PHARMACOLOGY OF CANNABINOIDS

  • Ilonka Ferjan Inštitut za farmakologijo in eksperimentalno toksikologijo, Medicinska fakulteta, Univerza v Ljubljani, Korytkova 2, SI-1000 Ljubljana
  • Mojca Kržan Inštitut za farmakologijo in eksperimentalno toksikologijo, Medicinska fakulteta, Univerza v Ljubljani, Korytkova 2, SI-1000 Ljubljana
  • Metoda Lipnik-Štangelj Inštitut za farmakologijo in eksperimentalno toksikologijo, Medicinska fakulteta, Univerza v Ljubljani, Korytkova 2, SI-1000 Ljubljana
  • Lovro Žiberna Inštitut za farmakologijo in eksperimentalno toksikologijo, Medicinska fakulteta, Univerza v Ljubljani, Korytkova 2, SI-1000 Ljubljana
  • Lovro Stanovnik Inštitut za farmakologijo in eksperimentalno toksikologijo, Medicinska fakulteta, Univerza v Ljubljani, Korytkova 2, SI-1000 Ljubljana
  • Katarina Černe Inštitut za farmakologijo in eksperimentalno toksikologijo, Medicinska fakulteta, Univerza v Ljubljani, Korytkova 2, SI-1000 Ljubljana
Keywords: cannabis, endocannabinoid, , receptors, function, preparations, toxicity, legal status

Abstract

The discovery of cannabinoid receptors and endocannabinoid system has led to the potential therapeutic use of cannabis derivatives. Cannabinoids acting through the CB1 receptors modulate the release of other neurotransmitters in central nervous system, whereas the activation of peripheral CB2 receptors results in decreased inflammatory response and increased apoptosis of some tumor cells populations. The cannabinoids have been authorized for chemotherapy-induced nausea and vomiting; stimulation of appetite; to alleviate neuropathic pain and spasticity in multiple sclerosis, and to reduce pain in cancer patients. Efficacy in other diseases and clinical conditions should be proven in ongoing or future clinical trials. Isolation and identification of different cannabinoids from cannabis and synthesis of novel, more selective, derivatives widens their therapeutic potential. However, there are numerous adverse effects reported, especially when cannabinoids formulations with unknown quantitative and qualitative composition are used. Addiction, tolerance, withdrawal symptoms, increased risk of acute myocardial re-infarction, and increased risk of psychosis or worsening of psychosis are the most common adverse effects of cannabinoids. Acute adverse effects e. g. severe central nervous system depression, are more pronounced in children than in adults. Potential cannabinoid medicines should be subject to the same regulations as other potential drugs. Safety and efficacy of any potential drug candidate, regardless whether it is plant-derived or synthesized, should be proven in non-clinical studies and clinical trials, as well as the marketing authorization must be issued by the appropriate drug authority. Patients deserve a quality manufactured product, which always contains the specified amount of "Remedium cardinale."

Downloads

Download data is not yet available.

References

Borgelt LM, Franson KL, Nussbaum AM, Wang GS. The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy. 2013;33(2):195-209.

Adams IB, Martin BR. Cannabis: pharmacology and toxicology in animals and humans. Addiction. 1996;91(11):1585-1614.

Fonseca BM, Costa MA, Almada M, Correia-da-Silva G, Teixeira NA. Endogenous cannabinoids revisited: a biochemistry perspective. Prostaglandins & other lipid mediators. 2013;102-103:13-30.

Alger BE, Kim J. Supply and demand for endocannabinoids. Trends in neurosciences. 2011;34(6):304-315.

Oddi S, Fezza F, Pasquariello N, et al. Evidence for the intracellular accumulation of anandamide in adiposomes. Cellular and molecular life sciences : CMLS. 2008;65(5):840-850.

Muccioli GG. Endocannabinoid biosynthesis and inactivation, from simple to complex. Drug Discov Today. 2010;15(11-12):474-483.

Liu J, Wang L, Harvey-White J, et al. Multiple Pathways Involved in the Biosynthesis of Anandamide. Neuropharmacology. 2008;54(1):1-7.

