SCIENTIFIC RESEARCH PUBLICATIONS
Rates of self-directed perioperative cannabidiol use in patients undergoing total hip or knee arthroplasty
To evaluate the prevalence of self-directed cannabidiol (CBD) use in patients with end-stage degenerative hip and knee arthritis who underwent total hip arthroplasty and total knee arthroplasty. Anonymous surveys for 109 patients were completed at 6 weeks follow-up after either total hip arthroplasty or total knee arthroplasty at a single tertiary care US orthopedic hospital. Within the perioperative window encompassing both preoperative and postoperative periods, 22% (95% CI: 14-30%) of patients used CBD. There was no difference in pain satisfaction between patients who used CBD and patients who did not. Given high rates of self-directed perioperative CBD use and the mixed body of evidence, further research is needed to better understand whether CBD is safe and effective.
A clinician survey of use assessment, documentation, and education about cannabis in persons with cystic fibrosis
To help open the clinician dialogue regarding cannabis use in persons with cystic fibrosis (CF) in the United States, we aimed to describe current practices of use assessment and documentation processes related to cannabis.
Cannabidiol has therapeutic potential for myofascial pain in female and male parkinsonian rats
The musculoskeletal orofacial pain is a complex symptom of Parkinson's disease (PD) resulting in stomatognathic system dysfunctions aggravated by the disease rigidity and postural instability. We tested the effect of cannabidiol (CBD), a non-psychotomimetic constituent of Cannabis sativa, in PD-related myofascial pain. Wistar adult female and male rats orofacial allodynic and hyperalgesic responses were tested by Von Frey and formalin tests, before and 21 days past 6-OHDA lesion. Algesic response was tested after masseter muscle injection of CBD (10, 50, 100 μg in 10 μL) or vehicle. Males compared to females in all estrous cycles' phases presented reduced orofacial allodynia and hyperalgesia. According to the estrous cycle's phases, females presented distinct orofacial nociceptive responses, being the estrus phase well-chosen for nociceptive analysis after 6-OHDA lesion (phase with fewer hormone alterations and adequate length). Dopaminergic neuron lesion decreased mechanical and inflammatory nociceptive thresholds in females and males in a higher proportion in females. CBD local treatment reduced the increased orofacial allodynia and hyperalgesia, in males and females. The female rats were more sensitive to CBD effect considering allodynia, responding to the lowest dose. Although females and males respond to the effect of three doses of CBD in the formalin test, males showed a superior reduction in the hyperalgesic response. These results indicate that hemiparkinsonian female in the estrus phase and male answer differently to the different doses of CBD therapy and nociceptive tests. CBD therapy is effective for parkinsonism-induced orofacial nociception.
State of the science: cannabis and cannabinoids in palliative medicine-the potential
Cannabinoids are chemicals derived naturally from the cannabis plant or are synthetically manufactured. They interact directly with cannabinoid receptors or share chemical similarity with endocannabinoids (or both). Within palliative medicine, cannabinoid receptors (CB1 and CB2) may modulate some cancer symptoms: appetite, chemotherapy-induced nausea and vomiting, and mood, pain and sleep disorders. Opioid and cannabinoid receptors have overlapping neuroanatomical receptor distribution, particularly at the dorsal horn, dorsal striatum and locus coeruleus. They have a favourable safety profile compared with opioids, and cannabis-based medicines help chronic pain. While cannabidiol (CBD) has anti-inflammatory properties, tetrahydrocannabinol (THC) is the psychoactive substance for issues such as mood and sleep. Nabiximols (Sativex), a CBD:THC combination, is Food and Drug Administration approved for some multiple sclerosis symptoms and epilepsy. There has been a swift societal evolution in attitudes about use of cannabis and cannabinoid medicines for chronic pain. In the USA, 33 states have now legalised prescription-based medical cannabis for several medical conditions; Canada has had legislation since 2001 authorising medical use. The European Union (EU) recently declared all EU citizens must have access to medical cannabis over the next 4 years. The integration into medicine and routine clinical use of cannabis is fraught with information gaps, regulatory issues and scarcity of research. Each patient should have a comprehensive assessment and risk-benefit discussion before any cannabis-based intervention to avoid possible complications such as hallucinations, psychosis and potential cardiac harm.
Safety and Tolerability of Transdermal Cannabidiol Gel in Children With Developmental and Epileptic Encephalopathies: A Nonrandomized Controlled Trial
Developmental and epileptic encephalopathies (DEEs) are the most severe group of drug-resistant epilepsies. Alternatives to oral therapies are urgently needed to reduce seizures and improve developmental outcomes and comorbidities in this medically complex population.
Values and preferences towards medical cannabis among people living with chronic pain: a mixed-methods systematic review
To explore values and preferences towards medical cannabis among people living with chronic pain.
Cannabidiol in the prelimbic cortex modulates the comorbid condition between the chronic neuropathic pain and depression-like behaviour in rats: The role of medial prefrontal cortex 5-HT and CB receptors
The prelimbic division (PrL) of the medial prefrontal cortex (mPFC) is a cerebral division that is putatively implicated in the chronic pain and depression. We investigated the activity of PrL cortex neurons in Wistar rats that underwent chronic constriction injury (CCI) of sciatic nerve and were further subjected to the forced swimming (FS) test and mechanical allodynia (by von Frey test). The effect of blockade of synapses with cobalt chloride (CoCl), and the treatment of the PrL cortex with cannabidiol (CBD), the CB receptor antagonist AM251 and the 5-HT receptor antagonist WAY-100635 were also investigated. Our results showed that CoCl decreased the time spent immobile during the FS test but did not alter mechanical allodynia. CBD (at 15, 30 and 60 nmol) in the PrL cortex also decreased the frequency and duration of immobility; however, only the dose of 30 nmol of CBD attenuated mechanical allodynia in rats with chronic NP. AM251 and WAY-100635 in the PrL cortex attenuated the antidepressive and analgesic effect caused by CBD but did not alter the immobility and the mechanical allodynia when administered alone. These data show that the PrL cortex is part of the neural substrate underlying the comorbidity between NP and depression. Also, the previous blockade of CB cannabinoid receptors and 5-HT serotonergic receptors in the PrL cortex attenuated the antidepressive and analgesics effect of the CBD. They also suggest that CBD could be a potential medicine for the treatment of depressive and pain symptoms in patients with chronic NP/depression comorbidity.
Cannabis and Athletic Performance
Cannabis is widely used for both recreational and medicinal purposes on a global scale. There is accumulating interest in the use of cannabis and its constituents for athletic recovery, and in some instances, performance. Amidst speculation of potential beneficial applications, the effects of cannabis and its two most abundant constituents, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), remain largely un-investigated. The purpose of this review is to critically evaluate the literature describing the effects of whole cannabis, THC, and CBD, on athletic performance and recovery. While investigations of whole cannabis and THC have generally shown either null or detrimental effects on exercise performance in strength and aerobic-type activities, studies of sufficient rigor and validity to conclusively declare ergogenic or ergolytic potential in athletes are lacking. The ability of cannabis and THC to perturb cardiovascular homeostasis warrants further investigation regarding mechanisms by which performance may be affected across different exercise modalities and energetic demands. In contrast to cannabis and THC, CBD has largely been scrutinized for its potential to aid in recovery. The beneficial effects of CBD on sleep quality, pain, and mild traumatic brain injury may be of particular interest to certain athletes. However, research in each of these respective areas has yet to be thoroughly investigated in athletic populations. Elucidating the effects of whole cannabis, THC, and CBD is pertinent for both researchers and practitioners given the widespread use of these products, and their potential to interact with athletes' performance and recovery.
Cannabidiol microinjection into the nucleus accumbens attenuated nociceptive behaviors in an animal model of tonic pain
Cannabidiol, the major non-psychoactive constituent of Cannabis, has attracted much attention as a therapeutic agent for intractable chronic pain in many conditions. Nucleus accumbens (NAc) as a major site of action of cannabinoids is one of the main mediators of several analgesic agents especially in the persistent pain condition. The present study aimed to investigate the effect of cannabidiol microinjection into the NAc on the modulation of nociception induced by formalin injection into the rat's paw. Adult male Wistar rats weighing 220-250 g were underwent stereotaxic surgery for unilateral (right or left side) cannula placement into the NAc. After one week recovery period, intra-NAc administration of the cannabidiol or its vehicle, DMSO was performed in a volume of 0.5 µl, five minutes before the formalin test. The formalin test was performed using 50 µl injection of formalin (2.5%) into the plantar surface of the rat's hind paw. Intra-accumbal administration of cannabidiol attenuated the nociceptive responses during the early and late phases of the formalin test in a dose-dependent manner. However, the antinociceptive effect of cannabidiol was significantly higher in the late phase of the formalin test than that in the early phase. Therefore, a non-psychoactive cannabinoid, cannabidiol may be developed as therapeutic agents in conditions, such as persistent inflammatory pain for which primary treatments are insufficient or not possible.
Antinociceptive and Anti-Inflammatory Properties of Cannabidiol Alone and in Combination with Standardized Bioflavonoid Composition
Symptom-alleviating therapies for osteoarthritis (OA) management are inadequate. Long-term application of first-line treatments, such as nonsteroidal anti-inflammatory drugs, is limited due to associated side effects. We believe that a combination of traditionally used botanical extracts, which have diverse active components that target multiple inflammatory pathways, may provide a safe and efficacious alternative to address the multifactorial nature of OA. Recently, cannabidiol (CBD), the major nonpsychoactive component of the hemp plant, has gained renewed global attention for its pharmacological actions. It has shown promise in reducing pain and inflammation in preclinical models of arthritis. In this study, widely employed inflammatory and noninflammatory animal pain models, such as the hot plate test, visceral pain model (writhing test), and carrageenan-induced rat paw edema model, were utilized to evaluate the antinociceptive and anti-inflammatory activity of CBD alone and in combination with standardized bioflavonoid compositions. CBD was tested at 5, 10, 20, and 40 mg/kg orally and at 5% topically. Administered alone, CBD produced dose-correlated, statistically significant pain inhibition in all the models. Enhanced performance in pain and inflammation reduction was observed when CBD was orally administered in complex with the bioflavonoid compositions. Data from this study show that for clinically meaningful efficacy against OA, CBD may have to be delivered in higher dosage or formulated with other medicinal plants with similar activities.
An initial analysis of the UK Medical Cannabis Registry: Outcomes analysis of first 129 patients
Cannabis-based medicinal products (CBMPs) are prescribed with increased frequency, despite a paucity of high-quality randomized controlled trials. The aim of this study is to analyze the early outcomes of the first series of patients prescribed CBMPs in the UK with respect to effects on health-related quality of life and clinical safety.
Contribution of the Adenosine 2A Receptor to Behavioral Effects of Tetrahydrocannabinol, Cannabidiol and PECS-101
The cannabis-derived molecules, ∆ tetrahydrocannabinol (THC) and cannabidiol (CBD), are both of considerable therapeutic interest for a variety of purposes, including to reduce pain and anxiety and increase sleep. In addition to their other pharmacological targets, both THC and CBD are competitive inhibitors of the equilibrative nucleoside transporter-1 (ENT-1), a primary inactivation mechanism for adenosine, and thereby increase adenosine signaling. The goal of this study was to examine the role of adenosine A2A receptor activation in the effects of intraperitoneally administered THC alone and in combination with CBD or PECS-101, a 4'-fluorinated derivative of CBD, in the cannabinoid tetrad, elevated plus maze (EPM) and marble bury assays. Comparisons between wild-type (WT) and A2AR knock out (A2AR-KO) mice were made. The cataleptic effects of THC were diminished in A2AR-KO; no other THC behaviors were affected by A2AR deletion. CBD (5 mg/kg) potentiated the cataleptic response to THC (5 mg/kg) in WT but not A2AR-KO. Neither CBD nor THC alone affected EPM behavior; their combination produced a significant increase in open/closed arm time in WT but not A2AR-KO. Both THC and CBD reduced the number of marbles buried in A2AR-KO but not WT mice. Like CBD, PECS-101 potentiated the cataleptic response to THC in WT but not A2AR-KO mice. PECS-101 also reduced exploratory behavior in the EPM in both genotypes. These results support the hypothesis that CBD and PECS-101 can potentiate the cataleptic effects of THC in a manner consistent with increased endogenous adenosine signaling.
Approved cannabinoids for medical purposes - Comparative systematic review and meta-analysis for sleep and appetite
Cannabinoids are used for numerous disease indications. However, cannabinoids can also produce adverse effects; for example, they can disturb physiological functions such as sleep and appetite. The medical use of cannabinoids refers to a wide variety of preparations and products. Approved cannabinoid products include dronabinol ((-)-trans-Δ-tetrahydrocannabinol (THC), nabilone (a THC analogue), and cannabidiol (CBD) that differ in their pharmacology and may thus have different adverse effects on sleep and appetite.
Prevalence of Cannabidiol Use in Patients With Spine Complaints: Results of an Anonymous Survey
Cannabidiol (CBD) is a cannabis derivative that has been popularized as a medicinal product with analgesic and anti-inflammatory effects. Given the anecdotal observations that several patients have reported use of CBD for spine-related pain, this study was designed to characterize CBD consumption patterns and perceived effects in patients with spine-related complaints.
