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(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. -
) (51) International Patent Classification: Columbia V5G 1G3
) ( (51) International Patent Classification: Columbia V5G 1G3 (CA). PANDEY, Nihar R.; 10209 A 61K 31/4525 (2006.01) C07C 39/23 (2006.01) 128A St, Surrey, British Columbia V3T 3E7 (CA). A61K 31/05 (2006.01) C07D 405/06 (2006.01) (74) Agent: ZIESCHE, Sonia et al.; Gowling WLG (Canada) A61P25/22 (2006.01) LLP, 2300 - 550 Burrard Street, Vancouver, British Colum¬ (21) International Application Number: bia V6C 2B5 (CA). PCT/CA2020/050165 (81) Designated States (unless otherwise indicated, for every (22) International Filing Date: kind of national protection av ailable) . AE, AG, AL, AM, 07 February 2020 (07.02.2020) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, (25) Filing Language: English DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (26) Publication Language: English HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, (30) Priority Data: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 16/270,389 07 February 2019 (07.02.2019) US OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (63) Related by continuation (CON) or continuation-in-part SC, SD, SE, SG, SK, SL, ST, SV, SY, TH, TJ, TM, TN, TR, (CIP) to earlier application: TT, TZ, UA, UG, US, UZ, VC, VN, WS, ZA, ZM, ZW. US 16/270,389 (CON) (84) Designated States (unless otherwise indicated, for every Filed on 07 Februaiy 2019 (07.02.2019) kind of regional protection available) . -
Federal Register/Vol. 85, No. 178/Monday, September 14, 2020
Federal Register / Vol. 85, No. 178 / Monday, September 14, 2020 / Notices 56631 agreements. All non-confidential DEPARTMENT OF JUSTICE ADDRESSES: Written comments should written submissions will be available for be sent to: Drug Enforcement public inspection at the Office of the Drug Enforcement Administration Administration, Attention: DEA Federal Secretary and on EDIS. [Docket No. DEA–713] Register Representative/DPW, 8701 The Commission vote for these Morrissette Drive, Springfield, Virginia 22152. All requests for a hearing must determinations took place on September Importer of Controlled Substances Application: Cerilliant Corporation be sent to: Drug Enforcement 8, 2020. Administration, Attn: Administrator, The authority for the Commission’s AGENCY: Drug Enforcement 8701 Morrissette Drive, Springfield, determination is contained in section Administration, Justice. Virginia 22152. All request for a hearing 337 of the Tariff Act of 1930, as ACTION: Notice of application. should also be sent to: (1) Drug amended (19 U.S.C. 1337), and in Part SUMMARY: Cerilliant Corporation has Enforcement Administration, Attn: 210 of the Commission’s Rules of applied to be registered as an importer Hearing Clerk/OALJ, 8701 Morrissette Practice and Procedure (19 CFR part of basic class(es) of controlled Drive, Springfield, Virginia 22152; and 210). substance(s). Refer to Supplemental (2) Drug Enforcement Administration, Attn: DEA Federal Register By order of the Commission. Information listed below for further Representative/DPW, 8701 Morrissette Issued: September 8, 2020. drug information. DATES: Drive, Springfield, Virginia 22152. Lisa Barton, Registered bulk manufacturers of the affected basic class(es), and SUPPLEMENTARY INFORMATION: In Secretary to the Commission. applicants therefore, may file written accordance with 21 CFR 1301.34(a), this [FR Doc. -
Synthetic Cannabinoids (60 Substances) A) Classical Cannabinoid
