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Current Reviews in Clinical and Experimental Pharmacology

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ISSN (Print): 2772-4328
ISSN (Online): 2772-4336

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Framework for the Design of Cannabis-Mediated Phase I Drug-Drug Interaction Studies

Author(s): Diana L. Shuster*, Gina Pastino and Dirk Cerneus

Volume 17, Issue 1, 2022

Page: [18 - 25] Pages: 8

DOI: 10.2174/2772432816666210813123716

Price: $65

Abstract

Cannabis has become legal in much of the United States similar to many other countries, for either recreational or medical use. The use of cannabis products is rapidly increasing while the body of knowledge of its myriad of effects still lags. In vitro and clinical data show that cannabis’ main constituents, delta-9-tetrahydrocannabinol and cannabidiol, can affect pharmacokinetics (PK), safety, and pharmacodynamics (PD) of other drugs. Within the context of clinical drug development, the widespread and frequent use of cannabis products has essentially created another special population: the cannabis user. We propose that all clinical drug development programs include a Phase 1 study to assess the drug-drug interaction potential of cannabis as a precipitant on the PK, safety, and if applicable, the PD of all new molecular entities (NMEs) in a combination of healthy adult subjects as well as frequent and infrequent cannabis users. This data should be required to inform drug labeling and aid health care providers in treating any patient, as cannabis has quickly become another common concomitant medication and cannabis users, a new special population.

Keywords: Cannabis, marijuana, delta-9-tetrahydrocannabinol, cannabidiol, clinical pharmacology, drug-drug interactions.