Oral cannabinoid preparations for the treatment of chronic migraine: a retrospective study
To explore the effectiveness and safety of 3 oral cannabinoid preparations (FM2®, Bedrocan® and Bediol®) in the treatment of chronic migraine.
The Lived Experience of Managing HIV and Chronic Pain: Qualitative Interviews with Patients and Healthcare Providers
People living with HIV (PLWH) experience higher rates of comorbid chronic pain conditions compared to the general population. Managing HIV and chronic pain, two stigmatized health conditions, can exacerbate physical and psychological suffering. The current qualitative study was designed to increase our understanding of the experience of living with HIV and chronic pain. Twenty participants were recruited from a hospital-based immunology center to participate in individual in-depth qualitative interviews. The interviews focused on the experience of living with (or managing) chronic pain for PLWH. All interviews were audio recorded, transcribed and double-coded. Several themes emerged from our applied thematic analysis of the transcripts. The primary theme was that pain remained poorly managed among PLWH. Patients engaged in a variety of pain management strategies and described benefits from both traditional pain management interventions (e.g., pharmacology, physical therapy) as well as non-traditional approaches (e.g., medical marijuana, cannabidiol products, and spirituality). Other themes that emerged included barriers related to health insurance and the need to validate the patient pain experience. PLWH and chronic pain described compounding effects of managing two chronic health conditions, including perceived immune system over-activation, heightened awareness of illness, and negative mindset. More research is needed to improve care for those managing these often co-occurring health conditions.
The emerging role of cannabidiol (CBD) products; a survey exploring the public's use and perceptions of CBD
The market value of cannabidiol (CBD) is growing as people seek holistic ways of managing their health. The aim of this study was to explore the public's perceptions and use of CBD products, including where products were sourced, knowledge transfer and opinions on quality, safety and efficacy of CBD products. An online questionnaire was distributed via social and professional networks, in addition to face-to-face data collection days, which employed convenience and snowball sampling methods. A total of 597 participant responses were analysed, of which 10.9% (n = 65) claimed to use CBD products for a range of ailments, including anxiety and pain. CBD products were bought from healthcare stores, vape stores, pharmacies and online. Of those who did not personally use CBD (n = 532), 35% claimed they would like to try it. A positive attitude towards the safety and efficacy of CBD was attributed to CBD being a natural product. The study highlighted that the public continue to seek natural alternatives to supplement and maintain their health; hence, the popularity of CBD continues to rise. The lack of clinical evidence and regulation of CBD needs to be addressed to facilitate safe and effective use of CBD.
Response to "Comment on 'Cannabinoids in dermatologic surgery'"
Cellular distribution of cannabinoid-related receptors TRPV1, PPAR-gamma, GPR55 and GPR3 in the equine cervical dorsal root ganglia
The activation of cannabinoid and cannabinoid-related receptors by endogenous, plant-derived or synthetic cannabinoids may exert beneficial effects on pain perception. Of the cannabinoids contained in Cannabis sativa, cannabidiol (CBD) does not produce psychotropic effects and seems to represent a molecule having great therapeutic potential. Cannabidiol acts on a great number of cannabinoid and cannabinoid-related G-protein coupled receptors and ionotropic receptors which have, to date, been understudied in veterinary medicine particularly in equine medicine.
Medical cannabis and cannabis-based medicine show both potential efficacy and potential harms: Cross-sectional comparison with controls on self-rated and interviewer-rated outcomes within the Danish pilot program on medical cannabis
Denmark launched a pilot program of medical cannabis in January 2018. The aim was to establish whether medical cannabis and cannabis-based medicine (MC/CBM) were superior and safe compared to conventional treatment, regardless of the indications for which people received such medication.
The Role of Cannabis, Cannabidiol and Other Cannabinoids in Chronic Pain. The Perspective of Physicians
Currently, there is a renewed interest in treatments with medical cannabis and cannabinoids. Based on an increasing number of publications over the last decades that permitted new insights into mechanisms, efficacy and safety of cannabinoids, the use of cannabinergic medications is authorised in an increasing number of European and non-European countries. The alleviation of chronic, painful conditions is, since thousands of years, one of the primary reasons for the use of cannabis. Depending on the country, a wide range of medicinal cannabis preparations are available:ranging from defined cultivars of medical cannabis, mainly varying in their THC:CBD ratio, that are inhaled or taken as whole plant extracts,to highly purified single cannabinoids, such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD),or mixtures of two enriched extracts, standardised to a 1:1 ratio of THC:CBD (nabiximols). Although conflicting opinions continue to exist, the majority of reviews in the past concluded that medical cannabis and cannabinoids play a significant role in the management of pain. Surprisingly, systematic studies to date do not support an "entourage effect" of the other plant constituents of cannabis (mainly terpenoids) in treatment of chronic pain. An emerging cannabinoid is CBD which is the only cannabinergic medication available at present that does not cause the typical "cannabis high"; it is not a "controlled substance". However, despite years of research, there is either no study or no well-conducted, head-to-head, comparison available between different cannabis cultivars, between pure cannabinoids, and between pure cannabinoids and extracts. It remains unanswered which is the optimal treatment approach.
Cannabidiol: Knowledge, Beliefs, and Experiences of Patients With Cancer
Cannabidiol (CBD) is purported to work for a variety of therapeutic indications. Interest in CBD products has significantly increased as patients with cancer seek ways to improve symptom control and quality of life.
Cannabidiol treatment in hand osteoarthritis and psoriatic arthritis: a randomized, double-blind placebo-controlled trial
Cannabidiol (CBD) is increasingly used as analgesic medication even though the recent International Association for the Study of Pain presidential task force on cannabis and cannabinoid analgesia found a lack of trials examining CBD for pain management. The present trial examines CBD as add on analgesic therapy in patients with hand osteoarthritis or psoriatic arthritis experiencing moderate pain intensity despite therapy. Using a randomized double-blind, placebo-controlled design, patients received synthetic CBD 20-30mg or placebo daily for 12 weeks. Primary outcome was pain intensity during the last 24 hours (0-100mm); safety outcomes were percentage of patients experiencing adverse events and a characterization of serious adverse events. Explorative outcomes included change in Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), Pain Catastrophizing Scale (PCS) and Health Assessment Questionnaire (HAQ-DI).One hundred and thirty-six patients were randomized 129 were included in the primary analysis. Between group difference in pain intensity at 12 weeks was 0.23mm (95%CI -9.41 to 9.90; p = 0.96). 22% patients receiving CBD and 21% receiving placebo experienced a reduction in pain intensity of more than 30mm. We found neither clinically nor statistically significant effect of CBD for pain intensity in patients with hand osteoarthritis and psoriatic arthritis when compared to placebo. Additionally, no statistically significant effects were found on sleep quality, depression, anxiety, or pain catastrophizing scores.
Cannabidiol-based natural health products for companion animals: Recent advances in the management of anxiety, pain, and inflammation
Recent advances in cannabidiol (CBD) use in canines and felines for anxiety management, pain management, and anti-inflammatory effects were reviewed using a literature search conducted with the following keywords: CBD, anxiety, inflammation, pain, dogs, cats, and companion animals. For decades, research on CBD has been hindered due to the status of cannabis (C. sativa L.) as an illicit drug. Limited safety data show that CBD is well-tolerated in dogs, with insufficient information on the safety profile of CBD in cats. Upon oral supplementation of CBD, elevation in liver enzymes was observed for both dogs and cats, and pharmacokinetics of CBD are different in the two species. There is a significant gap in the literature on the therapeutic use of CBD in cats, with no feline data on anxiety, pain, and inflammation management. There is evidence that chronic osteoarthritic pain in dogs can be reduced by supplementation with CBD. Furthermore, experiments are required to better understand whether CBD has an influence on noise-induced fear and anxiolytic response. Preliminary evidence exists to support the analgesic properties of CBD in treating chronic canine osteoarthritis; however, there are inter- and intra-species differences in pharmacokinetics, tolerance, dosage, and safety of CBD. Therefore, to validate the anxiety management, pain management, and anti-inflammatory efficacy of CBD, it is essential to conduct systematic, randomized, and controlled trials. Further, the safety and efficacious dose of CBD in companion animals warrants investigation.
The Effectiveness of Cannabis and Cannabis Derivatives in Treating Lower Back Pain in the Aged Population: A Systematic Review
Cannabis is increasingly used in the management of pain, though minimal research exists to support its use since approval. Reduction in stigma has led to a growing interest in pharmaceutical cannabinoids as a possible treatment for lower back pain (LBP). The objective of this review was to assess the role and efficacy of cannabis and its derivatives in the management of LBP and compile global data related to the role of cannabis in the management of LBP in an aging population.
A Rare Case of Vaping-Induced Spontaneous Pneumomediastinum
Vaping is the process of inhaling an aerosol produced by heating a liquid or wax containing substances such as nicotine, cannabinoids (e.g., tetrahydrocannabinol, cannabidiol), flavoring, and additives (e.g., glycerol, propylene glycol). The presence of air or gas in the mediastinum is pneumomediastinum. We present a rare case of vaping-induced spontaneous pneumomediastinum. A young 20-year-old female patient with a history of vaping and no past medical history presented with acute chest pain to an emergency room. The urine drug screen was positive for cannabinoids. Imaging studies - chest x-ray and computed tomography of the chest - showed pneumomediastinum. The patient was discharged after a day of observation and counseling to quit vaping.
Behavioural and pharmacological effects of cannabidiol (CBD) and the cannabidiol analogue KLS-13019 in mouse models of pain and reinforcement
Cannabidiol (CBD) is a non-euphorigenic component of Cannabis sativa that prevents the development of paclitaxel-induced mechanical sensitivity in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN). We recently reported that the CBD structural analogue KLS-13019 shows efficacy in an in vitro model of CIPN. The present study was to characterize the behavioural effects of KLS-13019 compared to CBD and morphine in mouse models of CIPN, nociceptive pain and reinforcement.
Tetrahydrocannabinol and cannabidiol as an oromucosal spray in a 1:1 ratio: a therapeutic option for patients with central post-stroke pain syndrome?
Central pain after stroke due to brainstem infarction is very rare. Treatment is difficult and specific guidelines are lacking. This is the report of a 61-year-old female patient who, after a posterolateral left medulla oblongata insult with incomplete Wallenberg syndrome, subsequently developed a burning and tingling pain in the contralateral leg and a burning and shooting pain in the ipsilateral face in trigeminal branches 1 and 2. More than 3 years of therapy with amitriptyline, gabapentin, pregabalin and various grade II and III opioids was ineffective or showed intolerable side effects. The administration of tetrahydrocannabinol and cannabidiol as an oromucosal spray in a 1:1 ratio improved the pain situation and quality of life quickly and permanently. The encouraging results in the present case may suggest that treatment with medical cannabis should be considered in similar cases when standard therapies are insufficient.
Systematic review and meta-analysis of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators tested for antinociceptive effects in animal models of injury-related or pathological persistent pain
We report a systematic review and meta-analysis of studies that assessed the antinociceptive efficacy of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators on pain-associated behavioural outcomes in animal models of pathological or injury-related persistent pain. In April 2019, we systematically searched 3 online databases and used crowd science and machine learning to identify studies for inclusion. We calculated a standardised mean difference effect size for each comparison and performed a random-effects meta-analysis. We assessed the impact of study design characteristics and reporting of mitigations to reduce the risk of bias. We meta-analysed 374 studies in which 171 interventions were assessed for antinociceptive efficacy in rodent models of pathological or injury-related pain. Most experiments were conducted in male animals (86%). Antinociceptive efficacy was most frequently measured by attenuation of hypersensitivity to evoked limb withdrawal. Selective cannabinoid type 1, cannabinoid type 2, nonselective cannabinoid receptor agonists (including delta-9-tetrahydrocannabinol) and peroxisome proliferator-activated receptor-alpha agonists (predominantly palmitoylethanolamide) significantly attenuated pain-associated behaviours in a broad range of inflammatory and neuropathic pain models. Fatty acid amide hydrolase inhibitors, monoacylglycerol lipase inhibitors, and cannabidiol significantly attenuated pain-associated behaviours in neuropathic pain models but yielded mixed results in inflammatory pain models. The reporting of criteria to reduce the risk of bias was low; therefore, the studies have an unclear risk of bias. The value of future studies could be enhanced by improving the reporting of methodological criteria, the clinical relevance of the models, and behavioural assessments. Notwithstanding, the evidence supports the hypothesis of cannabinoid-induced analgesia.
Exploring the use of cannabis as a substitute for prescription drugs in a convenience sample
The use of cannabis as medicine (CaM) both prescribed and non-prescribed has increased markedly in the last decade, mirrored in a global shift in cannabis policy towards a more permissive stance. There is some evidence that cannabis functions as a substitute for prescription drugs, particularly opioids; however, more knowledge is needed on the motives of substitution users, their patterns of use, and perceived effects of substitution use.