Fine PG, Rosenfeld MJ. The endocannabinoid system, cannabinoids, and pain. Rambam Maimonides medical journal. 2013;4(4):e0022.

Zogopoulos P, Vasileiou I, Patsouris E, Theocharis SE. The role of endocannabinoids in pain modulation. Fundamental & clinical pharmacology. 2013;27(1):64-80.

Freund TF, Katona I, Piomelli D. Role of endogenous cannabinoids in synaptic signaling. Physiological reviews. 2003;83(3):1017-1066.

Fong TM. Constitutive activity in cannabinoid receptors. Advances in pharmacology. 2014;70:121-133.

Howlett AC. Cannabinoid inhibition of adenylate cyclase: relative activity of constituents and metabolites of marihuana. Neuropharmacology. 1987;26(5):507-512.

Devane WA, Dysarz FA, 3rd, Johnson MR, Melvin LS, Howlett AC. Determination and characterization of a cannabinoid receptor in rat brain. Molecular pharmacology. 1988;34(5):605-613.

Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. 1990;346(6284):561-564.

Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature. 1993;365(6441):61-65.

McPartland JM, Glass M. Functional mapping of cannabinoid receptor homologs in mammals, other vertebrates, and invertebrates. Gene. 2003;312:297-303.

Galiegue S, Mary S, Marchand J, et al. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. European journal of biochemistry / FEBS. 1995;232(1):54-61.

Skaper SD, Buriani A, Dal Toso R, et al. The ALIAmide palmitoylethanolamide and cannabinoids, but not anandamide, are protective in a delayed postglutamate paradigm of excitotoxic death in cerebellar granule neurons. Proceedings of the National Academy of Sciences of the United States of America. 1996;93(9):3984-3989.

Van Sickle MD, Duncan M, Kingsley PJ, et al. Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science. 2005;310(5746):329-332.

Pertwee RG. Cannabinoid receptors and pain. Progress in neurobiology. 2001;63(5):569-611.

Luongo L, Maione S, Di Marzo V. Endocannabinoids and neuropathic pain: focus on neuron-glia and endocannabinoid-neurotrophin interactions. The European journal of neuroscience. 2014;39(3):401-408.

Costa B, Giagnoni G, Franke C, Trovato AE, Colleoni M. Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation. British journal of pharmacology. 2004;143(2):247-250.

Wang W, Cao X, Liu C, Liu L. Cannabinoid WIN 55,212-2 inhibits TRPV1 in trigeminal ganglion neurons via PKA and PKC pathways. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2012;33(1):79-85.

Ryberg E, Larsson N, Sjogren S, et al. The orphan receptor GPR55 is a novel cannabinoid receptor. British journal of pharmacology. 2007;152(7):1092-1101.

Moriconi A, Cerbara I, Maccarrone M, Topai A. GPR55: Current knowledge and future perspectives of a purported "Type-3" cannabinoid receptor. Current medicinal chemistry. 2010;17(14):1411-1429.

Mechoulam R, Hanus L, Fride E. Towards cannabinoid drugs--revisited. Progress in medicinal chemistry. 1998;35:199-243.

Mechoulam R, Fride E, Di Marzo V. Endocannabinoids. European journal of pharmacology. 1998;359(1):1-18.

De Petrocellis L, Bisogno T, Ligresti A, Bifulco M, Melck D, Di Marzo V. Effect on cancer cell proliferation of palmitoylethanolamide, a fatty acid amide interacting with both the cannabinoid and vanilloid signalling systems. Fundamental & clinical pharmacology. 2002;16(4):297-302.

Di Marzo V, De Petrocellis L. Why do cannabinoid receptors have more than one endogenous ligand? Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 2012;367(1607):3216-3228.

Clinical Trials.Dosegljivo 29. 4. 2015 s spletne strani: https://clinicaltrials.gov/.

Pacher P, Mechoulam R. Is lipid signaling through cannabinoid 2 receptors part of a protective system? Progress in lipid research. 2011;50(2):193-211.

Walker JM, Hohmann AG, Martin WJ, Strangman NM, Huang SM, Tsou K. The neurobiology of cannabinoid analgesia. Life sciences. 1999;65(6-7):665-673.

