Skip to main content
SpringerLink
Log in

Effect of oxytocin on craving and stress response in marijuana-dependent individuals: a pilot study

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Stress has been shown to be a significant factor in the maintenance of marijuana use. Oxytocin is a hypothalamic neuropeptide that has been shown to moderate behavioral responding to stress as well as play a role in the neuroadaptations that occur as a consequence of long-term drug use.

Objectives

The current study evaluated the impact of oxytocin pretreatment on craving, stress, and anxiety responses following a psychosocial stress task in marijuana-dependent individuals.

Methods

In a laboratory setting, baseline measurements of craving (assessed using the Marijuana Craving Questionnaire; MCQ), salivary cortisol and dehydroepiandrosterone (DHEA), stress, and anxiety were collected in 16 participants (age 19–40) meeting DSM-IV criteria for marijuana dependence. Participants were then administered either oxytocin 40 IU (n = 8) or placebo (n = 8) nasal spray prior to completion of the Trier Social Stress Task (TSST). Measurements were repeated pre-TSST, immediately post-TSST, and 5-, 35-, and 60-min post-TSST.

Results

Oxytocin reduced both MCQ total score and DHEA levels from before to after the TSST. It also decreased anxiety, but not subjective stress ratings.

Conclusions

Although preliminary, these results suggest that oxytocin may play a role in the amelioration of stress-induced reactivity and craving in marijuana-dependent individuals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Baumgartner T, Heinrichs M, Vonlanthen A, Fischbacher U, Fehr E (2008) Oxytocin shapes the neural circuitry of trust and trust adaptation in humans. Neuron 58:639–650

    Article  PubMed  CAS  Google Scholar 

  • Bonn-Miller MO, Zvolensky MJ, Bernstein A (2007) Marijuana use motives: concurrent relations to frequency of past 30-day use and anxiety sensitivity among young adult marijuana smokers. Addict Behav 32:49–62

    Article  PubMed  Google Scholar 

  • Bremner JD, Southwick SM, Darnell A, Charney DS (1996) Chronic PTSD in Vietnam combat veterans: course of illness and substance abuse. Am J Psychiatry 153:369–375

    PubMed  CAS  Google Scholar 

  • Butovsky E, Juknat A, Elbaz J, Shabat-Simon M, Eilam R, Zangen A, Altstein M, Vogel Z (2006) Chronic exposure to Delta9-tetrahydrocannabinol downregulates oxytocin and oxytocin-associated neurophysin in specific brain areas. Mol Cell Neurosci 31:795–804

    Article  PubMed  CAS  Google Scholar 

  • Cardoso C, Ellenbogen MA, Orlando MA, Bacon SL, Joober R (2012) Intranasal oxytocin attenuates the cortisol response to physical stress: a dose response study. Psychoneuroendocrinology. doi:10.1016/j.psyneuen.2012.07.013

  • Carson DS, Cornish JL, Guastella AJ, Hunt GE, McGregor IS (2010) Oxytocin decreases methamphetamine self-administration, methamphetamine hyperactivity, and relapse to methamphetamine-seeking behaviour in rats. Neuropharmacology 58:38–43

    Article  PubMed  CAS  Google Scholar 

  • Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Erlbaum, Hillsdale

    Google Scholar 

  • Copeland J, Swift W, Rees V (2001) Clinical profile of participants in a brief intervention program for cannabis use disorder. J Subst Abuse Treat 20:45–52

    Article  PubMed  CAS  Google Scholar 

  • Cui SS, Bowen RC, Gu GB, Hannesson DK, Yu PH, Zhang X (2001) Prevention of cannabinoid withdrawal syndrome by lithium: involvement of oxytocinergic neuronal activation. J Neurosci 21:9867–9876

    PubMed  CAS  Google Scholar 

  • de Oliveira DC, Zuardi AW, Graeff FG, Queiroz RH, Crippa JA (2012) Anxiolytic-like effect of oxytocin in the simulated public speaking test. J Psychopharmacol 26:297–504

    Article  Google Scholar 

  • Dickerson SS, Kemeny ME (2004) Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research. Psychol Bull 130:355–391

