Therapeutic Use of Synthetic Cannabinoids: Still an Open Issue?

Clinical Therapeutics

Volumn 40, Issue 9, 2018, Pages 1457-1466

  De Luca, Maria Antonietta ^a   Fattore, Liana ^b  

^a UNIVERSITY OF CAGLIARI   (Italy)

^b CNR   (Italy)

Author keywords

medical cannabis; spice drugs; synthetic cannabinoid; therapeutic potential

Indexed keywords

3 (1 NAPHTHOYL) 1 PENTYLINDOLE; CANNABINOID 1 RECEPTOR; CANNABINOID 2 RECEPTOR; CANNABINOID DERIVATIVE; CANNABINOID RECEPTOR AFFECTING AGENT; ENDOCANNABINOID; SYNTHETIC CANNABINOID; UNCLASSIFIED DRUG; CANNABINOID; CANNABINOID RECEPTOR; CANNABINOID RECEPTOR AGONIST; DRUG; LIGAND; MEDICAL CANNABIS;

ARTICLE; CANNABIS SATIVA; CLINICAL EVALUATION; DRUG MARKETING; DRUG POTENCY; HUMAN; MEDICAL HISTORY; NONHUMAN; RISK FACTOR; STRUCTURE ACTIVITY RELATION; ANIMAL; METABOLISM;

ANIMALS; CANNABINOID RECEPTOR AGONISTS; CANNABINOIDS; ENDOCANNABINOIDS; HUMANS; LIGANDS; MEDICAL MARIJUANA; RECEPTORS, CANNABINOID; SYNTHETIC DRUGS;

EID: 85043586837     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2018.08.002     Document Type: Article

References (71)

