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Biobehavioral and affective stress responses during nicotine withdrawal: Influence of regular cannabis co-use

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Abstract

Background

Co-use of cannabis is increasing in nicotine users and presents additional challenges in addressing nicotine dependence. This study examined the links between regular co-use of cannabis and nicotine with biobehavioral and affective changes in response to stress during nicotine withdrawal and ad libitum use.

Methods

Participants (N = 79) who regularly used nicotine-only, cannabis-only, both substances, or neither substance were invited to attend two laboratory stress assessment sessions. For nicotine users, one session occurred during ad libitum nicotine use and one occurred after abstinence from nicotine. During the stress sessions, participants provided saliva samples for cortisol assay and completed measures of subjective states. Cardiovascular measures were collected during resting baseline, exposure to acute stressors, and a recovery rest period.

Results

Nicotine-only users had higher average cortisol levels in the second lab session (nicotine withdrawal) relative to the first lab session (ad libitum nicotine use). Compared to nicotine non-users, nicotine users reported less positive affect and exhibited attenuated cortisol and systolic blood pressure (BP) stress responses. Cannabis users exhibited exaggerated diastolic BP responses to stress compared to cannabis non-users, and co-users of nicotine and cannabis had higher levels of cannabis craving than cannabis-only users (p < .01).

Conclusions

This study partially replicated earlier findings on the effects of chronic nicotine use and provided novel results regarding the influence of cannabis co-use on physiological and affective responses to stress in nicotine users during nicotine withdrawal.

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References

  • Adamopoulos D, van de Borne P, Argacha JF (2008) New insights into the sympathetic, endothelial and coronary effects of nicotine. Clin Exp Pharmacol Physiol 35:458–463

    Article  CAS  PubMed  Google Scholar 

  • Ahrnsbrak R, Bose J, Hedden SL, Lipari RN, Park-Lee E (2016) Key substance use and mental health indicators in the United States: results from the 2016 National Survey on Drug Use and Health (HHS Publication No. SMA 17-5044, NSDUH Series H-52). Rockville, MD: Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. Retrieved from https://www.samhsa.gov/data/

  • Akre C, Michaud PA, Berchtold A, Suris JC (2010) Cannabis and tobacco use: where are the boundaries? A qualitative study on cannabis consumption modes among adolescents. Health Educ Res 25:74–82

    Article  PubMed  Google Scholar 

  • al’Absi M, Hatsukami D, Davis GL (2005) Attenuated adrenocorticotropic responses to psychological stress are associated with early smoking relapse. Psychopharmacology 181:107–117

    Article  PubMed  Google Scholar 

  • al’Absi M, Wittmers LE, Erickson J, Hatsukami DK, Crouse B (2003) Attenuated adrenocortical and blood pressure responses to psychological stress in ad libitum and abstinent smokers. Pharmacol Biochem Behav 74:401–410

    Article  PubMed  Google Scholar 

  • Barrett SP, Darredeau C, Pihl RO (2006) Patterns of simultaneous polysubstance use in drug using university students. Hum Psychopharmacol 21:255–263

    Article  PubMed  Google Scholar 

  • Bluett RJ, Báldi R, Haymer A, Gaulden AD, Hartley ND, Parrish WP, Baechle J, Marcus DJ, Mardam-Bey R, Shonesy BC, Uddin MJ, Marnett LJ, Mackie K, Colbran RJ, Winder DG, Patel S (2017) Endocannabinoid signalling modulates susceptibility to traumatic stress exposure. Nat Commun 8:14782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonn-Miller MO, Zvolensky MJ, Johnson KA (2010) Uni-morbid and co-occurring marijuana and tobacco use: examination of concurrent associations with negative mood states. J Addict Dis 29:68–77

    Article  PubMed  PubMed Central  Google Scholar 

  • Boorman E, Zajkowska Z, Ahmed R, Pariante CM, Zunszain PA (2016) Crosstalk between endocannabinoid and immune systems: a potential dysregulation in depression? Psychopharmacology 233:1591–1604

    Article  CAS  PubMed  Google Scholar 

  • Childs E, de Wit H (2009) Hormonal, cardiovascular, and subjective responses to acute stress in smokers. Psychopharmacology 203:1–12

