2. The endocannabinoid system and drug addiction: basal and stress-related endocannabinoid plasma levels in chronic cocaine users and prescription opioid users

Stress is proposed as a key risk factor for developing drug addiction and for relapse, maintaining the vicious circle of drug addiction. A growing body of work indicates that the endocannabinoid system plays a crucial role in the regulation of stress response due to its stress buffering effects in animals and humans. Moreover, the endocannabinoid system has been recently linked to reward processing and addiction. However, most of the findings come from animal studies and translational human studies are missing so far.

Plasma levels of endocannabinoids from two different substance user groups (cocaine users [N = 160] and prescription opioid users [N = 23]; healthy controls [total N = 168]) at baseline as well as after acute laboratory stress induction (5 time points) will be analyzed to address two main objectives: 1. To determine if chronic cocaine and opioid users show differences in basal (tonic) endocannabinoid signaling compared to healthy controls. 2. To test if chronic cocaine and opioid users show differences in phasic endocannabinoid signaling in response to acute stress compared to healthy controls.

We expect that chronic cocaine and opioid users will show altered basal and stress-related endocannabinoid plasma levels compared to healthy controls consistent with a dysfunctional physiological stress system.

The mechanistic understanding arising from this project could have profound implications for addiction research, as well as for the development of novel and improved treatments for opioid and cocaine (stress-related) relapse and abstinence by targeting the endocannabinoid system in a pharmaco-therapeutic setting. Disclosure of interest statement: Data from previous studies used for this project were funded by grants from the Swiss National Science Foundation (grant nr.: http://p3.snf.ch/Project-146326 & http://p3.snf.ch/Project-162639). Dr. Kroll has been recently awarded the NARSAD Young Investigator Grant by the Brain and Behavior Research Foundation (BBRF; Grant nr.: 30549) for the present project. No pharmaceutical grants were received in the development of this study.