A cannabis oracle? Delphi method not a substitute for randomized controlled trials of cannabinoids as therapeutics
With millions of people using cannabinoids to treat a host of medical conditions, clinicians want guidance on how to utilize cannabinoids as pharmacotherapy in their practices. The Delphi method is a systematic, interactive forecasting method that aims to develop consensus best practices where guidelines are not available. BODY: A multidisciplinary group of global cannabinoid experts utilized a modified Delphi process to develop three protocols for the dosing and administration of cannabinoids to treat chronic pain. Two protocols recommend cannabidiol (CBD), for which there is limited evidence as an analgesic, starting well below doses required for other indications. Guidance on prescribing CBD for pain may demonstrate consensus recommendations based upon suboptimal evidence.
Consensus recommendations on dosing and administration of medical cannabis to treat chronic pain: results of a modified Delphi process
Globally, medical cannabis legalization has increased in recent years and medical cannabis is commonly used to treat chronic pain. However, there are few randomized control trials studying medical cannabis indicating expert guidance on how to dose and administer medical cannabis safely and effectively is needed.
Therapeutic Potential for Cannabinoids in Sports Medicine: Current Literature Review
Cannabidiol and other cannabinoids are being used more frequently for sports medicine-related conditions. This review will help sports medicine clinicians answer questions that their athletes and active patients have about the potential effectiveness of cannabinoids on common sports medicine conditions. In the article, the authors compare cannabidiol and delta-9-tetrahydrocannabinol effects, noting the difference on the endocannabinoid and nonendocannabinoid receptors. The theoretical benefits of these two compounds and the current legality in the United States surrounding cannabidiol and delta-9-tetrahydrocannabinol use also are addressed.
Specific phytocannabinoid compositions are associated with analgesic response and adverse effects in chronic pain patients treated with medical cannabis
Medical cannabis (MC) treatment for chronic pain is increasing, but evidence regarding short- and long-term efficacy and associated adverse effects (AEs) of the different cannabis plant components is limited. Most reports focus on two phytocannabinoids, (-)-Δ-trans-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). This study, aimed to identify patterns of phytocannabinoid compositions associated with MC treatment response and with related AEs. Participants in this multicenter prospective cohort were patients with chronic non-cancer pain that were prescribed MC by physicians. Data was collected before MC treatment, at one month (short-term) and at 12 months (long-term). Simultaneously, liquid chromatography mass spectrometry identification and quantification of phytocannabinoids from the cultivars were performed. The monthly dose of each phytocannabinoid for each patient was z-scaled and clustered into ten groups to assess the difference in analgesic treatment response (≥30%/50% pain intensity reduction) and AEs rates. We identified ten clusters that had similar analgesic treatment response rates. However, there were significant differences in AEs rates both at short- and long-term. We identified specific phytocannabinoid compositions that were associated with overall AEs rates (5% compared to 53% at short-term and 44% at long-term) and with specific AEs rates such as MC related central nervous system, gastrointestinal and psychological AEs. To conclude, Evaluating only Δ9-THC or CBD is insufficient to find associations with MC related AEs. Therefore, comprehensive profiling of phytocannabinoids is needed to discover associations to related AEs and help physicians prescribe safer cannabis with less AEs while still relieving pain.
Selling cannabidiol products in Canada: A framing analysis of advertising claims by online retailers
In Canada, the legalization of cannabis has enabled cannabidiol (CBD) to become a popular commercial product, increasingly used for medical or therapeutic purposes. There are currently over one thousand CBD products available globally, ranging from oil extracts to CBD-infused beverages. Despite increased usage and availability, the evidence supporting the medical efficacy of CBD is limited. Anecdotal evidence suggests CBD sellers represent their products for medical use through direct medical claims or advice, which in Canada, is not allowed under the Cannabis Act without Health Canada approval. However, it is not clear the extent of sellers making health claims or other strategies used to promote medical usage of CBD. The objective of this study is to determine how CBD sellers advertise their products online to consumers.
Cannabidiol Inhibition of Murine Primary Nociceptors: Tight Binding to Slow Inactivated States of Na1.8 Channels
The nonpsychoactive phytocannabinoid cannabidiol (CBD) has been shown to have analgesic effects in animal studies but little is known about its mechanism of action. We examined the effects of CBD on intrinsic excitability of primary pain-sensing neurons. Studying acutely dissociated capsaicin-sensitive mouse DRG neurons at 37°C, we found that CBD effectively inhibited repetitive action potential firing, from 15-20 action potentials evoked by 1 s current injections in control to 1-3 action potentials with 2 μm CBD. Reduction of repetitive firing was accompanied by a reduction of action potential height, widening of action potentials, reduction of the afterhyperpolarization, and increased propensity to enter depolarization block. Voltage-clamp experiments showed that CBD inhibited both TTX-sensitive and TTX-resistant (TTX-R) sodium currents in a use-dependent manner. CBD showed strong state-dependent inhibition of TTX-R channels, with fast binding to inactivated channels during depolarizations and slow unbinding on repolarization. CBD alteration of channel availability at various voltages suggested that CBD binds especially tightly [ (dissociation constant), ∼150 nm] to the slow inactivated state of TTX-R channels, which can be substantially occupied at voltages as negative as -40 mV. Remarkably, CBD was more potent in inhibiting TTX-R channels and inhibiting action potential firing than the local anesthetic bupivacaine. We conclude that CBD might produce some of its analgesic effects by direct effects on neuronal excitability, with tight binding to the slow inactivated state of Na1.8 channels contributing to effective inhibition of repetitive firing by modest depolarizations. Cannabidiol (CBD) has been shown to inhibit pain in various rodent models, but the mechanism of this effect is unknown. We describe the ability of CBD to inhibit repetitive action potential firing in primary nociceptive neurons from mouse dorsal root ganglia and analyze the effects on voltage-dependent sodium channels. We find that CBD interacts with TTX-resistant sodium channels in a state-dependent manner suggesting particularly tight binding to slow inactivated states of Na1.8 channels, which dominate the overall inactivation of Na1.8 channels for small maintained depolarizations from the resting potential. The results suggest that CBD can exert analgesic effects in part by directly inhibiting repetitive firing of primary nociceptors and suggest a strategy of identifying compounds that bind selectively to slow inactivated states of Na1.8 channels for developing effective analgesics.
A placebo-controlled investigation of the analgesic effects, abuse liability, safety and tolerability of a range of oral cannabidiol doses in healthy humans
Preclinical studies demonstrate that cannabidiol (CBD) elicits an antinociceptive response in animal models of neuropathic pain; in humans, limited data are available to support such analgesic effects. Few studies have examined CBD's analgesic effects when administered without other compounds, and little is known regarding dose-dependent effects in noncannabis users.
Use and caregiver-reported efficacy of medical cannabis in children and adolescents in Switzerland
Evidence on the use and efficacy of medical cannabis for children is limited. We examined clinical and epidemiological characteristics of medical cannabis treatment and caregiver-reported effects in children and adolescents in Switzerland. We collected clinical data from children and adolescents (< 18 years) who received Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), or a combination of the two between 2008 and 2019 in Switzerland. Out of 205 contacted families, 90 agreed to participate. The median age at the first prescription was 11.5 years (interquartile range (IQR) 6-16), and 32 patients were female (36%). Fifty-one (57%) patients received CBD only and 39 (43%) THC. Patients were more likely to receive THC therapy if one of the following symptoms or signs were present: spasticity, pain, lack of weight gain, vomiting, or nausea, whereas seizures were the dominant indication for CBD therapy. Improvements were reported in 59 (66%) study participants. The largest treatment effects were reported for pain, spasticity, and frequency of seizures in participants treated with THC, and for those treated with pure CBD, the frequency of seizures. However, 43% of caregivers reported treatment interruptions, mainly because of lack of improvement (56%), side effects (46%), the need for a gastric tube (44%), and cost considerations (23%).Conclusions: The effects of medical cannabis in children and adolescents with chronic conditions are unknown except for rare seizure disorders, but the caregiver-reported data analysed here may justify trials of medical cannabis with standardized concentrations of THC or CBD to assess its efficacy in the young. What is Known: • The use of medical cannabis (THC and CBD) to treat a variety of diseases among children and adolescents is increasing. • In contrast to adults, there is no evidence to support the use of medical cannabis to treat chronic pain and spasticity in children, but substantial evidence to support the use of CBD in children with rare seizure disorders. What is New: • This study provides important insights into prescription practices, dosages, and treatment outcomes in children and adolescents using medical cannabis data from a real-life setting. • The effects of medical cannabis in children and adolescents with chronic conditions shown in our study support trials of medical cannabis for chronic conditions.
Cannabidiol (CBD) Use by Older Adults for Acute and Chronic Pain
Legalization of cannabidiol (CBD) products has ignited interest in clinical practice and research. One desired indication includes possible pain-relieving effects of CBD. The purposes of the current article are to (1) clarify terminology relevant to cannabinoids; (2) explain and understand the pharmacotherapeutics of CBD; (3) examine research of the current use of CBD by older adults for treating pain; (4) discuss safety considerations with using CBD products; and (5) provide best practice recommendations for clinicians as they advise their older adult patients. A review of the literature demonstrated mixed results on the efficacy of CBD in relieving pain in older adults. There is inconsistency in the labeling of over-the-counter CBD products that can result in safety issues and will require more federal quality control. Likewise, gaps in knowledge regarding safety and efficacy of CBD use in older adults are vast and require further research. [(7), 6-15.].
Cannabidiol effectively reverses mechanical and thermal allodynia, hyperalgesia, and anxious behaviors in a neuropathic pain model: Possible role of CB1 and TRPV1 receptors
The incidence of chronic pain is high in the general population and it is closely related to anxiety disorders, which promote negative effects on the quality of life. The cannabinoid system has essential participation in the pain sensitivity circuit. In this perspective, cannabidiol (CBD) is considered a promising strategy for treating neuropathic pain. Our study aimed to evaluate the effects of sub-chronic systemic treatment with CBD (0.3, 3, 10, or 30 mg/kg, i.p.) in male in rats submitted to chronic constriction injury of the sciatic nerve (CCI) or not (SHAM) and assessed in nociceptive tests (von Frey, acetone, and hot plate, three days CBD's treatment) and in the open field test (OFT, two days CBD's treatment). We performed a screening immunoreactivity of CB1 and TRPV1 receptors in cortical and limbic regions tissues, which were collected after 1.5 h of behavioral tests on the 24th experimental day. This study presents a dose-response curve to understand better the effects of low doses (3 mg/kg) on CBD's antiallodynic and anxiolytic effects. Also, low doses of CBD were able to (1) reverse mechanical and thermal allodynia (cold) and hyperalgesia, (2) reverse anxious behaviors (reduction of the % of grooming and freezing time, and increase of the % of center time in the OFT) induced by chronic pain. The peripheral neuropathy promoted the increase in the expression of CB1 and TRPV1 receptors in the anterior cingulate cortex (ACC), anterior insular cortex (AIC), basolateral amygdala (BLA), dorsal hippocampus (DH), and ventral hippocampus (VH). CBD potentiated this effect in the ACC, AIC, BLA, DH, and VH regions. These results provide substantial evidence of the role of the ACC-AIC-BLA corticolimbic circuit, and BLA-VH for pain regulation. These results can be clinically relevant since they contribute to the evidence of CBD's beneficial effects on treating chronic pain and associated comorbidities such as anxiety.
CBD Promotes Oral Ulcer Healing via Inhibiting CMPK2-Mediated Inflammasome
Oral ulcer is a common oral inflammatory lesion accompanied by severe pain but with few effective treatments. Cannabidiol (CBD) is recently emerging for its therapeutic potential in a range of diseases, including inflammatory conditions and cancers. Here we show that CBD oral spray on acid- or trauma-induced oral ulcers on mice tongue inhibits inflammation, relieves pain, and accelerates lesion closure. Notably, the enrichment of genes associated with the NOD, LRR, and NLRP3 pyrin domain-containing protein 3 (NLRP3) inflammasome pathway is downregulated after CBD treatment. The expression of cleaved-gasdermin D (GSDMD) and the percentage of pyroptotic cells are reduced as well. In addition, CBD decreases the expression of cytidine/uridine monophosphate kinase 2 (CMPK2), which subsequently inhibits the generation of oxidized mitochondria DNA and suppresses inflammasome activation. These immunomodulating effects of CBD are mostly blocked by peroxisome proliferator activated receptor γ (PPARγ) antagonist and partially antagonized by CB receptor antagonist. Our results demonstrate that CBD accelerates oral ulcer healing by inhibiting CMPK2-mediated NLRP3 inflammasome activation and pyroptosis, which are mediated mostly by PPARγ in the nucleus and partially by CB in the plasma membrane.
[Cannabis and cannabinoids for the treatment of acute and chronic pain]
Since the Act on the medical use of cannabis, at which cannabis-based medicines and cannabinoids became law, there has been an exponential increase in prescriptions for the acquisition of cannabis for medical purposes. The aim of this leading article is to compile and assess the currently available relevant clinical evidence for the use of cannabis and cannabinoids for treatment of acute and chronic pain. Based on the systematic literature review "Cannabis-Potential and risks (CAPRIS)" commissioned by the German Federal Ministry of Health and the recently published recommendations of the European Pain Federation EFIC, this article aims to give an orientation aid for the decision-making process in the clinical routine.
