Heidi Hanson - 7 PTSD Feedback Loops

This post comes from the Healing from Trauma blog by Heidi Hanson, many of whose posts are being compiled into a book tentatively called the Trauma Healing Resource Book.

This particular post, which was shared with me by some friends on Facebook, presents some of the essential experiences of PTSD within the context of feedback loops. Based on the experience of my clients, this seems quite useful.

7 PTSD Feedback Loops

by Heidi Hanson

In the book I have been working on, Trauma Healing Resource Book (tentative title), which chronicles my healing journey through PTSD, I identify 7 Feedback Loops that act like quicksand, pulling one further into PTSD even as one desires to find one’s way out. This needs further research, but feedback loops could be one reason some cases of PTSD become chronic.

Note: This article and all articles on this blog are based on my personal experience as someone recovering from PTSD. Much is theoretical material, however it is material I consider worth being studied in depth in a scientific manner at some point in time.

Excerpt from the book:

Definition: The technical definition of a feedback loop is “a system where outputs are fed back into the system as inputs, increasing or decreasing effects.” *

I would define a feedback loop related to human psychology as a group of external life circumstances and internal patterns that keep reinforcing each other, making it difficult to change either the circumstances or the patterns.

Feedback loops can be propelled by internal patterns of thoughts, perceptions, emotions, and behaviors, each element stimulating the next.

Negative feedback loops frequently lead to downward spirals, in which case some aspect of the situation worsens slightly every time one or several loops are completed.

Experiences of trauma may lead us to develop mental habits; feedback loops are mechanisms that keep maintaining and deepening these habits. One could theorize that feedback loops contribute to reinforcing specific neural pathways in the brain and to developing chronic imbalances in the nervous system and physiology.

Negative feedback loops lead to what I call a “trauma-based reality.” This is when we perceive all of our reality through a filter created from our past traumatic experiences. The “normal” reality we experienced prior to the traumatic experiences can only be sensed for brief moments.

In the following illustration, the individual is in a room dancing with trauma, and through the windows she can see momentary glimpses of the reality that exists outside of the trauma-based reality.


Book Illustration: Trauma-based Dance Floor
Sometimes, dancing, I catch hints of Life, outside
I have identified seven feedback loops based on my own experiences. I’m sure there are more; there are also variations on these seven, not included here.

* http://psychology.wikia.com/wiki/Feedback_loop

1. A Dangerous World Feedback Loop

Synonyms: Magnifying Triggers Feedback Loop, Environmental Triggers Feedback Loop

This feedback loop occurs when we have experienced trauma, and we happen to be in an environment that continuously triggers memories of the trauma. If constantly triggered, we can be reminded of the trauma and automatically feel fear over and over again, which makes the environment around us seem more frightening, and we end up imprinting the idea of trauma more and more deeply onto the environment. Seeing increasingly more danger makes us more likely to experience triggers, and makes the triggers more impactful when they come.

It’s not just the perception of the environment as more and more dangerous that increases the impact of the triggers. Being triggered a lot can gradually increase our sensitivity and raise our overall level of hyperarousal. In turn, feeling more sensitive increases the impact of the triggers.

In this scenario, all levels of danger are perceived as a red alert – there are no orange and yellow alerts; danger is stuck on High setting and only increases from there.

This feedback loop is one reason it is so important to get to an environment that gives some relief from triggers, or change the environment (get rid of furniture, redecorate, put new scents in the air etc.).

If the amount of stress puts the system into immobility more and more frequently, this feedback loop can lead to the Immobility Downward Spiral – getting increasingly immobile e.g. feeling numb, unresponsive, still, paralyzed.

I noticed this Dangerous World Feedback Loop and Immobility Downward Spiral happening early on in my experience of PTSD. This is an illustration that shows how too many triggers can feel like an invasion, or a kind of poison that is constantly being inserted into the brain and nervous system, causing the mind to go into meltdown or immobility on a regular basis.

2. Constricted Reality Feedback Loop / Downward Spiral

Synonyms: Self-isolation Feedback Loop, Resource Avoidance Downward Spiral, Resource Rejection Downward Spiral

Being extremely sensitive and being hit constantly by a wide variety of triggers can also lead to a Constricted Reality Feedback Loop. In this case, each time some life situation is associated with trauma, we may decide to avoid it as well as anything related to it. In the following illustration, we see that this individual’s hypersensitivity to triggers in his community make him cut off his connection, automatically and without thought, to resource after resource, until he is alone in his room, isolated and disconnected from the rest of the world.

