Therapeutic Use Of Cannabinoids Research Articles

Therapeutic Use of Cannabinoids in Critically Ill Patients: A Survey of Intensive Care Physicians in Germany.

Background: In the course of the legalization of cannabis for therapeutic purposes in Germany, there has been growing interest in the medical use of cannabinoids. To date, the therapeutic potential of cannabinoids for the treatment of critically ill patients has not been explored. Objectives: This study aims to understand better whether and how frequently cannabinoids have been administered to critically ill patients in recent years. Study Design: Initially, a survey was conducted among physicians working in intensive care units (ICUs) at the Hannover Medical School. Subsequently, 653 physicians working in ICUs throughout Germany were surveyed. The frequency and regimen of cannabinoid therapy initiated by the participating physicians in the last 2 years at the time of the survey were characterized. Results: Eight out of 9 physicians at Hannover Medical School and 59 out of 653 physicians in ICUs in Germany participated. At Hannover Medical School, 6 out of 8 physicians and in ICUs in Germany, 16 out of 59 physicians had used cannabinoids in some patients (mainly 9-10) during the 2-year period studied, with dronabinol in doses between 1 and 20 mg being their cannabinoid of choice. Metabolic and psychological distress and medication savings, followed by pain and nausea/vomiting, were the most frequently cited indications for cannabinoid therapy. No relevant safety issues arrived. Lack of personal experience, limited evidence, and gaps in knowledge were the most commonly cited reservations about cannabinoid use. Conclusions: During a 2-year period, dronabinol is used in a few critically ill patients in ICUs. The main indications are to reduce metabolic and psychological distress and to save medication. The majority of participating physicians indicated that the use of cannabinoids in the context of critical care medicine needs further exploration.

Therapeutic use of cannabinoids for the treatment of neurodegenerative disorders: a potential breakthrough.

Respected Editor, Marijuana, also known as cannabis, is a plant-based illicit drug notorious for its recreational purposes. However, in recent years its extracts are being extensively studied for their overall therapeutic effects. Active substances found in marijuana that interact with the endocannabinoid system are known as cannabinoids, the primary examples being 9-tetrahydrocannabinol (9-THC) and Cannabidiol (CBD). These cannabinoids ligand to receptors such as CB1 (found in CNS) and CB2 (found in immune system cells) to prevent the release of neurotransmitters and modulate immune cell migration as well as cytokine release, respectively (1). In recent years, there has been a surge of interest in the neuroprotective potential of marijuana; however, investigators could not make firm conclusions about the effectiveness of these treatments. A comprehensive review by Bahji A et al. (2022) found an evident link between cannabidiol-based products and relief from the motor as well as behavioural and psychological symptoms spanning Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD) (2). Here we discuss the effects of marijuana and its derivatives on the treating significant neurodegenerative disorders. Dronabinol (2.5 mg) seemed to lessen the disordered behaviours as assessed by the Cohen-Mansfield Agitation Inventory in 12 patients of AD (p=0.05) (3). Sherman et al. (2018) reported the association of cannabis administration with weight and pain management in AD patients. The adverse effects are typically well tolerated at the levels supplied, even though cannabis is linked to an increased risk of euphoria, sleepiness and psychosis (1). On the other hand, for HD, nabilone (1 or 2 mg) had a substantial therapeutic benefit in a different 10-week placebo-controlled crossover experiment as determined by the overall motor and chorea score on the Unified Huntington's Disease Rating Scale (UHDRS) (4). Available reviews revealed variable evidence suggesting the clinical benefits of cannabis in treating motor symptoms in patients with PD. A randomized trial found that compared to a placebo, giving a single dosage of 300 mg of CBD successfully decreased tremor amplitude (5). Neurological diseases, including the neurodegenerative diseases, comprise 8.7% of the disease burden in lower- middle- income countries (such as Pakistan) (6). Currently, there is no real cure for neurodegenerative disorders, only symptomatic management, such as dopamine treatment for PD or cholinesterase inhibitors for dementia. Cannabinoids might be the lifeline all neurodegenerative disorder patients have been waiting for. ---Continue

