A systematic review of cannabidiol dosing in clinical populations

Aims: Cannabidiol is a cannabis-derived medicinal product with potential application in a wide-variety of contexts, however its effective dose in different disease states remains unclear. This review aimed to investigate what doses have been applied in clinical populations, in order to understand the active range of cannabidiol in a variety of medical contexts. Methods: Publications involving administration of cannabidiol alone were collected by searching PubMed, EMBASE and ClinicalTrials.gov. Results: A total of 1038 articles were retrieved, of which 35 studies met inclusion criteria covering 13 medical contexts. 23 studies reported a significant improvement in primary outcomes (e.g. psychotic symptoms, anxiety, seizures), with doses ranging betwee

Treatment of Fragile X Syndrome with Cannabidiol: A Case Series Study and Brief Review of the Literature.

Fragile X syndrome (FXS) is an X-linked dominant disorder caused by a mutation in the fragile X mental retardation 1 gene. Cannabidiol (CBD) is an exogenous phytocannabinoid with therapeutic potential for individuals with anxiety, poor sleep, and cognitive deficits, as well as populations with endocannabinoid deficiencies, such as those who suffer from FXS. The objective of this study was to provide a brief narrative review of recent literature on endocannabinoids and FXS and to present a case series describing three patients with FXS who were treated with oral CBD-enriched (CBD+) solutions. We review recent animal and human studies of endocannabinoids in FXS and present the cases of one child and two adults with FXS who were treated with various oral botanical CBD+ solutions delivering doses of 32.0 to 63.9 mg daily. Multiple experimental and clinical models of FXS combine to highlight the therapeutic potential of CBD for management of FXS. All three patients described in the case series exhibited functional benefit following the use of oral CBD+ solutions, including noticeable reductions in social avoidance and anxiety, as well as improvements in sleep, feeding, motor coordination, language skills, anxiety, and sensory processing. Two of the described patients exhibited a reemergence of a number of FXS symptoms following cessation of CBD+ treatment (e.g., anxiety), which then improved again after reintroduction of CBD+ treatment. Findings highlight the importance of exploring the therapeutic potential of CBD within the context of rigorous clinical trials

Insights into the pathogenesis of nicotine addiction. Could a salivary biosensor be useful in Nicotine Replacement Therapy (NRT)?

Nicotine has gained the attention of the medical community due to its insidious addictive mechanisms which lead to chronic consumption. The multitude of compounds derived from tobacco smoke have local and systemic negative impacts, resulting in a large number of smoking-related pathologies. The present review offers insights into nicotine addiction physiopathology, as well as social and medical implications, with emphasis on its correlation with Advanced Glycation End Products (AGEs). Therapeutic strategies and new approaches to nicotine assessment and cessation treatment are discussed, noting that such strategies could take into account the possibility of slow and gradual nicotine release from a device attached to a prosthetic piece, based on salivary nicotine-concentration feedback. This approach could offer real-time and home-based self-therapy monitoring by the physician and the patient for follow-up and improve long-term cessation treatment success- Graphical abstract

Phytocannabinoids as novel therapeutic agents in CNS disorders

The Cannabis sativa herb contains over 100 phytocannabinoid (pCB) compounds and has been used for thousands of years for both recreational and medicinal purposes. In the past two decades, characterisation of the body's endogenous cannabinoid (CB) (endocannabinoid, eCB) system (ECS) has highlighted activation of central CB1 receptors by the major pCB, Δ9-tetrahydrocannabinol (Δ9-THC) as the primary mediator of the psychoactive, hyperphagic and some of the potentially therapeutic properties of ingested cannabis. Whilst Δ9-THC is the most prevalent and widely studied pCB, it is also the predominant psychotropic component of cannabis, a property that likely limits its widespread therapeutic use as an isolated agent. In this regard, research focus has recently widened to include other pCBs including cannabidiol (CBD), cannabigerol (CBG), Δ9tetrahydrocannabivarin (Δ9-THCV) and cannabidivarin (CBDV), some of which show potential as therapeutic agents in preclinical models of CNS disease. Moreover, it is becoming evident that these non-Δ9-THC pCBs act at a wide range of pharmacological targets, not solely limited to CB receptors. Disorders that could be targeted include epilepsy, neurodegenerative diseases, affective disorders and the central modulation of feeding behaviour. Here, we review pCB effects in preclinical models of CNS disease and, where available, clinical trial data that support therapeutic effects. Such developments may soon yield the first non-Δ9-THC pCB-based medicines

New horizons for newborn brain protection: enhancing endogenous neuroprotection.

Intrapartum-related events are the third leading cause of childhood mortality worldwide and result in one million neurodisabled survivors each year. Infants exposed to a perinatal insult typically present with neonatal encephalopathy (NE). The contribution of pure hypoxia-ischaemia (HI) to NE has been debated; over the last decade, the sensitising effect of inflammation in the aetiology of NE and neurodisability is recognised. Therapeutic hypothermia is standard care for NE in high-income countries; however, its benefit in encephalopathic babies with sepsis or in those born following chorioamnionitis is unclear. It is now recognised that the phases of brain injury extend into a tertiary phase, which lasts for weeks to years after the initial insult and opens up new possibilities for therapy.There has been a recent focus on understanding endogenous neuroprotection and how to boost it or to supplement its effectors therapeutically once damage to the brain has occurred as in NE. In this review, we focus on strategies that can augment the body's own endogenous neuroprotection. We discuss in particular remote ischaemic postconditioning whereby endogenous brain tolerance can be activated through hypoxia/reperfusion stimuli started immediately after the index hypoxic-ischaemic insult. Therapeutic hypothermia, melatonin, erythropoietin and cannabinoids are examples of ways we can supplement the endogenous response to HI to obtain its full neuroprotective potential. Achieving the correct balance of interventions at the correct time in relation to the nature and stage of injury will be a significant challenge in the next decade