Engels FK, de Jong FA, Sparreboom A, et al. Medicinal cannabis does not influence the clinical pharmacokinetics of irinotecan and docetaxel. The oncologist. 2007;12(3):291-300.

Bland TM, Haining RL, Tracy TS, Callery PS. CYP2C-catalyzed delta9-tetrahydrocannabinol metabolism: kinetics, pharmacogenetics and interaction with phenytoin. Biochemical pharmacology. 2005;70(7):1096-1103.

Wall ME, Perez-Reyes M. The metabolism of delta 9-tetrahydrocannabinol and related cannabinoids in man. Journal of clinical pharmacology. 1981;21(8-9 Suppl):178S-189S.

Lemberger L, Tamarkin NR, Axelrod J, Kopin IJ. Delta-9-tetrahydrocannabinol: metabolism and disposition in long-term marihuana smokers. Science. 1971;173(3991):72-74.

Hill AJ, Williams CM, Whalley BJ, Stephens GJ. Phytocannabinoids as novel therapeutic agents in CNS disorders. Pharmacology & therapeutics. 2012;133(1):79-97.

Karler R, Turkanis SA. The cannabinoids as potential antiepileptics. Journal of clinical pharmacology. 1981;21(8-9 Suppl):437S-448S.

Devinsky O, Cilio MR, Cross H, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014;55(6):791-802.

Gloss D, Vickrey B. Cannabinoids for epilepsy. The Cochrane database of systematic reviews. 2012;6:CD009270.

Eubanks LM, Rogers CJ, Beuscher AEt, et al. A molecular link between the active component of marijuana and Alzheimer's disease pathology. Molecular pharmaceutics. 2006;3(6):773-777.

Iuvone T, Esposito G, Esposito R, Santamaria R, Di Rosa M, Izzo AA. Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells. Journal of neurochemistry. 2004;89(1):134-141.

Martin-Moreno AM, Brera B, Spuch C, et al. Prolonged oral cannabinoid administration prevents neuroinflammation, lowers beta-amyloid levels and improves cognitive performance in Tg APP 2576 mice. Journal of neuroinflammation. 2012;9:8.

Esposito L, Raber J, Kekonius L, et al. Reduction in mitochondrial superoxide dismutase modulates Alzheimer's disease-like pathology and accelerates the onset of behavioral changes in human amyloid precursor protein transgenic mice. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2006;26(19):5167-5179.

Krishnan S, Cairns R, Howard R. Cannabinoids for the treatment of dementia. The Cochrane database of systematic reviews. 2009(2):CD007204.

Lyman WD, Sonett JR, Brosnan CF, Elkin R, Bornstein MB. Delta 9-tetrahydrocannabinol: a novel treatment for experimental autoimmune encephalomyelitis. Journal of neuroimmunology. 1989;23(1):73-81.

Arevalo-Martin A, Vela JM, Molina-Holgado E, Borrell J, Guaza C. Therapeutic action of cannabinoids in a murine model of multiple sclerosis. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2003;23(7):2511-2516.

Baker D, Pryce G, Croxford JL, et al. Cannabinoids control spasticity and tremor in a multiple sclerosis model. Nature. 2000;404(6773):84-87.

McDonough P, McKenna JP, McCreary C, Downer EJ. Neuropathic orofacial pain: cannabinoids as a therapeutic avenue. The international journal of biochemistry & cell biology. 2014;55:72-78.

Stempelj M, Bavec A, Ferjan I. Regulation of nerve growth factor induced histamine and arachidonic acid release from rat mast cells by cannabinoids. Inflammation research : official journal of the European Histamine Research Society ... [et al.]. 2006;55 Suppl 1:S09-10.

Parolaro D, Rubino T, Vigano D, Massi P, Guidali C, Realini N. Cellular mechanisms underlying the interaction between cannabinoid and opioid system. Current drug targets. 2010;11(4):393-405.

Woodhams SG, Sagar DR, Burston JJ, Chapman V. The role of the endocannabinoid system in pain. Handbook of experimental pharmacology. 2015;227:119-143.

Anikwue R, Huffman JW, Martin ZL, Welch SP. Decrease in efficacy and potency of nonsteroidal anti-inflammatory drugs by chronic delta(9)-tetrahydrocannabinol administration. The Journal of pharmacology and experimental therapeutics. 2002;303(1):340-346.