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[1]
Hasin DS. US epidemiology of cannabis use and associated problems. Neuropsychopharmacology 2018; 43(1): 195-212.
[http://dx.doi.org/10.1038/npp.2017.198] [PMID: 28853439]
[2]
Cox EJ, Maharao N, Patilea-Vrana G, et al. A marijuana-drug interaction primer: Precipitants, pharmacology, and pharmacokinetics. Pharmacol Ther 2019; 201: 25-38.
[http://dx.doi.org/10.1016/j.pharmthera.2019.05.001] [PMID: 31071346]
[3]
Antoniou T, Bodkin J, Ho JM. Drug interactions with cannabinoids. CMAJ 2020; 192(9)E206
[http://dx.doi.org/10.1503/cmaj.191097] [PMID: 32122975]
[4]
Kauert GF, Ramaekers JG, Schneider E, Moeller MR, Toennes SW. Pharmacokinetic properties of delta9-tetrahydrocannabinol in serum and oral fluid. J Anal Toxicol 2007; 31(5): 288-93.
[http://dx.doi.org/10.1093/jat/31.5.288] [PMID: 17579974]
[5]
Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers 2007; 4(8): 1770-804.
[http://dx.doi.org/10.1002/cbdv.200790152] [PMID: 17712819]
[6]
Heuberger JAAC, Guan Z, Oyetayo O-O, et al. Population pharmacokinetic model of THC integrates oral, intravenous, and pulmonary dosing and characterizes short- and long-term pharmacokinetics. Clin Pharmacokinet 2015; 54(2): 209-19.
[http://dx.doi.org/10.1007/s40262-014-0195-5] [PMID: 25316574]
[7]
Zendulka O, Dovrtělová G, Nosková K, et al. Cannabinoids and cytochrome P450 interactions. Curr Drug Metab 2016; 17(3): 206-26.
[http://dx.doi.org/10.2174/1389200217666151210142051] [PMID: 26651971]
[8]
Ujváry I, Hanuš L. Human metabolites of cannabidiol: A review on their formation, biological activity, and relevance in therapy. Cannabis Cannabinoid Res 2016; 1(1): 90-101.
[http://dx.doi.org/10.1089/can.2015.0012] [PMID: 28861484]
[9]
Ohlsson A, Lindgren JE, Andersson S, Agurell S, Gillespie H, Hollister LE. Single-dose kinetics of deuterium-labelled cannabidiol in man after smoking and intravenous administration. Biomed Environ Mass Spectrom 1986; 13(2): 77-83.
[http://dx.doi.org/10.1002/bms.1200130206] [PMID: 2937482]
[10]
Consroe P, Laguna J, Allender J, et al. Controlled clinical trial of cannabidiol in Huntington’s disease. Pharmacol Biochem Behav 1991; 40(3): 701-8.
[http://dx.doi.org/10.1016/0091-3057(91)90386-G] [PMID: 1839644]
[11]
Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia 2015; 56(8): 1246-51.
[http://dx.doi.org/10.1111/epi.13060] [PMID: 26114620]
[12]
Leino AD, Emoto C, Fukuda T, Privitera M, Vinks AA, Alloway RR. Evidence of a clinically significant drug-drug interaction between cannabidiol and tacrolimus. Am J Transplant 2019; 19(10): 2944-8.
[http://dx.doi.org/10.1111/ajt.15398] [PMID: 31012522]
[13]
Yamreudeewong W, Wong HK, Brausch LM, Pulley KR. Probable interaction between warfarin and marijuana smoking. Ann Pharmacother 2009; 43(7): 1347-53.
[http://dx.doi.org/10.1345/aph.1M064] [PMID: 19531696]
[14]
Damkier P, Lassen D, Christensen MMH, Madsen KG, Hellfritzsch M, Pottegård A. Interaction between warfarin and cannabis. Basic Clin Pharmacol Toxicol 2019; 124(1): 28-31.
[http://dx.doi.org/10.1111/bcpt.13152] [PMID: 30326170]
[15]
Engels FK, de Jong FA, Sparreboom A, et al. Medicinal cannabis does not influence the clinical pharmacokinetics of irinotecan and docetaxel. Oncologist 2007; 12(3): 291-300.
[http://dx.doi.org/10.1634/theoncologist.12-3-291] [PMID: 17405893]
[16]
Kosel BW, Aweeka FT, Benowitz NL, et al. The effects of cannabinoids on the pharmacokinetics of indinavir and nelfinavir. AIDS 2002; 16(4): 543-50.
[http://dx.doi.org/10.1097/00002030-200203080-00005] [PMID: 11872997]
[17]
Dalton WS, Martz R, Rodda BE, Lemberger L, Forney RB. Influence of cannabidiol on secobarbital effects and plasma kinetics. Clin Pharmacol Ther 1976; 20(6): 695-700.