Synthetic cannabinoids (60 substances) a) Classical cannabinoid OH H OH H O Common name Chemical name CAS number Molecular Formula HU-210 3-(1,1’-dimethylheptyl)-6aR,7,10,10aR-tetrahydro-1- Synonym: 112830-95-2 C H O hydroxy-6,6-dimethyl-6H-dibenzo[b,d]pyran-9-methanol 25 38 3 11-Hydroxy-Δ-8-THC-DMH b) Nonclassical cannabinoids OH OH R2 R3 R4 R1 CAS Molecular Common name Chemical name R1 R2 R3 R4 number Formula rel-2[(1 S,3 R)-3- hydroxycyclohexyl]- 5- (2- methyloctan- 2- yl) CP-47,497 70434-82-1 C H O CH H H H phenol 21 34 2 3 rel-2[(1 S,3 R)-3- hydroxycyclohexyl]- 5- (2- methylheptan- 2- yl) CP-47,497-C6 - C H O H H H H phenol 20 32 2 CP-47,497-C8 rel-2- [(1 S,3 R)-3- hydroxycyclohexyl]- 5- (2- methylnonan- 2- yl) 70434-92-3 C H O C H H H H Synonym: Cannabicyclohexanol phenol 22 36 2 2 5 CAS Molecular Common name Chemical name R1 R2 R3 R4 number Formula rel-2[(1 S,3 R)-3- hydroxycyclohexyl]- 5- (2- methyldecan- 2- yl) CP-47,497-C9 - C H O C H H H H phenol 23 38 2 3 7 rel-2- ((1 R,2 R,5 R)-5- hydroxy- 2- (3- hydroxypropyl)cyclohexyl)- 3-hydroxy CP-55,940 83003-12-7 C H O CH H H 5-(2- methyloctan- 2- yl)phenol 24 40 3 3 propyl rel-2- [(1 S,3 R)-3- hydroxy-5,5-dimethylcyclohexyl]- 5- (2- Dimethyl CP-47,497-C8 - C H O C H CH CH H methylnonan-2- yl)phenol 24 40 2 2 5 3 3 c) Aminoalkylindoles i) Naphthoylindoles 1' R R3' R2' O N CAS Molecular Common name Chemical name R1’ R2’ R3’ number Formula [1-[(1- methyl- 2- piperidinyl)methyl]- 1 H-indol- 3- yl]- 1- 1-methyl-2- AM-1220 137642-54-7 C H N O H H naphthalenyl-methanone 26 26 2 piperidinyl -
Medicinal Chemistry Endeavors Around the Phytocannabinoids
CHEMISTRY & BIODIVERSITY – Vol. 4 (2007) 1707 REVIEW Medicinal Chemistry Endeavors around the Phytocannabinoids by Eric Stern and Didier M. Lambert* Drug Design and Discovery Center and Unite´ de Chimie pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, Faculte´ de Me´decine, Universite´ catholique de Louvain, Avenue E. Mounier 73, U.C.L. 73.40, B-1200 Bruxelles (phone: þ3227647347; fax: þ3227647363; e-mail: [email protected]) Over the past 50 years, a considerable research in medicinal chemistry has been carried out around the natural constituents of Cannabis sativa L. Following the identification of D9-tetrahydrocannabinol (D9-THC) in 1964, critical chemical modifications, e.g., variation of the side chain at C(3) and the opening of the tricyclic scaffold, have led to the characterization of potent and cannabinoid receptor subtype-selective ligands. Those ligands that demonstrate high affinity for the cannabinoid receptors and good biological efficacy are still used as powerful pharmacological tools. This review summarizes past as well as recent developments in the structure–activity relationships of phytocannabinoids. 1. Introduction. – Despite the wide uses of preparations of the hemp Cannabis sativa L. during the History, the modern pharmacology of natural cannabinoids has been hampered by the slow progress in the elucidations of the chemical structures of its major components. Indeed, it is nowadays known that more than 70 compounds derived from a diterpene structure are present in the plant [1], and this fact may explain the difficulty to obtain pure chemical entities in the past. In addition, the medicinal research for more than a half century has been driven by the search for the components responsible for the psychoactive effects of cannabis, this era in the history of the chemical research on cannabinoids have been recently reviewed [2][3]. -
Article 22 Regulation for Restriction of Synthetic Drugs
ARTICLE 22 REGULATION FOR RESTRICTION OF SYNTHETIC DRUGS SECTION 22.1 AUTHORITY This regulation is promulgated under the authority granted to the Needham Board of Health under Massachusetts General Laws Chapter 111, Section 31 which states that “boards of health may make reasonable health regulations”. SECTION 22.2 PURPOSE The Needham Board of Health has found that synthetic marijuana, consisting of plant or other material treated with various chemicals or other synthetic substances not approved for human consumption, may be marketed and sold as herbal incense in the greater Boston area, although they are being used in the same manner and for the same purposes as scheduled drugs. In addition, the use of