The Endocannabioids System and Their Implications in Various Disorders
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Analysis of Drugs Manual September 2019
Drug Enforcement Administration Office of Forensic Sciences Analysis of Drugs Manual September 2019 Date Posted: 10/23/2019 Analysis of Drugs Manual Revision: 4 Issue Date: September 5, 2019 Effective Date: September 9, 2019 Approved By: Nelson A. Santos Table of Contents CHAPTER 1 – QUALITY ASSURANCE ......................................................................... 3 CHAPTER 2 – EVIDENCE ANALYSIS ......................................................................... 93 CHAPTER 3 – FIELD ASSISTANCE .......................................................................... 165 CHAPTER 4 – FINGERPRINT AND SPECIAL PROGRAMS ..................................... 179 Appendix 1A – Definitions ........................................................................................... 202 Appendix 1B – Acronyms and Abbreviations .............................................................. 211 Appendix 1C – Instrument Maintenance Schedule ..................................................... 218 Appendix 1D – Color Test Reagent Preparation and Procedures ............................... 224 Appendix 1E – Crystal and Precipitate Test Reagent Preparation and Procedures .... 241 Appendix 1F – Thin Layer Chromatography................................................................ 250 Appendix 1G – Qualitative Method Modifications ........................................................ 254 Appendix 1H – Analytical Supplies and Services ........................................................ 256 Appendix 2A – Random Sampling Procedures -
Cannabinoids and Endocannabinoid System Changes in Intestinal Inflammation and Colorectal Cancer
cancers Review Cannabinoids and Endocannabinoid System Changes in Intestinal Inflammation and Colorectal Cancer Viktoriia Cherkasova, Olga Kovalchuk * and Igor Kovalchuk * Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 7X8, Canada; [email protected] * Correspondence: [email protected] (O.K.); [email protected] (I.K.) Simple Summary: In recent years, multiple preclinical studies have shown that changes in endo- cannabinoid system signaling may have various effects on intestinal inflammation and colorectal cancer. However, not all tumors can respond to cannabinoid therapy in the same manner. Given that colorectal cancer is a heterogeneous disease with different genomic landscapes, experiments with cannabinoids should involve different molecular subtypes, emerging mutations, and various stages of the disease. We hope that this review can help researchers form a comprehensive understanding of cannabinoid interactions in colorectal cancer and intestinal bowel diseases. We believe that selecting a particular experimental model based on the disease’s genetic landscape is a crucial step in the drug discovery, which eventually may tremendously benefit patient’s treatment outcomes and bring us one step closer to individualized medicine. Abstract: Despite the multiple preventive measures and treatment options, colorectal cancer holds a significant place in the world’s disease and mortality rates. The development of novel therapy is in Citation: Cherkasova, V.; Kovalchuk, critical need, and based on recent experimental data, cannabinoids could become excellent candidates. O.; Kovalchuk, I. Cannabinoids and This review covered known experimental studies regarding the effects of cannabinoids on intestinal Endocannabinoid System Changes in inflammation and colorectal cancer. In our opinion, because colorectal cancer is a heterogeneous Intestinal Inflammation and disease with different genomic landscapes, the choice of cannabinoids for tumor prevention and Colorectal Cancer. -
Marijuana: Drug of Abuse Or Therapeutic Option? Learning Objectives