Without any resources, it is unlikely he will be exposed to things that demonstrate that his triggers are false – in other words he won’t have experiences that deconstructs the triggers and rewire his brain to re-perceive reality in a new way, for example encountering someone who at first appears to be a perpetrator but is actually a friend, or an authority figure who appears to be abusive and turns out to actually be a resource. In this scenario there is no way for healing to happen because the individual is isolated from all potential resources.

This one is similar to the Dangerous World and Lack of Trust Feedback Loop (#5). They are all ways of illustrating how fear leads to fear, mistrust leads to more mistrust and isolation leads to more isolation, just with slight variations. Dangerous World has to do with one’s perception of danger, Lack of Trust is specifically in relation to other people, and Constricted Reality has to do with isolation from all types of resources in one’s community including places, events, groups, people etc.

Note: click on the image to see a larger version

3. Dissociation Feedback Loop

Being frequently dissociated means for much of the day we are not present in the body.

Some synonyms for this state of dissociation are:

• space cadet
• spaced out
• absent-minded
• head in the clouds
• not paying attention

This could lead to accidents which may be somewhat traumatizing. If traumatic, these accidents could possibly lead to further tendency to dissociate.

The illustration for this one may be simple, but being dissociative can create messy problems. Dissociation can lead to small accidents, like stubbing one’s toe; it can also lead to worse incidents, like doing things that are dangerous without knowing it. General disorganization can lead to problems, for example, a woman who is out late and misplaced her cell phone and is looking for it and then gets mugged whereas she would have been at home by that time if she had been more organized. Dissociation is an escape from the present and it may lead to bad decisions due to lack of awareness of details. Underneath dissociation is a wound(s) that causes tentativeness or rejection in relation to being in the body. In order to heal, we need to be committed to our bodies and ourselves, aware of our surroundings and alert to who is doing what with us, to prevent more accidents.

4. Hyperarousal Feedback Loop

Synonyms: Panic Loop

If we are in hyperarousal a large percentage of the time, it means the nervous system is strung tight like a rubber band pulled almost to the breaking point. We may be jumpy, prone to panic, tend to do things too quickly, rush about in too much of a hurry, and act on impulse. Hyperarousal makes it difficult to process information well because it keeps one stuck in a survival level of thinking, preventing access to the higher mind/rational thought. If we are panicking, we are also more easily manipulated by other people. This chaotic fear state could easily lead to getting into bad situations or accidents/injuries. It is possible this could lead to another trauma, which would only increase the hyperarousal.

5. Lack of Trust Feedback Loop

Synonyms: People Avoidance Feedback Loop, Other People Rejection Feedback Loop, Help Rejection Loop

Sometimes, a traumatic experience includes a breach of trust. Trust can be broken within a close relationship, such as with a partner or parent. Trust can also be violated by an authority figure we had confidence in. Sometimes, when we try to seek help with PTSD, we encounter healing practitioners who do not understand PTSD enough to help us, and can even do or say things that re-traumatize us. So, in some cases, we will develop a lack of trust.

Due to this lack of trust we may feel more comfortable spending time alone. Spending more time alone makes us more vulnerable to the symptoms of PTSD, because there is no information coming from outside to challenge the trauma-based reality. We avoid the very people and situations that may have a positive effect on the nervous system.

Not getting the help we need can lead to issues in the following areas:

1. Triggers automatically create hyperarousal; we do not learn ways to intervene.
2. We experience more triggers and this leads to more disregulation and hyperarousal.
3. Disregulation, hyperarousal, fear and anxiety cause confused information processing.
4. Due to difficulties with processing information we can’t figure out how to escape or change the situation.
5. Also, triggers lead us to remain in helplessness/immobility/paralysis; helplessness leads to not feeling one has the power to help themselves.
6. Low self-esteem remains unchallenged; low self esteem from trauma can stop us from seeking help.
7. When we perceive ourselves in a constricted reality, we may not see what exists outside it.
8. The level of sensitivity being unintentionally maintained can lead to more experiences of being traumatized by healing practitioners and other people trying to help.

Thus, the lack of trust seems to be justified by many aspects of our experience, and we spend more time avoiding people. Being alone with our PTSD symptoms can lead to experiencing reality as harsh and other people as unhelpful; we continue to avoid people and our reality becomes more and more constricted.