1. European Commission (2009) Pharmaceutical Sector Inquiry, Final Report.
2. European Commission Pharmaceutical Research and Manufacturers of America. 2015 Biopharmaceutical Research Industry Profile. 2015, Pharmaceutical Research and Manufacturers of America.
3. Mullard, A., New drugs cost US$2.6 billion to develop. Nat Rev Drug Discov, 13, 2014, 877.
4. Mechoulam, R, Gaoni, Y, Isolation, structure, and partial synthesis of an active constituent of hashish. J Am Chem Soc 86 (1964), 1646–1647.
5. Edery, H, Grunfeld, Y, Porath, G, et al. Structure-activity relationships in the tetrahydrocannabinol series. Modifications on the aromatic ring and it the side-chain. Arzneimittelforschung, 22, 1972 1995-20–3.
6. Devane, WA, Dysarz, FA 3rd, Johnson, MR, et al. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 34 (1988), 605–613.
7. Bidaut-Russell, M, Devane, WA, Howlett, AC, Cannabinoid receptors and modulation of cyclic AMP accumulation in the rat brain. J Neurochem 55 (1990), 21–26.
8. Fride, E, Perchuk, A, Hall, FS, et al. Behavioral methods in cannabinoid research. Methods Mol Med 123 (2006), 269–290.
9. Feigenbaum, JJ, Bergmann, F, Richmond, SA, et al. Nonpsychotropic cannabinoid acts as a functional N-methyl-D-aspartate receptor blocker. Proc Natl Acad Sci USA 86 (1989), 9584–9587.
10. Després, JP, Ross, R, Boka, G, et al. Effect of rimonabant on the high-triglyceride/ low-HDL-cholesterol dyslipidemia, intraabdominal adiposity, and liver fat: the ADAGIO-Lipids trial. Arterioscler Thromb Vasc Biol 29 (2009), 416–423.
11. Kowal, MA, Hazekamp, A, Grotenhermen, F, Review on clinical studies with cannabis and cannabinoids 2010-2014. Cannabinoids 2016 11 (2016), 1–18.
12. Malek, N, Starowicz, K, Dual-acting compounds targeting endocannabinoid and endovanilloid systems - a novel treatment option for chronic pain management. Front Pharmacol, 7, 2016, 257.
13. Kaur, R, Sidhu, P, Singh, S, What failed BIA 10–2474 Phase I clinical trial? Global speculations and recommendations for future Phase I trials. J Pharmacol Pharmacother 7 (2016), 120–126.
14. Panlilio, LV, Thorndike, EB, Nikas, SP, et al. Effects of fatty acid amide hydrolase (FAAH) inhibitors on working memory in rats. Psychopharmacology 233 (2016), 1879–1888.
15. Parker, LA, Limebeer, CL, Rock, EM, et al. A comparison of novel, selective fatty acid amide hydrolase (FAAH), monoacyglycerol lipase (MAGL) or dual FAAH/MAGL inhibitors to suppress acute and anticipatory nausea in rat models. Psychopharmacology 233 (2016), 2265–2275.
16. Trigo, JM, Le Foll, B, Inhibition of monoacylglycerol lipase (MAGL) enhances cue-induced reinstatement of nicotine-seeking behavior in mice. Psychopharmacology 233 (2016), 1815–1822.
17. Wilkerson, JL, Ghosh, S, Mustafa, M, et al. The endocannabinoid hydrolysis inhibitor SA-57: Intrinsic antinociceptive effects, augmented morphine-induced antinociception, and attenuated heroin seeking behavior in mice. Neuropharmacology 114 (2017), 156–167.
18. Huffman, JW, CB2 receptor ligands. Mini Rev Med Chem 5 (2005), 641–649.
19. Wiley, JL, Marusich, JA, Huffman, JW, et al. Hijacking of basic research: the case of synthetic cannabinoids. Methods Rep RTI Press, 2011 201117971.
20. Fattore, L, Fratta, W, Beyond THC: the new generation of cannabinoid designer drugs. Front Behav Neurosci, 5, 2011, 60.
21. De Luca, MA, Castelli, MP, Loi, B, et al. Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 and STS-135. Neuropharmacology 105 (2016), 630–638.
22. Miliano, C, Serpelloni, G, Rimondo, C, et al. Neuropharmacology of new psychoactive substances (NPS): focus on the rewarding and reinforcing properties of cannabimimetics and amphetamine-like stimulants. Front Neurosci, 10, 2016, 153.
23. Campbell, FA, Tramèr, MR, Carroll, D, et al. Are cannabinoids an effective and safe treatment option in the management of pain? a qualitative systematic review. BMJ 323 (2001), 13–16.
24. Taschler, U, Hasenoehrl, C, Storr, M, Schicho, R, Cannabinoid receptors in regulating the GI tract: experimental evidence and therapeutic relevance. Handb Exp Pharmacol 239 (2017), 343–362.
25. Smith, LA, Azariah, F, Lavender, VT, et al. Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy. Cochrane Database Syst Rev, 11, 2015, CD009464.