Handout for the Neuroscience Education Institute (NEI) online activity: Marijuana: Drug of Abuse or Therapeutic Option? Learning Objectives • Explain how cannabinoids affect the body and the brain • Educate patients about: – Evidence of efficacy for mental health and other conditions – Potential risks of cannabis use Timeline 1989? 90?: Discovery of ~2000 BC: binding site 2015: Elimination of Chinese 1943: Marijuana for THC— 1992: US Public Health emperors removed from CB1 Endogenous Service oversight cannabinoid recommend listing as a 1963: 1964: THC receptor for obtaining anandamide marijuana as medication in US Cannabidiol isolated marijuana for discovered medicine Pharmacopeia isolated research purposes 1995: 1851: Marijuana 1961: United 1970: Marijuana is Endogenous Aug 11 2016: listed as a Nations Single labeled Schedule I cannabinoid 2-AG DEA declines to medication in US Convention on by the US discovered reschedule Pharmacopeia Narcotic Drugs: Substance Abuse marijuana marijuana said to Act; this restricts be dangerous with both personal use no medical value and access for research purposes THE INTERSECTION OF THE HEALTHCARE AND CANNABIS INDUSTRIES What is Cannabis? 500 chemicals 100 cannabinoids Best understood: THC and CBD Scheduling of Controlled Substances No medicinal value, high Moderate to Lower High potential Low potential potential for low potential potential for for abuse for abuse abuse for abuse abuse Schedule I Schedule II Schedule III Schedule IV Schedule V Marijuana Cocaine Tylenol w/ Tramadol Robitussin AC Heroin -
And Anxiety-Related Behavioral Effects of Repeated Nicotine As a Stressor: the Role of Cannabinoid Receptors Tamaki Hayase
Hayase BMC Neuroscience 2013, 14:20 http://www.biomedcentral.com/1471-2202/14/20 RESEARCH ARTICLE Open Access Working memory- and anxiety-related behavioral effects of repeated nicotine as a stressor: the role of cannabinoid receptors Tamaki Hayase Abstract Background: Like emotional symptoms such as anxiety, modulations in working memory are among the frequently-reported but controversial psychiatric symptoms associated with nicotine (NC) administration. In the present study, repeated NC-induced modulations in working memory, along with concurrently-observed anxiety- related behavioral alterations, were investigated in mice, and compared with the effects of a typical cognition- impairing stressor, immobilization stress (IM). Furthermore, considering the structural and functional contributions of brain cannabinoid (CB) receptors in NC-induced psychiatric symptoms including emotional symptoms, the interactive effects of brain CB receptor ligands (CB ligands) and NC and/or IM on the working memory- and anxiety-related behaviors were examined. Results: Statistically significant working memory impairment-like behavioral alterations in the Y-maze test and anxiety-like behavioral alterations in the elevated plus-maze (EPM) test were observed in the groups of mice treated with 0.8 mg/kg NC (subcutaneous (s.c.) 0.8 mg/kg treatment, 4 days) and/or IM (10 min treatment, 4 days). In the group of mice treated with NC plus IM (NC-IM group), an enhancement of the behavioral alterations was observed. Among the CB type 1 (CB1) antagonist AM 251 (AM), the non-selective CB agonist CP 55,940 (CP), and the CB1 partial agonist/antagonist virodhamine (VD), significant recovering effects were provided by AM (0.2-2.5 mg/kg) and VD (5 mg/kg) against the working memory impairment-like behaviors, whereas significant anxiolytic-like effects (recoveries from both attenuated percentage of entries into open arms and attenuated percentage of time spent on open arms) were provided by VD (1–10 mg/kg) and CP (2 mg/kg) against the anxiety-like behaviors. -
Cannabinoids in Dermatology: a Scoping Review
Volume 24 Number 6| June 2018| Dermatology Online Journal || Review 24(6): 1 Cannabinoids in dermatology: a scoping review Lauren R M Eagelston1 MD, Nazanin Kuseh Kalani Yazd1 BS, Ravi R Patel2 MD, Hania K Flaten1 BS, Cory A Dunnick3,4 MD, Robert P Dellavalle3,4 MD PhD MSPH Affiliations: 1University of Colorado School of Medicine, Aurora, Colorado, USA, 2Gwinnett Medical Center, Lawrenceville, Georgia, USA, 3University of Colorado School of Medicine, Department of Dermatology, Aurora, Colorado, 4Denver Veterans Affairs Medical Center (VAMC), Department of Dermatology, Denver, Colorado Corresponding Author: Robert P. Dellavalle MD PhD MSPH, Professor of Dermatology, Chief of Dermatology Service, Department of Veteran Affairs Medical Center, 1055 Clermont Rm 6A-105 Mail Stop 16, Denver, CO 80220, Tel: 303.339.8020 x2475, Email: [email protected] Introduction Abstract The cannabinoids are a diverse class of The therapeutic applications of cannabis and pharmacologically active compounds that are cannabinoids are an increasingly conspicuous topic