The Lack of Trust Feedback Loop can lead to a Constricted Reality Feedback Loop/Downward Spiral.

6. Trauma Seeking Feedback Loop

Synonyms: Resolution Block Feedback Loop

Peter Levine has theorized that one of the key reasons human beings do not process and release trauma within minutes like animals do is because we have developed a higher brain, the neocortex. The neocortex gives us great advantages such as the ability to think rationally, but it can also suppress the pent-up trauma related energies the system needs to process and release successfully in order to heal PTSD, such as rage and terror.

In the trauma seeking feedback loop, we may get into a situation where there is the possibility for the pent-up energy to completely release once and for all. We may suddenly feel powerful, primitive uncontrollable rage, hatred, sorrow, fear, or shame. But because of the controls we maintain, we do not recognize this as the opportunity it is. Rather, we think something is terribly wrong with us and force ourselves to push the emotions back down, and thus fail to release the pent-up energy. In other words, when the reptilian brain’s instinctive manner of releasing trauma begins, the neocortex or rational mind automatically suppresses it to escape and avoid the powerful emotions. When the experience is over, we have stabilized again but nothing has changed and the system continues to unconsciously seek a way to discharge the trapped life energy and return to a truly non-traumatized state of calm alertness. The system will unconsciously seek out another situation to stir up these powerful emotions, in the hopes that they will finally be processed to completion.

7. Survival Mode Feedback Loop

Synonyms: Problematic Memory Encoding Loop, Arrested in Time Loop, Siege Mode Loop

The seventh feedback loop is the state of being immersed in survival instincts, a perpetual state in relation to the reptilian brain managing an eternal moment of shock and trauma, without ever coming out. This is most likely due to the way traumatic memories are encoded. It creates a kind of life in siege mode, a severe experience of life, a survival focused life. Even if one’s survival needs are met one may feel like life is about surviving in basic ways and not about living/thriving (the higher level needs on Maslow’s hierarchy are not in the picture).

The experience of being in shock becomes a timeless moment, a never-ending moment, from which the body does not re-enter time. It is as if the reptilian brain is telling you you are still in shock and need to survive, dominating your experience and keeping you in survival mode forever. The experience cannot be metabolized, psychologically, by the system, and until it becomes metabolized it is holding you hostage. In order for it to be metabolized, the times of the worst dissociation (shock) need to be integrated in the body and brain/memory in a different way than they were at the time of the trauma. There are theories to the effect that the memory of the trauma needs to be moved from short-term to long-term memory.

So the theory about how this one works is that because going into these memories feels too threatening, the procedure seems complex, one lacks skills and also lacks skilled help, one never figures out how to integrate the moments of the worst dissociation, and so the person remains stuck in time and in survival mode. Sorry this one is not clearer, when I understand it better I will update this section.

One feedback loop I have not included in this article is Learned Helplessness. Learned Helplessness (Seligman) is a kind of feedback loop because if we are in a situation in which we are legitimately helpless, we learn that in those kinds of situations we are helpless. Then, when in a similar situation, we behave helplessly even if we truly have power to act. This reinforces our perception of our self and internal experience (felt sense) of being helpless. And so it continues. Learned helplessness is related to depression; I am not sure the relation to PTSD. In my case, because I was injured I have felt helpless in a lot of situations and I feel much more helpless than I did before. I would have to do more research to understand if this is learned helplessness as defined by Seligman or something else.

When I first found Somatic Experiencing and realized how much of healing PTSD is just about using somatic techniques to calm the nervous system and re-enter the body, I thought it would be a clear road out. I was wrong. I am still falling into these feedback loops on a regular basis, and I’m still trying to find ways to outsmart the downward spirals.There is a lot more work to be done, and my first step is to simply acknowledge that these feedback loops are still here and still need addressing.

__________________

Heidi Hanson is an artist and writer in Asheville, North Carolina currently working on an illustrated book chronicling her journey healing from Post Traumatic Stress Disorder.

The Endocannabinoid System as a Possible Target for Treating Post-Traumatic Stress Disorder

Around 15-35% of those who experience serious trauma are likely to develop post-traumatic stress disorder (PTSD), and among those who have experienced abuse, neglect, or other adversity in childhood, the number tends toward the high end. Of those who develop PTSD , more than a third will fail to recover even after many years of therapy and medications (Darves-Bornoz et al., 2008). These people demonstrate considerable impairments in their overall quality of life, including physical health and psycho-social functioning (Schelling et al., 1998).