Attitudes and Knowledge Regarding the Therapeutic Use of Cannabinoids among Community Pharmacists: A Pilot Cross-Sectional Study in Amman, Jordan

There is an increasing interest in the therapeutic use of cannabis worldwide, with a number of cannabinoid-derived drugs currently approved by the Food and Drug Administration (FDA) for certain indications. This study was conducted via a printed questionnaire and aimed to explore the attitudes and knowledge regarding the therapeutic use of cannabis and cannabinoids among community pharmacists residing in Amman, Jordan. The results revealed a neutral to low agreement level regarding the medical usefulness of cannabis; however, a higher agreement level was observed for FDA-approved cannabinoid-derived drugs. The majority of the participants reported that they did not learn enough regarding cannabinoids, do not adequately remember what they have learned, and do not actively look for information after graduation. The average percentages of correct identification of cannabis/cannabinoid FDA-approved drug indications, common adverse effects, interacting drugs, and cautions/contraindications were 40.6%, 53%, 49.4%, and 57.3%, respectively, with an overall correct identification rate of 51.1% of the participants. In conclusion, the results indicate an inadequate level of knowledge with a significant room for improvement regarding the various aspects of cannabinoid pharmacology.

Eye Tracking in Patients with Parkinson's Disease Treated with Nabilone-Results of a Phase II, Placebo-Controlled, Double-Blind, Parallel-Group Pilot Study.

The topic of the therapeutic use of cannabinoids in Parkinson’s disease (PD) is broadly discussed and frequently comes up in the outpatient clinic. So far, there are only a few randomized clinical trials assessing the effects of cannabinoids in PD. We are able to demonstrate a reduction in non-motor symptom (NMS) burden after the administration of nabilone. As impairment of attention and working memory have been described earlier as possible side effects, we assess cognitive performance using saccadic paradigms measured by an eye tracker. We do not observe a significant difference in any of the saccadic paradigms between PD patients on placebo versus those treated with nabilone. We, therefore, conclude that top-down inhibitory control is not affected by the tetrahydrocannabinol analogue. Nabilone did not significantly worsen cognitive performance and appears to be safe to use in selected PD patients who suffer from disabling NMS.

Sex-Dependent Prescription Patterns and Clinical Outcomes Associated With the Use of Two Oral Cannabis Formulations in the Multimodal Management of Chronic Pain Patients in Colombia.

To date, the therapeutic use of cannabinoids in chronic pain management remains controversial owing to the limited clinical evidence found in randomized clinical trials (RCTs), the heterogeneous nature of the clinical indication, and the broad range of cannabis-based medicinal products (CBMPs) used in both experimental and observational clinical studies. Here we evaluate patient-reported clinical outcomes (PROMS) in a cohort of adult patients, diagnosed with chronic pain of diverse etiology, who received adjuvant treatment with oral, cannabis-based, magistral formulations between May and September 2021 at the Latin American Institute of Neurology and Nervous System (ILANS-Zerenia) in Bogotá, Colombia. During this period, 2,112 patients completed a PROMS questionnaire aimed at capturing the degree of clinical improvement of their primary symptom and any potential side effects. Most participants were female (76.1%) with an average age of 58.7 years old, and 92.5% (1,955 patients) reported some improvement in their primary symptom (p < 0.001). Two monovarietal, full-spectrum, cannabis formulations containing either cannabidiol (CBD 30 mg/mL; THC <2 mg/mL) or a balanced composition (THC 12 mg/mL; CBD 14 mg/mL) accounted for more than 99% of all prescriptions (59.5 and 39.8%, respectively). The degree of improvement was similar between both formulations, although males reported less effectiveness in the first 4 weeks of treatment. Sex-specific differences were also found in prescription patterns, with male patients increasing the intake of the balanced chemotype overtime. For many patients (71.7%) there were no adverse side effects associated to the treatment and those most reported were mild, such as somnolence (13.0%), dizziness (8.1%) and dry mouth (4.2%), which also appeared to fade over time. Our results constitute the first real-world evidence on the clinical use of medicinal cannabis in Colombia and suggest that cannabis-based oral magistral formulations represent a safe and efficacious adjuvant therapeutic option in the management of chronic pain.