Temporomandibular Myofascial Pain Syndrome-Aetiology and Biopsychosocial Modulation. A Narrative Review
This review elaborates on the aetiology, diagnosis, and treatment of temporomandibular (TMD) myofascial pain syndrome (MPS) regulated by psychosocial factors. MPS impairs functioning in society due to the accompanying pain. Directed and self-directed biopsychosocial profile modulation may be beneficial in the treatment of MPS. Moreover, nutrition is also a considerable part of musculoskeletal system health. A fruit and vegetable diet contributes to a reduction in chronic pain intensity because of its anti-inflammatory influence. Cannabidiol (CBD) oils may also be used in the treatment as they reduce stress and anxiety. A promising alternative treatment may be craniosacral therapy which uses gentle fascia palpation techniques to decrease sympathetic arousal by regulating body rhythms and release fascial restrictions between the cranium and sacrum. MPS is affected by the combined action of the limbic, autonomic, endocrine, somatic, nociceptive, and immune systems. Therefore, the treatment of MPS should be deliberated holistically as it is a complex disorder.
Biomechanical Effects of Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD), the Major Constituents of Cannabis, in a Sprague Dawley Rat Achilles Tendon Surgical Repair Model: A Pilot Study
The use of cannabis is common among athletes and the US population at large. Cannabinoids are currently being evaluated as alternatives to opioid medications for chronic pain management. However, the effects of recreational and/or medical use of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on musculoskeletal injury and healing remain largely unknown.
Modulatory Potential of Cannabidiol on the Opioid-Induced Inflammatory Response
Opioids are effective analgesics; however, there are many negative consequences of chronic use. One important side effect of chronic opioid use is the continuous engagement of the immune response that can exacerbate chronic pain. The opioid, morphine, initiates a Toll-like receptor 4 (TLR4) signaling cascade that drives the activation of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome proteins, resulting in cytokine production and effectively creating a positive feedback loop for continuous TLR4 activation. In addition to driving cytokine production, morphine drives changes in proinflammatory lipid signaling. The alteration of both cytokine and lipid signaling systems by morphine suggests that its chronic use leads to a pathological immune response that would benefit from targeted therapy. Engaging the endogenous cannabinoid system has shown therapeutic benefit, particularly regarding its anti-inflammatory and immunosuppressive effects. Promising preclinical and clinical investigations suggest that cannabidiol (CBD) is an effective adjuvant for treatment of symptoms of opioid use disorders; however, the mechanism through which CBD drives this outcome is unclear. One potential source of insight into this mechanism is in how CBD regulates immune regulators such as cytokines and lipid signaling systems, including endocannabinoids and related immune-responsive lipids. In this review, we outline the immune response to chronic opioid use as well as CBD in the context of a lipopolysaccharide-induced immune response and speculate on the mechanism of CBD as a modulator of chronic opioid-induced immune system dysregulation.
Integrative Medicine: Cannabis and Cannabis-Related Drugs
is a genus of flowering herbs in the Cannabaceae family. Federal law defines dried plant material preparations of the subspecies as . The term refers to all products derived from plants. The active compounds in cannabis are cannabinoids, which include delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the psychoactive component, whereas CBD has no psychoactive effects. There are three Food and Drug Administration (FDA)-approved cannabis-related drugs. Dronabinol and nabilone (Cesamet) are approved for chemotherapy-induced nausea and vomiting; cannabidiol (Epidiolex) is approved for two pediatric epilepsy syndromes. FDA-approved cannabis-related drugs, marijuana, and cannabis formulations have been studied for the management of other conditions and symptoms (eg, cachexia, chemotherapy-induced nausea and vomiting, chronic pain, muscle spasticity) and have shown varying effectiveness. CBD formulations have been shown to be effective for certain forms of epilepsy. However, marijuana, cannabis-containing products, and cannabis-derived products in general are not approved by the FDA for any indication. Adverse effects include impaired executive function, cognition, and driving. Physicians can recommend use of marijuana under medical marijuana laws but cannot prescribe it, as it is classified as a Schedule I controlled substance. Laws regulating use of marijuana and cannabis products vary among states.
Health Claims About Cannabidiol Products: A Retrospective Analysis of U.S. Food and Drug Administration Warning Letters from 2015 to 2019
Cannabidiol (CBD) products are increasingly available to consumers in the United States and are subject to regulation by the U.S. Food and Drug Administration (FDA). CBD products cannot be marketed as unapproved new drugs with claims of therapeutic benefit. In addition, because CBD is the active ingredient in a FDA-approved CBD product, Epidiolex, CBD cannot be marketed as, or in, food products or dietary supplements. The FDA has issued Warning Letters to promote voluntary regulatory compliance. These letters provide insights as to the types of violations for CBD products detected in the U.S. market. The goal of this retrospective study was to content analyze Warning Letters issued by the FDA to identify illicit marketing of CBD products. Warning Letters issued by the FDA between 2015 and 2019 were content analyzed using a deductive approach. We extracted year of issuance, issuing office, and claim types that are currently prohibited by the FDA, including (i) unapproved new drug, (ii) misbranded drug, (iii) false and/or misleading, (iv) FDA-approved/endorsed, (v) dietary supplement, and (vi) adulterated food product. In addition, we documented the disease or conditions the product claimed to affect, pharmacological effects, and location of violation. Of the 39 Warning Letters issued, 97% were for violations made on company websites and 56% were for social media accounts. Almost all letters (97%) cited violations of marketing CBD as an unapproved new drug. These illicit therapeutic claims were made for >125 unique health problems, including cancer (87.2%), diabetes (71.8%), inflammation (66.7%), pain (66.7%), and arthritis (66.7%). The majority of letters (79.5%) also cited illicit marketing of CBD as a dietary supplement or food product. CBD was promoted as having 16 unique pharmacological effects, including anti-inflammatory (53.8%), anticancer (43.6%), and antipsychotic (30.8%). CBD products have been unlawfully advertised online as unauthorized drugs with health claims that promote therapeutic benefits and as dietary supplements. Efforts are needed to regulate and monitor illicit advertising so consumers are not misled about the risks and benefits of CBD use.
Utilization and Impact of Complementary and Alternative Medicines in Symptomatic Autoimmune Hepatitis Patients
Complementary and alternative medicine (CAM) use has become increasingly common. It is also prevalent in patients with chronic liver disease, but the scope, depth, and safety of use is not well known.
Availability and Promotion of Cannabidiol (CBD) Products in Online Vape Shops
Vaping products containing cannabidiol (CBD), a cannabis-derived compound used in wellness products and available in all 50 US states, were recently implicated in outbreaks of poisonings. Little is known about the commercial availability of CBD products in vape shops (i.e., stores that sell e-cigarettes). To document the availability and marketing of CBD products in online vape shops, in June 2020, we used the Google Chrome browser without cached data to collect the first two pages of search results generated by five Google queries ( = 100 search results) indicative of shopping for vaping products (e.g., "order vapes"). We then determined whether and what type of CBD products could be mail-ordered from the returned websites, and whether any explicit health claims were made about CBD. Over a third of the search results ( = 37; 37.0%) directed to vape shops that allowed visitors to also mail-order CBD. These shops sold 12 distinct categories of CBD products-some with direct analogs of tobacco or cannabis products including CBD cigarettes, edibles, flowers, pre-rolled joints, and vapes. Two vape shops made explicit health claims of the therapeutic benefits of CBD use, including in the treatment of anxiety, inflammation, pain, and stress. The abundance and placement of CBD in online vape shops suggests a growing demand and appeal for CBD products among e-cigarette users. Additional surveillance on the epidemiology of CBD use and its co-use with tobacco is warranted.
The endocannabinoid system, cannabis, and cannabidiol: Implications in urology and men's health
The endocannabinoid system is a neuromodulatory system responsible for partial regulation of cognitive and emotional processes in the human central nervous system such as behavior, mood disorders, and neurologic disorders such as epilepsy. The endocannabinoid system is also prevalent throughout the peripheral nervous system and human body and its receptors and signaling pathways are present and active in areas including the male and female reproductive tracts and organ systems such as the urologic and gastrointestinal system.
Cannabidiol use and effectiveness: real-world evidence from a Canadian medical cannabis clinic
Cannabidiol (CBD) is a primary component in the cannabis plant; however, in recent years, interest in CBD treatments has outpaced scientific research and regulatory advancement resulting in a confusing landscape of misinformation and unsubstantiated health claims. Within the limited results from randomized controlled trials, and lack of trust in product quality and known clinical guidelines and dosages, real-world evidence (RWE) from countries with robust regulatory frameworks may fill a critical need for patients and healthcare professionals. Despite growing evidence and interest, no real-world data (RWD) studies have yet investigated patients' reports of CBD impact on symptom control in the common expression of pain, anxiety, depression, and poor wellbeing. The objective of this study is to assess the impact of CBD-rich treatment on symptom burden, as measured with a specific symptom assessment scale (ESAS-r).
Targeting the endocannabinoid system for management of HIV-associated neuropathic pain: A systematic review
Human immunodeficiency virus (HIV) infection and antiretroviral therapy can independently induce HIV-associated neuropathic pain (HIV-NP). There is a dearth of drugs or therapeutic modalities that can alleviate HIV-NP. Smoked cannabis has been reported to improve pain measures in patients with neuropathic pain. Cannabis, phytocannabinoids, and the endocannabinoids such N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG), produce some of their effects via cannabinoid receptors (CBRs). Endocannabinoids are degraded by various enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase. We searched PubMed, Google Scholar, clinicaltrials.gov and clinicaltrialsregister.eu using various key words and their combinations for published papers that studied HIV-NP and cannabis, cannabinoids, or endocannabinoids up to 27th December 2020. All original research articles that evaluated the efficacy of molecules that modulate the endocannabinoid system (ECS) for the prevention and/or treatment of pain in HIV-NP animal models and patients with HIV-NP were included. The PubMed search produced a total of 117 articles, whereas the Google Scholar search produced a total of 9467 articles. Amongst the 13 articles that fulfilled the inclusion criteria 11 articles were found in both searches whereas 2 articles were found in Google Scholar only. The clinicaltrials.gov and clinicaltrialsregister.eu searches produced five registered trials of which three were completed and with results. Ten preclinical studies found that the endocannabinoids (2-AG and AEA), synthetic mixed CB1R/CB2R agonist WIN 55,212-2, a CB2R-selective phytocannabinoid β-caryophyllene, synthetic CB2R-selective agonists (AM1710, JWH015, JWH133 and Gp1a, but not HU308); FAAH inhibitors (palmitoylallylamide, URB597 and PF-3845) and a drug combination of indomethacin plus minocycline, which produces its effects in a CBR-dependent manner, either prevented the development of and/or attenuated established HIV-NP. Two clinical trials demonstrated greater efficacy of smoked cannabis over placebo in alleviating HIV-NP, whereas another clinical trial demonstrated that cannabidivarin, a cannabinoid that does not activate CBRs, did not reduce HIV-NP. The available preclinical results suggest that targeting the ECS for prevention and treatment of HIV-NP is a plausible therapeutic option. Clinical evidence shows that smoked cannabis alleviates HIV-NP. Further research is needed to find out if non-psychoactive drugs that target the ECS and are delivered by other routes than smoking could be useful as treatment options for HIV-NP.
Cannabidiol Product Dosing and Decision-Making in a National Survey of Individuals with Fibromyalgia
Many people with fibromyalgia use cannabidiol (CBD) products despite limited rigorous evidence of benefit. In the current study, we conducted a secondary analysis of a cross-sectional survey of N = 878 people with fibromyalgia to investigate naturalistic decision making around CBD product choices, use patterns, and dosing. We subgrouped participants based on use of high-THC cannabis (HTC) in the past year (yes/no) as previous studies have shown that HTC use influences CBD use patterns. The study population was largely female (93.6%), white (91.5%) and 55.5 years old on average. Participants typically purchased CBD products online or at dispensaries, with purchasing driven by personal research (63%) rather than endorsement from medical professionals (16%). Overall, tinctures and topicals were the most common administration routes endorsed. However, participants in the past-year HTC group used inhalation routes far more frequently than those who did not (39.8% vs 7.1%). Among participants using CBD tinctures or edibles, the average dose per session was 16 mg and 24 to 27 mg per day, although approximately one-third of participants did not know what dose of CBD they used. Participants using both inhalation and non-inhalation administration routes reported greater symptom relief than those using non-inhalation routes alone. However, there was no consistent relationship between CBD dose and reported effects, possibly due to expectancy effects around CBD products or interindividual variability. Our granular investigation reveals variability of CBD product dosing practices for fibromyalgia, and how past-year HTC use influences CBD product use. Future clinical trials should investigate the potential benefits of low-dose (<50mg) botanical CBD products. Perspective: This article shows that past-year HTC use strongly influences how people with fibromyalgia choose and use CBD products. Participants typically used <50 mg/d of CBD, and there was no relationship between higher CBD dose and reported therapeutic benefit. Future clinical trials should investigate therapeutic benefits of low dose CBD.