Obviously, the current treatment approaches (SSRI antidepressants, cognitive-behavioral therapy, and exposure therapy) are not working for a significant number of people.

One of the innovations in recent years has been the use of beta-blockers (high blood pressure medication) to reduce anxiety, hypervigilance, flashbacks, and nightmares. The one I see most often is Prazosin, which seems to work, in part, by reducing adrenaline levels, thereby decreasing anxiety.

Prazosin is an alpha-adrenergic blocker originally used to treat hypertension. "The reason we think it works in the setting of nightmares is that prazosin crosses the blood–brain barrier, so it gets into the brain and kind of dampens the norepinephrine effects, which we think contribute to nightmares," Dr. King said.

In my experience, the side-effects of this medication are far less intrusive and long-lasting than those of the SSRI and SNRI medications. The benefits, even if it is only improved sleep can be considerable for those who are good responders.

In this new article from Frontiers in Behavioral Neuroscience, the authors propose that a potential target for treating the anxiety and hypervigilance symptoms, as well as many of the other symptoms (avoidance, arousal, and re-experiencing), is the endocannabinoid system. A quick Google Scholar search turned up a lot of research in this area, including these articles:

• Fraser, GA. (2009). The Use of a Synthetic Cannabinoid in the Management of Treatment-Resistant Nightmares in Posttraumatic Stress Disorder (PTSD). CNS Neuroscience & Therapeutics, 15; 84–88. doi: 10.1111/j.1755-5949.2008.00071.x

• Hill, MN and Gorzalka, BB. (2009). The Endocannabinoid System and the Treatment of Mood and Anxiety Disorders. CNS & Neurological Disorders - Drug Targets, 8, 451-458.  

• Viveros, MP, Marco, EM, Llorente, R, and Lopez-Gallardo, M. (2007). Endocannabinoid System and Synaptic Plasticity: Implications for Emotional Responses. Neural Plasticity, Article ID 52908, 12 pages. doi: 10.1155/2007/52908

My issue with this Frontiers article is that the authors don't even mention possible treatments for PTSD that do not involve a pill. While I have many clients who need medication, at least in the short term, in order to get benefit from therapy, I have many who do not need medications, or who have enough affect regulation to manage the difficult symptoms when they come up.

No matter how many cool drugs are developed, we should always try to treat people without drugs first and foremost. Even with the medications that seem to have few side effects, such as the concepts proposed below, there are ALWAYS side effects.

The endocannabinoid system regulates memory, appetite, energy balance/metabolism, stress response, immune functions, pain perception, body temperature, and even neurogenesis. There is no way we can manipulate this system for one outcome and not impact its functions in other areas of the body.

Full Citation: 

Trezza V and Campolongo P. (2013, Aug 9). The endocannabinoid system as a possible target to treat both the cognitive and emotional features of post-traumatic stress disorder (PTSD). Frontiers in Behavioral Neuroscience, 7:100. doi: 10.3389/fnbeh.2013.00100

The endocannabinoid system as a possible target to treat both the cognitive and emotional features of post-traumatic stress disorder (PTSD)

Viviana Trezza [1] and Patrizia Campolongo [2]

1. Department of Sciences, Section of Biomedical Sciences and Technologies, University “Roma Tre,” Rome, Italy
2. Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy

Abstract

Post-traumatic stress disorder (PTSD) is a psychiatric disorder of significant prevalence and morbidity, whose pathogenesis relies on paradoxical changes of emotional memory processing. An ideal treatment would be a drug able to block the pathological over-consolidation and continuous retrieval of the traumatic event, while enhancing its extinction and reducing the anxiety symptoms. While the latter benefit from antidepressant medications, no drug is available to control the cognitive symptomatology. Endocannabinoids regulate affective states and participate in memory consolidation, retrieval, and extinction. Clinical findings showing a relationship between Cannabis use and PTSD, as well as changes in endocannabinoid activity in PTSD patients, further suggest the existence of a link between endocannabinoids and maladaptive brain changes after trauma exposure. Along these lines, we suggest that endocannabinoid degradation inhibitors may be an ideal therapeutic approach to simultaneously treat the emotional and cognitive features of PTSD, avoiding the unwanted psychotropic effects of compounds directly binding cannabinoid receptors.

