any adverse effects. CBD is one of many cannabinoids found in marijuana and marijuana-derived products. It is generally considered safe unlike its more psychoactive counterpart, tetrahydrocannabinol (THC), which has been linked to seizures, respiratory depression, and cardiovascular complications. CBD has surged in popularity recently, being marketed in oils, capsules, and candies as a health supplement, claiming to treat a wide variety of medical conditions such as glaucoma, pain, and even having beneficial effects on cancer prevention. Most currently available studies do not look at isolated CBD nor their synthetic equivalents, and purity is not guaranteed, thus leading to unforeseen side effects and toxicities. Moreover, these compounds do not show on traditional toxicology screens, posing a diagnostic dilemma for physicians. This case of respiratory depression and cardiovascular compromise in a relatively healthy man is just one example of the importance of considering synthetic CBD toxicity in the differential diagnosis, as there is little data available for recognizing and treating this condition.

is an aromatic annual flowering plant with several botanical varieties, used for different purposes, like the production of fibers, the production of oil from the seeds, and especially for recreational or medical purposes. Phytocannabinoids (terpenophenolic compounds derived from the plant), include the well-known psychoactive cannabinoid Δ-tetrahydrocannabinol, and many non-psychoactive cannabinoids, like cannabidiol. The endocannabinoid system (ECS) comprises of endocannabinoid ligands, enzymes for synthesis and degradation of such ligands, and receptors. This system is widely distributed in the gastrointestinal tract, where phytocannabinoids exert potent effects, particularly under pathological (i.e., inflammatory) conditions. Herein, we will first look at the hemp plant as a possible source of new functional food ingredients and nutraceuticals that might be eventually useful to treat or even prevent gastrointestinal conditions. Subsequently, we will briefly describe the ECS and the general pharmacology of phytocannabinoids. Finally, we will revise the available data showing that non-psychoactive phytocannabinoids, particularly cannabidiol, may be useful to treat different disorders and diseases of the gastrointestinal tract. With the increasing interest in the development of functional foods for a healthy life, the non-psychoactive phytocannabinoids are hoped to find a place as nutraceuticals and food ingredients also for a healthy gastrointestinal tract function.

Cannabis use in the management of musculoskeletal diseases has gained advocacy since several states have legalized its recreational use. Cannabidiol (CBD), a commercially available, non-neurotropic marijuana constituent, has shown promise in arthritic animal models by attenuating pro-inflammatory immune responses. Additional research has demonstrated the benefit of CBD in decreasing the endogenous pain response in mice subjected to acute arthritic conditions, and further studies have highlighted improved fracture healing following CBD use in murine mid-femoral fractures. However, there is a lack of high-quality, novel research investigating the use of CBD in human musculoskeletal diseases aside from anecdotal accounts and retrospective reviews, perhaps due to legal ramifications limiting the enrollment of patients. The purpose of this review article is to highlight the extent of current research on CBD and its biochemical and pharmacologic efficacy in the treatment of joint disease, as well as the evidence for use of CBD and cannabis in patients undergoing joint arthroplasty. Based on available literature relying on retrospective data and case reports, it is challenging to propose a recommendation for CBD use in perioperative pain management. Additionally, a number of CBD products currently available as supplements with different methods of administration, and it is important to remember that these products are non-pharmaceuticals. However, given the increased social relevance of CBD and cannabis-based medicines, future, prospective controlled studies evaluating their efficacy are needed.

The South African (SA) Constitutional Court recently decriminalised the private cultivation, possession and use of cannabis by adults. Cannabis contains varying amounts of the cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), depending on various cultivation factors. No commercial plant-derived cannabis products are currently registered by the SA Health Products Regulatory Authority (SAHPRA) for medical use. Such products are therefore unregulated, but are freely available in SA, and may be of inadequate quality and unverified composition, and not guaranteed to be safe or effective. SAHPRA has to date approved only one synthetic medical cannabis product, dronabinol. Evidence supporting benefit from medical cannabis exists for two drug-resistant childhood forms of epilepsy, Dravet syndrome and Lennox-Gastaut syndrome. Adjuvant therapy with medical cannabis can reduce seizure frequency for Lennox-Gastaut syndrome and Dravet syndrome by 18.8% and 22.8%, respectively, and may be beneficial for other rare forms of epilepsy. There is moderate evidence for chemotherapy-induced nausea and vomiting with the synthetic cannabinoids. Multiple sclerosis-associated spasticity showed a small clinical improvement in self-reported spasticity when a purified form of THC/CBD was added to existing therapy. Currently, low-level or no convincing evidence exists for the use of medical cannabis for chronic pain, sleep and weight disorders, and neuropsychiatric disorders. Cannabis is associated with a greater risk of adverse effects than active and placebo controls, and may be involved in clinically significant drug-drug interactions. The evolving regulatory and legal landscape on the use of medical cannabis will guide prescription and recreational use in the coming years.