26. Badowski, ME, Perez, SE, Clinical utility of dronabinol in the treatment of weight loss associated with HIV and AIDS. HIV AIDS 8 (2016), 37–45.
27. de Lago, E, Moreno-Martet, M, Cabranes, A, et al. Cannabinoids ameliorate disease progression in a model of multiple sclerosis in mice, acting preferentially through CB1 receptor-mediated anti-inflammatory effects. Neuropharmacology 62 (2012), 2299–2308.
28. Fraguas-Sánchez, AI, Fernández-Carballido, A, Torres-Suárez, AI, Phyto-, endo- and synthetic cannabinoids: promising chemotherapeutic agents in the treatment of breast and prostate carcinomas. Expert Opin Investig Drugs 25 (2016), 1311–1323.
29. Ramer, R, Hinz, B, Antitumorigenic targets of cannabinoids: current status and implications. Expert Opin Ther Targets 20 (2016), 1219–1235.
30. Croxford, JL, Therapeutic potential of cannabinoids in CNS disease. CNS Drugs 17 (2003), 179–202.
31. Little, JP, Villanueva, EB, Klegeris, A, Therapeutic potential of cannabinoids in the treatment of neuroinflammation associated with Parkinson's disease. Mini Rev Med Chem 11 (2011), 582–590.
32. De Luca, MA, Fattore, L, Cannabinoids and drug addiction. Fattore, L, (eds.) Cannabinoids in neurologic and mental disease, 2015, Academic Press, 289–313.
33. Riedel, G, Fadda, P, McKillop-Smith, S, et al. Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice. Br J Pharmacol 156 (2009), 1154–1166.
34. Fois, GR, Fattore, L, Murineddu, G, et al. The novel cannabinoid antagonist SM-11 reduces hedonic aspect of food intake through a dopamine-dependent mechanism. Pharmacol Res 113 (2016), 108–115.
35. Seely, KA, Lapoint, J, Moran, JH, Fattore, L, Spice drugs are more than harmless herbal blends: a review of the pharmacology and toxicology of synthetic cannabinoids. Prog Neuropsychopharmacol Biol Psychiatry 39 (2012), 234–243.
36. Bäckberg, M, Tworek, L, Beck, O, Helander, A, Analytically confirmed intoxications involving MDMB-CHMICA from the STRIDA Project. J Med Toxicol 13 (2017), 52–60.
37. Hermanns-Clausen, M, Kithinji, J, Spehl, M, et al. Adverse effects after the use of JWH-210: a case series from the EU Spice II plus project. Drug Test Anal 8 (2016), 1030–1038.
38. Barceló B, Pichini, S, López-Corominas, V, et al. Acute intoxication caused by synthetic cannabinoids 5F-ADB and MMB-2201: a case series. Forensic Sci Int 273 (2017), 10–14.
39. Abouchedid, R, Ho, JH, Hudson, S, et al. Acute toxicity associated with use of 5F-derivations of synthetic cannabinoid receptor agonists with analytical confirmation. J Med Toxicol 12 (2016), 396–401.
40. Moeller, S, Lücke, C, Struffert, T, et al. Ischemic stroke associated with the use of a synthetic cannabinoid (spice). Asian J Psychiatr 25 (2017), 127–130.
41. Takematsu, M, Hoffman, RS, Nelson, LS, et al. A case of acute cerebral ischemia following inhalation of a synthetic cannabinoid. Clin Toxicol (Phila) 52 (2014), 973–975.
42. Freeman, MJ, Rose, DZ, Myers, MA, et al. Ischemic stroke after use of the synthetic marijuana “spice”. Neurology 81 (2013), 2090–2093.
43. Bernson-Leung, ME, Leung, LY, Kumar, S, Synthetic cannabis and acute ischemic stroke. J Stroke Cerebrovasc Dis 23 (2014), 1239–1241.
44. Lavie, G, Teichner, A, Shohami, E, et al. Long term cerebroprotective effects of dexanabinol in a model of focal cerebral ischemia. Brain Res 901 (2001), 195–201.
45. Maas, AI, Murray, G, Henney, H 3rd, et al. Efficacy and safety of dexanabinol in severe traumatic brain injury: results of a phase III randomised, placebo-controlled, clinical trial. Lancet Neurol 5 (2006), 38–45.
46. Raheemullah, A, Laurence, TN, Repeated thrombosis after synthetic cannabinoid use. J Emerg Med 51 (2016), 540–543.
47. Mir, A, Obafemi, A, Young, A, Kane, C, Myocardial infarction associated with use of the synthetic cannabinoid K2. Pediatrics 128 (2011), e1622–e1627.
48. Sevinc, MM, Kinaci, E, Bayrak, S, et al. Extraordinary cause of acute gastric dilatation and hepatic portal venous gas: chronic use of synthetic cannabinoid. World J Gastroenterol 21 (2015), 10704–10708.
49. Lemos, NP, Driving under the influence of synthetic cannabinoid receptor agonist XLR-11. J Forensic Sci 59 (2014), 1679–1683.