* * * * *

Post-traumatic stress disorder (PTSD) is a psychiatric disorder of significant prevalence and morbidity (Layton and Krikorian, 2002). In the overall population, more than two thirds of persons may experience a serious traumatic event at some point in lifetime (Javidi and Yadollahie, 2012). Although not everyone develops PTSD after experiencing a traumatic event, the lifetime prevalence of PTSD is high, being estimated as 8.2% in Europe and in the United States, up to 9.2% in Canada (Kessler et al., 1995; Darves-Bornoz et al., 2008; Van Ameringen et al., 2008). More than a third of PTSD patients fail to recover even after many years of treatment (Darves-Bornoz et al., 2008), showing a significant impairments in many aspects of health-related quality of life, including psychosocial functioning (Schelling et al., 1998).

Feeling afraid is a natural response to threats and triggers many physiological changes to prepare the body to defend against the danger or to avoid it. In PTSD, this reaction is changed or damaged. Even if anxiety is a common symptom of PTSD patients, the pathogenesis of the disorder relies on paradoxical changes of memory processing (Cohen et al., 2006;Parsons and Ressler, 2013). From a physiological point of view, memories characterized by a strong emotional salience tend to be well consolidated, they are often retrieved in our brain and therefore tend not to be extinct; from an evolutionary perspective, this is of crucial importance for survival. However, in PTSD patients, all or part of this processes may become maladaptive. Three symptom categories characterize the disorder: (1) persistent re-experience of the traumatic event; (2) persistent symptoms of increased arousal; and (3) persistent avoidance of stimuli associated with the trauma, which may include amnesia for important aspects of the traumatic event (Brewin, 2001). These symptoms reflect excessive retrieval of traumatic memories that are again consolidated, thus cementing the traumatic memory trace, and retaining its vividness and power to evoke distress for decades or even a lifetime (de Quervain et al., 2009). It appears from this symptomatology that three phases of memory processing may become maladaptive and of crucial importance in the development and maintenance of PTSD: consolidation, retrieval, and extinction.

PTSD is heterogeneous in its nature, and often associated with other psychiatric comorbidities; for these reasons, treating PTSD is rather difficult, and the disorder may persist over the patient's lifetime (Albucher and Liberzon, 2002). The therapeutic options to treat the anxiety symptoms of PTSD currently include serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOi), anticonvulsants, atypical antipsychotics and benzodiazepines (Albucher and Liberzon, 2002). Although SSRIs emerge as the preferred first line treatment to treat the anxiety symptoms of PTSD (Dow and Kline, 1997; Ipser et al., 2006), a large proportion of patients fails to respond to these medications (Ipser et al., 2006). Furthermore, no suitable treatment is currently available to treat the maladaptive cognitive features of PTSD and/or to prevent its development. This limitation is due to the scarce knowledge of PTSD neurobiology that hampers the identification of new pharmacological targets to treat this disorder. As Albucher and Liberzon (2002) pointed out, the diversity of the symptoms such as flashbacks, nightmares, hyperarousal, avoidance, numbing, anxiety, anger, impulsivity, or aggression suggests the involvement of multiple neurotransmitter systems (Goodman et al., 2012; Packard and Goodman, 2012).

An ideal pharmacological treatment for PTSD would be a drug able to block the pathological over consolidation and continuous retrieval of the traumatic event, while enhancing its extinction and reducing the anxiety symptoms. Although no such drug is currently available, recent clinical (Fraser, 2009; Hauer et al., 2013; Neumeister et al., 2013) and preclinical (Lutz, 2007; Akirav, 2011; Berardi et al., 2012; Ganon-Elazar and Akirav, 2012) studies point to the endocannabinoid system as a possible ideal therapeutic target to treat both the emotional and cognitive dysfunctions characterizing PTSD (Neumeister, 2013).

