PTSD: Virtual Reality Therapy Part Two: Condemnation

[grace]

PTSD: Virtual Reality Therapy Part Two: Condemnation

Dr. Phil Leveque Salem-News.com

6 November 2008

http://www.salem-news.com/articles/novembe...que_11-6-08.php

 

Phillip Leveque has spent his life as a Combat Infantryman, Physician Pharmacologist and Toxicologist.

 

(MOLALLA, Ore.) - I previously in posted Part One that as a PTSD victim, observer in battle of this, and a physician taking care of over 400 PTSD Vet victims, that I felt that Virtual Reality Therapy (VRT) would not work for the most seriously affected PTSD Vet victims although it might for minimally or moderately affected victims.

 

As a physician taking care of these patients after they have given up and absolutely rejected VA treatment I have accepted what these VA "rejects" have told me. These Vets have told me of the excessive variety and amount of medications tried on them as human "guinea pigs" which usually made them worse from the adverse side effects. Even newspapers and TV news have indicated about one thousand Vet suicides per month from VA medical malpractice.

 

The concept that Virtual Reality Therapy for PTSD probably has some value for minimally affected victims but for severe "rubber room" victims it certainly has no place. These are the most needful patients. It appears that the success with minimally affected Vets has given the psychology therapists the psychological chutzpah to assume that VRT would work for the most seriously affected PTSD victims.

 

Whether these psychologists have been able to back and forth "talk" with extremely serious PTSD victims in the 7-8-9-10 category, I doubt it. They are so bad they can't even endure seeing the word PTSD.

 

I was astonished to see on my computer 43 pages of stories indicating the great promise of VRT (did they have good Public Relations personnel?). Ok, Ill accept that for the minimally affected Vets.

 

I also looked up Vets comments on VA pharmaceutical therapy which rarely had an even slightly warm comment. Some of the comments about the psychoneurotic wards in Walter Reed Hospital made me cringe in disbelief. The rest appear not much better.

 

I know from my own experience as a Combat Infantryman in World War II that alcoholic or nicotine use for temporary escapes from battle were what helped keep us going. I have known about cannabis/marijuana as similar medicine for about 60 years.

 

When my 400 or so Vietnam Vets told me that cannabis gave better relief than Army medications or beer or booze, I paid attention. Some will say to use Marinol which is pure THC and legal medicine. However it's not the same as the natural substance and produces a large amount of "panic attacks" and paranoia in the 10mg dose.. It is used orally and once it is absorbed, panic attacks can continue for several hours. Inhaled vapors (NOT SMOKE) can be easily adjusted to effective dosage.

 

Now, Nov 5, 2008, Michigan has become the 13th state approving/allowing medical cannabis/marijuana. We are approaching one million legal medical cannabis users. With the U.S. Govt saying some 70 million use it illegally (for medical purposes).

 

It is time for the U.S. Govt. employees to get over their REEFER MADNESS and regard cannabis/marijuana as the very useful/successful medicine that it is.

 

In the meantime millions of Vets and their families are suffering. PTSD is the worst sequel of battle and the VA is "supposed" to be taking care of us. WHAT A DISGRACE.

 

Part One in this series is available here: PTSD Virtual Reality Therapy: Fraudulent High-Priced Boondoggle: Part

[Smokin Moose]

PTSD is caused by trauma

 

PTSD occurs as a result of trauma. Not everyone develops PTSD, after experiencing a trauma. Researchers are still trying to work out why some people develop PTSD. Current thinking is that it is something to do with personality, type of trauma, support provided, genetics and previous exposure to trauma.

 

There is some controversy as to how many Australians live with Post Traumatic Stress Disorder. Generally studies suggest anywere between 3 - 6% of the Australian Population live with PTSD. That means that at least a quarter of a million Australians have this disorder. The various prevalence rates could be caused by under diagnosis of the condition, due to people denying they have the disorder and the difficult nature of recognising the disorder.

 

Screening for PTSD

 

There is a variety of ways to screen for PTSD. Below is a short screening scale for PTSD, defined by the fourth edition of the Diagnostic Screening Manual (DSM IV). This scale was created by Naomi Breslau and her research team in 1999, based on practical PTSD cases.

 

Answer yes or no to the following questions...

 

* Do you avoid reminders of an experience by staying away from places, people or activities?

* Have you lost interest in activities that were once important or enjoyable?

* Have you begun to feel more distant or isolated from other people?

