Verhindert die Aktivierung des Cannabinoid-Systems die Ausbildung intrusiver Erinnerungen nach traumatischen Ereignissen?
Allgemeine, Kognitive und Mathematische Psychologie
Zusammenfassung der Projektergebnisse
Preliminary findings indicate a potential role of the cannabinoid system in emotional learning and intrusive memories, which are central symptoms of posttraumatic stress disorder (PTSD). However, the biological mechanisms underlying intrusion formation after trauma exposure remain poorly understood. Low endocannabinoid activity may increase vulnerability to developing intrusive memories after trauma, whereas higher endocannabinoid activity could enhance resilience. We aimed to examine whether an increased activation of Cannabinoid-Rezeptor Typ 1 (CB1R) during the acquisition or consolidation of a stressful event could prevent the subsequent development of intrusive memories. A secondary aim was to evaluate the impact of genetic variants, including the polygenic risk score for PTSD, as well as hypothalamicpituitary-adrenal (HPA) axis activation and noradrenergic system involvement, on intrusive symptoms after trauma. We conducted a three-armed, randomized, double-blind, and placebo-controlled study to evaluate the effects of a single administration of 5 mg dronabinol (cannabinoid) on the acquisition or consolidation of intrusive memories. Participants were randomly assigned to receive oral dronabinol either before or after watching a trauma film or a placebo at both time points. To induce intrusive memories, healthy women (N = 291) were exposed to a validated trauma film paradigm designed to simulate stressful real-life events and provoke short-term intrusive memories in healthy individuals. The trauma film successfully elicited significant physiological stress responses, evidenced by increased cortisol levels and salivary alphaamylase (sAA) activity, indicating activation of the HPA axis and the sympathetic nervous system. As expected, participants developed intrusive memories, which were recorded through diary entries over the four days following the trauma film. The mean total number of intrusive memories in the three groups was as follows: dronabinol before the trauma film (M = 4.12, SD = 3.9), dronabinol after the trauma film (M = 4.53, SD = 4.78), and placebo (M = 4.54, SD = 4.61). Dronabinol did not significantly reduce intrusive memories. However, it interacted with time, influencing cortisol and sAA levels and highlighting its potential role in modulating stress responses. These findings suggest that while dronabinol may not directly affect intrusive memory formation, it could alter stress reactivity dynamics. The study contrasts with prior research suggesting that cannabinoids impair negative emotional memory consolidation and promote the extinction of adverse stimuli. Although Delta-9-Tetrahydrocannabinol (THC) has shown some effectiveness in reducing intrusive memories in clinical populations, findings remain inconsistent. The lack of a significant effect in the current study may be due to a ceiling effect or the relatively low distress levels in participants, as early trauma interventions are typically most effective in highly distressed individuals. A more detailed analysis of the current data is required, particularly to investigate the roles of genetic variables, HPA axis activation, and the noradrenergic system in intrusive symptoms following trauma. These aspects will be further examined within the next six months.