Cannabinoid-Related Acute Pancreatitis: An Update from International Literature and Individual Case Safety Reports.

In addition to the growing interest of different cannabinoids for therapeutic purposes, the safety profile of these substances has changed, with the recent identification of new events such as acute pancreatitis. The aim of this study was to characterize cannabinoid-related acute pancreatitis, based on the recent literature and the analysis of pharmacovigilance data available worldwide. Nine national and international pharmacovigilance databases were requested for individual case safety reports of acute pancreatitis related to cannabinoid exposure. A systematic review was performed searching in PubMed®, Web of Science®, and Google Scholar® for any publication dealing with acute pancreatitis and cannabinoid exposure (cannabis, cannabinoid, cannabidiol, tetrahydrocannabinol, nabilone, dronabinol), to identify case reports, observational studies, clinical trials, or reviews. All queries were updated on 1 January, 2021. Twenty-two individual case safety reports were identified in the pharmacovigilance databases and 51 in the literature, corresponding to a predominantly young male population (74% of men, median age 28 interquartile range [21-39]) using recreational Cannabis sativa with high intensity. A therapeutic purpose was identified in 13 cases (including tetrahydrocannabinol, cannabidiol, and dronabinol). The outcome was often favorable after dechallenge (except three deaths), and frequent recurrences were observed in the case of rechallenge or sustained consumption. Eleven cross-sectional studies and one ecological study showed an increasing trend of cannabis use in in-patients with acute pancreatitis, with a significantly lower in-hospital mortality. This review underlines that acute pancreatitis is a potential adverse effect of cannabinoid use. It remains often unrecognized and can occur during recreational or therapeutic use. The development of the therapeutic use of cannabinoids in frail patients deserves a better investigation of the benefit-risk ratio of these different products.

Risks and Benefits of Cannabis and Cannabinoids in Psychiatry.

The United States is in the midst of rapidly changing laws regarding cannabis. The increasing availability of cannabis for recreational and medical use requires that mental health clinicians be knowledgeable about evidence to be considered when counseling both patients and colleagues. In this review, the authors outline the evidence from randomized double-blind placebo-controlled trials for therapeutic use of cannabinoids for specific medical conditions and the potential side effects associated with acute and chronic cannabis use. Searches of PubMed and PsycInfo were conducted for articles published through July 2021 reporting on "cannabis" or "cannabinoids" or "medicinal cannabis." Additional articles were identified from the reference lists of published reviews. Articles that did not contain the terms "clinical trial" or "therapy" in the title or abstract were not reviewed. A total of 4,431 articles were screened, and 841 articles that met criteria for inclusion were reviewed by two or more authors. There are currently no psychiatric indications approved by the U.S. Food and Drug Administration (FDA) for cannabinoids, and there is limited evidence supporting the therapeutic use of cannabinoids for treatment of psychiatric disorders. To date, evidence supporting cannabinoid prescription beyond the FDA indications is strongest for the management of pain and spasticity. As cannabinoids become more available, the need for an evidence base adequately evaluating their safety and efficacy is increasingly important. There is considerable evidence that cannabinoids have a potential for harm in vulnerable populations such as adolescents and those with psychotic disorders. The current evidence base is insufficient to support the prescription of cannabinoids for the treatment of psychiatric disorders.

Cannabis and Its Potential Protective Role Against Inflammatory Bowel Disease: A Scoping Review.

Globally, around 15%-40% of patients suffering from inflammatory bowel disease (IBD) use Cannabis for pain reduction, increased appetite, and reduced need for other medications. Although many patients report having benefited by using Cannabis in IBD, there is still a lack of consensus regarding the use of Cannabis in IBD. The aim is to identify, explore and map literature on the potential protective role of Cannabis against IBD through this scoping review. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed during the search to answer the focal question: (1) Does Cannabis play a protective role against IBD as assessed by clinical remission; (2) If yes, what is the mechanism of action for this protective role. There were only three randomized controlled trials (RCTs) and three observational studies that satisfied the selection criteria of this scoping review. Although promising results including the improvement in general well-being/ Harvey-Bradshaw Index, health perception enhancement [4.1±1.43 to 7±1.42 (p = 0.0002)], weight gain, Crohn's Disease Activity Index (CDAI) score<150, Mayo scores (4-10), and reduction in clinical complications have been found in some studies, its medical use in IBD is still questionable due to the lack of high-quality evidence. Future RCTs studies should determine the cannabis treatment parameters and validate its safety and effectiveness in the IBD setting. The highlights include: the current literature provides inconclusive evidence concerning the protective role of cannabis for IBD patients; limited research evidence regarding the therapeutic use of cannabinoids for IBD warrants future investigation via RCTs; cannabis provides some benefits to IBD patients by improving their general well-being perceptions, Harvey-Bradshaw Index, Mayo scores, and minimizing their clinical complications.