[http://dx.doi.org/10.1002/cpt1976206695] [PMID: 791563]
[18]
Jusko WJ, Schentag JJ, Clark JH, Gardner M, Yurchak AM. Enhanced biotransformation of theophylline in marihuana and tobacco smokers. Clin Pharmacol Ther 1978; 24(4): 405-10.
[http://dx.doi.org/10.1002/cpt1978244406] [PMID: 688731]
[19]
Freeman TP, Lorenzetti V. ‘Standard THC units’: A proposal to standardize dose across all cannabis products and methods of administration. Addiction 2020; 115(7): 1207-16.
[http://dx.doi.org/10.1111/add.14842] [PMID: 31606008]
[20]
Haney M, Malcolm RJ, Babalonis S, et al. Oral cannabidiol does not alter the subjective, reinforcing or cardiovascular effects of smoked cannabis. Neuropsychopharmacology 2016; 41(8): 1974-82.
[http://dx.doi.org/10.1038/npp.2015.367] [PMID: 26708108]
[21]
Newmeyer MN, Swortwood MJ, Barnes AJ, Abulseoud OA, Scheidweiler KB, Huestis MA. Free and glucuronide whole blood cannabinoids’ pharmacokinetics after controlled smoked, vaporized, and oral cannabis administration in frequent and occasional cannabis users: identification of recent cannabis intake. Clin Chem 2016; 62(12): 1579-92.
[http://dx.doi.org/10.1373/clinchem.2016.263475] [PMID: 27899456]
[22]
Fattore L, Fratta W. How important are sex differences in cannabinoid action? Br J Pharmacol 2010; 160(3): 544-8.
[http://dx.doi.org/10.1111/j.1476-5381.2010.00776.x] [PMID: 20590564]
[23]
Cooper ZD, Craft RM. Sex-dependent effects of cannabis and cannabinoids: a translational perspective. Neuropsychopharmacology 2018; 43(1): 34-51.
[http://dx.doi.org/10.1038/npp.2017.140] [PMID: 28811670]
[24]
Reece AS, Hulse GK. Cannabis teratology explains current patterns of coloradan congenital defects: the contribution of increased cannabinoid exposure to rising teratological trends. Clin Pediatr (Phila) 2019; 58(10): 1085-123.
[http://dx.doi.org/10.1177/0009922819861281] [PMID: 31288542]
[25]
Braillon A, Bewley S. Committee Opinion No. 722: Marijuana use during pregnancy and lactation. Obstet Gynecol 2018; 131(1): 164.
[http://dx.doi.org/10.1097/AOG.0000000000002429] [PMID: 29266063]
[26]
Gundersen TD, Jørgensen N, Andersson AM, et al. Association between use of marijuana and male reproductive hormones and semen quality: A study among 1,215 healthy young men. Am J Epidemiol 2015; 182(6): 473-81.
[http://dx.doi.org/10.1093/aje/kwv135] [PMID: 26283092]
[27]
Pacey AA, Povey AC, Clyma JA, et al. Modifiable and non-modifiable risk factors for poor sperm morphology. Hum Reprod 2014; 29(8): 1629-36.
[http://dx.doi.org/10.1093/humrep/deu116] [PMID: 24899128]
[28]
Diagnostic and statistical manual of mental disorders. 5th ed. American Psychiatric Association Publishing 2013.
[29]
Steigerwald S, Wong PO, Khorasani A, Keyhani S. The form and content of cannabis products in the United States. J Gen Intern Med 2018; 33(9): 1426-8.
[http://dx.doi.org/10.1007/s11606-018-4480-0] [PMID: 29770952]
[30]
Spindle TR, Cone EJ, Schlienz NJ, et al. Acute effects of smoked and vaporized cannabis in healthy adults who infrequently use cannabis: A crossover trial. JAMA Netw Open 2018; 1(7)e184841
[http://dx.doi.org/10.1001/jamanetworkopen.2018.4841] [PMID: 30646391]
[31]
Swortwood MJ, Newmeyer MN, Andersson M, Abulseoud OA, Scheidweiler KB, Huestis MA. Cannabinoid disposition in oral fluid after controlled smoked, vaporized, and oral cannabis administration. Drug Test Anal 2017; 9(6): 905-15.
[http://dx.doi.org/10.1002/dta.2092] [PMID: 27647820]
[32]
Hazekamp A, Ruhaak R, Zuurman L, van Gerven J, Verpoorte R. Evaluation of a vaporizing device (Volcano) for the pulmonary administration of tetrahydrocannabinol. J Pharm Sci 2006; 95(6): 1308-17.
