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

Detection and Characterization of Delta-9-Tetrahydrocannabinol and Novel Synthetic Cannabinoid Metabolites using Human Liver Microsomes

Marijuana and synthetic cannabinoids are the most commonly used and trafficked illicit drug. ∆9-tetrahydrocannabinol (THC) is the primary active compound in marijuana. Synthetic cannabinoids were created as a method to study the effects of cannabinoids on the endocannabinoid system, which consists of endogenous cannabinoids, cannabinoid receptors, and the synthetic and degrading enzymes responsible for the synthesis and degradation of endocannabinoids. Cannabinoids activate the same receptors as endocannabinoids. Synthetic cannabinoids gained popularity as recreational drugs due to their ability to avoid detection. Synthetic cannabinoids have been found to have a greater binding affinity to the cannabinoid CB1 receptor than THC. They are also shown to have a greater affinity at the CB1 receptor than the CB2receptor. With the current legalization status of marijuana for both recreational and medicinal use, it is important to know the effects that these compounds can have on the body. The purpose of this experiment was to characterize the metabolites of THC and three other synthetic cannabinoids metabolized by human liver microsomes. The three synthetic cannabinoids chosed for this project are JWH-302, JWH-237, and mepirapim. These cannabinoids are all related to very popular synthetic cannabinoids. An AB SCIEX 3200 mass spectrometer (LC/MS/MS) in multiple reaction monitoring (MRM) mode with electrospray ionization (ESI) was used to characterize the metabolites. This is part of a bigger project that aims to use rat models to find the effects of THC and synthetic cannabinoids on the cardiovascular and renal systems

SYNTHETIC CANNABINOIDS: CHARACTERIZING THEIR USE AND CESSATION

Since their introduction to the United States in 2008, synthetic cannabinoids became the most widely used recreational drug behind marijuana, then regressed to an estimated prevalence of less than 1%. Contrary to expectations for a drug declining in use, emergency department presentations and acute poisonings related to the use of synthetic cannabinoids are increasing. Alongside this phenomenon, a growing body of literature is beginning to uncover a relationship between psychosis and synthetic cannabinoid use. A current gap in the literature exists surrounding harm prevention methods and targeted intervention strategies for users of synthetic cannabinoids. To date, no known studies have examined individuals with a history of use of these substances and investigated the reasons they decided to discontinue recreational use. The purpose of the current study was to fill this gap in the literature while also further confirming and expanding existing research on the characterization of synthetic substance use, perceived harm of synthetic cannabinoids, and users’ knowledge about synthetic cannabinoids. Cross sectional survey methods in a non-experimental comparative design was utilized with participants recruited through the online crowd sourcing platform Amazon MTurk. Significant motivating factors for both discontinuation and continuation of synthetic cannabinoid use were found including personal experience, accessibility, preference towards other substance, and questions surrounding the source and purity of the synthetic cannabinoids. It was also found that individuals who currently use synthetic cannabinoids have less general knowledge about the substance class when compared to individuals who have discontinued use. These results suggest that psychoeducational campaigning surrounding general knowledge about the substance class as well as information on the physiological effects of synthetic cannabinoids may be an effective harm reduction method

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

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

Synthetic Cannabinoid Use and Descriptive Norms among Collegiate Student-Athletes

Synthetic cannabinoids have gained popularity over the past decade, especially among young adults, due to sharing similar psychoactive properties with Tetrahydrocannabinol (THC). A limited number of studies have examined synthetic cannabinoid use among college students but none have examined use exclusively by collegiate student-athletes. The objective of this study was to examine synthetic cannabinoid use among collegiate student-athletes. In the spring of 2013, 3,276 freshmen and transfer collegiate student-athletes from 47 NCAA Division I, II, and III institutions participated in a web-based survey on substance use. Bivariate logistic regression was used to analyze the relationship between collegiate student-athlete characteristics, substance use, and descriptive norms with lifetime use of synthetic cannabinoids. Sixty-two individuals (1.9%) reported lifetime use of synthetic cannabinoids, and 3 (0.1%) reported past-30-day use. Males, current drinkers, and athletes who used hookah and marijuana in the past 30 days were more likely to use synthetic cannabinoids. Peer use of synthetic cannabinoids was estimated to be higher than actual use, and such overestimation was positively associated with personal use of synthetic cannabinoids. Our findings suggest that campaigns addressing normative beliefs should be implemented on college campuses to prevent synthetic cannabinoid use among college students and collegiate student-athletes

Recent trends in analytical methods to determine new psychoactive substances in hair