    Article  PubMed  Google Scholar 

  • Ditzen B, Schaer M, Gabriel B, Bodenmann G, Ehlert U, Heinrichs M (2009) Intranasal oxytocin increases positive communication and reduces cortisol levels during couple conflict. Biol Psychiatry 65:728–731

    Article  PubMed  CAS  Google Scholar 

  • Domes G, Heinrichs M, Glascher J, Buchel C, Braus DF, Herpertz SC (2007) Oxytocin attenuates amygdala responses to emotional faces regardless of valence. Biol Psychiatry 62:1187–1190

    Article  PubMed  CAS  Google Scholar 

  • First MB, Spitzer RL, Gibbon M, Williams JBW (1994) Structured clinical interview for Axis 1 DSM-IV Disorder—patient edition (SCIP-I/P, version 2.0). Biometrics Research Department, New York

    Google Scholar 

  • Francis DD, Diorio J, Plotsky PM, Meaney MJ (2002) Environmental enrichment reverses the effects of maternal separation on stress reactivity. J Neurosci 22:7840–7843

    PubMed  CAS  Google Scholar 

  • Fries AB, Ziegler TE, Kurian JR, Jacoris S, Pollak SD (2005) Early experience in humans is associated with changes in neuropeptides critical for regulating social behavior. Proc Natl Acad Sci U S A 102:17237–17240

    Article  CAS  Google Scholar 

  • Galen LW, Henderson MJ (1999) Validation of cocaine and marijuana effect expectancies in a treatment setting. Addict Behav 24:719–724

    Article  PubMed  CAS  Google Scholar 

  • Heim C, Young LJ, Newport DJ, Mletzko T, Miller AH, Nemeroff CB (2009) Lower CSF oxytocin concentrations in women with a history of childhood abuse. Mol Psychiatry 14:954–958

    Article  PubMed  CAS  Google Scholar 

  • Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U (2003) Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry 54:1389–1398

    Article  PubMed  CAS  Google Scholar 

  • Heishman SJ, Evans RJ, Singleton EG, Levin KH, Copersino ML, Gorelick DA (2009) Reliability and validity of a short form of the Marijuana Craving Questionnaire. Drug Alcohol Depend 102:35–40

    Article  PubMed  Google Scholar 

  • Hyman SM, Sinha R (2009) Stress-related factors in cannabis use and misuse: implications for prevention and treatment. J Subst Abuse Treat 36:400–413

    Article  PubMed  Google Scholar 

  • Izawa S, Sugaya N, Shirotsuki K, Yamada KC, Ogawa N, Ouchi Y, Nagano Y, Suzuki K, Nomura S (2008) Salivary dehydroepiandrosterone secretion in response to acute psychosocial stress and its correlations with biological and psychological changes. Biol Psychol 79:294–298

    Article  PubMed  Google Scholar 

  • Kalimi M, Shafagoj Y, Loria R, Padgett D, Regelson W (1994) Anti-glucocorticoid effects of dehydroepiandrosterone (DHEA). Mol Cell Biochem 131:99–104

    Article  PubMed  CAS  Google Scholar 

  • Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S, Gruppe H, Mattay VS, Gallhofer B, Meyer-Lindenberg A (2005) Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci 25:11489–11493

    Article  PubMed  CAS  Google Scholar 

  • Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E (2005) Oxytocin increases trust in humans. Nature 435:673–676

    Article  PubMed  CAS  Google Scholar 

  • Kovacs GL, Sarnyai Z, Szabo G (1998) Oxytocin and addiction: a review. Psychoneuroendocrinology 23:945–962

    Article  PubMed  CAS  Google Scholar 

  • Labuschagne I, Phan KL, Wood A, Angstadt M, Chua P, Heinrichs M, Stout JC, Nathan PJ (2010) Oxytocin attenuates amygdala reactivity to fear in generalized social anxiety disorder. Neuropsychopharmacology 35:2403–2413

    Article  PubMed  CAS  Google Scholar 

  • Lee CM, Neighbors C, Woods BA (2007) Marijuana motives: young adults’ reasons for using marijuana. Addict Behav 32:1384–1394