Hermanson DJ, Gamble-George JC, Marnett LJ, Patel S. Substrate-selective COX-2 inhibition as a novel strategy for therapeutic endocannabinoid augmentation. Trends in pharmacological sciences. 2014;35(7):358-367.

Noyes R, Jr., Brunk SF, Avery DA, Canter AC. The analgesic properties of delta-9-tetrahydrocannabinol and codeine. Clinical pharmacology and therapeutics. 1975;18(1):84-89.

Frank B, Serpell MG, Hughes J, Matthews JN, Kapur D. Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study. Bmj. 2008;336(7637):199-201.

Martin-Sanchez E, Furukawa TA, Taylor J, Martin JL. Systematic review and meta-analysis of cannabis treatment for chronic pain. Pain medicine. 2009;10(8):1353-1368.

Wilsey B, Marcotte T, Deutsch R, Gouaux B, Sakai S, Donaghe H. Low-dose vaporized cannabis significantly improves neuropathic pain. The journal of pain : official journal of the American Pain Society. 2013;14(2):136-148.

Boychuk DG, Goddard G, Mauro G, Orellana MF. The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review. Journal of oral & facial pain and headache. 2015;29(1):7-14.

de Vries M, van Rijckevorsel DC, Wilder-Smith OH, van Goor H. Dronabinol and chronic pain: importance of mechanistic considerations. Expert opinion on pharmacotherapy. 2014;15(11):1525-1534.

Reynolds TD, Osborn HL. The use of cannabinoids in chronic pain. BMJ case reports. 2013;2013.

Romero-Zerbo SY, Bermudez-Silva FJ. Cannabinoids, eating behaviour, and energy homeostasis. Drug testing and analysis. 2014;6(1-2):52-58.

Koch M, Varela L, Kim JG, et al. Hypothalamic POMC neurons promote cannabinoid-induced feeding. Nature. 2015;519(7541):45-50.

Osei-Hyiaman D. Endocannabinoid system in cancer cachexia. Current opinion in clinical nutrition and metabolic care. 2007;10(4):443-448.

Engeli S. Central and peripheral cannabinoid receptors as therapeutic targets in the control of food intake and body weight. Handbook of experimental pharmacology. 2012(209):357-381.

Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet. 2007;370(9600):1706-1713.

The European Medicines Agency recommends suspension of the marketing authorisation of Acomplia. European Medicines Agency; 2008.Dosegljivo 25. 4. 2015 s spletne strani: http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2009/11/WC500014774.pdf.

National Toxicology P. NTP Toxicology and Carcinogenesis Studies of 1-Trans-Delta(9)-Tetrahydrocannabinol (CAS No. 1972-08-3) in F344 Rats and B6C3F1 Mice (Gavage Studies). National Toxicology Program technical report series. 1996;446:1-317.

Chan PC, Sills RC, Braun AG, Haseman JK, Bucher JR. Toxicity and carcinogenicity of delta 9-tetrahydrocannabinol in Fischer rats and B6C3F1 mice. Fundamental and applied toxicology : official journal of the Society of Toxicology. 1996;30(1):109-117.

Oesch S, Gertsch J. Cannabinoid receptor ligands as potential anticancer agents--high hopes for new therapies? The Journal of pharmacy and pharmacology. 2009;61(7):839-853.

Pourkhalili N, Ghahremani MH, Farsandaj N, et al. Evaluation of anti-invasion effect of cannabinoids on human hepatocarcinoma cells. Toxicology mechanisms and methods. 2013;23(2):120-126.

Torres S, Lorente M, Rodriguez-Fornes F, et al. A combined preclinical therapy of cannabinoids and temozolomide against glioma. Molecular cancer therapeutics. 2011;10(1):90-103.

Velasco G, Carracedo A, Blazquez C, et al. Cannabinoids and gliomas. Molecular neurobiology. 2007;36(1):60-67.

Rosenkrantz H. Cannabis, marihuana, and cannabinoid toxicological manifestations in man and animals. In: Fehr KO, Kalant H. Cannabis and Health Hazards: Proceedings of an ARF/WHO Scientific Meeting on Adverse Health and Behavioral Consequences of Cannabis Use: Toronto: Addiction Research Foundation; 1983. p. 91-175.

