Robert J. Ursano

The role of endocannabinoid function in posttraumatic stress disorder: Modulating the risk phenotype and rendering effects of trauma

Posttraumatic stress disorder (PTSD) is a debilitating consequence of trauma in military and civilian settings. Substantial evidence implicates endocannabinoid function in three dimensions associated with risk for the disorder and in the etiology of essential symptoms. Negative (fear-avoidance) and positive (approach-reward) systems, and a dispositional dimension of control, modulate risk for PTSD and rely heavily on endocannabinoid function. Moreover, animal models associate an exaggerated fear response, characteristic of PTSD, with compromised endocannabinoid signaling, while plasticity in the same system renders effects of trauma in early life, fundamentally altering the stress response. Further implicating the endocannabinoid system, PTSD often co-occurs with cannabis use. Cannabis appears to alleviate negative affect states and symptoms of PTSD, possibly by normalizing endocannabinoid function. While this diverse evidence recommends the endocannabinoid system as a therapeutic target, it also reveals complexities that complicate efforts to develop such therapies. Scientific analysis of endocannabinoid function in PTSD will facilitate these efforts, while also informing a developing discussion on medical and recreational use of marijuana.

Pandemics: Health Care Emergencies

Introduction Pandemics have a global reach of mass destruction and historically have been more devastating than any other type of disaster. Over many centuries, only the humanmade disasters of war and the intentional extermination of ethnic groups have competed with the lethality of infectious disease outbreaks. Th e history of the infl uenza pandemic – occurring about every 10– 30 years – has marked global reach and concern for mass illness, chronic disability, and death. In centuries past, this concern included the plague, polio, tuberculosis, and smallpox. Th e Spanish Infl uenza pandemic of 1918– 1919, during which an estimated 20– 40 million people died (more people than died in World War I), is a reminder of the deadly potential of this global disaster ( http:// virus.stanford.edu/ uda/ ). Th ough prevention, early detection, and treatment interventions appear to be lowering the number of people infected, there has been a steady rise in human infectious disease outbreaks over the past three decades (Smith et al., 2014 ). In the past decade alone, outbreaks of Severe Acute Respiratory Syndrome (SARS), H1N1 “swine” Infl uenza, and Ebola resulted in significant concern throughout the international community. Middle East Respiratory Syndrome (MERS) and, more recently, the Zika virus have caused signifi cant morbidity and mortality. Th ese outbreaks all represented signifi cant threats to global health security and highlighted the mental health issues that are relevant to a pandemic outbreak. Expanding world populations produce urbanization with increased population density that favors disease transmission, and climate change modifi es global ecologies that infl uence the likelihood of transmitting infectious organisms (Morse, 1995 ). Th e largescale migration of animals and people creates a growing public health concern of epidemic risk. Th e global mobility of people and various disease vectors are primary mechanisms by which new infectious agents spread rapidly to a population with no previous exposure and no immunity, bringing disease vectors (e.g., certain species of mosquitoes) to new environments. Th ese factors have been essential elements in the genesis of all global infectious disease outbreaks since the turn of the century. For example, at the time of the Hajj each year in the 12th month of the Islamic (lunar) calendar, more than one million people travel to Mecca – nearly half from nonArab countries. Similarly, for the smaller ritual Umrah, more than 2.5 million traveled in 2004 to Mecca. Th is mass migration raises the potential for major public health and infection control problems (Ahmed et al., 2006 ). Other times of human migration – holidays and vacations – and the “human migratory patterns” are routes of transmission as well. Pandemics and other infectious disease outbreaks result in psychological stressors and behavioral responses. Unlike other natural or humanmade disaster events, infectious organisms cannot be perceived with the naked eye. Most people do not know they have been impacted until they are infected with potentially lethal consequences. Th e protracted and evolving nature of these events can result in escalating worry and distress. Like other disasters, the media plays a signifi cant role in shaping public perception. Trust in government authorities and perceptions regarding their ability to manage an outbreak directly impact the degree to which the public participates in health risk behaviors designed to avoid infection, treat illness, and prevent spread of disease. Th e use of infectious outbreaks to inspire fear by political fi gures, community leaders, and the media to further unrelated agendas has colored the overall experience of these events by the population. Th e ability of governments to eff ectively respond is complicated by the fact that infectious diseases may fi rst emerge during political unrest, revolution, or war. Empirical data is more limited regarding the mental health impacts of pandemics than for other Pandemics: Health Care Emergencies