Cannabinoids are compounds that are naturally present in Cannabis sativa L., which interact with cannabinoid receptors in the nervous system, known as CB1 and CB2 receptors. The most abundant and well-known cannabinoid that can be isolated from cannabis is 9-tetrahydrocannabinol (THC). The structure of this compound specifically allows interaction with the CB1 and CB2 receptors, known as cannabimimetic activity. Other compounds have since been produced, inspired by THC, which have been designed to elicit similar pharmacological responses, and therefore are beneficial as analgesics. These compounds are known as synthetic cannabinoids. Synthetic cannabinoids, while potentially useful as therapeutic treatments for pain, are currently also popular as recreational drugs. Herbal products that contain synthetic cannabinoids are sold as “legal highs,” as few of these compounds are illegal according to the Controlled Drugs and Substances Act. These products are prepared by combining synthetic cannabinoids and plant material, and are smoked similar to marijuana. As the legality of many synthetic cannabinoids is quickly decreasing, as evidenced by the March 2011 emergency scheduling of five such compounds, it is becoming increasingly likely that these products will soon become popular exhibits to be submitted to controlled substances laboratories for testing. If a previously smoked product is submitted, there could potentially be effects due to the burning, the presence of the plant or paper substrate, and other synthetic cannabinoids that could directly diminish the facility of analysis. The aim of this thesis was to investigate these effects using four synthetic cannabinoids (AM-2201, JWH-015, HU-211, and RCS-4) and four substrates (tobacco, rolling paper, mint, and rosemary). Results demonstrated diminished peak areas, which are likely due to the introduction of these variables, which include burning the drug of abuse, and spiking the drug of abuse onto various matrices. The trend of lower peak areas further suggests that burning, the presence of plant material, and other cannabinoids potentially all compromise the facility of analyzing synthetic cannabinoid products. The act of burning one synthetic cannabinoid in particular, AM-2201, appeared to greatly decrease the capability to detect the analyte, as did the application of AM-2201 to various substrates. Furthermore, the ability to detect AM-2201 appeared to vary greatly between results obtained from analyzing samples applied to different substrates. Analysis of cannabinoid mixtures demonstrated that GC/MS analysis of different cannabinoids gave various peak areas although the concentrations remained consistent. Peak area ratios of cannabinoid mixtures that were extracted from substrates were found to not differ significantly between the specific substrates studied. This research supports that all of these variables should therefore be considered in regards to analysis of herbal products containing synthetic cannabinoids.

The primary goal of this study was to investigate the awareness and prevalence of Spice and K2 usage among a population of college students, as well as the demographics of such users. The study also sought to determine whether or not students prefer these products over natural cannabis, in addition to examining the most popular methods of obtainment and the most commonly reported side effects of K2 and Spice usage. Participants consisted of 643 undergraduate students enrolled at the University of North Texas during the fall 2011 semester. Findings indicate that while students exhibit a relatively high awareness of K2 and Spice, usage of these products is not a prevalent occurrence. Implications of the findings are discussed.

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.

In recent years, there has been a rise in the use of New Psychoactive Substances (NPS) that mimic the effects of controlled drugs and licensed medicines, which have become a significant public health concern globally. Synthetic cannabinoids, a rapidly expanding category of NPS, with much higher potency and binding affinity to the cannabinoid receptors than ∆9-tetrahydrocannabinol (THC), have led to serious psychiatric complications and other adverse effects. This project aims to synthesize and analyze four potential metabolites of a synthetic cannabinoid, ADB-5´Br-BUTINACA, to determine if the synthesized metabolites correspond to those produced in human hepatocytes. The metabolites were synthesized by alkylation, amide coupling, and hydrolysis/TFA treatment and analyzed using high-performance liquid chromatography-mass spectrometry (HPLC-MS) and nuclear magnetic resonance (NMR). The reaction strategy combined all three steps into a single process, making it significantly easier to carry out and not requiring much expertise. The results suggest that the synthetic approach used in this project was successful in generating the desired potential metabolites, with overall yields varying from 27.5 % to 57.6 % and high purities ranging from 95.6 % to 99.3 %. However, the overall yields were lower than expected due to product loss during the transfer of the solution mixture, the possibility of side reactions, and incomplete conversion. Further optimization of reaction conditions may be necessary to improve the yield of the synthesized metabolites.

