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Review
. 2020 Jul 1:212:107993.
doi: 10.1016/j.drugalcdep.2020.107993. Epub 2020 Apr 26.

The state of clinical outcome assessments for cannabis use disorder clinical trials: A review and research agenda

Mallory J E Loflin  1 , Brian D Kiluk  2 , Marilyn A Huestis  3 , Will M Aklin  4 , Alan J Budney  5 , Kathleen M Carroll  6 , Deepak Cyril D'Souza  6 , Robert H Dworkin  7 , Kevin M Gray  8 , Deborah S Hasin  9 , Dustin C Lee  10 , Bernard Le Foll  11 , Frances R Levin  12 , Joshua A Lile  13 , Barbara J Mason  14 , Aimee L McRae-Clark  8 , Ivan Montoya  4 , Erica N Peters  15 , Tatiana Ramey  4 , Dennis C Turk  16 , Ryan Vandrey  10 , Roger D Weiss  17 , Eric C Strain  10
Affiliations
Review

The state of clinical outcome assessments for cannabis use disorder clinical trials: A review and research agenda

Mallory J E Loflin et al. Drug Alcohol Depend. .

Abstract

There is considerable variability in the use of outcome measures in clinical trials for cannabis use disorder (CUD), and a lack of consensus regarding optimal outcomes may have hindered development and approval of new pharmacotherapies. The goal of this paper is to summarize an evaluation of assessment measures and clinical endpoints for CUD clinical trials, and propose a research agenda and priorities to improve CUD clinical outcome assessments. The primary recommendation is that sustained abstinence from cannabis should not be considered the primary outcome for all CUD clinical trials as it has multiple limitations. However, there are multiple challenges to the development of a reliable and valid indicator of cannabis reduction, including the lack of a standard unit of measure for the various forms of cannabis and products and the limitations of currently available biological and self-report assessments. Development of a core toolkit of assessments is needed to both allow flexibility for study design, while facilitating interpretation of outcomes across trials. Four primary agenda items for future research are identified to expedite development of improved clinical outcome assessments for this toolkit: (1) determine whether minimally invasive biologic assays could identify an acute level of cannabis use associated with psychomotor impairment or other cannabis-related harms; (2) create an indicator of quantity of cannabis use that is consistent across product types; (3) examine the presence of cannabis-specific functional outcomes; and (4) identify an optimal duration to assess changes in CUD diagnostic criteria.

Keywords: CUD; Cannabis use disorder; Clinical outcome assessment; Clinical trial; Endpoints; Outcome measures.

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Conflict of interest statement

Conflicts of Interest

The views expressed in this article are those of the authors. None of the authors have current financial conflicts of interest specifically related to the issues discussed in this article. At the time of the meeting, several authors previously received consulting fees or honoraria from one or more pharmaceutical or device companies, which are described below. All other authors declare no conflicts.

Author ML serves on the scientific advisory board for FSD pharma, and has received consulting fees from Zynerba Pharmaceuticals and conference travel funding from Tilray Inc in the past 36 months.

Author MH is an advisor for Cannabix, a company that is one of many working on a cannabis breath test. At the time of submission, MH has not received payment for this consultation.

Author RD in the past 36 months has received compensation from Abide, Adynxx, Analgesic Solutions, Aptinyx, Asahi Kasei, Astellas, AstraZeneca, Biogen, Biohaven, Boston Scientific, Braeburn, Celgene, Biogen, Biohaven, Boston Scientific, Braeburn, Celgene, Centrexion, Chromocell, Clexio, Concert, Coronado, Daiichi Sankyo, Dong-A, Eli Lilly, Eupraxia, Glenmark, Grace, Hope, Hydra, Immune, Johnson & Johnson, Medavante, Neumentum, NeuroBo, Novaremed, Novartis, NSGene, Olatec, Periphagen, Pfizer, Phosphagenics, Quark, Reckitt Benckiser, Regenacy, Relmada, Sandoz, Semnur, Sollis, Spinifex, Syntrix, Teva, Thar, Theranexus, Trevena, and Vertex.

Author BL has received Sativex drug product donations from GW Pharmaceuticals for NIH and CIHR funded studies and cannabis product donations from Prairie Plant System/Aurora for CIHR-funded studies. He also has a current grant related to the topic of CUD funded by Alkermes, and planned work with Alcohol Countermeasures Systems.

Author ES has served on advisory boards, received grant funding from, and/or consulted for: Alkermes, Analgesic Solutions, Caron, Egalet, Indivior Pharmaceuticals, Innocoll Pharmaceuticals, The Oak Group, Otsuka Pharmaceutical Development and Commercialization, and Pinney Associates. He has received honoraria from Medscape and the WHO. He is currently collaborating with Innovative Health Solutions, the makers of the Bridge Device.

Author RV has received consulting fees from Zynerba Pharmaceuticals, Battelle Memorial Institute, and Canopy Health Innovations Inc. He also receives compensation for being on the advisory boards for Insys Therapeutics, Brain Solutions Inc., and The Realm of Caring Foundation.

Author KG has received consulting fees from Pfizer, Inc.

Author RW has received consulting fees from GW Pharmaceuticals.

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