Cannabinoids and bladder symptoms in multiple sclerosis

BackgroundResearch on the health benefits of cannabis has been limited because use remains restricted or illegal in most countries. Medical cannabis has been legal in Canada since 2001 and recreational use became legal in October 2018. While there are data that support a biological mechanism by which cannabinoids can impact various other symptoms of MS, the evidence of effectiveness of cannabis as a treatment for bladder symptoms remains unsettled. We conducted an exploratory study to describe the current trends of cannabis product consumption among people with MS (PwMS) and their association with perceived benefits on MS symptoms. MethodsA cross-sectional survey study of PwMS, recruited from the MS Clinic in Calgary, Alberta, Canada was undertaken. Logistic regression analyses were performed to assess the associations between cannabis consumption and improvement in bladder function symptoms. ResultsThere were 775 respondents out of 2899 PwMS contacted by email. Among respondents, 734 reported cannabis use in the past 3 months. There were 275 (37.5%) respondents who reported cannabis use in the prior 3 months, and 73.8% of these reported at least weekly use of cannabis. Among all users, 78.1% reported a primary medical or therapeutic indication for consumption. The most common modes of cannabis consumption were oral-edible (69.0%) and smoked (57.1%), while 59.3% used more than one mode of consumption and 2.6% used five different modes. The most common reasons for cannabis use were for sleep (58.3%), pain (51.5%), relaxation (44.4%), muscle spasms (40.2%), anxiety (33.8%) and depression (22.9%). Among the 19 participants who reported bladder symptoms as a main reason for cannabis use, 89.5% reported “better” bladder symptoms when using cannabis. Cannabis consumption in the past 3 months was associated with a two-fold increased odds of reporting improvement in urinary frequency, urinary urgency, bladder leakage and wetness, pad use and bladder emptying. ConclusionsCannabis is commonly used in this survey study of personal cannabis use among PwMS. Patterns of use, dosing, frequency and mode of delivery are diverse among survey respondents. This pilot study provides some initial glimpses into real world therapeutic use of cannabinoids among PwMS for bladder symptoms.

Differential Effects of Childhood Vs. Adulthood Trauma in Cannabinoid Receptor Type 1 (CB1R) Availability in Post-Traumatic Stress Disorder (PTSD): A Review of Literature and Pilot Positron Emission Tomography (PET) Study

Trauma-induced alterations in the endocannabinoid (eCB) system have been reported in animal models and few human studies of post-traumatic stress disorder (PTSD), but there is no consensus on the direction of these changes. Given the potential therapeutic use of cannabinoids in PTSD treatment, it is critical to understand the nature of the eCB system alterations in individuals with PTSD.

Emerging Promise of Cannabinoids for the Management of Pain and Associated Neuropathological Alterations in Alzheimer's Disease.

Alzheimer’s disease (AD) is an irreversible chronic neurodegenerative disorder that occurs when neurons in the brain degenerate and die. Pain frequently arises in older patients with neurodegenerative diseases including AD. However, the presence of pain in older people is usually overlooked with cognitive dysfunctions. Most of the times dementia patients experience moderate to severe pain but the development of severe cognitive dysfunctions tremendously affects their capability to express the presence of pain. Currently, there are no effective treatments against AD that emphasize the necessity for increasing research to develop novel drugs for treating or preventing the disease process. Furthermore, the prospective therapeutic use of cannabinoids in AD has been studied for the past few years. In this regard, targeting the endocannabinoid system has considered as a probable therapeutic strategy to control several associated pathological pathways, such as mitochondrial dysfunction, excitotoxicity, oxidative stress, and neuroinflammation for the management of AD. In this review, we focus on recent studies about the role of cannabinoids for the treatment of pain and related neuropathological changes in AD.

