Use of Medicinal Cannabis and Synthetic Cannabinoids in Posttraumatic Stress Disorder (PTSD): a systematic review

Background and Objectives: Post-traumatic stress disorder (PTSD) is a common psychiatric disorder resulting from a traumatic event, is manifested through hyperarousal, anxiety, depressive symptoms, and sleep disturbances. Despite several therapeutic approaches being available, both pharmacological and psychological, recently a growing interest has developed in using cannabis and synthetic cannabinoids stems from their consideration as more efficient and better tolerated alternatives for the treatment of this condition. The present paper aims to evaluate the clinical and therapeutic potentials of medical cannabis and synthetic cannabinoids in treating PTSD patients. Methods: A systematic electronic search was performed, including all papers published up to May 2019, using the following keywords (((cannabis[Title/Abstract]) OR (synthetic cannabinoids [Title/Abstract])) AND ((PTSD[Title/Abstract]) OR (Posttraumatic stress disorder[Title/Abstract]))) for the topics ‘Cannabis’, ‘Synthetic Cannabinoids’, ‘PTSD’, and MESH terms, on the PubMed, Cochrane Library, and Web of Science online databases. For data gathering purposes, PRISMA guidelines were followed. Results were organized into two groups, considering cannabis and synthetic cannabinoids as different therapeutic approaches for PTSD. Results: Present data show that cannabis and synthetic cannabinoids, both acting on the endocannabinoids system, may have a potential therapeutic use for improving PTSD symptoms, e.g., reducing anxiety, modulating memory-related processes, and improving sleep. Conclusions: Even though the current literature suggests that cannabis and synthetic cannabinoids may have a role in the treatment of PTSD, there is currently limited evidence regarding their safety and efficacy. Therefore, additional research is needed in order to better understand the effectiveness and therapeutic usage of these drug classes and monitor their safety.Peer reviewe

Endocannabinoid system and anticancer properties of cannabinoids

Cannabinoids impact human body by binding to cannabinoids receptors (CB1 and CB2). The two main phytocannabinoids are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC interacts with CB1 receptors occurring in central nervous system and is responsible for psychoactive properties of marijuana. CBD has low affinity to CB1 receptor, has no psychoactive characteristics and its medical applications can be wider. CB receptors are part of a complex machinery involved in regulation of many physiological processes – endocannabinoid system. Cannabinoids have found some applications in palliative medicine, but there are many reports concerning their anticancer affects. Agonists of CB1 receptors stimulate accumulation of ceramides in cancer cells, stress of endoplasmic reticulum (ER stress) and, in turn, apoptosis. Effects of cannabinoids showing low affinity to CB receptors is mediated probably by induction of reactive oxygen species production. Knowledge of antitumor activity of cannabinoids is still based only on preclinical studies and there is a necessity to conduct more experiments to assess the real potential of these compounds

Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation

Since the discovery of the endocannabinoid system consisting of cannabinoid receptors, endogenous ligands, and biosynthetic and metabolizing enzymes, interest has been renewed in investigating the promise of cannabinoids as therapeutic agents. Abundant evidence indicates that cannabinoids modulate immune responses. An inflammatory response is triggered when innate immune cells receive a danger signal provided by pathogen- or damage-associated molecular patterns engaging pattern-recognition receptors. Toll-like receptor family members are prominent pattern-recognition receptors expressed on innate immune cells. Cannabinoids suppress Toll-like receptor-mediated inflammatory responses. However, the relationship between the endocannabinoid system and innate immune system may not be one-sided. Innate immune cells express cannabinoid receptors and produce endogenous cannabinoids. Hence, innate immune cells may play a role in regulating endocannabinoid homeostasis, and, in turn, the endocannabinoid system modulates local inflammatory responses. Studies designed to probe the interaction between the innate immune system and the endocannabinoid system may identify new potential molecular targets in developing therapeutic strategies for chronic inflammatory diseases. This review discusses the endocannabinoid system and Toll-like receptor family and evaluates the interaction between them

A theoretical structure-affinity relationship study of some cannabinoid derivatives

Indexación: ScieloA ZINDO/1 quantum-chemical structure-affinity relationship study with the KPG model is presented for the in vitro interaction of a group of classical, indole-derived and aminoalkylindole-derived cannabinoids with CB and CB2 receptors. From this work the following conclusions are obtained. CB and CB2 CB2 receptor affinities are regulated by different mechanisms involving orbital and charge control. Nevertheless CB and CB2 classical ligands share three common features: a hydrogen bond to a lysine (for CB ) or serine (for CB), a fully aromatic ring and a branched carbon side chain. In the case of indole-derived and aminoalkylindole-derived cannabinoids orientation and alignment rules have been defined as a basis for the comparison of noncongeneric molecules. In this way it was possible to associate the location of molecular fragments of these systems with known molecular systems such as classical cannabinoids. For aminoalkyhndoles we have proposed the locus with which they bind to a second receptor site that is available to WIN-55212-2 but not to classical cannabinoids. On the basis of our results we propose a new molecule that should help to discriminate between the above two receptor sites.http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-97072008000100013&nrm=is

The therapeutic aspects of the endocannabinoid system (ECS) for cancer and their development: from nature to laboratory