    Article  CAS  PubMed  Google Scholar 

  • Conway KP, Green VR, Kasza KA, Silveira ML, Borek N, Kimmel HL, Sargent JD, Stanton CA, Lambert E, Hilmi N, Reissig CJ, Jackson KJ, Tanski SE, Maklan D, Hyland AJ, Compton WM (2018) Co-occurrence of tobacco product use, substance use, and mental health problems among youth: findings from wave 1 (2013–2014) of the population assessment of tobacco and health (PATH) study. Addict Behav 76:208–217

    Article  PubMed  Google Scholar 

  • Cuttler C, Spradlin A, Nusbaum AT, Whitney P, Hinson JM, McLaughlin RJ (2017) Blunted stress reactivity in chronic cannabis users. Psychopharmacology 234:2299–2309

    Article  CAS  PubMed  Google Scholar 

  • DeAngelis BN, al’Absi M (2020) Regular cannabis use is associated with blunted affective, but not cardiovascular, stress responses. Addict Behav 107:106411

    Article  PubMed  PubMed Central  Google Scholar 

  • Fox HC, Tuit KL, Sinha R (2013) Stress system changes associated with marijuana dependence may increase craving for alcohol and cocaine. Hum Psychopharmacol 28:40–53

    Article  CAS  PubMed  Google Scholar 

  • Gilbert DG, Meliska CJ, Plath LC (1997) Noise stress does not modulate effects of smoking/nicotine on beta-endorphin, cortisol, ACTH, glucose, and mood. Psychopharmacology 130:197–202

    Article  CAS  PubMed  Google Scholar 

  • Goodwin RD, Shevorykin A, Carl E, Budney AJ, Rivard C, Wu M, McClure EA, Hyland A, Sheffer CE (2022) Daily cannabis use is a barrier to tobacco cessation among tobacco quitline callers at 7-month follow-up. Nicotine Tob Res 24:1684–1688

    Article  PubMed  PubMed Central  Google Scholar 

  • Grant BF, Saha TD, Ruan WJ, Goldstein RB, Chou SP, Jung J, Zhang H, Smith SM, Pickering RP, Huang B, Hasin DS (2016) Epidemiology of DSM-5 drug use disorder: Results from the national epidemiologic survey on alcohol and related conditions–III. JAMA Psychiatry 73(1):39–47. https://doi.org/10.1001/jamapsychiatry.2015.2132

    Article  PubMed  PubMed Central  Google Scholar 

  • Grewal S, Sekhon TS, Walia L, Gambhir RS (2015) Cardiovascular response to acute cold stress in non-obese and obese healthy adults. Ethiop J Health Sci 25(1):47–52. https://doi.org/10.4314/ejhs.v25i1.7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG (2009) Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 42(2):377–381. https://doi.org/10.1016/j.jbi.2008.08.010

    Article  PubMed  Google Scholar 

  • Harris P.A. et al (2019) The REDCap consortium: Building an international community of software platform partners. J Biomed Inform 95:103208. https://doi.org/10.1016/j.jbi.2019.103208

    Article  PubMed  PubMed Central  Google Scholar 

  • Heatherton TF, Kozlowski LT, Frecker RC, Fagerström K-O (1991) The Fagerström test for nicotine dependence: a revision of the Fagerström Tolerance Questionnaire. Br J Addict 86(9):1119–1127. https://doi.org/10.1111/j.1360-0443.1991.tb01879.x

    Article  CAS  PubMed  Google Scholar 

  • Hillard CJ, Beatka M, Sarvaideo J (2016) Endocannabinoid signaling and the hypothalamic-pituitary-adrenal axis. Compr Physiol 7:1–15

    PubMed  PubMed Central  Google Scholar 

  • King GR, Ernst T, Deng W, Stenger A, Gonzales RM, Nakama H, Chang L (2011) Altered brain activation during visuomotor integration in chronic active cannabis users: relationship to cortisol levels. J Neurosci 31:17923–17931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kirschbaum C, Scherer G, Strasburger CJ (1994) Pituitary and adrenal hormone responses to pharmacological, physical, and psychological stimulation in habitual smokers and nonsmokers. Clin Investig 72:804–810