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis.

In recent years, and even more since its legalization in several jurisdictions, cannabis and the endocannabinoid system have received an increasing amount of interest related to their potential exploitation in clinical settings. Cannabinoids have been suggested and shown to be effective in the treatment of various conditions. In cancer, the endocannabinoid system is altered in numerous types of tumours and can relate to cancer prognosis and disease outcome. Additionally, cannabinoids display anticancer effects in several models by suppressing the proliferation, migration and/or invasion of cancer cells, as well as tumour angiogenesis. However, the therapeutic use of cannabinoids is currently limited to the treatment of symptoms and pain associated with chemotherapy, while their potential use as cytotoxic drugs in chemotherapy still requires validation in patients. Along with cannabinoids, cannabis contains several other compounds that have also been shown to exert anti-tumorigenic actions. The potential anti-cancer effects of cannabinoids, terpenes and flavonoids, present in cannabis, are explored in this literature review.

Localization of cannabinoid and cannabinoid related receptors in the cat gastrointestinal tract

A growing body of literature indicates that activation of cannabinoid receptors may exert beneficial effects on gastrointestinal inflammation and visceral hypersensitivity. The present study aimed to immunohistochemically investigate the distribution of the canonical cannabinoid receptors CB1 (CB1R) and CB2 (CB2R) and the putative cannabinoid receptors G protein-coupled receptor 55 (GPR55), nuclear peroxisome proliferator-activated receptor alpha (PPARα), transient receptor potential ankyrin 1 (TRPA1), and serotonin receptor 5-HT1a 5-HT1aR) in tissue samples of the gastrointestinal tract of the cat. CB1R-immunoreactivity (CB1R-IR) was observed in gastric epithelial cells, intestinal enteroendocrine cells (EECs) and goblet cells, lamina propria mast cells (MCs), and enteric neurons. CB2R-IR was expressed by EECs, enterocytes, and macrophages. GPR55-IR was expressed by EECs, macrophages, immunocytes, and MP neurons. PPARα-IR was expressed by immunocytes, smooth muscle cells, and enteroglial cells. TRPA1-IR was expressed by enteric neurons and intestinal goblet cells. 5-HT1a receptor-IR was expressed by gastrointestinal epithelial cells and gastric smooth muscle cells. Cannabinoid receptors showed a wide distribution in the feline gastrointestinal tract layers. Although not yet confirmed/supported by functional evidences, the present research might represent an anatomical substrate potentially useful to support, in feline species, the therapeutic use of cannabinoids during gastrointestinal inflammatory diseases.

Cannabinoids and the endocannabinoid system in anxiety, depression, and dysregulation of emotion in humans.

This review is to summarize most recent evidence published in the last 18 months on medical and recreational use of cannabis and cannabinoids in relation to anxiety, depression (unipolar and bipolar), and dysregulation of emotions as part of posttraumatic stress disorders (PTSD) and emotionally instable personality disorders. It also covers the investigation of endocannabinoids as potential biomarkers in these conditions. This is important with increasing medicinal use of cannabinoids and growing social tolerance towards recreational cannabis use. There is some recent evidence suggesting cannabinoids, cannabidiol or cannabidiol-enriched cannabis preparations have anxiolytic properties. In addition, depression may be worsened by cannabis use, however, randomized controlled trials (RCT) are lacking. New evidence also suggests that cannabidiol or cannabidiol-enriched cannabis use for PTSD and emotion regulation can induce hyporesponse to fear and stress. Further, several lines of evidence point to the endocannabinoid system as a key player in some of the reviewed disorders, in particular anxiety and PTSD. The most recent evidence for a therapeutic use of cannabinoids in the reviewed conditions is weak and lacking well designed RCTs. However, there is some indication of the role of the endocannabinoid system in these conditions that warrant further studies.

Cannabinoids and the expanded endocannabinoid system in neurological disorders.

Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Δ9-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, especially in relation to the unwanted central effects that result from activation of cannabinoid receptor 1 (CB1), which have limited the therapeutic use of drugs that activate or inactivate this receptor. The discovery of CB2 and of endogenous cannabinoid receptor ligands (endocannabinoids) raised new possibilities for safe targeting of this endocannabinoid system. However, clinical success has been limited, complicated by the discovery of an expanded endocannabinoid system - known as the endocannabinoidome - that includes several mediators that are biochemically related to the endocannabinoids, and their receptors and metabolic enzymes. The approvals of nabiximols, a mixture of THC and the non-psychotropic cannabinoid cannabidiol, for the treatment of spasticity and neuropathic pain in multiple sclerosis, and of purified botanical cannabidiol for the treatment of otherwise untreatable forms of paediatric epilepsy, have brought the therapeutic use of cannabinoids and endocannabinoids in neurological diseases into the limelight. In this Review, we provide an overview of the endocannabinoid system and the endocannabinoidome before discussing their involvement in and clinical relevance to a variety of neurological disorders, including Parkinson disease, Alzheimer disease, Huntington disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, stroke, epilepsy and glioblastoma.

Abstract 2018: Cannabinoid receptor 2 agonist JWH-015 inhibits growth and metastasis of triple negative breast cancers through regulation of autophagy mechanism

Abstract Metastasis to distant organs is the major cause of mortality associated with breast cancer. Triple-negative breast cancer (TNBC) subtype has been shown to be associated with worst patient survival due to high metastasis rate and lack of targeted therapies. Therefore, there is an utmost need to develop novel therapeutic strategies against TNBC growth and metastasis. Cannabinoids are known to possess anti-cancer activity. However, the associated psychotropic activity limits the therapeutic use of Cannabinoids in breast cancer patients. Here, we used synthetic cannabinoid JWH-015 which activates cannabinoid receptor 2 (CB2) and is devoid of psychotropic activity. In vitro molecular analysis revealed that JWH-015 induces TNBC cell death by activating autophagy associated apoptosis. In addition, we have further shown using in vivo tumor models, that JWH-015 potentially inhibits TNBC growth and metastasis through activation of autophagy mechanisms. Further analysis showed that JWH-015 treated tumors recruited the reduced number of macrophages compared to vehicle control treated tumors. In addition, there were more anti-tumor M1-type macrophages present in JWH-015 treated tumors. Conversely, vehicle control treated tumors possessed a higher number of pro-tumor M2-type macrophages. These observations have established the anti-metastatic potential of JWH-015 in different TNBC pre-clinical mouse models. The mechanistic studies have elaborated the role of JWH-015-induced autophagy in promoting tumor cell death to inhibit TNBC growth and metastasis. Citation Format: Nabanita Chatterjee, Subhadip Das, Dinesh K. Ahirwar, Sanjay Mishra, Ramesh Ganju. Cannabinoid receptor 2 agonist JWH-015 inhibits growth and metastasis of triple negative breast cancers through regulation of autophagy mechanism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2018.

Development and validation of an assay to measure cannabidiol and Δ9-tetrahydrocannabinol in human EDTA plasma by UHPLC-MS/MS

The therapeutic use of cannabinoids has increased with providers often recommending cannabinoid-containing products with limited pre-clinical and clinical pharmacokinetic studies. An ultra-performance liquid chromatography with triple quadrupole mass spectrometry method was developed and validated for the determination of cannabidiol and Δ9-tetrahydrocannabinol in human ethylenediaminetetraacetic acid (EDTA) plasma. The cannabinoids are extracted from plasma with a liquid-liquid procedure utilizing methyl tert-butyl ether. UHPLC Separation was achieved with a Waters Acquity HSS T3 column (100 × 2.1 mm, 1.8 μm) under isocratic conditions (18:82:0.02 water:methanol:formic acid v/v/v). The run time was 8.5 min. Detection of analytes was achieved using electrospray ionization and triple quadrupole selected reaction monitoring. Standard curve concentrations ranged from 0.5 to 250 ng/mL for cannabidiol and Δ9-tetrahydrocannabinol. The intra- and inter-day accuracy (% bias) and precision (relative standard deviation) were <9.20% in low, medium, and high quality control samples. The validated method was applied to the analysis of donated human EDTA plasma. The assay provides an important patient monitoring capability to determine variability in clinical pharmacokinetics during use of cannabinoid-containing products.