[New targeted compounds-biosynthesis of phytocannabinoids]
Phytocannabinoids are bioactive terpenoids that are exclusive to Cannabis sativa L. The main pharmacologically active phytocannabinoids are Δ9-tetrahydrocannabinol and cannabidiol, both target endogenous cannabinoid receptors. Δ9-tetrahydrocannabinol and cannabidiol have extensive therapeutic potential due to their participation in many physiological and pathological processes in human body by activating the endocannabinoid system. At present, Δ9-tetrahydrocannabinol, cannabidiol and their analogues or combination preparations are used to treat epilepsy, vomiting in patients with cancer chemotherapy, spasticity in multiple sclerosis and relieve neuropathic pain and pain in patients with advanced cancer. With the further exploration of the application value of Δ9-tetrahydrocannabinol and cannabidiol as well as the increasing demand for standardization of pharmaceutical preparations, it is imminent to achieve large-scale production of Δ9-tetrahydrocannabinol and cannabidiol in the pharmaceutical industry. In this article, pharmacological research progress of phytocannabinoids in recent years, biosynthetic pathways of phytocannabinoids and the mechanism of key enzymes as well as various product development strategies of cannabinoids in pharmaceutical industry are reviewed. By exploring the potential of synthetic biology as an alternative strategy for the source of phytocannabinoids, it will provide a theoretical basis for the research and development of microbial engineering for cannabinoids synthesis, and promote the large-scale production of medicinal cannabinoids.
The Effects of Cannabinoids on Pro- and Anti-Inflammatory Cytokines: A Systematic Review of Studies
Some cannabinoids have been identified as anti-inflammatory agents; however, their potential therapeutic or prophylactic applications remain controversial. The aim of this systematic review was to provide a timely and comprehensive insight into cannabinoid-mediated pro- and anti-inflammatory cytokine responses in preclinical studies. A systematic search was conducted using PubMed, Web of Science, EMBASE, and Scopus. Eligible studies where cannabinoids had been evaluated for their effect on inflammation in animal models were included in the analysis. Data were extracted from 26 of 4247 eligible full text articles, and risk of bias was assessed using the SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) tool. Studies examined cannabidiol (CBD; =20); cannabigerol (CBG; =1); delta 9-tetrahydrocannabinol (THC; =2); THC and CBD separately (=1); and THC and CBD in combination (=2). Tumor necrosis factor alpha, interleukin (IL)-1β, IL-6, and interferon gamma were the most commonly studied pro-inflammatory cytokines and their levels were consistently reduced after treatment with CBD, CBG, or CBD+THC, but not with THC alone. The association between cannabinoid-induced anti-inflammatory response and disease severity was examined. In 22 studies where CBD, CBG, or CBD in combination with THC were administered, a reduction in the levels of at least one inflammatory cytokine was observed, and in 24 studies, some improvements in disease or disability were apparent. THC alone did not reduce pro-inflammatory cytokine levels (=3), but resulted in improvements in neuropathic pain in one study. This review shows that CBD, CBG, and CBD+THC combination exert a predominantly anti-inflammatory effect , whereas THC alone does not reduce pro-inflammatory or increase anti-inflammatory cytokines. It is anticipated that this information could be used to inform human clinical trials of cannabinoids, focusing on CBD and CBG to reduce inflammation across a range of pathophysiological processes.
Cannabidiol in low back pain: scientific rationale for clinical trials in low back pain
The pooled worldwide prevalence of low-back pain-related presentations in primary care varies between 6.8% and 28.4% in the high-income countries rendering it a major healthcare/economy problem. To best manage this complex bio-psycho-social condition a 360-degree approach is needed, as the psycho-social components are often more important than the scant pathophysiology. Pattern analysis of cannabis users suggested that attempts to alleviate musculo-skeletal pain is often seen as a major drive to use cannabinoids.
Cannabinoid Use Among Liver Transplant Recipients
The effect of cannabinoids on liver transplant outcomes is an area of active research. We aimed to investigate marijuana (MJ) and cannabidiol (CBD) use among liver transplant recipients at the University of Colorado Hospital (UCH), specifically prevalence, habits, and predictors of use. Liver transplant recipients followed at UCH with valid email addresses were sent an informed consent postcard and survey invitation. This exploratory survey was conducted using REDCap. IBM SPSS Statistics software was used for statistical analysis. Of 1227 recipients who were sent surveys, 538 people responded. On average, respondents were 59 years old, with 63.7% male and 81.7% White. Hepatitis C virus (HCV; 30.4%) and alcohol use (17.7%) were the most common etiologies of liver disease. Among respondents, 23.8% reported current MJ use. Methods of use included smoking (72.4%), ingestion (55.3%), and vaporization (31.7%). Top reasons for MJ use were recreation (56.5%), anxiety (54.8%), and pain (53.2%). Among respondents, 21.0% currently used CBD, usually in the form of creams or lotions (58.9%) and to relieve pain (84.9%) and anxiety (31.1%). In multivariable analysis, age (odds ratio [OR], 0.941; 95% confidence interval [CI], 0.923-0.959; P < 0.001), diabetes mellitus (OR, 0.357; 95% CI, 0.171-0.746; P = 0.01), HCV cirrhosis (OR, 3.949; 95% CI, 2.281-6.835; P < 0.001), alcohol-related cirrhosis (OR, 2.101; 95% CI, 1.202-3.671; P = 0.01), and current tobacco use (OR, 2.918; 95% CI, 1.065-7.990; P = 0.04) were significant predictors of MJ use. Our study shows that cannabinoid use after liver transplant is common. MJ use is associated with decreasing age, alcohol-related and HCV cirrhosis, and tobacco use. Anxiety, pain, and recreation were top reasons for its use. Transplant teams should address reasons why their patients use MJ and CBD and develop programs to mitigate anxiety and pain after transplant. Further studies are needed to examine effects of cannabinoids on liver transplant outcomes.
The CANBACK trial: a randomised, controlled clinical trial of oral cannabidiol for people presenting to the emergency department with acute low back pain
To assess the analgesic efficacy and safety of single-dose oral cannabidiol (CBD) as an adjunct to standard care for patients presenting to an emergency department with acute low back pain.
Developing a real-world evidence base for prescribed cannabis in the United Kingdom: preliminary findings from Project Twenty21
The therapeutic potential of medical cannabis to treat a variety of conditions is becoming increasingly recognised. Globally, a large number of countries have now legalised cannabis for medical uses and a substantial number of patients are able to access their medications. Yet in the UK, where medical cannabis was legalised in November 2018, only a handful of NHS prescriptions have been written, meaning that most patients are unable to access the medicine. Reasons for this are manyfold and include the perceived lack of clinical evidence due to the challenges of studying medical cannabis through randomised controlled trials. In order to develop the current evidence base, the importance of incorporating real-world data (RWD) to assess the effectiveness and efficacy of medical cannabis has gradually become recognised. The current paper provides a detailed outline of Project Twenty21 (T21), the UK's first medical cannabis registry, launched in August 2020. We provide the rationale for T21 and describe the methodology before reporting the characteristics of the 'first patients' enrolled in the registry. We describe the health status of all patients enrolled into the project during its first 7 months of operation and the sociodemographic characteristics and primary presenting conditions for these patients, as well as details of the medical cannabis prescribed to these individuals. By 12th March 2021, 678 people had been enrolled into T21; the majority (64%) were male and their average age was 38.7 years (range = 18-80). The most commonly reported primary conditions were chronic pain (55.6%) and anxiety disorders (32.0%) and they reported high levels of multi-morbidity, including high rates of insomnia and depression. We also present preliminary evidence from 75 patients followed up after 3 months indicating that receipt of legal, prescribed cannabis was associated with a significant increase in self-reported health, assessed using the visual analogue scale of the EQ-5D-5L (Cohen's d = .77, 95% CI = .51-1.03). Our initial findings complement reports from other large-scale databases globally, indicating that the current RWD is building up a pattern of evidence. With many clinicians demanding better and faster evidence to inform their decisions around prescribing medical cannabis, the current and future results of T21 will expand the existing evidence base on the effectiveness of cannabis-based medical products (CBMPs).
Substituting Cannabidiol for Opioids and Pain Medications Among Individuals With Fibromyalgia: A Large Online Survey
People report substituting cannabis for pain medications, but whether cannabidiol (CBD) is used similarly remains unknown. CBD products can be CBD alone (isolate), hemp extract (containing <0.3% Δ-9-tetrahydrocannabinol [THC], other cannabinoids, and terpenes), or CBD-cannabis (containing >0.3% THC). In a secondary analysis from a cross-sectional survey, we examined substitution patterns among n = 878 individuals with fibromyalgia who currently used CBD. We sub-grouped participants by most commonly used CBD product (CBD isolate, hemp, CBD-cannabis, no preference) and whether they substituted CBD for medications. We investigated rationale for substituting, substitution-driven medication changes, CBD use patterns, and changes in pain-related symptoms (eg, sleep, anxiety). The study population was 93.6% female and 91.5% Caucasian, with an average age of 55.5 years. The majority (n = 632, 72.0%) reported substituting CBD products for medications, most commonly NSAIDs (59.0%), opioids (53.3%), gabapentanoids (35.0%), and benzodiazepines (23.1%). Most substituting participants reported decreasing or stopping use of these pain medications. The most common reasons for substitution were fewer side effects and better symptom management. Age, hemp products, past-year use of marijuana, and higher somatic burden were all associated with substituting (P's ≤ .05). Those who substituted reported larger improvements in health and pain than those who did not. Participants using CBD-cannabis reported significantly more substitutions than any other group (P's ≤ .001) and larger improvements in health, pain, memory, and sleep than other subgroups. This widespread naturalistic substitution for pain medications suggests the need for more rigorous study designs to examine this effect. PERSPECTIVE: This article shows that people with fibromyalgia are deliberately substituting CBD products for conventional pain medications despite the dearth of evidence suggesting CBD products may be helpful for fibromyalgia. CBD's medication-sparing and therapeutic potential should be examined in more rigorous study designs.
Lack of efficacy of cannabidiol for relieving back pain: time to re-set expectations?
Safety and tolerability of nabiximols oromucosal spray: a review of real-world experience in observational studies, registries, and case reports
: Nabiximols oromucosal spray,a cannabis-based medicine containing a balanced ratio of Δ-9-tetrahydrocannabinol and cannabidiol, is approved widely as an add-on therapy for symptomatic relief of spasticity in people with multiple sclerosis (MS). Most safety data for nabiximols derive from use in MS spasticity, with some data available from the analgesia area.
Oral efficacy of Δ(9)-tetrahydrocannabinol and cannabidiol in a mouse neuropathic pain model
The psychoactive and non-psychoactive constituents of cannabis, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have synergistic analgesic efficacy in animal models of neuropathic pain when injected systemically. However, the relevance of this preclinical synergy to clinical neuropathic pain studies is unclear because many of the latter use oral administration. We therefore examined the oral effectiveness of these phytocannabinoids and their interactions in a mouse chronic constriction injury (CCI) model of neuropathic pain. THC produced a dose-dependent reduction in mechanical and cold allodynia, but also induced side-effects with similar potency. CBD also reduced allodynia, albeit with lower potency than THC, but did not produce cannabinoid-like side-effects at any dose tested. Combination THC:CBD produced a dose-dependent reduction in allodynia, however, it displayed little to no synergy. Combination THC:CBD produced substantial, synergistic side-effects which increased with the proportion of CBD. These findings demonstrate that oral THC and CBD, alone and in combination, have analgesic efficacy in an animal neuropathic pain model. Unlike prior systemic injection studies, combination THC:CBD lacks analgesic synergy when delivered orally. Furthermore, both THC and combination THC:CBD display a relatively poor therapeutic window when delivered orally. This suggests that CBD provides a safer, albeit lower efficacy, oral treatment for nerve injury induced neuropathic pain than THC-containing preparations. This article is part of the special issue on 'Cannabinoids'.
Authorization Patterns, Safety, and Effectiveness of Medical Cannabis in Quebec
Despite increasing demand for data, little is known about the authorization patterns, safety, and effectiveness of medical cannabis products. We conducted a 2 year observational study of adult patients who were legally authorized a medical cannabis product from a single licensed producer; we captured and analyzed authorized cannabis use patterns by cannabinoid profile (tetrahydrocannabinol [THC]-dominant; cannabidiol [CBD]-dominant; and balanced (THC:CBD) and clinical outcomes using standardized outcome measures every 3 months for 12 months at a network of medical cannabis clinics in Quebec, Canada. We recruited 585 patients (average age 56.5 years), of whom 61% identified as female and 85% reported pain as their primary complaint. Over 12 months, there was a significant increase in the number of products authorized (=2.59, =0.01). The proportion of authorizations for a THC-dominant or CBD-dominant product increased relative to the proportion of authorizations for a balanced (THC:CBD) product (all <0.01). Symptom improvement over time was observed for pain, tiredness, drowsiness, anxiety, and well-being. Patients authorized THC-dominant products exhibited less symptom improvement for anxiety and well-being relative to those authorized CBD-dominant or balanced (THC:CBD) products. Medical cannabis was well tolerated across all product profiles. These real-world data reveal changes in medical cannabis authorization patterns and suggest that symptom improvement may vary by cannabinoid profile over 12 months of follow-up.