New Psychoactive Substances (NPS) belong to several chemical classes, including phenethylamines, piperazines, synthetic cathinones and synthetic cannabinoids. Development and validation of analytical methods for the determination of NPS both in traditional and alternative matrices is of crucial importance to study drug metabolism and to associate consumption to clinical outcomes and eventual intoxication symptoms. Among different biological matrices, hair is the one with the widest time window to investigate drug-related history and demonstrate past intake. The aim of this paper was to overview the trends of the rapidly evolving analytical methods for the determination of NPS in hair and the usefulness of these methods when applied to real cases. A number of rapid and sensitive methods for the determination of NPS in hair matrix has been recently published, most of them using liquid chromatography coupled to mass spectrometry. Hair digestion and subsequent solid phase extraction or liquid-liquid extraction were described as well as extraction in organic solvents. For most of the methods limits of quantification at picogram per milligram hair were obtained. The measured concentrations for most of the NPS in real samples were in the range of picograms of drug per milligram of hair. Interpretation of the results and lack of cut-off values for the discrimination between chronic consumption and occasional use or external contamination are still challenging. Methods for the determination of NPS in hair are continually emerging to include as many NPS as possible due to the great demand for their detection

Pyrolytic Fate of Synthetic Cannabinoids

Since the introduction of herbal incense products into the illicit drug market, one of the most concerning factors has been the uncertainty regarding their health effects. Side effects such as anxiety/agitation, increased heartbeat, hallucinations, and suicidal tendencies are commonly reported with the use of products containing synthetic cannabinoid. However, a largely unknown toxicity and pharmacology is still associated with synthetic cannabinoids and long-term health effects have yet to be discussed.;Prior scientific studies have not focused on the big-picture in terms of the pyrolysis of traditional drugs of abuse that are smoked or the relatively new synthetic cannabinoids. Numerous agencies and statistics have reported the number of health-related incidents regarding the use of synthetic cannabinoids, but there has yet to be peer-reviewed reports seeking to understand what caused these health effects. Therefore, the purpose of this research was to investigate the pyrolytic fate of JWH-018, JWH-030, JWH-081, and UR-144 and the smaller components which comprise these synthetic cannabinoids.;Studying a number of the most common components that comprise a large number of the synthetic cannabinoids allows for a broad-ranging, cost-effective dissemination of results. A comprehensive approach was taken for identifying the pyrolytic products observed with a series of indole and naphthalene containing compounds. In doing so, a baseline of pyrolytic products that can form was established and it was found that a number of polyaromatic hydrocarbons, heterocyclic amines, and other hazardous or potentially hazardous compounds were generated.;Analysis of the synthetic cannabinoids in this study showed that known carcinogenic compounds and potentially harmful pyrolytic products, such as carbazole, naphthalene, and benz[a]anthracene, are generated during smoking. The synthetic cannabinoids JWH-071 and JWH-018 were also, respectively, identified as pyrolytic products of JWH-018 and JWH-081. Furthermore, a number of compounds that were not identified have been reported which may, like the additionally generated synthetic cannabinoids, also retain activity at the cannabinoid receptors

Heroin Adulterated with the Novel Synthetic Cannabinoid, 5F-MDMB-PINACA: A Case Series

Introduction: Heroin can be adulterated with various substances that may or may not have pharmacological effects. Here we report a case series of 8 patients who presented to the emergency department after overdose with intravenous heroin preparation adulterated with the synthetic cannabinoid methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (5F-MDMB-PINACA).Case Series: Except for one patient, all of them presented with a typical initial opioid toxidrome consisting of central nervous system and respiratory depression along with pinpoint pupils. Naloxone was given to them, triggering severe agitation and combative behavior along with overlapping features of anticholinergic and sympathomimetic toxidrome. All patients required multiple doses of benzodiazepines. Three were successfully treated with physostigmine.Discussion: 5F-MDMB-PINACA is a synthetic cannabinoid that was added to heroin in samples obtained from patients reported in this case series. Patients demonstrated significant agitation after receiving naloxone for opioid toxidrome, presumably because of the removal of the depressant effect of opioids, which unmasked the excitatory effects of the synthetic cannabinoids. Three patients required physostigmine along with the benzodiazepines for control of their agitation, urine retention and abnormal vitals, suggesting the possibility of an anticholinergic toxidrome to have developed in these patients.Conclusion: Heroin contaminated with 5F-MDMB-PINACA exhibits variable severities of anticholinergic effects, some on presentation and others only after opiate antagonism