* Do you find it hard to feel love or affection for other people?

* Have you begun to feel that there is no point in planning for the future?

* Have you had more trouble than usual falling or staying asleep?

* Do you become jumpy or easily startled by ordinary noise or movements?

 

If you answered yes to 4 or more of these questions, it is recommended that you talk to your GP about PTSD. This screening measure is not 100% accurate, so a GP is needed for diagnosis.

 

PTSD is best treated with cannabis. I am a sufferer of PTSD after being imprisoned in Sagmalicar Prison in Istanbul, Turkey. I have been using a tincture of cannabis to suppress my night terrors and nightmares, with profound success.

 

Here is the science to support this claim.

 

PTSD, Anxiety, Extinguishing Painful Memories and the Endogenous Cannabinoid System

 

by Ally (aka pflover)

“Preserve Neural Plasticity!”

 

Published in: Treating Yourself: The Alternative Medical Journal

 

“My wife is very grateful to have a 'friendly husband' as opposed to a grouchy, complaining, in-pain, morphine- and Prozac-affected husband. My wife will gladly testify at any hearing as to the effect of medical marijuana on my PTSD. If anyone dares to tell her that medical marijuana does not work for PTSD -- they'd better prepare to lose that argument! She lives with me -- she knows!”

 

- Rick Fabian, http://www.letfreedomgrow.com/articles/rick_fabian.htm

 

Post Traumatic Stress Disorder (PTSD) results from extreme attack on psychological wellbeing involving threat of loss of life or intense physical harm. Individuals stricken with this malady frequently find themselves reliving the memories of the trauma through “flashbacks” during waking hours and night terrors and nightmares when asleep, the latter two resulting in insomnia which further compromises psychological wellbeing. PTSD can completely undermine an individual’s attempts to operate as a functional member of society.

 

Who develops PTSD, you might ask? Historically, veterans have brought the most attention to this condition as is made evident by the older names “Shell Shock” and “battle/combat fatigue”. This is despite the fact that soldiers only compose one group suffering from this condition. As of yet, there are no known cut and dry rules about exactly who will or who won't develop PTSD. Depending on the severity, in 5%-80% of individuals, experiencing one of the following events will trigger onset of the disorder: violent military duty, car accidents, domestic abuse, surgery, sexual abuse/assault, child abuse, torture, terror tactics, severe natural disasters, etc (Wikipedia, 1). The following quote typifies the life of many PTSD suffers:

 

“I’ve been a deputy sheriff as well as a police chief and a private investigator, but the PTSD always made me crash and burn. I’ve lost everything several times, and for the last few years I have been rebuilding again. My doctors have told me to retire and try to maintain as normal a life as possible.”

 

- Michael McKenna, http://www.rxmarihuana.com/pstd.htm

 

In order to alleviate their symptoms and pursue a normal life style many suffers turn to cannabis with successful results. The relaxing, and anxiolitic (anti-anxiety) effects of cannabis under some conditions have been know for centuries but it is only recently that we have begun understand the complex way in which cannabinoids and the endocannabinoid (eCB) system modulate the expression of anxiety-type behavior.

 

There are three main factors that are important to the study and understanding of PTSD. These are aversive memory formation, if the aversive memory or fear is cue-induced vs contextual, and finally the extinction of the aversive memory or fear. In humans, aversive memory formation occurs during the traumatic event(s) that initiate PTSD. In animal models of PTSD, a mild but inescapable foot shock or repeated loud tones can form aversive memories in rodents. In humans, a vet easily startled by loud noises would be experiencing cue-induced fear where as an accident victim having a panic attack from the feeling of being in the driver's seat of a car has experienced contextual fear. For rodents in the lab, cue-induce fear is produced by the repeated pairing of a loud noise with a foot shock a second later. The cue-induce fear is expressed by the rodent when it is next exposed to the noise. Contextual fear in the lab is often elicited by the pairing of a series of loud tones with a unique environment. The contextual fear is expressed when the rodent is later placed in the same unique environment minus the tones. Extinction of the aversive memory for both lab animals and humans usually involves repeated exposure and habituation to the cue or context that elicits the fear minus the original fearful stimulus until fear is no longer elicited by that cue or context. For the accident victim this would be getting in the car, then the drivers seat and then actually driving. For the mouse who was shocked after hearing a loud noise it would be repeatedly hearing that noise without experiencing foot shock. There are other factors of PTSD in humans which are important to treatment but are not necessary for the study of PTSD in the lab.