No description available.

Synthetic cannabinoids have become a growing concern in society. The extensive list of synthetic cannabinoids and the abuse rate has drawn the attention by government agencies throughout the world. These synthetic cannabinoids can adopt a number of different structures, while still acting on endogenous cannabinoid (CB1 and CB2) receptors. In addition, due to structural modifications of these synthetic cannabinoids, many of these compounds can bind to CB1 and CB2 receptors with greater affinity causing severe adverse and life-threatening effects. Because of their structural dissimilarity to the phytocannabinoid Δ9-THC, combating the rapid growth and emergence of synthetic cannabinoids with conventional THC-based methods has become an ongoing struggle. The purpose of this research was to develop and validate a robust and reliable method to accurately identify and quantify 17 synthetic cannabinoids in human whole blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was validated in accordance to SWGTOX guidelines for quantitative analysis using the following analytes: 4-cyano-CUMYL-BUTINACA, 5F-3,5-ABPFUPPYCA, 5F-ADB-PINACA, 5F- PY-PINACA, ADB-PINACA, APP-PICA, CUMYL-THPINACA, EMB-FUNICACA, JWH-250, MDMB-FUBICA, MEP-CHMICA, MO-CHMINACA, NM2201, PB-22, RCS-8, UR144, and XLR11. With this developed method, total analysis time was 8 minutes with samples eluting from 3.8 to 5.8 minutes. Calibration curves for each analyte had acceptable R2 values > 0.99 using a weighting factor of 1/x. A linear dynamic range of 0.5 – 25 ng/mL was used for all analytes, except for APP-PICA and NM2201 which were quantifiable at 0.1 ng/mL and PB-22 which used a quadratic model. Extraction of analytes using supported liquid extraction (SLE) cartridge improved sample-prep time by more than half, compared to traditional solid phase extraction (SPE) methods. Percent recovery of analytes using SLE was determined to be from 54.92 to 83.36%. Bias and Precision was assessed at 1, 3, 7, and 20 ng/mL for all analytes. All samples had acceptable calculated percent bias and percent coefficient of variation (%CV) within ±20%. No carryover was observed with this method. Matrix effect, using 10 different sources, did not have any interfering effects on detection and quantification of analytes. Ionization suppression and enhancement was observed at various levels, from -4.47 to 76.67%, but had little effect on other validation parameters. Analysis of other commonly encountered drugs (clonazepam, diazepam, (+) methadone, morphine, fentanyl, cocaine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 25I-NBOMe, and phencyclidine (PCP)) does not show any source of interference. The overall development and validation of this method demonstrates a sensitive and reliable way to positively identify 17 different synthetic cannabinoids in human whole blood in rapid time. / 2020-01-31

Novel Psychoactive Substances (NPS) also known as "legal highs" replicate the effects of illegal substances such as ecstasy and cocaine. The most common NPS reported are stimulants and synthetic cannabinoids. Despite the Psychoactive Ban (2016) recent reports identified the UK as having the largest market of NPS use anywhere in Europe. These substances have a short history of consumption and consequently little is known about their effects and health implications. Despite this, the sale of NPS is easily achieved through the internet and street dealers. Increased reports of negative health consequences from NPS consumption and research findings highlighting the willingness of young people to consume drugs without knowing what they are, mean it is vital that we investigate young people's understandings and perceptions of them. At present there are very few in-depth qualitative studies on NPS. A series of 7 focus groups with a range of young people (40=N: aged 16- 24 years) across the Merseyside area were carried out. Research sites included colleges, youth groups, supported living accommodations, and youth drug and alcohol services. Focus group interviews explored participants' perceptions of NPS and were followed up with a few semi structured interviews with selected participants. The direction of the study focused on mainly on synthetic cannabinoids which may reflect the age of the study's population. Using thematic analysis informed by a social constructionist perspective, three main themes were identified around stigma and identity, attractive features of NPS and risk. Findings showed that young people's perceptions of these substances were dependent on their level of experience with illegal substances and NPS. A novel finding was that synthetic cannabinoid use is employed in the normalisation of cannabis use. Local, national and policy recommendations are made on how youth and health services in both educational and specialised services could work more closely and effectively with young people NPS. They also identify a need among young people for specific guidelines on how to use the Internet and Print media in relation to previous knowledge and experience.