    Article  CAS  PubMed  Google Scholar 

  • Marco EM, Laviola G (2012) The endocannabinoid system in the regulation of emotions throughout lifespan: a discussion on therapeutic perspectives. J Psychopharmacol 26:150–163

    Article  CAS  PubMed  Google Scholar 

  • Matthews KA, Stoney CM (1988) Influences of sex and age on cardiovascular responses during stress. Psychosom Med 50(1):46–56

    Article  CAS  PubMed  Google Scholar 

  • Meier E, Vandrey R, Rubin N, Pacek LR, Jensen JA, Donny EC, Hecht SS, Carmella SG, Murphy SE, Luo X, Stepanov I, Ikuemonisan J, Severson H, Al’absi M, Hatsukami DK (2020) Cigarette smokers versus cousers of cannabis and cigarettes: exposure to toxicants. Nicotine Tob Res 22:1383–1389

    Article  CAS  PubMed  Google Scholar 

  • Mizrahi R, Suridjan I, Kenk M, George TP, Wilson A, Houle S, Rusjan P (2013) Dopamine response to psychosocial stress in chronic cannabis users: a PET study with [11C]-+-PHNO. Neuropsychopharmacology 38:673–682

    Article  CAS  PubMed  Google Scholar 

  • Moore BA, Budney AJ (2001) Tobacco smoking in marijuana-dependent outpatients. J Subst Abus 13:583–596

    Article  CAS  Google Scholar 

  • National Conference of State Legislatures (2020) State medical marijuana laws

  • Ney LJ, Matthews A, Bruno R, Felmingham KL (2018) Modulation of the endocannabinoid system by sex hormones: implications for posttraumatic stress disorder. Neurosci Biobehav Rev 94:302–320

    Article  CAS  PubMed  Google Scholar 

  • Parolaro D, Realini N, Vigano D, Guidali C, Rubino T (2010) The endocannabinoid system and psychiatric disorders. Exp Neurol 224:3–14

    Article  CAS  PubMed  Google Scholar 

  • Peters EN, Budney AJ, Carroll KM (2012) Clinical correlates of co-occurring cannabis and tobacco use: a systematic review. Addiction 107:1404–1417

    Article  PubMed  PubMed Central  Google Scholar 

  • Pickworth WB, Fant RV (1998) Endocrine effects of nicotine administration, tobacco and other drug withdrawal in humans. Psychoneuroendocrinology 23:131–141

    Article  CAS  PubMed  Google Scholar 

  • Rabin RA, George TP (2015) A review of co-morbid tobacco and cannabis use disorders: possible mechanisms to explain high rates of co-use. Am J Addict 24:105–116

    Article  PubMed  Google Scholar 

  • Ramo DE, Delucchi KL, Hall SM, Liu H, Prochaska JJ (2013) Marijuana and tobacco co-use in young adults: patterns and thoughts about use. J Stud Alcohol Drugs 74:301–310

    Article  PubMed  PubMed Central  Google Scholar 

  • Ream GL, Benoit E, Johnson BD, Dunlap E (2008) Smoking tobacco along with marijuana increases symptoms of cannabis dependence. Drug Alcohol Depend 95(3):199–208. https://doi.org/10.1016/j.drugalcdep.2008.01.011

    Article  PubMed  PubMed Central  Google Scholar 

  • Rotermann M, Macdonald R (2018) Analysis of trends in the prevalence of cannabis use in Canada, 1985 to 2015. Health Rep 29:10–20

    PubMed  Google Scholar 

  • Soldz S, Huyser DJ, Dorsey E (2003) The cigar as a drug delivery device: youth use of blunts. Addiction 98:1379–1386

    Article  PubMed  Google Scholar 

  • Steigerwald S, Wong PO, Cohen BE, Ishida JH, Vali M, Madden E, Keyhani S (2018) Smoking, vaping, and use of edibles and other forms of marijuana among U.S. adults. Ann Intern Med 169:890–892

    Article  PubMed  PubMed Central  Google Scholar 

  • Tan H, Ahmad T, Loureiro M, Zunder J, Laviolette SR (2014) The role of cannabinoid transmission in emotional memory formation: implications for addiction and schizophrenia. Front Psychiatry 5:73

