Measuring Within-Individual Cannabis Reduction in Clinical Trials: a Review of the Methodological Challenges

  • Rachel L. TomkoEmail author
  • Kevin M. Gray
  • Marilyn A. Huestis
  • Lindsay M. Squeglia
  • Nathaniel L. Baker
  • Erin A. McClure
Cannabis (A McRae-Clark B Sherman, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Cannabis


Purpose of Review

Cannabis abstinence, traditionally, is the primary outcome in cannabis use disorder (CUD) treatment trials. Due to the changing legality of cannabis, patient goals, and preliminary evidence suggesting that individuals who reduce their cannabis use may show functional improvements, cannabis reduction is a desirable alternative outcome in CUD trials. We review challenges in measuring cannabis reduction and the evidence to support various definitions of reduction.

Recent Findings

Reduction in number of cannabis use days was associated with improvements in functioning across several studies. Reductions in quantity of cannabis used was inconsistently associated with improvements in functioning, though definitions of quantity varied across studies. Different biomarkers may be used depending on the reduction outcome.


Biologically confirmed reductions in frequency of cannabis use days may represent a viable endpoint in clinical trials for cannabis use disorder. Additional research is needed to better quantify reduction in cannabis amounts.


Cannabis use disorder Harm reduction Cannabis quantification Randomized controlled trial Biomarkers Δ9-tetrahydrocannabinol 


Funding Information

Effort was supported by National Institutes of Health grants from the National Institute of Drug Abuse (R01 DA042114), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12 HD055885), and the National Institute on Alcohol Abuse and Alcoholism (K23 AA025399).

Compliance with Ethical Standards

Conflict of Interest

Marilyn A. Huestis provides consultation to Pinney & Associates, Inc., Canopy Health Innovations, Intelligent Fingerprinting, Cannabix, Evanostics, Inc., and the Center for Forensic Science Research and Education. Kevin M. Gray provides consultation to Pfizer, Inc.

Human and Animal Rights and Informed Consent

This article does not contain any original studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Rachel L. Tomko
    • 1
    Email author
  • Kevin M. Gray
    • 1
  • Marilyn A. Huestis
    • 2
  • Lindsay M. Squeglia
    • 1
  • Nathaniel L. Baker
    • 3
  • Erin A. McClure
    • 1
  1. 1.Department of Psychiatry and Behavioral SciencesMedical University of South CarolinaCharlestonUSA
  2. 2.Institute of Emerging Health ProfessionsThomas Jefferson UniversityPhiladelphiaUSA
  3. 3.Department of Public Health SciencesMedical University of South CarolinaCharlestonUSA

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