Recent studies have shown that cannabidiol (CBD) could have a great therapeutic potential for treating disorders such as chronic pain and anxiety. In the target article, the authors propose that CBD modulates serotonergic transmission and reverses allodynia and anxiety-like behaviour in a rat model of neuropathic pain. Furthermore, this study shows an antinociceptive effect mediated by TRPV and partially by 5-HT receptors, as well as an anxiolytic effect mediated by 5-HT receptors. De Gregorio D, McLaughlin RJ, Posa L, Ochoa-Sanchez R, Enns J, Lopez-Canul M, Aboud M, Maione S, Comai S, and Gobbi G. Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain. PAIN 2019;160:36-150.

While cannabis has been medically legal in Vermont since 2004 and recreationally legal since 2018 there has been minimal published research regarding the use and practices in the adult population. This gap in understanding results in primary care providers having difficulty navigating conversations surrounding cannabinoid use. The purpose of this research was to identify current use and perceptions of cannabinoids, including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in adult primary care patients in Vermont. An anonymous written survey was given to 1009 Vermont primary care patients aged 18 years and older. All measures were patient-reported and included use of CBD and THC products, perceived helpfulness for certain medical conditions, knowledge of CBD and THC, perceived knowledge of their provider, and concerns regarding cannabis legalization. 45% of adult primary care patients reported using cannabinoids in the past year. Only 18% of patients reported their provider as being a good source of information regarding cannabis. Of the patients who used cannabis in the past year, a majority reported it helpful for conditions such as anxiety and depression, arthritis, pain, sleep, and nausea. Primary care providers need to be knowledgeable about cannabinoids to best support patient care. In addition, with a significant number of patients reporting cannabinoids helpful for medical conditions common in primary care, it is important that research continue to identify the potential benefits and harms of cannabis.

The Cannabis sativa plant has been used medicinally and recreationally for thousands of years, but recently only relatively some of its constituents have been identified. There are more than 550 chemical compounds in cannabis, with more than 100 phytocannabinoids being identified, including Δ-tetrahydrocannabinol (THC) and cannabidiol (CBD). These phytocannabinoids work by binding to the cannabinoid receptors, as well as other receptor systems. Also within cannabis are the aromatic terpenes, more than 100 of which have been identified. Cannabis and its constituents have been indicated as therapeutic compounds in numerous medical conditions, such as pain, anxiety, epilepsy, nausea and vomiting, and post-traumatic stress disorder. This chapter provides an overview of some of the biological effects of a number of the cannabinoids and terpenes, as well as discussing their known mechanisms of action and evidence of potential therapeutic effects.

Chronic neuropathic pain (NP) is a growing clinical problem for which effective treatments, aside from non-steroidal anti-inflammatory drugs and opioids, are lacking. Cannabinoids are emerging as potentially promising agents to manage neuroimmune effects associated with nociception. In particular, Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and their combination are being considered as therapeutic alternatives for treatment of NP. This study aimed to examine whether sex affects long-term outcomes on persistent mechanical hypersensitivity 7 weeks after ceasing cannabinoid administration. Clinically relevant low doses of THC, CBD, and a 1:1 combination of THC:CBD extracts, in medium chain triglyceride (MCT) oil, were orally gavaged for 14 consecutive days to age-matched groups of male and female sexually mature Sprague Dawley rats. Treatments commenced one day after surgically inducing a pro-nociceptive state using a peripheral sciatic nerve cuff. The analgesic efficacy of each phytocannabinoid was assessed relative to MCT oil using hind paw mechanical behavioural testing once a week for 9 weeks. In vivo intracellular electrophysiology was recorded at endpoint to characterize soma threshold changes in primary afferent sensory neurons within dorsal root ganglia (DRG) innervated by the affected sciatic nerve. The thymus, spleen, and DRG were collected post-sacrifice and analyzed for long-term effects on markers associated with T lymphocytes at the RNA level using qPCR. Administration of cannabinoids, particularly the 1:1 combination of THC, elicited a sustained mechanical anti-hypersensitive effect in males with persistent peripheral NP, which corresponded to beneficial changes in myelinated Aβ mechanoreceptive fibers. Specific immune cell markers associated with T cell differentiation and pro-inflammatory cytokines, previously implicated in repair processes, were differentially up-regulated by cannabinoids in males treated with cannabinoids, but not in females, warranting further investigation into sexual dimorphisms that may underlie treatment outcomes.

The uses for cannabis and its synthetic derivatives continue to grow, as the regulatory status surrounding the drug becomes more legalized. Cannabis is composed of many chemical compounds, called cannabinoids, of which cannabidiol and 9-tetrahydrocannabinol have been studied for medicinal uses. As a modality for treatment of pain, cannabis may have benefit for use in treatment of neuropathic pain, with limited data for use in rheumatic pain. However, there are both short-term and long-term adverse effects with cannabis use that should be monitored in those who use cannabis for medicinal purposes, which include worsened anxiety and potential development of cannabis use disorder.