The endocannabinoid system (ECS) is a group of neuromodulatory lipids and their receptors, which are widely distributed in mammalian tissues. ECS regulates various cardiovascular, nervous, and immune system functions inside cells. In recent years, there has been a growing body of evidence for the use of synthetic and natural cannabinoids as potential anticancer agents. For instance, the CB1 and CB2 receptors are assumed to play an important role inside the endocannabinoid system. These receptors are abundantly expressed in the brain and fatty tissue of the human body. Despite recent developments in molecular biology, there is still a lack of knowledge about the distribution of CB1 and CB2 receptors in the human kidney and their role in kidney cancer. To address this gap, we explore and demonstrate the role of the endocannabinoid system in renal cell carcinoma (RCC). In this brief overview, we elucidate the therapeutic aspects of the endocannabinoid system for various cancers and explain how this system can be used for treating kidney cancer. Overall, this review provides new insights into cannabinoids' mechanisms of action in both in vivo and in vitro models, and focuses on recent discoveries in the field

New Insights into Cannabis Consumption; Abuses and Possible Therapeutic Effects

Cannabis is one of the oldest psychotropic drugs known to humanity. The paper assesses the current knowledge on the cannabis, including the mechanisms of action and the therapeutic potential of cannabinoids. Three varieties of Cannabis plant are recognised: Cannabis sativa, Cannabis indica, and Cannabis ruderalis. The variety indica is used predominantly to obtain the drugs. Cannabis herb is usually named marijuana, while the cannabis oleoresin secreted by the glandular hairs found mainly on the flowering or fruiting tops of the plant is known as hashish. More than 400 known chemicals are present in cannabis, at least 70 of which are called cannabinoids. The major psychoactive constituent in cannabis is delta-9-tetrahydrocannabinol (Δ9-THC). It is now recognized that there are three types of cannabinoids: natural (phytocannabinoids), endogenous cannabinoids, and synthetic cannabioids. 2 (CB2) receptors, found predominantly in peripheral tissues with immune functions have been cloned. Therefore, the concept of endogenous cannabinoid system (endocannabinoid system, SEC) has been developed. Based on the current scientific evidence, there are several effects of cannabinoids with potential therapeutic use: antiemetic, analgesic in cancerous pains, and chronic neuropathic pain, in multiple sclerosis or spinal cord injuries. Cannabis consume can result in a state of drug dependency and cannabis withdrawal has been included in DSM-V. Cannabis plant remains controversial in the twenty-first century and the potential therapeutic of specific cannabinoid compounds and medical marijuana remains under active medical research

New Synthetic Cannabinoids Metabolism and Strategies to Best Identify Optimal Marker Metabolites.

Synthetic cannabinoids (SCs) were initially developed as pharmacological tools to probe the endocannabinoid system and as novel pharmacotherapies, but are now highly abused. This is a serious public health and social problem throughout the world and it is highly challenging to identify which SC was consumed by the drug abusers, a necessary step to tie adverse health effects to the new drug\u27s toxicity. Two intrinsic properties complicate SC identification, their often rapid and extensive metabolism, and their generally high potency relative to the natural psychoactive Δ 9 -tetrahydrocannabinol in cannabis. Additional challenges are the lack of reference standards for the major urinary metabolites needed for forensic verification, and the sometimes differing illicit and licit status and, in some cases, identical metabolites produced by closely related SC pairs, i.e., JWH-018/AM-2201, THJ-018/THJ-2201, and BB-22/MDMB-CHMICA/ADB-CHMICA. We review current SC prevalence, establish the necessity for SC metabolism investigation and contrast the advantages and disadvantages of multiple metabolic approaches. The human hepatocyte incubation model for determining a new SC\u27s metabolism is highly recommended after comparison to human liver microsomes incubation, in silico prediction, rat in vivo, zebrafish, and fungus Cunninghamella elegans models. We evaluate SC metabolic patterns, and devise a practical strategy to select optimal urinary marker metabolites for SCs. New SCs are incubated first with human hepatocytes and major metabolites are then identified by high-resolution mass spectrometry. Although initially difficult to obtain, authentic human urine samples following the specified SC exposure are hydrolyzed and analyzed by high-resolution mass spectrometry to verify identified major metabolites. Since some SCs produce the same major urinary metabolites, documentation of the specific SC consumed may require identification of the SC parent itself in either blood or oral fluid. An encouraging trend is the recent reduction in the number of new SC introduced per year. With global collaboration and communication, we can improve education of the public about the toxicity of new SC and our response to their introduction

Market Analysis of Synthetic Drugs: Amphetamine-type Stimulants, New Psychoactive Substances

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

Cannabinoid signalling in TNF-alpha induced IL-8 release

Original article can be found at: http://www.sciencedirect.com/science/journal/00142999 Copyright Elsevier B.V. DOI : 10.1016/j.ejphar.2006.04.015Peer reviewe

Detecting a signal in the noise : Monitoring the global spread of novel psychoactive substances using media and other open source information

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Date of Acceptance: 16/02/2015To determine the feasibility and utility of using media reports and other open-source information collected by the Global Public Health Intelligence Network (GPHIN), an event-based surveillance system operated by the Public Health Agency of Canada, to rapidly detect clusters of adverse drug events associated with ‘novel psychoactive substances’ (NPS) at the international levelPeer reviewedFinal Published versio