Administering synthetic cannabinoids shortly after a traumatic event can prevent the development of PTSD-like symptoms in rats, including those triggered by reminders of the trauma. This conclusion comes from a study by Nachshon Korem and Irit Akirav of the Department of Psychology at the University of Haifa, published in the journal Neuropsychopharmacology. The researchers emphasize that these findings clarify how cannabis-like compounds affect the brain in the aftermath of trauma and support the need for human trials to explore whether cannabinoids could help prevent post-traumatic stress disorder and related anxiety conditions.
Post-traumatic stress disorder (PTSD) affects a significant portion of the population. In Israel, for example, health authorities estimate that roughly nine percent of people experience PTSD at some point, with even higher rates among high-risk groups such as combat veterans, prisoners, assault survivors, and civilians exposed to chronic conflict. A major challenge for individuals with PTSD is that exposure to trauma reminders — neutral or non-threatening events that evoke memories of the original trauma — can intensify symptoms. For instance, a loud alarm or sudden noise can trigger distress in a person whose trauma was associated with air-raid sirens.
Previous work by Dr. Irit Akirav found that administering cannabinoids within a specific time window after a traumatic event reduced PTSD-like symptoms in rats. Building on those results, this study, led by doctoral student Nachshon Korem together with Dr. Akirav, set out to determine whether cannabinoids could also blunt the effects of trauma reminders. Rats were used because their physiological and behavioral responses to stress and trauma are well-established models for understanding human neurobiology.
In the experiment, rats were subjected to a footshock to simulate a traumatic event and were later exposed to situational reminders on the third and fifth days after the shock. Within the therapeutic time window identified in earlier experiments, some rats received injections of a synthetic cannabinoid compound while others did not. All animals then underwent an extinction protocol — a laboratory procedure analogous to exposure therapy in humans that aims to reduce conditioned fear and other trauma-related responses.
Behavioral results showed that rats treated with the cannabinoid shortly after the trauma did not develop several hallmark PTSD-like symptoms. Treated animals demonstrated normal extinction learning, lower startle responses, typical sensitivity to pain, and preserved synaptic plasticity in the nucleus accumbens, a brain region involved in reward and emotional processing. By contrast, untreated rats exposed to trauma reminders displayed impaired extinction learning, exaggerated startle reactions, altered pain sensitivity, and disrupted plasticity in the nucleus accumbens.
The researchers also compared cannabinoids to sertraline, a selective serotonin reuptake inhibitor (SSRI) commonly prescribed for PTSD with modest efficacy. Cannabinoid-treated rats performed better than sertraline-treated rats on many measures; for some outcomes, behavior in the cannabinoid group resembled that of trauma-exposed rats who had not encountered trauma reminders. In practical terms, cannabinoids appeared to neutralize the additional negative impact of reminders, effectively making those reminder effects “disappear.”
To understand the neural mechanisms behind these behavioral changes, the team examined receptor expression in brain regions associated with emotion and memory. Rats exposed to trauma and reminders exhibited increased levels of two stress- and emotion-related receptors: the cannabinoid receptor CB1 and the glucocorticoid receptor (GR). Elevated expression of these receptors was observed in the hippocampus and prefrontal cortex, areas that play key roles in forming and storing traumatic memories. Importantly, administration of cannabinoids prevented the trauma- and reminder-induced increases in CB1 and GR expression in these brain regions.
These findings suggest that trauma and subsequent reminders alter connectivity and receptor regulation within the brain’s fear and memory circuits, and that timely cannabinoid treatment can block those maladaptive changes. The work provides a neurobiological basis for the protective effects seen at the behavioral level and highlights a potential preventive approach for PTSD.
Contact: Omri Salner – University of Haifa
Source: University of Haifa press release
Image Source: Image credited to Vienna Dioscurides (public domain)
Original Research: Nachshon Korem and Irit Akirav, “Cannabinoids Prevent the Effects of a Footshock Followed by Situational Reminders on Emotional Processing,” Neuropsychopharmacology. Published online June 5, 2014. DOI: 10.1038/npp.2014.132