these products has become particularly popular among teens and young adults. Based on information and reports from hospitals, emergency room doctors, and police agencies, individuals who use these products experience dangerous side effects including convulsions, hallucinations, and dangerously elevated heart rates. This is evidence that synthetic marijuana products are harmful if inhaled or consumed, and present a significant public health danger. These synthetic compounds and others have a high potential for abuse and lack of any accepted medical use, these dangerous products, while not approved for human consumption, are marketed and sold in a form that allows for such consumption, putting at risk the individuals who come into contact with them. Therefore, the Needham Board of Health adopts this regulation for the purpose and with the intent to protect the public health and safety of the Town of Needham and its residents from the threat posed by the availability and use of synthetic marijuana, synthetic stimulants, synthetic hallucinogens, and other dangerous products by prohibiting persons from trafficking in, possessing, and using them within the town. -
Synthetic Cannabinoids, Forensic & Legal Aspects
Synthetic Cannabinoids, Forensic & Legal Aspects Marilyn A. Huestis, PhD Chief, Chemistry & Drug Metabolism National Institute on Drug Abuse, National Institutes of Health Council of Forensic Medicine Istanbul, Turkey August 18, 2011 Synthetic Cannabinoid Overview Cannabinoid pharmacology Chemistry of synthetic cannabinoids Metabolism of synthetic cannabinoids Controlled drug administration studies Analytical methods for the identification of synthetic cannabinoids in biological & non-biological matrices Current legal status of synthetic cannabinoids Cannabis Mechanisms of Action THC binds to cannabinoid receptors & modulates endogenous cannabinoid & other neurotransmitter systems CB-1 receptors primarily in central nervous & cardiovascular systems CB-2 receptors primarily in immune system Non-CB1, non-CB2 receptors G-protein receptors discovered & cloned in late 1980’s Endogenous cannabinoids include anandamide, 2-AG, virodhamine, N-arachidonyl dopamine (NADA), oleamide, 2-arachidonyl glyceryl ether (noladin ether) & others High CB1 Receptor Density Hypothalamus Appetite, Hormones & Sexual behavior Neocortex High cognitive function & Sensory data Basal Ganglia integration Motor control & planning Hippocampus Memory & Learning Amygdala Anxiety, Emotion & Fear Cerebellum Brain Stem Motor control & Spinal Cord & coordination Vomiting reflex & Pain sensation Cannabinoid Mechanisms of Action Receptor distribution in brain correlates with areas involved in physiological, psychomotor & cognitive effects High density in caudate -
2 Spice English Presentation
Spice Spice contains no compensatory substances Специи не содержит компенсационные вещества Spice is a mix of herbs (shredded plant material) and manmade chemicals with mind-altering effects. It is often called “synthetic marijuana” because some of the chemicals in it are similar to ones in marijuana; but its effects are sometimes very different from marijuana, and frequently much stronger. It is most often labeled “Not for Human Consumption” and disguised as incense. Eliminationprocess • The synthetic agonists such as THC is fat soluble. • Probably, they are stored as THC in cell membranes. • Some of the chemicals in Spice, however, attach to those receptors more strongly than THC, which could lead to a much stronger and more unpredictable effect. • Additionally, there are many chemicals that remain unidentified in products sold as Spice and it is therefore not clear how they may affect the user. • Moreover, these chemicals are often being changed as the makers of Spice alter them to avoid the products being illegal. • To dissolve the Spice crystals Acetone is used endocannabinoids synhtetic THC