The central endocannabinoid system is a neuroactive lipid signaling system in the brain which shows functional activity since early stages of brain development; by controlling neurotransmitter release, it plays a relevant role in brain function during both pre- and post-natal life (Fernandez-Ruiz et al., 2000; Harkany et al., 2007; Trezza et al., 2008; Campolongo et al., 2009b, 2011). The endocannabinoid system consists of cannabinoid receptors (CB1 and CB2), their endogenous lipid ligands (endocannabinoids) and the enzymatic machinery for endocannabinoid synthesis and degradation (Piomelli, 2003; Di Marzo et al., 2005). Due to the wide expression of cannabinoid receptors throughout limbic regions of the brain, endocannabinoids control both emotional behavior and cognitive processes (Riedel and Davies, 2005; Campolongo et al., 2007, 2009a; Hill and Gorzalka, 2009; Atsak et al., 2012; Campolongo et al., 2012). Thus, while preclinical studies assessing the consequences of cannabinoid receptor blockade or activation on emotional responses have yielded sometimes controversial results, consensus exists that endocannabinoids have an essential role in maintaining emotional homeostasis (Haller et al., 2002,2004; Hill and Gorzalka, 2009; Moreira and Wotjak, 2010; Parolaro et al., 2010; Ruehle et al., 2012). Similarly, evidence exists that administration of cannabinoid drugs in animals influences memory consolidation, retrieval and extinction (Marsicano et al., 2002; Niyuhire et al., 2007; Marsicano and Lafenetre, 2009; Atsak et al., 2012; Campolongo et al., 2013). In particular, systemic administration of cannabinoid agonists impairs memory retrieval (Niyuhire et al., 2007) while facilitating memory extinction (Lutz, 2007). Direct evidence has been provided that endocannabinoids modulate emotional memory processing acting in the basolateral complex of the amygdala (BLA), in the hippocampus (de Oliveira Alvares et al., 2005, 2008; Campolongo et al., 2009a; Atsak et al., 2012) and in the prefrontal cortex (Egerton et al., 2006), key brain regions involved in memory consolidation, retrieval and extinction of emotionally arousing experiences (McGaugh, 2004; Quirk and Mueller, 2008;Roozendaal et al., 2008; Herry et al., 2010), and dysfunctional in PTSD patients (Bremner et al., 2008; Hughes and Shin, 2011).

Interestingly, emerging empirical work has indicated a link between traumatic event exposure and cannabis use. Data from the National Comorbidity Study demonstrated that adults suffering from PTSD were three times more likely to have cannabis dependence as compared with those without PTSD (Kessler et al., 1995). Studies involving military veterans have demonstrated an even higher rate of cannabis abuse among military veterans with PTSD (Stewart et al., 1998; Bonn-Miller et al., 2011). A positive association between PTSD and cannabis use among teenagers has also been reported (Cornelius et al., 2010). These results could be partially explained by recent data demonstrating that PTSD patients present important changes of plasma endocannabinoid levels and elevation in amygdala-hippocampal-cortico-striatal CB1 receptor availability (Hauer et al., 2013; Neumeister, 2013; Neumeister et al., 2013). The comorbidity between cannabis abuse and PTSD is always described in literature as a negative aspect, with the increase in substance abuse after a disaster as a cause for public long-term health consequences.

However, another side of the coin needs to be considered. It is possible that PTSD patients use cannabis as a self-medication. In support of this hypothesis, one study among Vietnam veterans indicated that cannabis use was helpful in managing PTSD symptoms, with particular respect to the hyperarousal state (Bremner et al., 1996). It has been shown that there is a correlation between post-traumatic stress symptom severity and motivation to use marijuana in order to cope with emotional distress (Bonn-Miller et al., 2007). Although the majority of the currently available clinical studies highlights the beneficial effects of cannabis use in PTSD patients, the positive association between cannabis use and relief from PTSD symptoms is not an universal finding. Thus, it has also been documented that, in certain conditions, cannabis abuse may facilitate PTSD development (Cougle et al., 2011). This may be due to the fact that direct activation of cannabinoid receptors by the active ingredient of cannabis, Delta-9-tetrahydrocannabinol, leads to a rapid down-regulation of the endocannabinoid signaling system (Hirvonen et al., 2012), resulting in tolerance. The complex scenario that emerges from the clinical setting makes it difficult to draw final conclusions about the relationship between cannabis use and PTSD.

Preclinical studies allow to control for the confounding variables that characterize the clinical observations, and therefore can provide essential information to elucidate the link between endocannabinoids and emotional memory processing, from physiological to pathological conditions. Thus, as highlighted above, it has been demonstrated that cannabinoid compounds strongly facilitate memory extinction in animals (Marsicano et al., 2002; Lutz, 2007), while impairing memory retrieval (Niyuhire et al., 2007; Atsak et al., 2012). It is thus tempting to speculate that cannabinoid compounds can attenuate the excessive retrieval of the traumatic event experienced by PTSD patients, while facilitating its extinction. Memory consolidation for emotionally salient events is also affected by cannabinoid drugs, although the results of the preclinical studies performed so far are controversial. Thus, it has been shown that post-training administration of cannabinoid receptor direct or indirect agonists facilitates memory consolidation in the inhibitory avoidance task (Campolongo et al., 2009a; Hauer et al., 2011).