Cannabidiol (CBD), the major non-psychoactive constituent of L., has gained traction as a potential treatment for intractable chronic pain in many conditions. Clinical evidence suggests that CBD provides therapeutic benefit in certain forms of epilepsy and imparts analgesia in certain conditions, and improves quality of life. CBD continues to be Schedule I or V on the list of controlled substances of the Drug Enforcement Agency of the United States. However, preparations labeled CBD are available publicly in stores and on the streets. However, use of CBD does not always resolve pain. CBD purchased freely entails the risk of adulteration by potentially hazardous chemicals. As well, CBD use by pregnant women is rising and poses a major health-hazard for future generations. In this mini-review, we present balanced and unbiased pre-clinical and clinical findings for the beneficial effects of CBD treatment on chronic pain and its deleterious effects on prenatal development.

Cannabidiol (CBD) has become widely available owing to recent changes in federal and state regulations. Although it is marketed for many health conditions, a recent survey found that the most common reason for taking CBD was for the treatment of pain. The endocannabinoid system (ECS) is present at essentially all levels of the anterolateral system, which is responsible for the perception and modulation of pain. In addition to its effects on the ECS, CBD interacts with other important signaling systems involved in the regulation of pain. Thus, there is a physiological basis to investigate CBD for the treatment of pain. Although CBD has been found to reduce pain in several animal models of inflammatory and neuropathic pain, studies to date lack sufficient rigor to provide more than modest evidence for the analgesic activity of CBD. To date, only 1 controlled clinical study has been published evaluating the effect of CBD in the treatment of pain. This study was fraught with numerous deficiencies in design, such that the results are uninformative. Because studies to date have found a high level of variability in the content of CBD products, product quality is a major concern. Although limited preclinical studies suggest that CBD may alter the metabolism of drugs metabolized by cytochromes P450, the lack of clinical studies makes it impossible to assess the clinical significance of these observations. At present, there is insufficient evidence to recommend CBD for the treatment of pain. The safety of the compound in patients with chronic illness remains untested, and pharmacists should caution patients about its use in the absence of clinical supervision.

Cannabis can synthetize more than 400 compounds, including terpenes, flavonoids, and more than 100 phytocannabinoids. The main phytocannabinoids are Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabis-based products are used as medicines in several countries. In this text, we present an overview of the main neurochemical mechanisms of action of the phytocannabinoids, especially THC and CBD. We also reviewed the indications and adverse effects of the main cannabis-based medicinal products. THC acts as a partial agonist at cannabinoid 1/2 receptors (CB). It is responsible for the characteristic effects of cannabis, such as euphoria, relaxation, and changes in perceptions. THC can also produce dysphoria, anxiety, and psychotic symptoms. THC is used therapeutically in nausea and vomiting due to chemotherapy, as an appetite stimulant, and in chronic pain. CBD acts as a noncompetitive negative allosteric modulator of the CB receptor, as an inverse agonist of the CB receptor, and as an inhibitor of the reuptake of the endocannabinoid anandamide. Moreover, CBD also activates 5-HT serotonergic receptors and vanilloid receptors. Its use in treatment-resistant epilepsy syndromes is approved in some countries. CBD does not produce the typical effects associated with THC and has anxiolytic and antipsychotic effects. Some of the most common adverse effects of CBD are diarrhea, somnolence, nausea, and transaminase elevations (with concomitant use of antiepileptics). The mechanisms of action involved in both the therapeutic and adverse effects of the phytocannabinoids are not fully understood, involving not only the endocannabinoid system. This "promiscuous" pharmacology could be responsible for their wide therapeutic spectrum.

Cannabinoids have been long studied for their therapeutic properties, particularly for their use in the treatment of pain. As new therapies are sought after to treat conditions of chronic pain, so is a better understanding of the ligands and their target receptors or channels. A recently published cryo-EM structure showed the putative binding location of a well-known cannabinoid ligand, cannabidiol (CBD), in TRPV2, a channel that has been implicated in inflammation and chronic pain. TRPV2, along with TRPV1, TRPV3, TRPV4, TRPA1, and TRPM8 all have the capability to be modulated by cannabinoid ligands and are located in the peripheral nervous system. Here, we analyze the putative CBD binding site in each of these channels and compare structural and sequential information with experimental data.

Central neuropathic pain (CNP) is often refractory to available therapeutic strategies and there are few evidence-based treatment options. Many patients with neuropathic pain are not diagnosed or treated properly. Thus, consensus-based recommendations, adapted to the available drugs in the country, are necessary to guide clinical decisions.