cannabinoids CB1 and CB2 agonister Binds to cannabinoidreceptor CB1 CB2 - In the brain -in the immune system Decreased avtivity in the cell ____________________ Maria Ellgren Since some of the compounds have a longer toxic effects compared to naturally THC, as reported: • negative effects that often occur the day after consumption, as a general hangover , but without nausea, mentally slow, confused, distracted, impairment of long and short term memory • Other reports mention the qualitative impairment of cognitive processes and emotional functioning, like all the oxygen leaves the brain. -
Hb 185 an Act Listing Synthetic
62nd Legislature HB0185 AN ACT LISTING SYNTHETIC MARIJUANA AND SALVIA AS DANGEROUS DRUGS; REQUIRING RULEMAKING BY THE DEPARTMENT OF PUBLIC HEALTH AND HUMAN SERVICES; PROVIDING PENALTIES; AMENDING SECTIONS 44-12-102, 45-9-101, 45-9-102, 45-9-110, 50-31-306, 50-31-310, AND 50-32-222, MCA; AND PROVIDING AN IMMEDIATE EFFECTIVE DATE. BE IT ENACTED BY THE LEGISLATURE OF THE STATE OF MONTANA: Section 1. Section 44-12-102, MCA, is amended to read: "44-12-102. Things subject to forfeiture. (1) The following are subject to forfeiture: (a) all controlled substances that have been manufactured, distributed, prepared, cultivated, compounded, processed, or possessed in violation of Title 45, chapter 9; (b) all money, raw materials, products, and equipment of any kind that are used or intended for use in manufacturing, preparing, cultivating, compounding, processing, delivering, importing, or exporting any controlled substance in violation of Title 45, chapter 9, except items used or intended for use in connection with quantities of marijuana in amounts less than 60 grams; (c) except as provided in subsection (2)(d), all property that is used or intended for use as a container for anything enumerated in subsection (1)(a) or (1)(b); (d) except as provided in subsection (2), all conveyances, including aircraft, vehicles, and vessels, that are used or intended for use in any manner to facilitate the commission of a violation of Title 45, chapter 9; (e) all books, records, and research products and materials, including formulas, microfilm, tapes, and data, -
Shlomi Cohen, Israel Manela, Eli More , Et Al. V. Pharmos Corp. , Et Al
UNITED STATES DISTRICT COURT DISTRICT OF NEW JERSEY _____________________________________ ) SHLOMI COHEN, ISRAEL MANELA, and ELI ) Case No. ____________ MORE, individually and on behalf of all others ) similarly situated, ) ) CLASS ACTION COMPLAINT ) Plaintiffs, ) ) JURY TRIAL DEMANDED v. ) ) HAIM AVIV; GAD RIESENFELD; and PHARMOS ) CORP., ) ) Defendants. ) _____________________________________ ) Plaintiffs, by undersigned counsel, for plaintiffs’ Class Action Complaint, allege the following upon personal knowledge as to plaintiffs and plaintiffs’ own acts, and upon information and belief based upon the investigation of plaintiffs’ attorneys as to all other matters. The investigation includes the review and analysis of public statements and publicly-filed documents of Pharmos Corp. ("Pharmos" or the "Company"), press releases, news articles and related literature. Plaintiffs believe that further substantial evidentiary support will exist for the allegations set forth below after a reasonable opportunity for discovery. SUMMARY OF ACTION 1. This is a securities class action on behalf of investors who purchased common stock of the Pharmos during the period from August 23, 2004 through December 17, 2004 (the "Class Period"). 2. Pharmos is a bio-pharmaceutical company that develops drugs to treat a range of neuro-inflammatory disorders. Pharmos’s main product, Dexanabinol, is a synthetic non- psychotropic cannabinoid for the treatment of traumatic brain injury. 3. Pharmos’s common stock is listed on the Nasdaq under the ticker symbol “PARS”; and as of November 1, 2004, Pharmos had 94.3 million shares outstanding. 4. Throughout the Class Period, defendants repeatedly touted Dexanabinol, causing Pharmos’ stock price to climb dramatically. In fact, Dexanabinol was simply ineffective in treating Traumatic Brain Injury, and defendants were aware of or recklessly disregarded evidence of that ineffectiveness. -