An Update of Current Cannabis-Based Pharmaceuticals in Pain Medicine.

Cannabis users have long reported therapeutic properties of the plant for a variety of conditions, some of which include nausea, emesis, seizures, cancer, neurogenic diseases and pain control. Research has elucidated many cannabinoid pharmacodynamic and pharmacokinetic properties, expanding the potential use of cannabinoids as a medical therapy. Due to the inconsistent delivery and control of the active components involved with smoking, pharmaceutical companies are investigating and prioritizing routes other than smoke inhalation for therapeutic use of cannabinoids. In this relatively new field of pharmaceutical development, ongoing drug development promises great benefit from targeted endocannabinoid receptor agonism. Available in Canada and Europe, nabiximols, a specific extract from the Cannabis plant, has demonstrated great benefit in the treatment of pain related to spasticity in multiple sclerosis, cancer and otherwise chronic pain conditions. The cannabidiol oral solution Epidiolex®, which is available in the USA, is indicated for management of refractory epilepsy but may offer therapeutic relief to chronic pain conditions as well. Current investigative drugs, such as those developed by Cara Therapeutics and Zynerba Pharmaceuticals, are synthetic cannabinoids which show promise to specifically target neuropsychiatric conditions and chronic pain symptoms such as neuropathy and allodynia. The objective of this review is to provide clinicians with an update of currently available and promising developmental cannabis pharmaceutical derivatives which may stand to greatly benefit patients with otherwise difficult-to-treat chronic conditions.

Self-Reported Effectiveness and Safety of Trokie® Lozenges: A Standardized Formulation for the Buccal Delivery of Cannabis Extracts.

Therapeutic use of cannabinoids, the main active ingredients of Cannabis sativa L., is often hindered by their limited bioavailability and undesirable psychoactivity. We conducted an observational study in December 2016 and another one in February 2018 to investigate respectively: (i) the effectiveness of Trokie® lozenges, a standardized formulation containing cannabis extracts, to deliver cannabinoids via buccal absorption and (ii) its long-term safety. Participants were members of the Palliative Care Corporation health clinic, registered California cannabis patients, and had a diagnosis of chronic non-cancer pain. For the effectiveness study, 49 participants were asked to self-report pain perception before and after 1–12 weeks of taking Trokie® lozenges, using an 11-point pain intensity numeric rating scale (PI-NRS). A mean reduction in PI-NRS score of 4.9 ± 2.0 points was observed. Onset of analgesia typically varied between 5 and 40 min, which seems consistent with, at least partial, buccal absorption. In the safety study, 35 participants were asked to complete a questionnaire about adverse events (AEs) associated with Trokie® lozenges. AEs were reported by 16 subjects (46%), the most common being dizziness/unsteadiness (N = 7), bad taste (N = 5), and throat irritation/dry mouth (N = 4). None of the self-reported AEs resulted in a serious medical situation and most of them had limited impact on daily functions. Despite the AEs, 90% of participants reported being “satisfied” or “very satisfied” with the product. These observations suggest that buccal administration of standardized extracts via Trokie® lozenges may represent an efficacious and safe approach to cannabis administration.

Clinical Use of Cannabinoids for Symptom Control in Multiple Sclerosis.

The endocannabinoid system was discovered in 1988 but has received little attention for its potential therapeutic possibilities. That has started to change, and since 2000, a significant number of clinical trials of cannabinoids, principally for the control of spasticity in multiple sclerosis, have been undertaken. These studies have been difficult because of the nature of the disease and have involved patients for whom other therapies have failed or proved inadequate. This paper outlines the background to the use of cannabinoids available and discusses the principles of practice associated with their safe use. The focus has been on nabiximols, being the most studied and the only cannabinoid that has been both adequately researched for use in multiple sclerosis and granted a license by the regulators. However, what has emerged is that the effect for many patients can be much wider than just control of spasticity. Within and outside of neurology there seems to be an expanding range of possibilities for the therapeutic use of cannabinoids.