    Article  PubMed  PubMed Central  Google Scholar 

  • Torres SJ, Turner AI, Jayasinghe SU, Reynolds J, Nowson CA (2014) The effect of overweight/obesity on cardiovascular responses to acute psychological stress in men aged 50-70 years. Obes Facts 7(6):339–350. https://doi.org/10.1159/000369854

    Article  PubMed  PubMed Central  Google Scholar 

  • Tsuda A, Steptoe A, West R, Fieldman G, Kirschbaum C (1996) Cigarette smoking and psychophysiological stress responsiveness: effects of recent smoking and temporary abstinence. Psychopharmacology 126:226–233

    Article  CAS  PubMed  Google Scholar 

  • Vandrey RG, Budney AJ, Hughes JR, Liguori A (2008) A within-subject comparison of withdrawal symptoms during abstinence from cannabis, tobacco, and both substances. Drug Alcohol Depend 92:48–54

    Article  CAS  PubMed  Google Scholar 

  • Voci S, Zawertailo L, Baliunas D, Masood Z, Selby P (2020) Is cannabis use associated with tobacco cessation outcome? An observational cohort study in primary care. Drug Alcohol Depend 206:107756

    Article  PubMed  Google Scholar 

  • Volkow ND, Hampson AJ, Baler RD (2017) Don’t worry, be happy: endocannabinoids and cannabis at the intersection of stress and reward. Annu Rev Pharmacol Toxicol 57:285–308

    Article  CAS  PubMed  Google Scholar 

  • Weinberger AH, Delnevo CD, Wyka K, Gbedemah M, Lee J, Copeland J, Goodwin RD (2020) Cannabis use is associated with increased risk of cigarette smoking initiation, persistence, and relapse among adults in the United States. Nicotine Tob Res 22:1404–1408

    Article  PubMed  Google Scholar 

  • Worley NB, Hill MN, Christianson JP (2018) Prefrontal endocannabinoids, stress controllability and resilience: a hypothesis. Prog Neuro-Psychopharmacol Biol Psychiatry 85:180–188

    Article  CAS  Google Scholar 

  • Wu LT, Brady KT, Mannelli P, Killeen TK (2014) Cannabis use disorders are comparatively prevalent among nonwhite racial/ethnic groups and adolescents: a national study. J Psychiatr Res 50:26–35

    Article  PubMed  Google Scholar 

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Acknowledgements

We would like to thank the following individuals for their help with collecting and managing data for these studies: Emma Carlberg, Milki Gemeda, Hailey Glewwe, Madeline Hartig, Benjamin Hodapp, Ryan Johnson, Dustyn Leff, Andrine Lemieux, Daniela Morales, Jake Robinson, Alexia Patel, Soni Rraklli Uccellini, and Josh Schlueter. We would also like to thank Cara Hegg, Lynsie Radovich, and Kate Root for their help in conducting assays.

Funding

This research was supported in part by National Institutes of Health grants R01DA016351 and R01DA027232.

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Authors and Affiliations

  1. Department of Family Medicine and Biobehavioral Health, University of Minnesota Medical School, 1035 University Drive, Duluth, MN, 55812, USA

    Mustafa al’Absi, Briana N. DeAngelis & Motohiro Nakajima

  2. Eikei University of Hiroshima, Hiroshima, Japan

    Motohiro Nakajima

  3. School of Public Health, University of Minnesota, Twin Cities. Minneapolis, MN, USA

    James S. Hodges

  4. Dartmouth College, Hanover, USA

    Alan Budney

  5. Department of Psychiatry and Behavioral Sciences, University of Minnesota, Twin Cities. Minneapolis, MN, USA

    Dorothy Hatsukami

  6. Department of Family Medicine and Community Health, University of Minnesota, Twin Cities. Minneapolis, MN, USA

    Sharon Allen

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  1. Mustafa al’Absi
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Correspondence to Mustafa al’Absi.

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al’Absi, M., DeAngelis, B.N., Nakajima, M. et al. Biobehavioral and affective stress responses during nicotine withdrawal: Influence of regular cannabis co-use. Psychopharmacology 241, 253–262 (2024). https://doi.org/10.1007/s00213-023-06481-w

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