structurally and biologically similar to the primary as de-criminalization and legalization of these products continues to expand. A limited number of psychoactive compound derived from Cannabis cannabinoid compounds have been approved for a sativa -tetrahydrocannabinol (THC), [1-4]. There specific set of conditions. However, the current role are three classes of cannabinoids. Endogenous of cannabinoids for the treatment of dermatologic cannabinoids (endocannabinoids) occur conditions remains to be defined. We conducted a naturally/are constitutively produced in the bodies review of the current literature to determine the of humans and animals [3, 5, 6]. The most well-known applications of cannabinoids for the therapy of members of this class include 2-arachidonoyl- various skin diseases. -
Supporting Information
Supporting Information Blankman et al. 10.1073/pnas.1217121110 SI Materials and Methods RT-PCR. Total RNA was isolated from brain tissue of 6-wk-old −/− +/+ Materials. We purchased 2-arachidonoylglycerol (2-AG) from ABHD12 and ABHD12 mice using TRIzol (Invitrogen). Cayman Chemicals; 2-oleoylglycerol, pentadecanoic acid (PDA), First-strand cDNA was synthesized using the SuperScript III and dodecylmonoalkylglycerol ether (C12:0 MAGE) were pur- Reverse Transcriptase kit (Invitrogen) according to the manu- chased from Sigma-Aldrich. Monopentadecanoin (C15:0 MAG) facturer’s protocol. PCR amplification (25 cycles) of a 259 bp fragment of the ABHD12 cDNA was performed with primers 50- and monoheptadecanoin (C17:0 MAG) were purchased from Nu- 0 0 Chek-Prep. Phospholipids and lysophospholipids were purchased CTCAGTAGGAACACCATCGGAGC-3 and 5 -GCCAGGG- AAGTATCGGTATATCACTG-3. Amplification of a 245-bp from Avanti Polar Lipids. Fluorophosphonate (FP)-rhodamine 0 (1) and JZL184 (2) were synthesized as described previously. GAPDH product was performed as a control with primers 5 - GGTGAAGGTCGGTGTGAACGG-30 and 50-CCCATTTGA- 0 Generation of ABHD12−/− Mice. The α/β-hydrolase domain-con- TGTTAGTGGGGTCTCG-3 . Both sets of primers were de- taining (ABHD)12-targeting construct was generated by ampli- signed to span a >2-kb region of genomic DNA. fying 3.4- and 4.4-kb regions of the Abhd12 gene adjacent to the Untargeted liquid chromatography–mass spectrometry proteomic analysis. catalytic exon 8 from a BAC clone containing the Abhd12 locus Mouse brain membrane proteomes were prepared from 6-mo-old − − + + (clone ID RP23-193L22 from BACPAC Resources Center at ABHD12 / and ABHD12 / mice (n = 3 per genotype). -
Cannabigerol Is a Potential Therapeutic Agent in a Novel Combined Therapy for Glioblastoma
cells Article Cannabigerol Is a Potential Therapeutic Agent in a Novel Combined Therapy for Glioblastoma Tamara T. Lah 1,2,3,*, Metka Novak 1, Milagros A. Pena Almidon 4, Oliviero Marinelli 4 , Barbara Žvar Baškoviˇc 1, Bernarda Majc 1,3, Mateja Mlinar 1, Roman Bošnjak 5, Barbara Breznik 1 , Roby Zomer 6 and Massimo Nabissi 4 1 Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia; [email protected] (M.N.); [email protected] (B.Ž.B.); [email protected] (B.M.); [email protected] (M.M.); [email protected] (B.B.) 2 Faculty of Chemistry and Chemical Technology, University of Ljubljana, 1000 Ljubljana, Slovenia 3 Jožef Stefan International Postgraduate School, 1000 Ljubljana, Slovenia 4 School of Pharmacy, Experimental Medicine Section, University of Camerino, 62032 Camerino, Italy; [email protected] (M.A.P.A.); [email protected] (O.M.); [email protected] (M.N.) 5 Department of Neurosurgery, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; [email protected] 6 MGC Pharmaceuticals d.o.o., 1000 Ljubljana, Slovenia; [email protected] * Correspondence: [email protected]; Tel.: +386-41-651-629 Simple Summary: Among primary brain tumours, glioblastoma is the most aggressive. As early relapses are unavoidable despite standard-of-care treatment, the cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) alone or in combination have been suggested as a combined treatment strategy for glioblastomas. However, the known psychoactive effects of THC hamper its medical applications in these patients with potential cognitive impairment due to the progression of the Citation: Lah, T.T.; Novak, M.; Pena Almidon, M.A.; Marinelli, O.; disease. -
(12) United States Patent (10) Patent No.: US 9.435,817 B2 Benchikh Et Al