Can Cannabidiol Affect the Efficacy of Chemotherapy and Epigenetic Treatments in Cancer?
The success of cannabinoids with chronic neuropathic pain and anxiety has been demonstrated in a multitude of studies. With the high availability of a non-intoxicating compound, cannabidiol (CBD), an over-the-counter medication, has generated heightened interest in its use in the field of oncology. This review focuses on the widespread therapeutic potential of CBD with regard to enhanced wound healing, lowered toxicity profiles of chemotherapeutics, and augmented antitumorigenic effects. The current literature is sparse with regard to determining the clinically relevant concentrations of CBD given the biphasic nature of the compound's response. Therefore, there is an imminent need for further dose-finding studies in order to determine the optimal dose of CBD for both intermittent and regular users. We address the potential influence of regular or occasional CBD usage on therapeutic outcomes in ovarian cancer patients. Additionally, as the development of chemoresistance in ovarian cancer results in treatment failure, the potential for CBD to augment the efficacy of conventional chemotherapeutic and epigenetic drugs is a topic of significant importance. Our review is focused on the widespread therapeutic potential of CBD and whether or not a synergistic role exists in combination with epigenetic and classic chemotherapy medications.
Novel cannabidiol aspartame combination treatment (JW-100) significantly reduces ISGA score in atopic dermatitis: Results from a randomized double-blinded placebo-controlled interventional study
Atopic dermatitis (AD) is a common and chronic inflammatory skin disease that erupts periodically. Although the negative impact of the disorder on overall quality of life has been well established, new treatments for AD are still needed. Various studies have reported on cannabidiol's effectiveness in relieving pain and easing inflammation while not presenting major health risks.
Cannabidiol (CBD) and other drug use among young adults who use cannabis in Los Angeles
Cannabidiol (CBD) is purportedly a promising therapeutic agent to provide relief for a variety of medical conditions with mild or no psychoactive effects. However, little is known about young adults who use cannabis and CBD-dominant products, and associations between CBD use and other drug use.
Nabiximols in Chronic Neuropathic Pain: A Meta-Analysis of Randomized Placebo-Controlled Trials
Pooled analysis of nabiximols and placebo in randomized controlled studies (RCTs) of chronic neuropathic pain.
Inhaled Cannabis Suppresses Chemotherapy-Induced Neuropathic Nociception by Decoupling the Raphe Nucleus: A Functional Imaging Study in Rats
Efficacy of inhaled cannabis for treating pain is controversial. Effective treatment for chemotherapy-induced neuropathy represents an unmet medical need. We hypothesized that cannabis reduces neuropathic pain by reducing functional coupling in the raphe nuclei.
Cannabis sativa and Skin Health: Dissecting the Role of Phytocannabinoids
The use of is currently recognized to ease certain types of chronic pain, reduce chemotherapy-induced nausea, and improve anxiety. Nevertheless, few studies highlighted the therapeutic potential of extracts and related phytocannabinoids for a variety of widespread skin disorders including acne, atopic dermatitis, psoriasis, pruritus, and pain. This review summarized the current evidence on the effects of phytocannabinoids at the cutaneous level through the collection of and clinical studies published on PubMed, Scopus, Embase, and Web of Science until October 2020. Phytocannabinoids have demonstrated potential anti-inflammatory, antioxidant, anti-aging, and anti-acne properties by various mechanisms involving either CB/-dependent and independent pathways. Not only classical immune cells, but also several skin-specific actors, such as keratinocytes, fibroblasts, melanocytes, and sebocytes, may represent a target for phytocannabinoids. Cannabidiol, the most investigated compound, revealed photoprotective, antioxidant, and anti-inflammatory mechanisms at the cutaneous level, while the possible impact on cell differentiation, especially in the case of psoriasis, would require further investigation. Animal models and pilot clinical studies supported the application of cannabidiol in inflammatory-based skin diseases. Also, one of the most promising applications of non-psychotropic phytocannabinoids is the treatment of seborrheic disorders, especially acne. In conclusion, the incomplete knowledge of the role of the endocannabinoid system in skin disorders emerged as an important limit for pharmacological investigations. Moreover, the limited studies conducted on extracts suggested a higher potency than single phytocannabinoids, thus stimulating new research on phytocannabinoid interaction.
Pain response to cannabidiol in induced acute nociceptive pain, allodynia, and hyperalgesia by using a model mimicking acute pain in healthy adults in a randomized trial (CANAB I)
Preclinical studies have demonstrated the analgesic potential of cannabidiol (CBD). Those suggesting an effect on pain-processing receptors have brought CBD back into focus. This study assessed the effect of CBD on acute pain, hyperalgesia, and allodynia compared with placebo. Twenty healthy volunteers were included in this randomized, placebo-controlled, double-blinded, crossover study assessing pain intensities (using numeric rating scale), secondary hyperalgesia (von Frey filament), and allodynia (dry cotton swab) in a well-established acute pain model with intradermal electrical stimulation. The authors compared the effect of 800-mg orally administered CBD on pain compared with placebo. They further examined the effect on hyperalgesia and allodynia. Cannabidiol whole blood levels were also measured. Pain ratings (mean ± SD) did not differ significantly after CBD application compared with placebo (5.2 ± 0.7 vs 5.3 ± 0.7, P-value 0.928), neither did the areas of hyperalgesia and allodynia differ significantly after CBD application compared with placebo (hyperalgesia 23.9 ± 19.2 cm2 vs 27.4 ± 17.0 cm2, P-value 0.597; allodynia 16.6 ± 13.1 cm2 vs 17.3 ± 14.1 cm2, P-value 0.884). The CBD whole blood level (median, first to third quartile) was 2.0 µg/L (1.5-5.1) 60 minutes and 5.0 µg/L (4.0-10.4) 130 minutes after CBD application. Although the oral application of 800-mg CBD failed to show a significant effect, it is important to focus future research on different dosing, routes of administration, and CBD as a part of multimodal treatment strategies before negating its effects on acute pain.
Knowledge and Opinion on Cannabinoids Among Orthopaedic Traumatologists
Cannabinoids are an increasingly popular therapy among orthopaedic patients for musculoskeletal conditions. A paucity of evidence to support their use in orthopaedics exists, likely because of the incongruence of federal and state legalization and the stigma surrounding cannabis. The purpose of this study is to elucidate sentiments and knowledge base of the orthopaedic trauma community with regard to cannabinoid-containing compounds.
Cannabis-based medicines and pain: a review of potential synergistic and entourage effects
The recent legalization of medicinal cannabis in several jurisdictions has spurred the development of therapeutic formulations for chronic pain. Unlike pure delta-9-tetrahydrocannabinol (THC), full-spectrum products contain naturally occurring cannabinoids and have been reported to show improved efficacy or tolerability, attributed to synergy between cannabinoids and other components in the cannabis plant. Although 'synergy' indicates that two or more active compounds may produce an additive or combined effect greater than their individual analgesic effect, potentiation of the biological effect of a compound by related but inactive compounds, in combination, was termed the 'entourage effect'. Here, we review current evidence for potential synergistic and entourage effects of cannabinoids in pain relief. However, definitive clinical trials and functional studies are still required.
The effects of cannabidiol and analgesic expectancies on experimental pain reactivity in healthy adults: A balanced placebo design trial
Despite its frequent use for pain relief, no experimental pain research has tested the analgesic effects of cannabidiol (CBD) in humans. The goal of this study was to experimentally test the effects of CBD and expectancies for receiving CBD on human pain reactivity. Using a crossover, 2 × 2 factorial balanced placebo design, drug administration (given inactive substance or given active CBD) and verbal instruction sets (told inactive substance or told active CBD) were experimentally manipulated. Fifteen healthy adults each completed four separate experimental sessions. Participants were randomly assigned to different counterbalanced manipulation conditions at each session: control (told inactive-given inactive); expectancy (told active CBD-given inactive); drug (told inactive-given active CBD); and expectancy + drug (told active CBD-given active CBD). Primary outcomes were pain threshold, tolerance, intensity, unpleasantness, conditioned pain modulation (CPM), and offset analgesia (OA). There was a significant main effect of instructions on OA, such that the OA response was significantly larger when participants were told that they received CBD, regardless of drug content. Pain unpleasantness was significantly reduced in the drug, expectancy, and expectancy + drug conditions, relative to the control condition. The drug and expectancy conditions separately improved CPM, whereas the expectancy + drug and control conditions produced the lowest CPM change scores. We did not detect significant effects for pain threshold, tolerance, or intensity. Our results indicated that separate pain outcomes can be differentially affected by CBD and/or expectancies for receiving CBD. Future investigations of the psychological and pharmacological mechanisms underlying CBD analgesia are warranted. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Anti-seizure medications for Lennox-Gastaut syndrome
Lennox-Gastaut syndrome (LGS) is an age-specific epilepsy syndrome characterised by multiple seizure types, including drop seizures. LGS has a characteristic electroencephalogram, an onset before age eight years and an association with drug resistance. This is an updated version of the Cochrane Review published in 2013.
Application of medical cannabis in unstable angina and coronary artery disease: A case report
First discovered in 1990, the endocannabinoid system (ECS) was initially shown to have an intimate relationship with central areas of the nervous system associated with pain, reward, and motivation. Recently, however, the ECS has been extensively implicated in the cardiovascular system with contractility, heart rate, blood pressure, and vasodilation. Emerging data demonstrate modulation of the ECS plays an essential role in cardio metabolic risk, atherosclerosis, and can even limit damage to cardiomyocytes during ischemic events.
A Multicriteria Decision Analysis Comparing Pharmacotherapy for Chronic Neuropathic Pain, Including Cannabinoids and Cannabis-Based Medical Products
Pharmacological management of chronic neuropathic pain (CNP) still represents a major clinical challenge. Collective harnessing of both the scientific evidence base and clinical experience (of clinicians and patients) can play a key role in informing treatment pathways and contribute to the debate on specific treatments (e.g., cannabinoids). A group of expert clinicians (pain specialists and psychiatrists), scientists, and patient representatives convened to assess the relative benefit-safety balance of 12 pharmacological treatments, including orally administered cannabinoids/cannabis-based medicinal products, for the treatment of CNP in adults. A decision conference provided the process of creating a multicriteria decision analysis (MCDA) model, in which the group collectively scored the drugs on 17 effect criteria relevant to benefits and safety and then weighted the criteria for their clinical relevance. Cannabis-based medicinal products consisting of tetrahydrocannabinol/cannabidiol (THC/CBD), in a 1:1 ratio, achieved the highest overall score, 79 (out of 100), followed by CBD dominant at 75, then THC dominant at 72. Duloxetine and the gabapentinoids scored in the 60s, amitriptyline, tramadol, and ibuprofen in the 50s, methadone and oxycodone in the 40s, and morphine and fentanyl in the 30s. Sensitivity analyses showed that even if the pain reduction and quality-of-life scores for THC/CBD and THC are halved, their benefit-safety balances remain better than those of the noncannabinoid drugs. The benefit-safety profiles for cannabinoids were higher than for other commonly used medications for CNP largely because they contribute more to quality of life and have a more favorable side effect profile. The results also reflect the shortcomings of alternative pharmacological treatments with respect to safety and mitigation of neuropathic pain symptoms. Further high-quality clinical trials and systematic comprehensive capture of clinical experience with cannabinoids is warranted. These results demonstrate once again the complexity and multimodal mechanisms underlying the clinical experience and impact of chronic pain.
Antinociceptive effects of minor cannabinoids, terpenes and flavonoids in Cannabis
Cannabis has been used for centuries for its medicinal properties. Given the dangerous and unpleasant side effects of existing analgesics, the chemical constituents of Cannabis have garnered significant interest for their antinociceptive, anti-inflammatory and neuroprotective effects. To date, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) remain the two most widely studied constituents of Cannabis in animals. These studies have led to formulations of THC and CBD for human use; however, chronic pain patients also use different strains of Cannabis (sativa, indica and ruderalis) to alleviate their pain. These strains contain major cannabinoids, such as THC and CBD, but they also contain a wide variety of cannabinoid and noncannabinoid constituents. Although the analgesic effects of Cannabis are attributed to major cannabinoids, evidence indicates other constituents such as minor cannabinoids, terpenes and flavonoids also produce antinociception against animal models of acute, inflammatory, neuropathic, muscle and orofacial pain. In some cases, these constituents produce antinociception that is equivalent or greater compared to that produced by traditional analgesics. Thus, a better understanding of the extent to which these constituents produce antinociception alone in animals is necessary. The purposes of this review are to (1) introduce the different minor cannabinoids, terpenes, and flavonoids found in Cannabis and (2) discuss evidence of their antinociceptive properties in animals.