 

Recent advancements in the understanding of the eCB system and how it helps modulate the formation of memory and responses to stress have provided researchers with an explanation of how cannabis can act as a successful treatment agent for PTSD. Fride, et al., 2005 found that mice lacking the cannabiniod-1 (CB1) receptor, the receptor responsible for the effect cannabis has on the central nervous system (CNS), were significantly more likely to experience behavioral inhibition after repeat cue-induced stress as compared to wild type mice not lacking the CB1 receptor. Behavioral inhibition is one animal model of PTSD. These findings gave support to the theory that the cannabinoid system could effect the formation of PTSD. Further evidence comes from the location of CB1 receptors in the brain. The brain regions responsible for controlling memory formation and emotion also contain large numbers of CB1 receptors, (Joy, et al., 1999). In 2003, Costanzi, et al., also found that anandamide, the endogenous ligand for the CB1 receptor, dose-dependently inhibited stressful memory formation. Chronic stress has been found to produce cognitive impairment which is attenuated by the administration of cannabinoids. The same chronic stress was also found to produce significant downregulation (reduction in density) of CB1 receptors and decreases in amount of anandamide found in the hippocampus. The hippocampus is involved with the formation of complex contextual memories. These findings led the researchers to suggest deficiencies in CB1 receptor densities and/or production of anandamide in the hippocampus were critically involved in the development of the behavioral inflexibility and a tendency to perseverate and ruminate that are part of the symptomological profile of such stress induced neurological disorders as PTSD, (Hill, et al., 2005).

 

In 2002, Marsicano, et al. concluded that the endocannabinoid system was also involved with the extinction of cue-induced adverse memories. They determined this action was achieved through inhibition of GABA (gamma-aminobutyric acid) by way of pre-synaptic modulation of GABA release in the amygdala via activation of CB1 receptors. They also found anandamide levels were elevated in the basolateral amygdala (BLA) during memory extinction tests. The BLA is a brain region known to be involved with extinction of cue-induced fear (Tomaz, Dickinson-Anson, & McGaugh, 1992). It was later confirmed that synaptic transmission of GABA was decreased in the BLA by activation of the CB1 receptor (Azad, et al., 2003).

 

Since Marsicano's study in 2002, the dependence of extinction of cue-induced fear responses on the eCB system has begun to gained general acceptance by the scientific community (Chhatwal, et al., 2005; Mikics, et al., 2006; Kamprath, et al., 2006; Pamplona, et al., 2006; Niyuhire, et al., 2007; Varvel, et al., 2007). At the same time a more complex and complete picture has started to appear. One emerging trend points to modulation of the eCB system as more effective at aiding in extinction than direct activation of the CB1 receptor via an exogenous cannabinoid like THC (Chhatwal, et al., 2005; Patel & Hillard, 2006; Varvel, et al., 2007). At best, facilitation of extinction by exogenous cannabinoids is dependent on species and breed of rodent and on the cannabinoid tested, in the studies that have been carried out so far (Pamplona, et al., 2006). In most cases though exogenous cannabinoids like THC and WIN55212-2 produce no detectable change in extinction rates of cue-induced fear at doses tested. Modulation of the eCB system via inhibition of fatty-acid amide hydrolase (FAAH) appears to be a very promising means of facilitating extinction of cue-induced fears. FAAH is the primary enzyme responsible for the metabolic breakdown of anandamide. Inhibiting FAAH increases intercellular levels of anandamide and thus enhances the ability of anandamide to activate the CB1 receptor. In this way inhibition of FAAH appears to reliably facilitate extinction (Chhatwal, et al., 2005; Patel & Hillard, 2006; Varvel, et al., 2007). One recent study even found that mice with either genetically or pharmacologically compromised FAAH not only exhibited faster extinction rates in a spatial memory task but also faster rates of acquisition/learning of the task in the first place (Varvel, et al., 2007). Chhatwal and colleagues, 2005, also found that upon subsequent foot-shock rats treated with a FAAH inhibitor were less likely to re-acquire fearful behaviors after extinction than were none-treated animals.

