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Review ArticleReview Article

Sex/Gender Differences in the Time-Course for the Development of Substance Use Disorder: A Focus on the Telescoping Effect

Eleanor Blair Towers, Ivy L. Williams, Emaan I. Qillawala, Emilie F. Rissman and Wendy J. Lynch
Michael Nader, ASSOCIATE EDITOR
Pharmacological Reviews March 2023, 75 (2) 217-249; DOI: https://doi.org/10.1124/pharmrev.121.000361
Eleanor Blair Towers
Psychiatry and Neurobehavioral Sciences (E.B.T., I.L.W., E.I.Q., W.J.L.) and Medical Scientist Training Program (E.B.T.), University of Virginia, Charlottesville, Virginia, and Center for Human Health and the Environment and Program in Genetics, North Carolina State University, Raleigh, North Carolina (E.F.R.)
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Ivy L. Williams
Psychiatry and Neurobehavioral Sciences (E.B.T., I.L.W., E.I.Q., W.J.L.) and Medical Scientist Training Program (E.B.T.), University of Virginia, Charlottesville, Virginia, and Center for Human Health and the Environment and Program in Genetics, North Carolina State University, Raleigh, North Carolina (E.F.R.)
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Emaan I. Qillawala
Psychiatry and Neurobehavioral Sciences (E.B.T., I.L.W., E.I.Q., W.J.L.) and Medical Scientist Training Program (E.B.T.), University of Virginia, Charlottesville, Virginia, and Center for Human Health and the Environment and Program in Genetics, North Carolina State University, Raleigh, North Carolina (E.F.R.)
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Emilie F. Rissman
Psychiatry and Neurobehavioral Sciences (E.B.T., I.L.W., E.I.Q., W.J.L.) and Medical Scientist Training Program (E.B.T.), University of Virginia, Charlottesville, Virginia, and Center for Human Health and the Environment and Program in Genetics, North Carolina State University, Raleigh, North Carolina (E.F.R.)
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Wendy J. Lynch
Psychiatry and Neurobehavioral Sciences (E.B.T., I.L.W., E.I.Q., W.J.L.) and Medical Scientist Training Program (E.B.T.), University of Virginia, Charlottesville, Virginia, and Center for Human Health and the Environment and Program in Genetics, North Carolina State University, Raleigh, North Carolina (E.F.R.)
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Michael Nader
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Abstract

Sex/gender effects have been demonstrated for multiple aspects of addiction, with one of the most commonly cited examples being the “telescoping effect” where women meet criteria and/or seek treatment of substance use disorder (SUD) after fewer years of drug use as compared with men. This phenomenon has been reported for multiple drug classes including opioids, psychostimulants, alcohol, and cannabis, as well as nonpharmacological addictions, such as gambling. However, there are some inconsistent reports that show either no difference between men and women or opposite effects and a faster course to addiction in men than women. Thus, the goals of this review are to evaluate evidence for and against the telescoping effect in women and to determine the conditions/populations for which the telescoping effect is most relevant. We also discuss evidence from preclinical studies, which strongly support the validity of the telescoping effect and show that female animals develop addiction-like features (e.g., compulsive drug use, an enhanced motivation for the drug, and enhanced drug-craving/vulnerability to relapse) more readily than male animals. We also discuss biologic factors that may contribute to the telescoping effect, such as ovarian hormones, and its neurobiological basis focusing on the mesolimbic dopamine reward pathway and the corticomesolimbic glutamatergic pathway considering the critical roles these pathways play in the rewarding/reinforcing effects of addictive drugs and SUD. We conclude with future research directions, including intervention strategies to prevent the development of SUD in women.

Significance Statement One of the most widely cited gender/sex differences in substance use disorder (SUD) is the "telescoping effect,” which reflects an accelerated course in women versus men for the development and/or seeking treatment for SUD. This review evaluates evidence for and against a telescoping effect drawing upon data from both clinical and preclinical studies. We also discuss the contribution of biological factors and underlying neurobiological mechanisms and highlight potential targets to prevent the development of SUD in women.

Footnotes

    • Received April 6, 2021.
    • Revision received October 5, 2022.
    • Accepted October 25, 2022.
  • This work was supported by National Institutes of Health National Institute on Drug Abuse [Grants R01-DA024716, R01-DA052893, and R21-DA049992] (to W.J.L.), [Grant R01-DA048638] (to W.J.L. and E.F.R.), a National Institute of General Medical Sciences Pharmacological Sciences Training Grant [Grant 5T32-GM007055-47] (to E.B.T.), and an MSTP Training Grant [Grant T32-GM007267] (to E.B.T.).

  • No author has an actual or perceived conflict of interest with the contents of this article.

  • dx.doi.org/10.1124/pharmrev.121.000361.

  • Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 75 (2)
Pharmacological Reviews
Vol. 75, Issue 2
1 Mar 2023
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Review ArticleReview Article

Sex Differences in the Progression to Addiction

Eleanor Blair Towers, Ivy L. Williams, Emaan I. Qillawala, Emilie F. Rissman and Wendy J. Lynch
Pharmacological Reviews March 1, 2023, 75 (2) 217-249; DOI: https://doi.org/10.1124/pharmrev.121.000361

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Review ArticleReview Article

Sex Differences in the Progression to Addiction

Eleanor Blair Towers, Ivy L. Williams, Emaan I. Qillawala, Emilie F. Rissman and Wendy J. Lynch
Pharmacological Reviews March 1, 2023, 75 (2) 217-249; DOI: https://doi.org/10.1124/pharmrev.121.000361
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    • I. Introduction
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