    Article  PubMed  Google Scholar 

  • Lennartsson A-K, Kushnir MM, Bergquist J, Jonsdottir IH (2012) DHEA and DHEA-S response to acute psychosocial stress in healthy men and women. Biol Psychiatry 90:143–149

    Article  Google Scholar 

  • Light KC, Grewen KM, Amico JA, Boccia M, Brownley KA, Johns JM (2004) Deficits in plasma oxytocin responses and increased negative affect, stress, and blood pressure in mothers with cocaine exposure during pregnancy. Addictive Behaviors 29:1541–1564

    Article  PubMed  Google Scholar 

  • Linnen AM, Ellenbogen MA, Cardoso C, Joober R (2012) Intranasal oxytocin and salivary cortisol concentration during social rejection in university students. Stress 15:393–402

    Article  PubMed  CAS  Google Scholar 

  • Lipschitz DS, Rasmusson AM, Anyan W, Gueorguieva R, Billingslea EM, Cromwell PF, Southwick SM (2003) Posttraumatic stress disorder and substance use in inner-city adolescent girls. J Nerv Ment Dis 191:714–721

    Article  PubMed  Google Scholar 

  • Ludwig M, Leng G (2006) Dendritic peptide release and peptide-dependent behaviours. Nat Rev Neurosci 7:26–136

    Article  Google Scholar 

  • Maninger N, Wolkowitz OM, Reus VI, Epel ES, Mellon SH (2009) Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). Frontiers in Neuroendocrinology 30:65–91

    Article  PubMed  CAS  Google Scholar 

  • Melis MR, Melis T, Cocco C, Succu S, Sanna F, Pillolla G, Boi A, Ferri GL, Argiolas A (2007) Oxytocin injected into the ventral tegmental area induces penile erection and increases extracellular dopamine in the nucleus accumbens and paraventricular nucleus of the hypothalamus of male rats. Eur J Neurosci 26:1026–1035

    Article  PubMed  Google Scholar 

  • Morgan CA III, Southwick S, Hazlett G, Rasmusson A, Hoyt G, Zimolo Z, Charney D (2004) Relationships among plasma dehydroepiandrosterone sulfate and cortisol levels, symptoms of dissociation, and objective performance in humans exposed to acute stress. Arch Gen Psychiatry 61:819–825

    Article  PubMed  CAS  Google Scholar 

  • Pitman RK, Orr SP, Lasko NB (1993) Effects of intranasal vasopressin and oxytocin on physiologic responding during personal combat imagery in Vietnam veterans with posttraumatic stress disorder. Psychiatry Res 48:107–117

    Article  PubMed  CAS  Google Scholar 

  • SAMSHA (2010) Results from the 2009 National Survey on Drug Use and Health: Volume 1. Summary of National Findings. In: U.S. Department of Health and Human Services, S.A.M.H.S.A., Office of Applied Studies (Ed.)

  • Sarnyai Z, Babarczy E, Krivan M, Szabo G, Kovacs GL, Barth T, Telegdy G (1991) Selective attenuation of cocaine-induced stereotyped behaviour by oxytocin: putative role of basal forebrain target sites. Neuropeptides 19:51–56

    Article  PubMed  CAS  Google Scholar 

  • Sarnyai Z, Biro E, Babarczy E, Vecsernyes M, Laczi F, Szabo G, Krivan M, Kovacs GL, Telegdy G (1992a) Oxytocin modulates behavioural adaptation to repeated treatment with cocaine in rats. Neuropharmacology 31:593–598

    Article  PubMed  CAS  Google Scholar 

  • Sarnyai Z, Kovacs GL (1994) Role of oxytocin in the neuroadaptation to drugs of abuse. Psychoneuroendocrinology 19:85–117

    Article  PubMed  CAS  Google Scholar 

  • Sarnyai Z, Szabo G, Kovacs GL, Telegdy G (1992b) Opposite actions of oxytocin and vasopressin in the development of cocaine-induced behavioral sensitization in mice. Pharmacol Biochem Behav 43:491–494

    Article  PubMed  CAS  Google Scholar 

  • Schiff M, Zweig HH, Benbenishty R, Hasin DS (2007) Exposure to terrorism and Israeli youths’ cigarette, alcohol, and cannabis use. Am J Public Health 97:1852–1858