The Effects of Cannabis: Implications for the Surgical Patient
Cannabis use is increasingly prevalent. Cannabinoid receptors regulate pro-inflammatory cytokines, and compounds in marijuana exert diverse physiologic effects. As more patients use cannabis, clinicians should recognize implications of perioperative cannabis use. Although the role of cannabis use in perioperative pain control has been explored, little is known about its effect on perioperative wound healing or on hematologic, pulmonary, and cardiovascular physiology.
Endocannabinoid System as Therapeutic Target of PTSD: A Systematic Review
Post-Traumatic Stress Disorder (PTSD) is a complex disorder involving dysregulation of stress-related hormones and neurotransmitter systems. Research focused on the endocannabinoid system (eCBS) for anxiety and stress regulation, cognitive and emotional responses modulation and aversive memories extinction, leading to the hypothesis that it could represent a possible alternative treatment target for PTSD. In this systematic review, we summarize evidence about the efficacy and safety of medicinal cannabidiol (CBD), Δ-tetrahydrocannabinol (Δ-THC), and nabilone in PTSD treatment. The PRISMA statement guidelines were followed. A systematic literature search was conducted in MEDLINE/PubMed, Scopus and Web of Science by two independent researchers, who also performed data extraction and quality assessment. Among the initial 495 papers, 234 were screened for eligibility and 10 were included. Studies suggested that different medicinal cannabinoids at distinct doses and formulations could represent promising treatment strategies for the improvement of overall PTSD symptomatology as well as specific symptom domains (e.g., sleep disorders, arousal disturbances, suicidal thoughts), also influencing quality of life, pain and social impact. Although there is a robust rationale for treatment with drugs that target the eCBS and the results are promising, further studies are needed to investigate the safety and efficacy profile of their prolonged use.
Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain-Narrative Review
Neuropathic pain in humans results from an injury or disease of the somatosensory nervous system at the peripheral or central level. Despite the considerable progress in pain management methods made to date, peripheral neuropathic pain significantly impacts patients' quality of life, as pharmacological and non-pharmacological methods often fail or induce side effects. Topical treatments are gaining popularity in the management of peripheral neuropathic pain, due to excellent safety profiles and preferences. Moreover, topical treatments applied locally may target the underlying mechanisms of peripheral sensitization and pain. Recent studies showed that peripheral sensitization results from interactions between neuronal and non-neuronal cells, with numerous signaling molecules and molecular/cellular targets involved. This narrative review discusses the molecular/cellular mechanisms of drugs available in topical formulations utilized in clinical practice and their effectiveness in clinical studies in patients with peripheral neuropathic pain. We searched PubMed for papers published from 1 January 1995 to 30 November 2020. The key search phrases for identifying potentially relevant articles were "topical AND pain", "topical AND neuropathic", "topical AND treatment", "topical AND mechanism", "peripheral neuropathic", and "mechanism". The result of our search was 23 randomized controlled trials (RCT), 9 open-label studies, 16 retrospective studies, 20 case (series) reports, 8 systematic reviews, 66 narrative reviews, and 140 experimental studies. The data from preclinical studies revealed that active compounds of topical treatments exert multiple mechanisms of action, directly or indirectly modulating ion channels, receptors, proteins, and enzymes expressed by neuronal and non-neuronal cells, and thus contributing to antinociception. However, which mechanisms and the extent to which the mechanisms contribute to pain relief observed in humans remain unclear. The evidence from RCTs and reviews supports 5% lidocaine patches, 8% capsaicin patches, and botulinum toxin A injections as effective treatments in patients with peripheral neuropathic pain. In turn, single RCTs support evidence of doxepin, funapide, diclofenac, baclofen, clonidine, loperamide, and cannabidiol in neuropathic pain states. Topical administration of phenytoin, ambroxol, and prazosin is supported by observational clinical studies. For topical amitriptyline, menthol, and gabapentin, evidence comes from case reports and case series. For topical ketamine and baclofen, data supporting their effectiveness are provided by both single RCTs and case series. The discussed data from clinical studies and observations support the usefulness of topical treatments in neuropathic pain management. This review may help clinicians in making decisions regarding whether and which topical treatment may be a beneficial option, particularly in frail patients not tolerating systemic pharmacotherapy.
Adverse events of recreational cannabis use reported to the French addictovigilance network (2012-2017)
To describe the adverse events (AEs) of recreational cannabis use in France between 2012 and 2017.
Effects of Cannabidiol Chewing Gum on Perceived Pain and Well-Being of Irritable Bowel Syndrome Patients: A Placebo-Controlled Crossover Exploratory Intervention Study with Symptom-Driven Dosing
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders. Its pathophysiology is diverse and variable, involving disturbed gut-brain interactions, altered motility and secretion, visceral hypersensitivity, increased intestinal permeability, immune activation, and changes in gut microbiota. Complaints experienced by patients suffering from IBS and its co-morbidities strongly impair quality of life (QoL), and available treatments are often unsatisfactory. Anecdotal reports and preclinical data suggest that the endocannabinoid system and functionally related mechanisms could offer treatment targets. Cannabidiol (CBD) is a candidate agent of interest with a broad molecular target profile and the absence of psychoactive properties. In 32 female IBS patients, we explored the effect of a chewing gum formulation containing 50 mg CBD on abdominal pain and perceived well-being in a randomized, double-blinded, placebo-controlled cross-over trial. Chewing gums were used on-demand guided by pain symptoms with a maximum of six per day. Pain intensity was assessed by a visual analogue scale (scale 0.0-10.0), and QoL was evaluated with the IBS-36 questionnaire. There was no statistically significant difference in pain scores between CBD and placebo at a group level. Subgroup and individual analyses showed a highly variable picture. No indications were found for symptom-driven intake, which also remained lower than expected overall. With the current design, based on the assumption that IBS patients would adjust their intake to their perceived symptom relief, no differences at the group level were found between CBD and placebo gum in pain scores and the number of gums used. The low use of the gums also indicates that the benefits experienced by these patients generally did not outweigh practical disadvantages such as prolonged chewing throughout the day. The very high intra- and inter-individual variation in IBS symptoms warrant future trials that are more personalized, for example by applying an N-of-1 (rotating) design with individualized dose titration.
Cannabis sativa L. may reduce aggressive behaviour towards humans in shelter dogs
Among the phytocomplex components of Cannabis sativa L., cannabidiol (CBD) has a recognised therapeutic effect on chronic pain. Little is known about the veterinary use of CBD in dogs. Even less is known on the effects of CBD on dog behaviour, especially in shelters. The purpose of this study was to determine if CBD affects stress related behaviour in shelter dogs. The sample consisted of 24 dogs divided into two groups that were created by assigning the dogs alternately: 12 dogs were assigned to the treatment group and 12 to the control group. Extra virgin olive oil, titrated to 5% in CBD was given to treated group; the placebo consisted of olive oil only, dispensed daily for 45 days. Behavioural data were collected using the 'focal animal' sampling method with 'all occurrences' and '1/0' methods for 3 h: before (T), after 15 days (T), after 45 days of treatment (T) and after 15 days from the end of the treatment (T). Treated dogs showed reduced aggressive behaviour toward humans following the treatment (Friedman Test: χ = 13.300; df = 3; N = 12; p = .004; adj. sig. p = 0.027), but the difference in the decrease of aggressive behaviour between the two groups was not significant (Mann-Whitney U test, T-T: Z = - 1.81; N = 24; p = 0.078). Other behaviours indicative of stress, such as displacing activities and stereotypes, did not decrease. Despite some non-significant results, our findings suggest that it is worth doing more research to further investigate the effect of CBD on dog behaviour; this would be certainly valuable because the potential for improving the welfare of dogs in shelters is priceless.
Should You Recommend Cannabinoids for This Patient With Painful Neuropathy? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center
Cannabis includes 140 active cannabinoid compounds, the most important of which are tetrahydrocannabinol and cannabidiol (CBD). Tetrahydrocannabinol is primarily responsible for the intoxicating effects of cannabis; CBD has potential therapeutic effects, including reduction in chronic pain. Recent legislative changes have resulted in the legal availability of cannabinoids in all 50 states, as well as a marked increase in patients' interest in their use. Despite an abundance of data, albeit of varied quality, clinicians may feel poorly prepared to counsel patients seeking advice on the suitability of CBD products for various indications, particularly chronic neuropathic pain. In 2018, on the basis of a systematic review of the literature, a Canadian Evidence Review Group published a guideline with recommendations for clinicians on prescribing cannabinoids in primary care practice. The overall quality of evidence was low to very low. In a meta-analysis of 15 randomized trials of medical cannabis for treating chronic pain, 39% of patients achieved at least a 30% reduction in pain. The corresponding value for placebo-treated patients was 30%; the number needed to treat was 11. More evidence exists for neuropathic pain than for other types of noncancer pain. Here, a general internist with a focus on addiction medicine and an addiction psychiatrist discuss how they would apply the literature to make recommendations for a patient with painful diabetic neuropathy, including counseling on both potential benefits and harms.
Cannabis: A Toxin-Producing Plant with Potential Therapeutic Uses
For thousands of years, has been utilized as a medicine and for recreational and spiritual purposes. Phytocannabinoids are a family of compounds that are found in the cannabis plant, which is known for its psychotogenic and euphoric effects; the main psychotropic constituent of cannabis is Δ9-tetrahydrocannabinol (Δ9-THC). The pharmacological effects of cannabinoids are a result of interactions between those compounds and cannabinoid receptors, CB1 and CB2, located in many parts of the human body. Cannabis is used as a therapeutic agent for treating pain and emesis. Some cannabinoids are clinically applied for treating chronic pain, particularly cancer and multiple sclerosis-associated pain, for appetite stimulation and anti-emesis in HIV/AIDS and cancer patients, and for spasticity treatment in multiple sclerosis and epilepsy patients. Medical cannabis varies from recreational cannabis in the chemical content of THC and cannabidiol (CBD), modes of administration, and safety. Despite the therapeutic effects of cannabis, exposure to high concentrations of THC, the main compound that is responsible for most of the intoxicating effects experienced by users, could lead to psychological events and adverse effects that affect almost all body systems, such as neurological (dizziness, drowsiness, seizures, coma, and others), ophthalmological (mydriasis and conjunctival hyperemia), cardiovascular (tachycardia and arterial hypertension), and gastrointestinal (nausea, vomiting, and thirst), mainly associated with recreational use. Cannabis toxicity in children is more concerning and can cause serious adverse effects such as acute neurological symptoms (stupor), lethargy, seizures, and even coma. More countries are legalizing the commercial production and sale of cannabis for medicinal use, and some for recreational use as well. Liberalization of cannabis laws has led to increased incidence of toxicity, hyperemesis syndrome, lung disease cardiovascular disease, reduced fertility, tolerance, and dependence with chronic prolonged use. This review focuses on the potential therapeutic effects of cannabis and cannabinoids, as well as the acute and chronic toxic effects of cannabis use on various body systems.
Reasons for cannabidiol use: a cross-sectional study of CBD users, focusing on self-perceived stress, anxiety, and sleep problems
Public and medical interest in cannabidiol (CBD) has been rising, and CBD is now available from various sources. Research into the effects of low-dose CBD on outcomes like stress, anxiety, and sleep problems have been scarce, so we conducted an online survey of CBD users to better understand patterns of use, dose, and self-perceived effects of CBD.
Medical cannabis for the treatment of fibromyalgia syndrome: a retrospective, open-label case series
The use of cannabis for treating fibromyalgia syndrome (FMS) has not been comprehensively investigated. Thus, we have assessed the efficacy and adverse events (AEs) of short- and long-term medical cannabis (MC) treatment for FMS.
Cannabidiol Does Not Impair Anabolic Signaling Following Eccentric Contractions in Rats
Cannabidiol (CBD) has proven clinical benefits in the treatment of seizures, inflammation, and pain. The recent legalization of CBD in many countries has caused increased interest in the drug as an over-the-counter treatment for athletes looking to improve recovery. However, no data on the effects of CBD on the adaptive response to exercise in muscle are available. To address this gap, we eccentrically loaded the tibialis anterior muscle of 14 rats, injected them with a vehicle (n = 7) or 100 mg/kg CBD (n = 7), and measured markers of injury, inflammation, anabolic signaling, and autophagy 18 hr later. Pro-inflammatory signaling through nuclear factor kappa B (NF-kB) (Ser536) increased with loading in both groups; however, the effect was significantly greater (36%) in the vehicle group (p < .05). Simultaneously, anabolic signaling through ribosomal protein S6 kinase beta-1 (S6K1) (Thr389) increased after eccentric contractions in both groups with no difference between vehicle and CBD (p = .66). The ribosomal protein S6 phosphorylation (240/244) increased with stimulation (p < .001) and tended to be higher in the CBD group (p = .09). The ubiquitin-binding protein p62 levels were not modulated by stimulation (p = .6), but they were 46% greater in the CBD compared with the vehicle group (p = .01). Although liver weight did not differ between the groups (p = .99) and levels of proteins associated with stress were similar, we did observe serious side effects in one animal. In conclusion, an acute dose of CBD decreased pro-inflammatory signaling in the tibialis anterior without blunting the anabolic response to exercise in rats. Future research should determine whether these effects translate to improved recovery without altering adaptation in humans.