<p>Solid Phase Microextraction (SPME) is a popular sampling technique that can be paired with Gas Chromatography/Mass Spectrometry (GC-MS). SPME-GC-MS is used in forensic chemistry due to its simplification of the sample preparation process. Headspace-Solid Phase Microextraction (HS-SPME) is a technique where the sample is heated to generate volatiles in the headspace of the vial. A SPME fiber is then inserted into the vial and the compounds in the headspace will bind to the fiber. Total Vaporization- Solid Phase Microextraction (TV-SPME) is a technique that is derived from the HS-SPME technique. </p><p>In Chapter 1, the critical comparison of HS-SPME and TV-SPME is discussed. Samples including marijuana, essential oils, and CBD oil were utilized to compare the two techniques. The compounds of interest in marijuana are the three main cannabinoids: cannabinol (CBN), cannabidiol (CBD), and tetrahydrocannabinol (THC). The sample preparation and GC-MS parameters were kept the same for all samples to determine which SPME technique works best for these sample types and yielded the greatest sensitivity. It was found that HS-SPME shows greater sensitivity with CBN and equivalent sensitivity with essential oils, THC and CBD. </p><p>In Chapter 2, the detection of synthetic cannabinoids utilizing liquid-liquid injection as well as HS-SPME and TV-SPME is discussed. The detection of these compounds is important because this type of drug has become more prevalent in the United States because they can be chemically altered slightly so they still have the effects of a drug but can evade drug legislation. The detection of synthetic cannabinoids using liquid injection was found to be successful but detection using HS-SPME and TV-SPME was found to be unsuccessful. </p>In Chapter 3, the analyses of real and artificial saliva utilizing HS-SPME and TV-SPME is discussed. Determining the compounds present in real saliva and artificial saliva will be of importance for future research into determining if the presence of drugs in saliva can be analyzed with these techniques. The analyses of real and artificial saliva were found to be successful using HS-SPME, without derivatization, and TV-SPME, with and without derivatization. Many of the compounds present in the real saliva were detected and were confirmed to be compounds regularly found in saliva by other scientific literature.

Indiana University-Purdue University Indianapolis (IUPUI) / Solid Phase Microextraction (SPME) is a popular sampling technique that can be paired with Gas Chromatography/Mass Spectrometry (GC-MS). SPME-GC-MS is used in forensic chemistry due to its simplification of the sample preparation process. Headspace-Solid Phase Microextraction (HS-SPME) is a technique where the sample is heated to generate volatiles in the headspace of the vial. A SPME fiber is then inserted into the vial and the compounds in the headspace will bind to the fiber. Total Vaporization- Solid Phase Microextraction (TV-SPME) is a technique that is derived from the HS-SPME technique. In Chapter 1, the critical comparison of HS-SPME and TV-SPME is discussed. Samples including marijuana, essential oils, and CBD oil were utilized to compare the two techniques. The compounds of interest in marijuana are the three main cannabinoids: cannabinol (CBN), cannabidiol (CBD), and tetrahydrocannabinol (THC). The sample preparation and GC-MS parameters were kept the same for all samples to determine which SPME technique works best for these sample types and yielded the greatest sensitivity. It was found that HS-SPME shows greater sensitivity with CBN and equivalent sensitivity with essential oils, THC and CBD. In Chapter 2, the detection of synthetic cannabinoids utilizing liquid-liquid injection as well as HS-SPME and TV-SPME is discussed. The detection of these compounds is important because this type of drug has become more prevalent in the United States because they can be chemically altered slightly so they still have the effects of a drug but can evade drug legislation. The detection of synthetic cannabinoids using liquid injection was found to be successful but detection using HS-SPME and TV-SPME was found to be unsuccessful. In Chapter 3, the analyses of real and artificial saliva utilizing HS-SPME and TV-SPME is discussed. Determining the compounds present in real saliva and artificial saliva will be of importance for future research into determining if the presence of drugs in saliva can be analyzed with these techniques. The analyses of real and artificial saliva were found to be successful using HS-SPME, without derivatization, and TV-SPME, with and without derivatization. Many of the compounds present in the real saliva were detected and were confirmed to be compounds regularly found in saliva by other scientific literature.