Long Term Cerebroprotective Effects of Dexanabinol in a Model of Focal Cerebral Ischemia Gil Lavieaa,Cbaa, , Angella Teichner , Esther Shohami , Haim Ovadia , Ronen R
Brain Research 901 (2001) 195±201 www.elsevier.com/locate/bres Research report Long term cerebroprotective effects of dexanabinol in a model of focal cerebral ischemia Gil Lavieaa,cbaa, , Angella Teichner , Esther Shohami , Haim Ovadia , Ronen R. Leker * aDepartment of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hebrew University-Hadassah Medical School, Hadassah University Hospital, Ein Kerem, P.O. Box 12000, Jerusalem 91120, Israel bDepartment of Pharmacology, Hebrew University-Hadassah Medical School, Hadassah University Hospital, Jerusalem, Israel cDepartment of Neurological Sciences, University of Rome, La Sapienza, Rome, Italy Accepted 27 February 2001 Abstract In order to test the long-term cerebroprotective effects of dexanabinol, a synthetic non-competitive NMDA antagonist that also has anti-TNFa effects, spontaneously hypertensive rats underwent permanent middle cerebral artery occlusion (PMCAO). Rats were given vehicle or dexanabinol (4.5 mg/kg) 1, 3 or 6 h after PMCAO. The research consisted of 2 stages. In the short-term set of experiments animals (n55/group), were tested with a motor disability scale 24 h post PMCAO, then sacri®ced and the infarct volume was measured using 2,3,5-Triphenyltetrazolium chloride (TTC) staining. In the long-term set of experiments the rats (n57/group) were examined daily with a motor disability scale up to 30 days after PMCAO and then sacri®ced and infarct volumes were determined using TTC staining. Motor scores were signi®cantly improved in the dexanabinol treated rats (P,0.05 for all groups) at all the time points examined. Infarct volumes were signi®cantly reduced 24 h after PMCAO in the groups treated 1 or 3 h, but not 6 h after PMCAO compared with vehicle (Mean6S.D., 11.562.02, 1263.2 and 14.462.4% vs. -
Introduced B.,Byhansen, 16
LB301 LB301 2021 2021 LEGISLATURE OF NEBRASKA ONE HUNDRED SEVENTH LEGISLATURE FIRST SESSION LEGISLATIVE BILL 301 Introduced by Hansen, B., 16. Read first time January 12, 2021 Committee: Judiciary 1 A BILL FOR AN ACT relating to the Uniform Controlled Substances Act; to 2 amend sections 28-401, 28-405, and 28-416, Revised Statutes 3 Cumulative Supplement, 2020; to redefine terms; to change drug 4 schedules and adopt federal drug provisions; to change a penalty 5 provision; and to repeal the original sections. 6 Be it enacted by the people of the State of Nebraska, -1- LB301 LB301 2021 2021 1 Section 1. Section 28-401, Revised Statutes Cumulative Supplement, 2 2020, is amended to read: 3 28-401 As used in the Uniform Controlled Substances Act, unless the 4 context otherwise requires: 5 (1) Administer means to directly apply a controlled substance by 6 injection, inhalation, ingestion, or any other means to the body of a 7 patient or research subject; 8 (2) Agent means an authorized person who acts on behalf of or at the 9 direction of another person but does not include a common or contract 10 carrier, public warehouse keeper, or employee of a carrier or warehouse 11 keeper; 12 (3) Administration means the Drug Enforcement Administration of the 13 United States Department of Justice; 14 (4) Controlled substance means a drug, biological, substance, or 15 immediate precursor in Schedules I through V of section 28-405. 16 Controlled substance does not include distilled spirits, wine, malt 17 beverages, tobacco, hemp, or any nonnarcotic substance if such substance 18 may, under the Federal Food, Drug, and Cosmetic Act, 21 U.S.C.