Use and Perceptions of Cannabidiol Products in Canada and in the United States
This study aimed to characterize use and perceptions of cannabidiol (CBD) products. Participants aged 16-65 years in Canada (=15,042) and the United States (=30,288) completed measures on prevalence and patterns of CBD product use and perceptions of CBD oil as part of the 2019 International Cannabis Policy Study online survey. Past 12-month CBD product use was significantly more prevalent among respondents in the United States (26.1%) than in Canada (16.2%). Consumers in the United States and Canada reported using a range of CBD products, including drops (46.3% vs. 47.3%, respectively), topicals (26.0% vs. 16.7%), edibles/foods (23.8% vs. 17.6%), vape oils (18.9% vs. 13.3%), capsules (13.3% vs. 16.7%), and dried flower (10.1% vs. 16.1%). CBD was most commonly reported for management of pain, anxiety, and depression. Over half of CBD consumers in both countries reported that CBD oil was beneficial for health. Use of CBD products is common in both the United States and Canada, primarily to manage self-reported health conditions for which there is little or no evidence of efficacy. Clearer public health messaging regarding the therapeutic effects of CBD is warranted.
A Large-Scale Naturalistic Examination of the Acute Effects of Cannabis on Pain
Cannabis use for pain relief is commonly reported, yet laboratory studies and clinical trials suggest that cannabinoids are weak analgesics, and it is unclear whether perceived reductions in pain from before to after cannabis use relate to factors such as dose, method of administration, phytocannabinoid content, or the age or gender of the user. We determined whether inhalation of cannabis decreased self-reported pain ratings as well as whether user gender, age, time, method of administration, tetrahydrocannabinol (THC)/cannabidiol (CBD) content, or dose of cannabis contribute to changes in these ratings. We also examined whether tolerance may develop to the analgesic effects of cannabis over time. Archival data were obtained from Strainprint, a medical cannabis app that allows patients to track symptoms before and after using different strains and doses of cannabis. Latent change score models and multilevel models were used to analyze data from 131,582 sessions in which inhaled cannabis was used to treat "muscle pain," "joint pain," or "nerve pain." For all three pain symptoms, severity ratings decreased significantly after cannabis use. Women reported higher baseline and postcannabis pain severity than did men, and men reported larger decreases in pain than did women. Neither THC nor CBD content nor their interaction predicted reductions in pain ratings. However, vaping was associated with larger reductions in joint pain ratings than was smoking, and lower doses were associated with larger reductions in nerve pain ratings. Additionally, for all three pain symptoms, the dose of cannabis used to manage pain increased significantly over time. Inhaled cannabis reduces self-reported pain severity by ∼42-49%. However, these reductions appear to diminish across time, and patients use larger doses across time, suggesting that analgesic tolerance develops with continued use.
Therapeutic Efficacy of Cannabidiol (CBD): A Review of the Evidence from Clinical Trials and Human Laboratory Studies
Global policy changes have increased access to products containing cannabidiol (CBD), a primary constituent of hemp and cannabis. The CBD product industry has experienced tremendous growth, in part, because CBD is widely touted as an effective therapeutic for myriad health conditions. However, only 1 CBD product (Epidiolex®) has been approved by the U.S. Food and Drug Administration (FDA) to date. There is substantial interest among consumers and the medical and scientific communities regarding the therapeutic potential of CBD, including for novel indications that are not recognized by the FDA. The purpose of this review was to synthesize available evidence from clinical research regarding the efficacy of CBD as a therapeutic.
Evaluation of Patient Reported Safety and Efficacy of Cannabis From a Survey of Medical Cannabis Patients in Canada
With the medical use of cannabis permitted in Canada since 2001, patients seek to use this botanical drug to treat a range of medical conditions. However, many healthcare practitioners express the need for further scientific evidence around the use of medical cannabis. This real-world evidence study aimed to address the paucity of scientific data by surveying newly registered medical cannabis patients, before beginning medical cannabis treatment, and at one follow up 6 weeks after beginning medical cannabis treatment. The goal was to collect data on efficacy, safety and cannabis product type information to capture the potential impact medical cannabis had on patient-reported quality of life (QOL) and several medical conditions over a 6-week period using validated questionnaires. The 214 participants were mainly male (58%) and 57% of the population was older than 50. The most frequently reported medical conditions were recurrent pain, post-traumatic stress disorder (PTSD), anxiety, sleep disorders [including restless leg syndrome (RLS)], and arthritis and other rheumatic disorders. Here we report that over 60% of our medical cannabis cohort self-reported improvements in their medical conditions. With the use of validated surveys, we found significant improvements in recurrent pain, PTSD, and sleep disorders after 6 weeks of medical cannabis treatment. Our findings from patients who reported arthritis and other rheumatic disorders are complex, showing improvements in pain and global activity sub-scores, but not overall changes in validated survey scores. We also report that patients who stated anxiety as their main medical condition did not experience significant changes in their anxiety after 6 weeks of cannabis treatment, though there were QOL improvements. While these results show that patients find cannabis treatment effective for a broad range of medical conditions, cannabis was not a remedy for all the conditions investigated. Thus, there is a need for future clinical research to support the findings we have reported. Additionally, while real-world evidence has not historically been utilized by regulatory bodies, we suggest changes in public policy surrounding cannabis should occur to reflect patient reported efficacy of cannabis from real-world studies due to the uniqueness of medical cannabis's path to legalization.
A Review of the Potential Use of Pinene and Linalool as Terpene-Based Medicines for Brain Health: Discovering Novel Therapeutics in the Flavours and Fragrances of Cannabis
"Medicinal cannabis" is defined as the use of cannabis-based products for the treatment of an illness. Investigations of cannabis compounds in psychiatric and neurological illnesses primarily focus on the major cannabinoids, cannabidiol (CBD) and Δ-tetrahydrocannabinol (Δ-THC), which are hypothesised to benefit multiple illnesses manifesting cognitive impairment, neurodegeneration and neuro-inflammation, as well as chronic pain, epilepsy and post-traumatic stress disorder, respectively. The cannabis plant contains >500 compounds, including terpenes responsible for the flavour and fragrance profiles of plants. Recently, research has begun providing evidence on the potential use of certain plant-derived terpenes in modern medicine, demonstrating anti-oxidant, anti-inflammatory, and neuroprotective effects of these compounds. This review examined the effects of two key terpenes, pinene and linalool, on parameters relevant to neurological and psychiatric disorders, highlighting gaps in the literature and recommendations for future research into terpene therapeutics. Overall, evidence is mostly limited to preclinical studies and well-designed clinical trials are lacking. Nevertheless, existing data suggests that pinene and linalool are relevant candidates for further investigation as novel medicines for illnesses, including stroke, ischemia, inflammatory and neuropathic pain (including migraine), cognitive impairment (relevant to Alzheimer's disease and ageing), insomnia, anxiety, and depression. Linalool and pinene influence multiple neurotransmitter, inflammatory and neurotrophic signals as well as behaviour, demonstrating psycho-activity (albeit non-intoxicating). Optimising the phytochemical profile of cannabis chemovars to yield therapeutic levels of beneficial terpenes and cannabinoids, such as linalool, pinene and CBD, could present a unique opportunity to discover novel medicines to treat psychiatric and neurological illnesses; however, further research is needed.
From an Alternative Medicine to a New Treatment for Refractory Epilepsies: Can Cannabidiol Follow the Same Path to Treat Neuropsychiatric Disorders?
Although cannabis has been known for ages as an "alternative medicine" to provide relief from seizures, pain, anxiety, and inflammation, there had always been a limited scientific review to prove and establish its use in clinics. Early studies carried out by Carlini's group in Brazil suggested that cannabidiol (CBD), a non-psychotropic phytocannabinoid present in , has anticonvulsant properties in animal models and reduced seizure frequency in limited human trials. Over the past few years, the potential use of cannabis extract in refractory epilepsy, including childhood epilepsies such as Dravet's syndrome and Lennox-Gastaut Syndrome, has opened a new era of treating epileptic patients. Thus, a considerable number of pre-clinical and clinical studies have provided strong evidence that phytocannabinoids has anticonvulsant properties, as well as being promising in the treatment of different neuropsychiatric disorders, such as depression, anxiety, post-traumatic stress disorder (PTSD), addiction, neurodegenerative disorders and autism spectrum disorder (ASD). Given the advances of cannabinoids, especially CBD, in the treatment of epilepsy, would the same expectation regarding the treatment of other neuropsychiatric disorders be possible? The present review highlights some contributions from Brazilian researchers and other studies reported elsewhere on the history, pre-clinical and clinical data underlying the use of cannabinoids for the already widespread treatment of refractory epilepsies and the possibility of use in the treatment of some neuropsychiatric disorders.
Cannabidiol as a Treatment for Chronic Pain: A Survey of Patients' Perspectives and Attitudes
Cannabis products have become easily available and accessible after decriminalization of cannabis for recreational and medicinal use in many states. Cannabidiol (CBD) has been of increasing interest to patients and is being used to self-medicate a variety of ailments. However, very limited information is available to patients and providers to form an educated opinion regarding its indicated use to treat the many conditions this substance has been implied to be helpful for. The aim of this survey was to learn about participants' attitudes and views towards cannabis-based medicine (CBM) with a focus on perception of "CBD" and its potential role for pain management.
Duration of Neurocognitive Impairment With Medical Cannabis Use: A Scoping Review
While the recreational use of cannabis has well-established dose-dependent effects on neurocognitive and psychomotor functioning, there is little consensus on the degree and duration of impairment typically seen with medical marijuana use. Compared to recreational cannabis users, medical cannabis patients have distinct characteristics that may modify the presence and extent of impairment. The goal of this review was to determine the duration of acute neurocognitive impairment associated with medical cannabis use, and to identify differences between medical cannabis patients and recreational users. These findings are used to gain insight on how medical professionals can best advise medical cannabis patients with regards to automobile driving or safety-sensitive tasks at work. A systematic electronic search for English language randomized controlled trials (RCTs), clinical trials and systematic reviews (in order to capture any potentially missed RCTs) between 2000 and 2019 was conducted through Ovid MEDLINE and EMBASE electronic databases using MeSH terms. Articles were limited to medical cannabis patients using cannabis for chronic non-cancer pain or spasticity. After screening titles and abstracts, 37 relevant studies were subjected to full-text review. Overall, seven controlled trials met the inclusion/exclusion criteria and were included in the qualitative synthesis: six RCTs and one observational clinical trial. Neurocognitive testing varied significantly between all studies, including the specific tests administered and the timing of assessments post-cannabis consumption. In general, cognitive performance declined mostly in a THC dose-dependent manner, with steady resolution of impairment in the hours following THC administration. Doses of THC were lower than those typically reported in recreational cannabis studies. In all the studies, there was no difference between any of the THC groups and placebo on any neurocognitive measure after 4 h of recovery. Variability in the dose-dependent relationship raises the consideration that there are other important factors contributing to the duration of neurocognitive impairment besides the dose of THC ingested. These modifiable and non-modifiable factors are individually discussed.
Assessment of hemp oil-based cannabidiol use in a community-based pharmacy setting
The Agricultural Improvement Act of 2018 legalized the commercial use of hemp-based products, including cannabidiol (CBD). However, the U.S. Food and Drug Administration (FDA) does not currently regulate the commercial sale of hemp oil-based CBD, and there is no FDA-approved indication for its nonprescription formulations despite the growing demand for, and use of, hemp oil-based CBD.
Emerging role of cannabinoids and synthetic cannabinoid receptor 1/cannabinoid receptor 2 receptor agonists in cancer treatment and chemotherapy-associated cancer management
Cannabis was extensively utilized for its medicinal properties till the 19 century. A steep decline in its medicinal usage was observed later due to its emergence as an illegal recreational drug. Advances in technology and scientific findings led to the discovery of delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound of cannabis, that further led to the discovery of endogenous cannabinoids system consisting of G-protein-coupled receptors - cannabinoid receptor 1 and cannabinoid receptor 2 along with their ligands, mainly anandamide and 2-arachidonoylglycerol. Endocannabinoid (EC) is shown to be a modulator not only for physiological functions but also for the immune system, endocrine network, and central nervous system. Medicinal research and meta-data analysis over the last few decades have shown a significant potential for both THC and cannabidiol (CBD) to exert palliative effects. People suffering from many forms of advanced stages of cancers undergo chemotherapy-induced nausea and vomiting followed by severe and chronic neuropathic pain and weight loss. THC and CBD exhibit effective analgesic, anxiolytic, and appetite-stimulating effect on patients suffering from cancer. Drugs currently available in the market to treat such chemotherapy-induced cancer-related ailments are Sativex (GW Pharmaceutical), Dronabinol (Unimed Pharmaceuticals), and Nabilone (Valeant Pharmaceuticals). Apart from exerting palliative effects, THC also shows promising role in the treatment of cancer growth, neurodegenerative diseases (multiple sclerosis and Alzheimer's disease), and alcohol addiction and hence should be exploited for potential benefits. The current review discusses the nature and role of CB receptors, specific applications of cannabinoids, and major studies that have assessed the role of cannabinoids in cancer management.