Vaziri ND, Thomas R, Sterling M, et al. Toxicity with intravenous injection of crude marijuana extract. Clinical toxicology. 1981;18(3):353-366.

Schonwald S. Marijuana and Cannabinoids. In: Schonwald S. Medical toxicology: a synopsis and study guide: Lippincott Williams & Wilkins; 2001. p. 193-199.

Hall W, Degenhardt L. Adverse health effects of non-medical cannabis use. Lancet. 2009;374(9698):1383-1391.

Budney AJ, Hughes JR. The cannabis withdrawal syndrome. Current opinion in psychiatry. 2006;19(3):233-238.

Allsop DJ, Copeland J, Norberg MM, et al. Quantifying the clinical significance of cannabis withdrawal. PloS one. 2012;7(9):e44864.

Mittleman MA, Lewis RA, Maclure M, Sherwood JB, Muller JE. Triggering myocardial infarction by marijuana. Circulation. 2001;103(23):2805-2809.

Solowij N, Stephens RS, Roffman RA, et al. Cognitive functioning of long-term heavy cannabis users seeking treatment. Jama. 2002;287(9):1123-1131.

Tetrault JM, Crothers K, Moore BA, Mehra R, Concato J, Fiellin DA. Effects of marijuana smoking on pulmonary function and respiratory complications: a systematic review. Archives of internal medicine. 2007;167(3):221-228.

Pletcher MJ, Vittinghoff E, Kalhan R, et al. Association between marijuana exposure and pulmonary function over 20 years. Jama. 2012;307(2):173-181.

Arseneault L, Cannon M, Poulton R, Murray R, Caspi A, Moffitt TE. Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. Bmj. 2002;325(7374):1212-1213.

Castle DJ. Cannabis and psychosis: what causes what? F1000 medicine reports. 2013;5:1.

Linszen DH, Dingemans PM, Lenior ME. Cannabis abuse and the course of recent-onset schizophrenic disorders. Archives of general psychiatry. 1994;51(4):273-279.

Zammit S, Arsenault L, Cannon M, Murray R. Does cannabis cause schizophrenia? In: Castle D, Murray RM, D´Souza C. Marijuana and Madness. 2nd ed. Cambridge: Cambridge University Press; 2012. p. 169-183.

Huestis MA, Gorelick DA, Heishman SJ, et al. Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. Archives of general psychiatry. 2001;58(4):322-328.

Verdoux H, Gindre C, Sorbara F, Tournier M, Swendsen JD. Effects of cannabis and psychosis vulnerability in daily life: an experience sampling test study. Psychological medicine. 2003;33(1):23-32.

James W, Castle D. Addressing cannabis use in people with psychosis. In: Castle D, Murray RM, D´Souza C. Marijuana and Madness. 2nd ed. Cambridge: Cambridge University Press; 2012. p. 225-233.

Lubman DI, King JA, Castle DJ. Treating comorbid substance use disorders in schizophrenia. International review of psychiatry. 2010;22(2):191-201.

Andreasson S, Allebeck P, Engstrom A, Rydberg U. Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet. 1987;2(8574):1483-1486.

Caspi A, Moffitt TE, Cannon M, et al. Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biological psychiatry. 2005;57(10):1117-1127.

Hall W, Degenhardt L. What are the policy implications of the evidence on cannabis and psychosis? In: Castle D, Murray RM, D´Souza C. Marijuana and Madness. 2nd ed. Cambridge: Cambridge University Press; 2012. p. 55-65.

Lichtman AH, Martin BR. Cannabinoid tolerance and dependence. Handbook of experimental pharmacology. 2005(168):691-717.

Gonzalez S, Cebeira M, Fernandez-Ruiz J. Cannabinoid tolerance and dependence: a review of studies in laboratory animals. Pharmacology, biochemistry, and behavior. 2005;81(2):300-318.

National Toxicology Program. NTP technical report on the toxicology and carcinogenesis studies of 1-trans-delta9-tatrahydrocannabinol (CAS No. 1972-08-3) in F334/N rats and B6C3F1 mice. NTP TR 446.: Research Triangle Park; 1996.