USOO9435817B2 (12) United States Patent (10) Patent No.: US 9.435,817 B2 Benchikh et al. (45) Date of Patent: Sep. 6, 2016 (54) DETECTION OF SYNTHETIC OTHER PUBLICATIONS CANNABINOIDS C. V. Rao, “Immunology. A textbook”. Alpha Science Internatl. Ltd., 2005, pp. 63, 69-71.* (75) Inventors: Elouard Benchikh, Crumlin (GB); Weissman et al., “Cannabimimetic activity from CP-47,497, a Stephen Peter Fitzgerald, Crumlin derivative of 3-phenylcyclohexanol.” J. Pharmacol. Exp. Ther. (GB); Paul John Innocenzi, Crumlin 1982, vol. 223, No. 2, pp. 516-523.* (GB); Philip Andrew Lowry, Crumlin Wild, “The Immunoassay Handbook.” Third Ed., Elsevier, 2005, (GB); Ivan Robert McConnell, pp. 255-256.* Crumlin (GB) Melvin et al., “A cannabinoid derived prototypical analgesic,” J. Med. Chem., 1984, vol. 27, No. 1, pp. 67-71.* Dresen, S. et al., “Monitoring of Herbal Mixtures Potentially (73) Assignee: Randox Laboratories Limited, Containing Synthetic Cannabinoids as Psychoactive Compounds.” Crumlin (GB) J. Mass. Spectrometry, 2010, pp. 1186-1194, vol. 45. Goodrow, M.H. et al., “Strategies for Immunoassay Hapten (*) Notice: Subject to any disclaimer, the term of this Design,” in Immunoanalysis of Agrochemicals; Nelson, J. et al., patent is extended or adjusted under 35 ACS Symposium Series, 1995, Chapter 9, pp. 119-139, vol. 586. U.S.C. 154(b) by 590 days. Hudson, S. et al., “Use of High-Resolution Accurate Mass Spec trometry to Detect Reported and Previously Unreported Can (21) Appl. No.: 13/585,630 nabinomimetics in Herbal High Products,” J. Anal. Toxicol., 2010, pp. 252-260, vol. 34. Huffman, J. et al., “1-Pentyl-3-phenylacetylindoles, a New Class of (22) Filed: Aug. -
Cannabinoid Receptor and Inflammation
Cannabinoid Receptor and Inflammation Newman Osafo1, Oduro Yeboah1, Aaron Antwi1, and George Ainooson1 1Kwame Nkrumah University of Science and Technology September 11, 2020 Abstract The eventual discovery of endogenous cannabinoid receptors CB1 and CB2 and their endogenous ligands has generated interest with regards to finally understanding the endocannabinoid system. Its role in the normal physiology of the body and its implication in pathological states such as cardiovascular diseases, neoplasm, depression and pain have been subjects of scientific interest. In this review the authors focus on the endogenous cannabinoid pathway, the critical role of cannabinoid receptors in signaling and mediation of neurodegeneration and other inflammatory responses as well as its potential as a drug target in the amelioration of some inflammatory conditions. Though the exact role of the endocannabinoid system is not fully understood, the evidence found leans heavily towards a great potential in exploiting both its central and peripheral pathways in disease management. Cannabinoid therapy has already shown great promise in several preclinical and clinical trials. 1.0 Introduction Ethnopharmacological studies have shown the use of Cannabis sativa in traditional medicine for over a thousand years, with its widespread use promoted by its psychotropic effects (McCoy, 2016; Turcotte et al., 2016). The discovery of a receptor within human body, that is selectively activated by cannabinoids suggested the presence of at least one endogenous ligand for this receptor. This is confirmed by the discovery of two endogenously synthesized lipid mediators, 2-arachidonoyl-glycerol and arachidonoylethanolamide, which function as high-affinity ligands for a subfamily of cannabinoid receptors ubiquitously distributed in the central nervous system, known as the CB1 receptors (Turcotte et al., 2016). -
A Dissertation Entitled Uncovering Cannabinoid Signaling in C. Elegans
A Dissertation Entitled Uncovering Cannabinoid Signaling in C. elegans: A New Platform to Study the Effects of Medicinal Cannabis By Mitchell Duane Oakes Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Biology ________________________________________ Dr. Richard Komuniecki, Committee Chair _______________________________________ Dr. Bruce Bamber, Committee Member ________________________________________ Dr. Patricia Komuniecki, Committee Member ________________________________________ Dr. Robert Steven, Committee Member ________________________________________ Dr. Ajith Karunarathne, Committee Member ________________________________________ Dr. Jianyang Du, Committee Member ________________________________________ Dr. Amanda Bryant-Friedrich, Dean College of Graduate Studies The University of Toledo August 2018 Copyright 2018, Mitchell Duane Oakes This document is copyrighted material. Under copyright law, no parts of this document may be reproduced without the expressed permission of the author. An Abstract of Uncovering Cannabinoid Signaling in C. elegans: A New Platform to Study the Effects of Medical Cannabis By Mitchell Duane Oakes Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Biology The University of Toledo August 2018 Cannabis or marijuana, a popular recreational drug, alters sensory perception and exerts a range of medicinal benefits. The present study demonstrates that C. elegans exposed to -
Microgram Journal, Vol 2, Number 1
Washington, D. C. Office of Science and Education Vol.II,No.1 Division of Laboratory Operations January 1969 INDEXISSUE CORRECTION 11 "Structure Elucidation of 'LBJ' , by Sander W. Bellman, John W. Turczan, James Heagy and Ted M. Hopes, Micro Gram .!., 3, 6-13 (Dec. 1968) Page 7, third and fourth sentences under Discussion: Change to read: "The melting point of the acid moiety found in step (g) was 148-150°c., compared to the litera ture, v~lue of 151°c for the melting point of benzilic acid (2); thus the benzilic acid melting point gives support to the proposed structure for 'LBJ'. Spectral evidence also supports the proposed structure". MICRO-GRAMREVISION Please re-number the pages of your copies of Micro-Gram, Volume I. Re-number pages bearing printing only. Vol ume I will then be numbered from page 1, the front page of issue No. 1, through page 189 the last page of issue No. 12. To help with this task, pages contained within each issue are as follows: Issue Number Page Through 1 1 8 2 9 29 3 30 32 4 33 66 5 67 79 6 80 97 7 98 120 8 121 128 9 129 136 10 137 157 11 158 170 12 171 189 CAUTION: Use of this publication should be restricted to forensic analysts or others having a legitimate need for this material. From the Archive Library of Erowid Center http://erowid.org/library/periodicals/microgram -2- CANNABIS ,·,-...__/' Attached is a copy of 11A Short Rapid Method for the Identification of Cannabis." The method was developed by Mro H.D. -
Potential Cannabis Antagonists for Marijuana Intoxication
Central Journal of Pharmacology & Clinical Toxicology Bringing Excellence in Open Access Review Article *Corresponding author Matthew Kagan, M.D., Cedars-Sinai Medical Center, 8730 Alden Drive, Los Angeles, CA 90048, USA, Tel: 310- Potential Cannabis Antagonists 423-3465; Fax: 310.423.8397; Email: Matthew.Kagan@ cshs.org Submitted: 11 October 2018 for Marijuana Intoxication Accepted: 23 October 2018 William W. Ishak, Jonathan Dang, Steven Clevenger, Shaina Published: 25 October 2018 Ganjian, Samantha Cohen, and Matthew Kagan* ISSN: 2333-7079 Cedars-Sinai Medical Center, USA Copyright © 2018 Kagan et al. Abstract OPEN ACCESS Keywords Cannabis use is on the rise leading to the need to address the medical, psychosocial, • Cannabis and economic effects of cannabis intoxication. While effective agents have not yet been • Cannabinoids implemented for the treatment of acute marijuana intoxication, a number of compounds • Antagonist continue to hold promise for treatment of cannabinoid intoxication. Potential therapeutic • Marijuana agents are reviewed with advantages and side effects. Three agents appear to merit • Intoxication further inquiry; most notably Cannabidiol with some evidence of antipsychotic activity • THC and in addition Virodhamine and Tetrahydrocannabivarin with a similar mixed receptor profile. Given the results of this research, continued development of agents acting on cannabinoid receptors with and without peripheral selectivity may lead to an effective treatment for acute cannabinoid intoxication. Much work still remains to develop strategies that will interrupt and reverse the effects of acute marijuana intoxication. ABBREVIATIONS Therapeutic uses of cannabis include chronic pain, loss of appetite, spasticity, and chemotherapy-associated nausea and CBD: Cannabidiol; CBG: Cannabigerol; THCV: vomiting [8]. Recreational cannabis use is on the rise with more Tetrahydrocannabivarin; THC: Tetrahydrocannabinol states approving its use and it is viewed as no different from INTRODUCTION recreational use of alcohol or tobacco [9].