Two patient case reports are presented describing the use of cannabidiol (CBD) for the symptomatic relief of a lumbar compression fracture and in the mitigation of thoracic discomfort and dysesthesia secondary to a surgically resected meningioma.

Hemp () is an angiosperm plant belonging to the family. Its cultivation dates back to centuries. It has always been cultivated due to the possibility of exploiting almost all the parts of the plant: paper, fabrics, ropes, bio-compounds with excellent insulating capacity, fuel, biodegradable plastic, antibacterial detergents, and food products, such as flour, oils, seeds, herbal teas, and beer, are indeed obtained from hemp. Hemp flowers have also always been used for their curative effects, as well as for recreational purposes due to their psychotropic effects. Cannabis contains almost 500 chemical compounds, such as phytocannabinoids, terpenes, flavonoids, amino acids, fatty acids, vitamins, and macro-, and micro-elements, among others. When utilized as a food source, hemp shows excellent nutritional and health-promoting (nutraceutical) properties, mainly due to the high content in polyunsaturated fatty acids (especially those belonging to the ω-3 series), as well as in phenolic compounds, which seem effective in the prevention of common diseases such as gastrointestinal disorders, neurodegenerative diseases, cancer, and others. Moreover, hemp oil and other oils (i.e., olive oil and medium-chain triglyceride-MCT-oil) enriched in CBD, as well as extracts from hemp dried flowers ( extracts), are authorized in some countries for therapeutic purposes as a second-choice approach (when conventional therapies have failed) for a certain number of clinical conditions such as pain and inflammation, epilepsy, anxiety disorders, nausea, emesis, and anorexia, among others. The present review will synthetize the beneficial properties of hemp and hemp derivatives in animal nutrition and therapeutics.

Pinterest, a widely used social media platform, has shaped how people seek and share health information. Cannabidiol (CBD), a non-psychoactive component of cannabis is marketed as a treatment for many conditions and sales rose to more than 820 million in 2017. Yet CBD is mostly unregulated, legality is murky, and many of the health claims are not scientifically proven. This content analysis examined how CBD products were portrayed on Pinterest. : In 2018, using the search terms cannabidiol and CBD, researchers sampled every fifth pin to collect 226 relevant pins. A codebook was developed, pilot tested, and used to code pins. : The majority (91.6%) of pins positively portrayed CBD with many claiming a physical or mental benefit including anxiety, depression, pain, and inflammation relief. Most pins did not (98.2%) address potential side effects or recommend dosage. In this sample, user engagement was high with 85.2% of pins being saved and links to commercial sites selling CBD products, personal blogs, and social media accounts. : Social media has become a powerful source of health information. This study revealed widespread acceptance of the use of CBD products with minimal information from reliable public health sources represented.

Cannabidiol (CBD) is reported to produce pain relief, but the clinically relevant cellular and molecular mechanisms remain uncertain. The TRPV1 receptor integrates noxious stimuli and plays a key role in pain signaling. Hence, we conducted in vitro studies, to elucidate the efficacy and mechanisms of CBD for inhibiting neuronal hypersensitivity in cultured rat sensory neurons, following activation of TRPV1.

Cannabis is increasingly used in Parkinson disease (PD), despite little information regarding benefits and risks. To investigate the safety and tolerability of a range of doses of cannabidiol (CBD), a nonintoxicating component of cannabis, and it's effect on common parkinsonian symptoms. In this open-label study Coloradans with PD, substantial rest tremor, not using cannabis received plant-derived highly purified CBD (Epidiolex; 100 mg/mL). CBD was titrated from 5 to 20-25 mg/kg/day and maintained for 10-15 days. Fifteen participants enrolled, two were screen failures. All 13 participants (10 male), mean (SD) age 68.15 (6.05), with 6.1 (4.0) years of PD, reported adverse events, including diarrhea (85%), somnolence (69%), fatigue (62%), weight gain (31%), dizziness (23%), abdominal pain (23%), and headache, weight loss, nausea, anorexia, and increased appetite (each 5%). Adverse events were mostly mild; none serious. Elevated liver enzymes, mostly a cholestatic pattern, occurred in five (38.5%) participants on 20-25 mg/kg/day, only one symptomatic. Three (23%) dropped out due to intolerance. Ten (eight male) that completed the study had improvement in total and motor Movement Disorder Society Unified Parkinson Disease Rating Scale scores of 7.70 (9.39, mean decrease 17.8%, =0.012) and 6.10 (6.64, mean decrease 24.7%, =0.004), respectively. Nighttime sleep and emotional/behavioral dyscontrol scores also improved significantly. CBD, in the form of Epidiolex, may be efficacious in PD, but the relatively high dose used in this study was associated with liver enzyme elevations. Randomized controlled trials are needed to investigate various forms of cannabis in PD.