A cannabinoid refers to any natural or synthetic compound that interacts with the CB1 and CB2 receptors. There are currently three different groups of cannabinoids: endogenous cannabinoids, phytocannabinoids and synthetic cannabinoids. The most common phytocannabinoid is delta-9-tetrahydrocannabinol (THC), which is the active component in the Cannabis sativa or marihuana plant1–3. Two examples of synthetic cannabinoids that are present in case reports from 2012 to 2018 are AB-FUBINACA and AB-PINACA4–7. THC and synthetic cannabinoids are commonly encountered drugs in forensic toxicology cases, therefore, being able to extract these compounds and their metabolites is imperative for toxicological interpretation. There are a variety of commercially available sample preparation techniques for these analytes. Companies such as UCT, Biotage, Millipore-Sigma, Tecan, and Thermo Fisher Scientific manufacture these products. The focus of this research was to evaluate these techniques for their cleanliness, efficiency and cost effectiveness. Sample preparation techniques are designed to remove the different components of the matrix and other prescription or illicit substances present in the sample that could interfere with the assay, increase the analyte recovery, extraction efficiency, decrease variability, and clean-up the sample to allow for less instrument downtime and longer column life8. This study focused on comparing a liquid-liquid extraction (LLE), solid phase extraction (SPE), and supported liquid extraction (SLE). The primary purpose of this study was to develop and validate the three above mentioned sample preparation techniques for the analysis of THC, 11-hydroxy-THC, 11-nor-9-carboxy-THC (THCCOOH), AB-FUBINACA, AB-FUBINACA metabolite 3, and AB-PINACA in blood and urine. Parameters assessed followed Academy Standards Board (ASB) Standard 036, Standard Practices for Method Validation in Forensic Toxicology, including recovery, suppression, and matrix effects. For urine and blood analysis, the calibration range was determined to be 1 ng/mL to 50 ng/mL for all three techniques. Urine recovery was highest for the LLE method, with all compounds having a recovery greater than 50%. The SLE method had the lowest LOQ results for urine, with 0.5 ng/mL for 11-hydroxy-THC and THCCOOH, 0.75 ng/mL for THC, AB-FUBINCA and AB-FUBINACA metabolite 3, and 1 ng/mL for AB-PINACA. Ion suppression was reduced using the SLE method for urine along with having the shortest sample preparation time of 1 hr for up to 48 samples. For blood analysis, the LLE method had the greatest recovery of all analytes. The LLE method also had reduced suppression and matrix effects compared to the SPE method. Sample preparation was shorter for the SPE method, consuming 2 hrs for an average sample batch, compared to 4 hrs for the LLE method, which included a 2 hr freezing step. In conclusion, for urine analysis, all three sample preparation techniques were acceptable for the analysis of THC, synthetic cannabinoids, and their metabolites, with the SLE method being the preferred method. For blood analysis a LLE and SPE method were developed and are adequate for the analysis of THC, synthetic cannabinoids, and their metabolites, with the LLE method being the preferred method.