These findings suggest that activation of cannabinoid receptors shortly after experiencing a stressful event could facilitate the development of maladaptive memories of this event. This, in turn, may provide preclinical rationale to the finding that the use of drugs indirectly enhancing endocannabinoid activity, such as propofol, or the use/abuse of cannabis, shortly after the experience of an aversive event, may facilitate PTSD development in humans and has to be avoided in the aftermath of an aversive experience (Cougle et al., 2011; Hemmings and Mackie, 2011;Usuki et al., 2012). However, cannabinoid agonists administered to rats shortly after exposure to a series of intense stressful events have been reported to prevent the impairment in avoidance extinction induced by the traumatic experience (Ganon-Elazar and Akirav, 2009, 2012, 2013). These findings leave open the possibility that cannabinoid drugs may be good candidates for secondary prevention of PTSD, that is, may be a good therapeutic option immediately after trauma exposure (Zohar et al., 2011).

It clearly appears from this scenario that, if from one side the data about the effects of cannabinoid drugs on memory retrieval and extinction are quite consistent and suggest that these compounds may facilitate PTSD recovery, on the other side the role of cannabinoids in memory consolidation is still debated. More research is therefore warranted to determine the extent to which differences in doses, routes of administration, timing of exposure and behavioral tasks used may be responsible for the opposite effects of cannabinoid agonists on memory consolidation reported so far. Conversely, encouraging clinical data exist on the use of cannabinoid compounds after the onset of the pathology (weeks or months after the experience of a traumatic event, when the memory consolidation of the traumatic event is completed) (Passie et al., 2012).

A recent clinical trial to evaluate the effects of nabilone, a cannabinoid receptor agonist, on treatment-resistant nightmares in PTSD patients demonstrated that the majority of patients (72%) receiving nabilone experienced either cessation of nightmares or a significant reduction in nightmare intensity (Fraser, 2009). Subjective improvement in sleep time, the quality of sleep, and the reduction of daytime flashbacks were also noted by some patients (Fraser, 2009). This is the first report of the use of nabilone for the management of treatment-resistant nightmares in PTSD. Although this evidence is encouraging, further studies on larger cohorts and with a more accurate identification of possible side effects of chronic use of direct cannabinoid agonists are warranted. The use of drugs that directly bind and activate brain cannabinoid receptors is indeed limited by their abuse potential (Tanda and Goldberg, 2003; Economidou et al., 2007;Ashton, 2012).

Two alternative pharmacological approaches exist to target cannabinoid receptors in the brain, without inducing abuse liability (Gobbi et al., 2005; Bortolato et al., 2006; Justinova et al., 2008). First, it has recently been reported that the non-psychotomimetic constituent of cannabis cannabidiol facilitates disruption of contextual fear memories (Stern et al., 2012) in rats while inducing anti-anxiogenic-like effects in rats and humans (Bitencourt et al., 2008; Bergamaschi et al., 2011). Alternatively, several preclinical studies have identified endocannabinoid deactivation inhibitors as a novel therapeutic approach for the treatment of neuropsychiatric disorders. In particular, indirect cannabinoid agonists have been proposed as anxiolitic and antidepressant agents (Kathuria et al., 2003; Bortolato et al., 2006; Piomelli et al., 2006; Vinod and Hungund, 2006) and have been reported to facilitate extinction of fear memory in rodents (Bitencourt et al., 2008; Pamplona et al., 2008). Thus, these compounds may prove effective to ameliorate the anxiety symptoms of PTSD and, at the same time, an increase in the endocannabinoid tone may be useful to treat the cognitive features (Varvel et al., 2007) of the pathology. These dual effects make these drugs gold candidates in the treatment and prevention of PTSD. Much attention, however, has to be dedicated to the time framing of pharmacological treatment, with an attempt to avoid the first early phases of memory consolidation.

It clearly appears that a deeper insight into the role of endocannabinoid neurotransmission in emotional memory processing, both in physiological and pathological conditions, will shed light in the neurobiological basis of PTSD; this, in turn, will open new frontiers for alternative and more efficacious therapeutic approaches for a complete resolution of the pathology.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References are available at the Frontiers site.