Synthetic Cannabinoids : psychopharmacology, clinical aspects, and psy-chotic onset

This document is the Accepted Manuscript version of the following article: Giovanni Martinotti, Rita Santacroce, Duccio Papanti, Yasmine Elgharably, Mariya Prilutskaya, Ornella Corazza, ‘Synthetic Cannabinoids: Psychopharmacology, Clinical Aspects, and Psychotic Onset’, CNS & Neurological Disorders – Drug Targets, Vol. 16, 2017. Under embargo. Embargo end date: 13 April 2018. The published manuscript is available at EurekaSelect via: https://doi.org/10.2174/1871527316666170413101839. Published by Bentham Science.Synthetic Cannabinoids (SC) are the widest and most diffused class of Novel Psychoactive Substances. SC are chemically heterogeneous and structurally dissimilar from delta-9-tetrahydrocannabinol, being full agonists of the endocannabinoid system receptors CB1 and CB2. Desired effects include euphoria, talkativeness, feelings of joy and laughter, relaxation. With respect to cannabis, SC intake may also be associated with quicker arise of the effects, shorter duration of action, and larger levels of hangover. SC are more psychoactive than cannabis: symptoms may include a wide range of clinically relevant posi-tive, negative and cognitive psychopathological symptoms that mimic symptoms of schizophrenia. The risk of two widespread symptoms of SC intoxication, namely agitation and cardiotoxicity, exceeds this of traditional cannabis of 3.8 and 9.2 times respectively. A number of deaths have been related to SC ingestion, either on their own or in combination with other recreational drugs. Prompt and reliable in-formation available for health professionals, more specific analytic techniques, and designed preventive strategies are all required to face this unprecedented challenge.Peer reviewedFinal Accepted Versio

Market Analysis of Plant-based Drugs C. The Cannabis Market

An estimated quarter of a billion people, or around 5 per cent of the global adult population, used drugs at least once in 2015. Even more worrisome is the fact that about 29.5 million of those drug users, or 0.6 per cent of the global adult population, suffer from drug use disorders. This means that their drug use is harmful to the point that they may experience drug dependence and require treatment.The magnitude of the harm caused by drug use is underlined by the estimated 28 million years of "healthy" life (disability-adjusted life years (DALYs)) lost worldwide in 2015 as a result of premature death and disability caused by drug use.Of those years lost, 17 million were attributable solely to drug use disorders across all drug types. DALYs attributable to morbidity and mortality resulting from all causes of drug use have increased overall in the past decade.Yet, with fewer than one in six persons with drug use disorders provided with treatment each year, the availability of and access to science-based services for the treatment of drug use disorders and related conditions remain limited

An Analysis of the Incidence and Severity of Drug-Drug Interactions Between Prescribed Pharmaceuticals and Cannabinoids

The purpose of this research and systematic literature review is to identify the incidence and severity of drug-drug interactions between commonly prescribed medications and cannabinoids. In this review, four databases were searched including PubMed, CINAHL, and Embase from October 1 to January 5, 2019. A variety of key terms were used when searching. Works chosen for review were published after the year 2014, were peer reviewed, and included randomized control trials (RCTs), systematic literature reviews, and meta-analyses. For this review, 9 resources were selected. Much of the research presented shows evidence that medications that are substrates for CYP2C19, CYP2C9 and CYP1A2 are at the greatest risk of interaction with concomitant use of phytocannabinoids or synthetic cannabinoids. Furthermore, caution is recommended with medications metabolized via UGT or CES1, however information is currently limited and further research is necessary. The lack of universal standards for laboratory testing of cannabinoid products call into question the legitimacy of reported results in currently reported research as the contents of many cannabinoid products are inaccurately labeled

Does Cannabidiol Have a Benefit as a Supportive Care Drug in Cancer?

Cannabinoids have been purported as having a wide range of therapeutic uses although currently, there is minimal evidence to support these claims. Patients with advanced cancer experience many distressing symptoms, with some turning to medicinal cannabis to help alleviate these. Focus has fallen on cannabidiol (CBD) as a potential treatment for a variety of symptoms in advanced cancer due to the lack of psychoactive side effects and the potential molecular mechanisms of action associated with this cannabinoid. Many cannabinoid products are easily available in the community, and more countries are legalizing or allowing over the counter products. Studies show that CBD is generally well tolerated, but there are many potential drug interactions that have not been well studied. Few studies have specifically looked at the role of CBD in treating cancer symptoms, with most focusing on combination cannabinoid products. There are currently many unknowns associated with CBD, including which symptoms it might be best for, appropriate dosing, and route of administration. This is especially important in advanced cancer where patients often have significant organ dysfunction and frailty that could impact on the pharmacology of CBD. A small pilot study has shown promise for a role of CBD in the psychological symptoms associated with advanced cancer. Further research is currently underway to further clarify the role of CBD in this setting and to understand how best it might help our patients. Currently we advocate that CBD be used in supervised clinical trials, so that efficacy and adverse effects can be closely monitored