[http://dx.doi.org/10.1002/jps.20574] [PMID: 16637053]
[33]
Abrams DI, Vizoso HP, Shade SB, Jay C, Kelly ME, Benowitz NL. Vaporization as a smokeless cannabis delivery system: A pilot study. Clin Pharmacol Ther 2007; 82(5): 572-8.
[http://dx.doi.org/10.1038/sj.clpt.6100200] [PMID: 17429350]
[34]
Schwope DM, Karschner EL, Gorelick DA, Huestis MA. Identification of recent cannabis use: Whole-blood and plasma free and glucuronidated cannabinoid pharmacokinetics following controlled smoked cannabis administration. Clin Chem 2011; 57(10): 1406-14.
[http://dx.doi.org/10.1373/clinchem.2011.171777] [PMID: 21836075]
[35]
Toennes SW, Ramaekers JG, Theunissen EL, Moeller MR, Kauert GF. Pharmacokinetic properties of delta9-tetrahydrocannabinol in oral fluid of occasional and chronic users. J Anal Toxicol 2010; 34(4): 216-21.
[http://dx.doi.org/10.1093/jat/34.4.216] [PMID: 20465868]
[36]
Page RL II, Allen LA, Kloner RA, et al. Medical marijuana, recreational cannabis, and cardiovascular heatlh: A scientific statement from the American Heart Association. Circulation 2020; 142(10): e131-52.
[http://dx.doi.org/10.1161/CIR.0000000000000883] [PMID: 32752884]
[37]
DeFilippis EM, Bajaj NS, Singh A, et al. Marijuana use in patients with cardiovascular disease. J Am Coll Cardiol 2020; 75(3): 320-32.
[http://dx.doi.org/10.1016/j.jacc.2019.11.025] [PMID: 31976871]
[38]
Pacher P, Steffens S, Haskó G, Schindler TH, Kunos G. Cardiovascular effects of marijuana and synthetic cannabinoids: The good, the bad, and the ugly. Nat Rev Cardiol 2018; 15(3): 151-66.
[http://dx.doi.org/10.1038/nrcardio.2017.130] [PMID: 28905873]
[39]
Rezkalla S, Kloner RA. Cardiovascular effects of marijuana. Trends Cardiovasc Med 2019; 29(7): 403-7.
[http://dx.doi.org/10.1016/j.tcm.2018.11.004] [PMID: 30447899]
[40]
Bond A, Lader M. The use of analogue scales in rating subjective feelings. Br J Med Psychol 1974; 47: 211-8.
[http://dx.doi.org/10.1111/j.2044-8341.1974.tb02285.x]
[41]
Bowdle TA, Radant AD, Cowley DS, Kharasch ED, Strassman RJ, Roy-Byrne PP. Psychedelic effects of ketamine in healthy volunteers: Relationship to steady-state plasma concentrations. Anesthesiology 1998; 88(1): 82-8.
[http://dx.doi.org/10.1097/00000542-199801000-00015] [PMID: 9447860]
[42]
Schwope DM, Bosker WM, Ramaekers JG, Gorelick DA, Huestis MA. Psychomotor performance, subjective and physiological effects and whole blood Δ9-tetrahydrocannabinol concentrations in heavy, chronic cannabis smokers following acute smoked cannabis. J Anal Toxicol 2012; 36(6): 405-12.
[http://dx.doi.org/10.1093/jat/bks044] [PMID: 22589524]
[43]
Lejuez CW, Read JP, Kahler CW, et al. Evaluation of a behavioral measure of risk taking: The Balloon Analogue Risk Task (BART). J Exp Psychol Appl 2002; 8(2): 75-84.
[http://dx.doi.org/10.1037/1076-898X.8.2.75] [PMID: 12075692]
[44]
White TL, Lejuez CW, de Wit H. Test-retest characteristics of the Balloon Analogue Risk Task (BART). Exp Clin Psychopharmacol 2008; 16(6): 565-70.
[http://dx.doi.org/10.1037/a0014083] [PMID: 19086777]
[45]
Hopko DR, Lejuez CW, Daughters SB, et al. Construct validity of the Balloon Analogue Risk Task (BART): Relationship with MDMA use by inner-city drug users in residential treatment. J Psychopathol Behav Assess 2006; 28: 95-101.
[http://dx.doi.org/10.1007/s10862-006-7487-5]
[46]
Mann L, Burnett P, Radford M, Ford S. The Melbourne decision making questionnaire: an instrument for measuring patterns for coping with decisional conflict. J Behav Decis Making 1997; 10(1): 1-19.
[http://dx.doi.org/10.1002/(SICI)1099-0771(199703)10:1<1:AID-BDM242>3.0.CO;2-X]
[47]
Cherpitel CJ. Alcohol, injury, and risk-taking behavior: Data from a national sample. Alcohol Clin Exp Res 1993; 17(4): 762-6.
