Dynamic Observation Of Craving And BDNF And HPA Axis Changes Induced By Different Cues In Methamphetamine Users

Objective:Craving is the main driving factor for the formation,maintenance and relapse of drug addiction,but there is still a lack of objective biological markers to evaluate drug craving.Numbers of studies indicated that brain-derived neurotrophic factor（BDNF）and hypothalamic-pituitary-adrenal axis were closely related to drug addiction,which could be a biomarker for assessing cravings.Drug cravings are associated with reward and learning.We often assess cravings by comparing addicts’responses to cues related to natural rewards（such as sex）with drug cues.The relationship between methamphetamine abuse and sexual behavior is more complex than other addictive substances.The purpose of this study was to dynamically trace the craving response and the changes of BDNF,cortisol and adrenocorticotropic hormone in peripheral blood of methamphetamine users induced by different cues,and to explore the relationship between craving and peripheral blood indexes.Methods:25 MA addicts（withdrawal within 1 month）and 25healthy controls were exposed to three different types of clues（neutral clues,MA clues,and sex related clues）,measuring drug craving score,blood pressure,heart rate,extraction of venous blood,and use the self-made scale general demographic information collection and material usage after the induction of each cue.This procedure was repeated 1month later for MA addicts.Results:1.Compared with the control group,MA disorders had more significant subjective craving response to drug cues during the whole test（P<0.05）.2.In the first test（within 1 month of withdrawal）and after 1 month follow-up,MA dependent subjects had significant differences in subjective craving score induced by drug cues and sexual cues（P₁=0.011,P₂=0.048）,and drug cues induced more significant increase in craving.Baseline craving of MA users was positively correlated with changes in craving scores induced by drug cues（abstinence for one month:rs=0.402,P=0.047）and sexual cues（abstinence for 1 month:rs=0.464,P=0,024;Abstinence for 2 months:rs=0.644,P=0.001）.3.The serum BDNF concentration decreased significantly after drug cue exposure compared with sexual exposure（t=-0.42,P=0.022）,and the concentration was significantly lower than that of the controls（F=3.959,P=0.030）in the fist test.The level of serum BDNF between MA addicts and the healthy controls were on different after sexual cue exposure.After a month,the serum BDNF concentrations induced by both cues were lower than those of healthy controls（P=0.030）.4.The HPA axis stress response induced by both drug cues and sexual cues was inhibited in the first test（within 1 month of withdrawal）.After a month of follow-up,MA users exposed to both cues showed increases in ACTH and cortisol,with drug cues being more significant.5.After one month of follow-up,cortisol responses were significantly associated with changes of craving scores for both drug cues（rs=0.685,P<0.001）and sexual cues（rs=0.573,P=0.004）.6.Drug cravings was significantly correlated with anxiety and withdrawal symptom scores in the first test（SAS:rs=0.430,P=0.032;Withdrawal symptom score:rs=0.380,P=0.042）.After 1 month,baseline craving was significantly associated with anxiety scores（SAS:rs=0.44,P=0.04）.Conclusion:There is a positive correlation between cue-induced cortisol response and craving change,and there is a correlation between HPA axis and cue-induced craving change.Serum BDNF in MA dependent and healthy controls showed distinct changes when exposed to drug cues and sexual cues,suggesting that BDNF plays a regulatory role in cue induction and may be used as a biomarker to assess craving and relapse during withdrawal.In addition,with the increase of abstinence time,some functions of the peripheral stress system may recover.The prolongation of abstinence time may change the response of MA addicters to drug cues and sexual cues,then affect their motivation to relapse.