EXPERT APPRAISAL OF CRITERIA FOR NON-HUMAN PRIMATE MODEL FOR ADDICTION: AN INTERNATIONAL DELPHI STUDY
Authors: Su *Hang , Zhai Rongwei , Zhang Wenlei , Xiong Zhiqi , Zhao Min 
Published: February 2025

Abstract

Background
Substance use disorders (SUD) refer to a group of chronic relapsing disease of the brain, which is manifested by forced procuring drugs or stimulants, losing control when limiting drug intake and producing persistent negative emotional status, and disappears when drugs or stimulants are obtained again. SUD model is a specific animal behavior model, which could reflect the neurobiology, psychology, etiology, clinical therapeutics characteristics, or at least simulate one or some aspects of SUD. However, the great species differences between experimental animal and human may make it difficult to objectively evaluate the similarity between animals' behavioral phenotypes and human addictive behaviors. Non-human primates have superior brain functions and could perform complicated cognitive processes, which are currently better choice as an animal model of SUD. Therefore, building SUD model based on non-human primate self-administration may be an ideal animal model to study the neurobiological mechanism of SUD. However, the existing non-human primate addiction models have inevitable problems, it is difficult to simulate the development process of SUD and lack of objective indicators that could be used to evaluate animal addiction.

Aim
Given the strong rationale for applying non-human primate model for SUD, while acknowledging the heterogeneity and lack of specificity of current approaches, we aim to reach an expert consensus on recommendations for developing diagnostic criteria for non-human primate model in the context of SUD. Specifically, we aim to identify the best criteria terms for SUD with reference to the core symptoms of DSM-5 and ICD-11. To achieve this, we decide to use a Delphi approach to survey a pool of international experts in the field and reach a broad consensus via iterative consultation.

Method
Experts were identified based on a recent systematic review of addiction studies and diagnostic criteria, with a final search date of June 2022.

Results
A total of 160 potential experts from different regions of the world were categorized and ranked according to their country of residence, research impact and clinical experience. Of these, 40 experts were invited to participate. Of the initial 40 invitations, 21 experts met the criteria and were included in the study finally. In the first round, twelve items were proposed and rated. In the second round, six items remained, and two new items were introduced and rated: concomitant symptom and choosing drug over alternative non-drug rewards. The results showed that three criterion were deemed ‘very important’ or ‘extremely important’ and consistency remained stable after two rounds survey: The subject spent more time or effort trying to procure the drug than a relevant quantitative norm; The subject had high motivation (craving) to use the drug; and Relapse: after prolonged abstinence, when confronted with environmental cues or contexts, the subject returns faster than initially to its characteristic pre-abstinence drug use behavior.

Conclusion
In conclusion, the present study used a Delphi method to develop a subset of diagnostic criteria that can be used as addiction criteria for the NHP model, after obtaining the agreement of experts from different geographical locations.