    Article  PubMed  Google Scholar 

  • Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Weiller E, Hergueta T, Baker R, Dunbar GC (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59(Suppl 20):22–33

    Google Scholar 

  • Simons JS, Gaher RM, Correia CJ, Hansen CL, Christopher MS (2005) An affective-motivational model of marijuana and alcohol problems among college students. Psychol Addict Behav 19:326–334

    Article  PubMed  Google Scholar 

  • Sivukhina EV, Dolzhikov AA, Morozov Iu E, Jirikowski GF, Grinevich V (2006) Effects of chronic alcoholic disease on magnocellular and parvocellular hypothalamic neurons in men. Horm Metab Res 38:382–390

    Article  PubMed  CAS  Google Scholar 

  • Vaccari C, Lolait SJ, Ostrowski NL (1998) Comparative distribution of vasopressin V1b and oxytocin receptor messenger ribonucleic acids in brain. Endocrinology 139:5015–5033

    Article  PubMed  CAS  Google Scholar 

  • Vlahov D, Galea S, Ahern J, Resnick H, Kilpatrick D (2004) Sustained increased consumption of cigarettes, alcohol, and marijuana among Manhattan residents after September 11, 2001. Am J Public Health 94:253–254

    Article  PubMed  Google Scholar 

  • Williams JR, Insel TR, Harbaugh CR, Carter CS (1994) Oxytocin administered centrally facilitates formation of a partner preference in female prairie voles (Microtus ochrogaster). J Neuroendocrinol 6:247–250

    Article  PubMed  CAS  Google Scholar 

  • Wills TA, Sandy JM, Yaeger AM, Cleary SD, Shinar O (2001) Coping dimensions, life stress, and adolescent substance use: a latent growth analysis. J Abnorm Psychol 110:309–323

    Article  PubMed  CAS  Google Scholar 

  • Windle M, Wiesner M (2004) Trajectories of marijuana use from adolescence to young adulthood: predictors and outcomes. Dev Psychopathol 16:1007–1027

    Article  PubMed  Google Scholar 

  • Winstock AR, Lea T, Copeland J (2009) Lithium carbonate in the management of cannabis withdrawal in humans: an open-label study. J Psychopharmacol 23:84–93

    Article  PubMed  CAS  Google Scholar 

  • Witt DM, Winslow JT, Insel TR (1992) Enhanced social interactions in rats following chronic, centrally infused oxytocin. Pharmacol Biochem Behav 43:855–861

    Article  PubMed  CAS  Google Scholar 

  • Zak PJ, Stanton AA, Ahmadi S (2007) Oxytocin increases generosity in humans. PLoS ONE 2(11):e1128

    Google Scholar 

Download references

Acknowledgments

The authors would like to thank the individuals who participated in the study and acknowledge the contributions of the clinical research team, including Aaron Schott, Erin Lindley, Elisabeth Kryway, and Amanda Wagner. This project was supported by the South Carolina Clinical and Translational Research Institute, with an academic home at the Medical University of South Carolina, NIH/NCRR grant number UL1 RR029882.

Conflicts of interest

The authors have no conflicts of interest related to this investigation to report.

Author information

Authors and Affiliations

  1. Clinical Neuroscience Division, Department of Psychiatry, Medical University of South Carolina, 67 President Street, Charleston, SC, 29425, USA

    Aimee L. McRae-Clark, Megan Moran-Santa Maria & Kathleen T. Brady

  2. Department of Public Health Sciences, Medical University of South Carolina, 135 Cannon Street, Charleston, SC, 29425, USA

    Nathaniel L. Baker

Authors
  1. Aimee L. McRae-Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nathaniel L. Baker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Megan Moran-Santa Maria
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kathleen T. Brady
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aimee L. McRae-Clark.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOCX 116 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

McRae-Clark, A.L., Baker, N.L., Maria, M.MS. et al. Effect of oxytocin on craving and stress response in marijuana-dependent individuals: a pilot study. Psychopharmacology 228, 623–631 (2013). https://doi.org/10.1007/s00213-013-3062-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-013-3062-4

Keywords

Search

Navigation