Hashibe M, Straif K, Tashkin DP, Morgenstern H, Greenland S, Zhang ZF. Epidemiologic review of marijuana use and cancer risk. Alcohol. 2005;35(3):265-275.

Lacson JC, Carroll JD, Tuazon E, Castelao EJ, Bernstein L, Cortessis VK. Population-based case-control study of recreational drug use and testis cancer risk confirms an association between marijuana use and nonseminoma risk. Cancer. 2012;118(21):5374-5383.

International Agency For Research On Cancer (IARC). Report of the Advisory Group to Recommend Priorities for IARC Monographs during 2015-2019. IARC Monographs on the Evalution of Carcinogenic Risk to Humans. Lyon, France: World Health Organization; 2014. p. 16.

Hayatbakhsh MR, Flenady VJ, Gibbons KS, et al. Birth outcomes associated with cannabis use before and during pregnancy. Pediatric research. 2012;71(2):215-219.

Fried PA, Smith AM. A literature review of the consequences of prenatal marihuana exposure. An emerging theme of a deficiency in aspects of executive function. Neurotoxicology and teratology. 2001;23(1):1-11.

Macleod J, Oakes R, Copello A, et al. Psychological and social sequelae of cannabis and other illicit drug use by young people: a systematic review of longitudinal, general population studies. Lancet. 2004;363(9421):1579-1588.

Academy of Breastfeeding Medicine Protocol C, Jansson LM. ABM clinical protocol #21: Guidelines for breastfeeding and the drug-dependent woman. Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine. 2009;4(4):225-228.

Russo E, Mathre ML, Byrne A, et al. Chronic Cannabis Use in the Compassionate Investigational New Drug Program: An Examination of Benefits and Adverse Effects of Legal Clinical Cannabis. J Cannabis Therapeutics. 2002;2(1):3-58.

Drummer OH, Gerostamoulos J, Batziris H, et al. The involvement of drugs in drivers of motor vehicles killed in Australian road traffic crashes. Accident; analysis and prevention. 2004;36(2):239-248.

Castaneto MS, Gorelick DA, Desrosiers NA, Hartman RL, Pirard S, Huestis MA. Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications. Drug and alcohol dependence. 2014;144:12-41.

Vardakou I, Pistos C, Spiliopoulou C. Spice drugs as a new trend: mode of action, identification and legislation. Toxicology letters. 2010;197(3):157-162.

Zakon o proizvodnji in prometu s prepovedanimi drogami. Ur l 108/1999, 44/2000, 47/2004.

UN. Single Convention on Narcotic Drugs, 1961: UN General Assembly; 1961.

UN. Convention on Psychotropic Substances, 1971: United Nations; 1971.

Zakon o zdravilih Ur l 17/2014.

Pravilnik o razvrščanju, predpisovanju in izdajanju zdravil za uporabo v humani medicini. Ur l 59/2003, 114/2003, 86/2008, 45/2010.

Uredba o razvrstitvi prepovedanih drog. Ur l 49/2000, 49/2001, 78/2002, 53/2004, 122/2007, 102/2009, 95/2010, 58/2011.

Pravilnik o postopkih za izdajo dovoljenj za promet s prepovedanimi drogami. Ur l 8/2002.

Pravilnik o obliki in načinu vodenja evidenc in poročil o prepovedanih drogah. Ur l 131/2006.

Pravilnik o tehničnih in sanitarnih pogojih ter načinu zavarovanja prostorov za hrambo in izdajanje prepovedanih drog iz skupin I in II. Ur l 124/2007.

Pate DW. Chemical ecology of Cannabis. Journal of the International Hemp Association 1994;2(29):32-37.

Published
2015-06-29
How to Cite
1.
Ferjan I, Kržan M, Lipnik-Štangelj M, Žiberna L, Stanovnik L, Černe K. PHARMACOLOGY OF CANNABINOIDS. ZdravVestn [Internet]. 29Jun.2015 [cited 23Aug.2019];84(6). Available from: https://vestnik.szd.si/index.php/ZdravVest/article/view/1360
Section
Review