50. Peterson, BL, Couper, FJ, Concentrations of AB-CHMINACA and AB-PINACA and Driving Behavior in Suspected Impaired Driving Cases. J Anal Toxicol 39 (2015), 642–647.
51. Adamowicz, P, Lechowicz, W, The influence of synthetic cannabinoid UR-144 on human psychomotor performance - a case report demonstrating road traffic risks. Traffic Inj Prev 16 (2015), 754–759.
52. Karinen, R, Tuv, SS, Øiestad, EL, Vindenes, V, Concentrations of APINACA, 5F-APINACA, UR-144 and its degradant product in blood samples from six impaired drivers compared to previous reported concentrations of other synthetic cannabinoids. Forensic Sci Int 246 (2015), 98–103.
53. Canazza, I, Ossato, A, Vincenzi, F, et al. Pharmaco-toxicological effects of the novel third-generation fluorinate synthetic cannabinoids, 5F-ADBINACA, AB-FUBINACA, and STS-135 in mice: in vitro and in vivo studies. Hum Psychopharmacol, 32, 2017, e2601.
54. Canazza, I, Ossato, A, Trapella, C, et al. Effect of the novel synthetic cannabinoids AKB48 and 5F-AKB48 on “tetrad” sensorimotor, neurological and neurochemical responses in mice: in vitro and in vivo pharmacological studies. Psychopharmacology 233 (2016), 3685–3709.
55. Ossato, A, Canazza, I, Trapella, C, et al. Effect of JWH-250, JWH-073 and their interaction on “tetrad” sensorimotor, neurological and neurochemical responses in mice. Prog Neuropsychopharmacol Biol Psychiatry 67 (2016), 31–50.
56. Ossato, A, Vigolo, A, Trapella, C, et al. JWH-018 impairs sensorimotor functions in mice. Neuroscience, 300, 2015, 1741–1788.
57. Solimini, R, Busardò FP, Rotolo, MC, et al. Hepatotoxicity associated to synthetic cannabinoids use. Eur Rev Med Pharmacol Sci 21 (2017), 1–6.
58. Behonick, G, Shanks, KG, Firchau, DJ, et al. Four postmortem case reports with quantitative detection of the synthetic cannabinoid, 5F-PB-22. J Anal Toxicol 38 (2014), 559–562.
59. Zarifi, C, Vyas, S, Spice-y kidney failure: a case report and systematic review of acute kidney injury attributable to the use of synthetic cannabis. Perm J 21 (2017), 16–160.
60. Sweeney, B, Talebi, S, Toro, D, et al. Hyperthermia and severe rhabdomyolysis from synthetic cannabinoids. Am J Emerg Med 34:121 (2016), e1–e2.
61. Argamany, JR, Reveles, KR, Duhon, B, Synthetic cannabinoid hyperemesis resulting in rhabdomyolysis and acute renal failure. Am J Emerg Med 34:765 (2016), e1–e2.
62. Fattore, L, Synthetic cannabinoids-further evidence supporting the relationship between cannabinoids and psychosis. Biol Psychiatry, 79, 2016, 539–548.
63. van Amsterdam, J, Brunt, T, van den Brink, W, The adverse health effects of synthetic cannabinoids with emphasis on psychosis-like effects. J Psychopharmacol 29 (2015), 254–263.
64. Bassir Nia, A, Medrano, B, Perkel, C, et al. Psychiatric comorbidity associated with synthetic cannabinoid use compared to cannabis. J Psychopharmacol 30 (2016), 1321–1330.
65. Bijlsma, L, Ibáñez, M, Miserez, B, et al. Mass spectrometric identification and structural analysis of the third-generation synthetic cannabinoids on the UK market since the 2013 legislative ban. Forensic Toxicol 35 (2017), 376–388.
66. Waugh, J, Najafi, J, Hawkins, L, et al. Epidemiology and clinical features of toxicity following recreational use of synthetic cannabinoid receptor agonists: a report from the United Kingdom National Poisons Information Service. Clin Toxicol (Phila) 54 (2016), 512–518.
67. Bersani, FS, Santacroce, R, Coviello, M, et al. Cannabis: a self-medication drug for weight management? the never ending story. Drug Test Anal 8 (2016), 177–179.
68. De Luca, MA, Bimpisidis, Z, Melis, M, et al. Stimulation of in vivo dopamine transmission and intravenous self-administration in rats and mice by JWH-018, a Spice cannabinoid. Neuropharmacology 99 (2015), 705–714.
69. Fattore, L, Synthetic cannabinoids - further evidence supporting the relationship between cannabinoids and psychosis. Biol Psychiatry, 79, 2016, 539–748.
70. Weinstein, AM, Rosca, P, Fattore, L, London, ED, Synthetic cathinone and cannabinoid designer drugs pose a major risk for public health. Front Psychiatry, 8, 2017, 156.
71. Miliano, C, Margiani, G, Fattore, L, De Luca, MA, Sales and advertising channels of new psychoactive substances (NPS): internet, social networks, and smartphone apps. Brain Sci, 8, 2018, 123.