[http://dx.doi.org/10.1111/j.1530-0277.1993.tb00837.x] [PMID: 8214410]
[48]
Patton JH, Stanford MS, Barratt ES. Factor structure of the Barratt impulsiveness scale. J Clin Psychol 1995; 51(6): 768-74.
[http://dx.doi.org/10.1002/1097-4679(199511)51:6<768:AID-JCLP2270510607>3.0.CO;2-1] [PMID: 8778124]
[49]
Zuckerman M. Chap 16: Zuckerman-Kuhlman Personality Questionnaire (ZKPQ): An alternative five-factorial model Big five assessment Ashland. Hogrefe & Huber Publishers 2002; pp. 377-96.
[50]
Prentice KJ, Gold JM, Carpenter WT Jr. Optimistic bias in the perception of personal risk: Patterns in schizophrenia. Am J Psychiatry 2005; 162(3): 507-12.
[http://dx.doi.org/10.1176/appi.ajp.162.3.507] [PMID: 15741467]
[51]
Moskowitz H. Laboratory studies of the effects of alcohol on some variables related to driving. J Safety Res 1973; 5(3): 185-99.
[52]
Hart CL, Haney M, Vosburg SK, Comer SD, Foltin RW. Reinforcing effects of oral Delta9-THC in male marijuana smokers in a laboratory choice procedure. Psychopharmacology (Berl) 2005; 181(2): 237-43.
[http://dx.doi.org/10.1007/s00213-005-2234-2] [PMID: 15830233]
[53]
Kamien JB, Bickel WK, Higgins ST, Hughes JR. The effects of Δ9-THC on repeated acquisition and performance of response sequences and on self-reports in humans. Behav Pharmacol 1994; 5(1): 71-8.
[http://dx.doi.org/10.1097/00008877-199402000-00008] [PMID: 11224253]
[54]
Heishman SJ, Stitzer ML, Yingling JE. Effects of THC content on marijuana smoking behavior, subjective reports and performance. Pharmacol Biochem Behav 1989; 34(1): 173-9.
[http://dx.doi.org/10.1016/0091-3057(89)90369-9] [PMID: 2560548]
[55]
Kelly TH, Foltin RW, Emurian CS, Fischman MW. Multidimensional behavioral effects of marijuana. Prog Neuropsychopharmacol Biol Psychiatry 1990; 14(6): 885-902.
[http://dx.doi.org/10.1016/0278-5846(90)90075-R] [PMID: 2277852]
[56]
Kelly TH, Foltin RW, Emurian CS, Fischman MW. Performance-based testing for drugs of abuse: Dose and time profiles of marijuana, amphetamine, alcohol, and diazepam. J Anal Toxicol 1993; 17(5): 264-72.
[http://dx.doi.org/10.1093/jat/17.5.264] [PMID: 8107459]
[57]
Wilson WH, Ellinwood EH, Mathew RJ, Johnson K. Effects of marijuana on performance of a computerized cognitive-neuromotor test battery. Psychiatry Res 1994; 51(2): 115-25.
[http://dx.doi.org/10.1016/0165-1781(94)90031-0] [PMID: 8022946]
[58]
Alshaarawy O, Anthony JC. Cannabis smoking and serum C-reactive protein: A quantile regressions approach based on NHANES 2005-2010. Drug Alcohol Depend 2015; 147: 203-7.
[http://dx.doi.org/10.1016/j.drugalcdep.2014.11.017] [PMID: 25529540]
[59]
Alshaarawy O, Sidney S, Auer R, et al. Cannabis use and markers of systemic inflammation: The coronary artery risk development in young adults study. Am J Med 2019; 132(11): 1327-1334.e1.
[http://dx.doi.org/10.1016/j.amjmed.2019.04.045] [PMID: 31150645]
[60]
Pagano E, Iannotti FA, Piscitelli F, et al. Efficacy of combined therapy with fish oil and phytocannabinoids in murine intestinal inflammation. Phytother Res 2020.
[http://dx.doi.org/10.1002/ptr.6831]
[61]
Nedumaran B, Rudra P, Gaydos J, et al. Impact of regular cannabis use on biomarkers of lower urinary tract function. Urology 2017; 109: 223.e9-223.e16.
[http://dx.doi.org/10.1016/j.urology.2017.08.011] [PMID: 28827195]
[62]
Sachse-Seeboth C, Pfeil J, Sehrt D, et al. Interindividual variation in the pharmacokinetics of Delta9-tetrahydrocannabinol as related to genetic polymorphisms in CYP2C9. Clin Pharmacol Ther 2009; 85(3): 273-6.
[http://dx.doi.org/10.1038/clpt.2008.213] [PMID: 19005461]

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