 

The situation is not so clear for contextual fears. With contextual fear it is the context/environment that induces the fear response. This is in contrast to cue-induced fear where the presentation of a stimulus such as a loud noise elicits the fear response. Two different brain structures are responsible for cue-induced and contextual fear, the amygdala and the hippocampus, respectively. Therefore it might be expected that cannabinoids would effect these two types of fear differently. Early findings suggest this is the case. In 2006, Mikics and colleagues exposed rats to short sessions of foot-shocks and 24 hours later tested their fear response to the environment in which the shocks had occurred. They found that when WIN55212-2 was administered prier to behavioral testing 24 hours after the rats received shock an increase in the expression of contextual fear was observed. A CB1 receptor antagonist blocked this effect and when administered alone reduced the intensity of contextual expressed by the rats. In other words cannabinoids made them more afraid, while blocking cannabinoids reduced fear. One implication of this finding is that exogenous cannabinoids like smoking cannabis could exacerbate the experience of preexisting contextual fears.

 

If only things were that simple. Later the same year, Pamplona and colleagues found that WIN55212-2 facilitated extinction of contextual fear in rats both immediately and 30 days after acquisition of contextual fear. Furthermore, the CB1 receptor antagonist rimonabant disrupted extinction both immediately and at the 30 day fear extinction sessions. It is clear the role of cannabinoids in contextual fear requires further elucidation before we can predict how cannabinoids will effect this more complex form of associative fear learning.

 

 

People suffering from PTSD often also experience affective disorders like major depression or bipolar disorder and generalized anxiety disorder. They also experience increased startle response, irritability, nightmares/terrors, and insomnia. One theory proposed by Hill and Gorzalka in 2005 suggested that the eCB system plays a major role in major depression. First they site the fact that both the genetic disruption and pharmacological blockade of the CB1 receptor resulted in a state analogous to major depression and generalized anxiety, two closely related disorders. Hill and Gorzalka also point out that the eCB system is down-regulated by chronic stress. There is also evidence that the eCB system is involved with the regulation of stress and general anxiety. In general, genetic CB1 receptor deficits or pharmacological blockade of CB1 receptors both produce anxiety and depression in rodents. Where as FAAH inhibition produces anxiolitic effects (Viveros, Marco, & File, 2005; Carrier, Patel, & Hillard, 2005). In a test of general anxiety in mice Patel and Hillard, 2006, found that the CB1 agonists WIN5212-2 and CP 55,940 (40 times more potent than THC) both produced an anxiolitic effect at the lowest dose tested. THC however was found to produce a dose-dependent anxiety-like response. One FAAH/anandamide-uptake inhibitor produced an anxiolitic effect at lower doses but had no effect at the highest dose tested while another pure FAAH inhibitor produced only a dose-dependent anxiolitic effect.

 

It has long been thought that the neurotransmitter serotonin plays a role in depression and anxiety. Braida et al., 2007 found that both THC and an anandamide uptake inhibitor were dose-dependently anxiolitic and that this was blocked by a serotonin 1A (5-HTA1) receptor antagonist. They also found that co-administration of a sub-threshold dose of a 5-HTA1 receptor agonist with a sub-threshold dose of either THC or the uptake inhibitor produced a synergistic anxiolitic effect together. This led them to conclude that serotonin played a modulatory role in the anxiolitic effect of both exogenous and endogenous cannabinoids.

 

Estrogen produces anxiolitic and anti-depressant effects. Estrogen has been shown to regulate FAAH. Hill, Karacabeyli and Gorzalka, 2007, found that estrogen induced anxiolitic properties were blocked but the administration of a CB1 receptor antagonist. Furthermore, FAAH inhibition produced much of the same anxiolitic effects as estrogen in the tasks tested. This led the researchers to conclude that FAAH inhibition might be a viable treatment option for depression and anxiety disorders in women. This is also important to PTSD since the lifetime prevalence of PTSD in women (10.4%) is a little more than twice as high as in men (5%) (Wikipedia, 1). Again, this provides further evidence that eCB modulation should be a pharmacological target of future anxiety treatments.

 

As stated above, issues with sleep also afflict PTSD suffers. In rats, anandamide changes sleep patterns by increasing slow-wave sleep and REM sleep at the expense of wakefulness (Murillo-Rodríguez, et al., 2001). Sleep deprivation also produces increases in slow-wave sleep and REM sleep once sleep does occur. This phenomenon is known as the rebound effect or sleep rebound. Navarro et al., 2003 found that administration of a cannabinoid antagonist before sleep rebound prevented the REM rebound and that sleep deprivation did not change CB1 receptor densities in rat brains. However sleep deprivation plus 2 hours sleep rebound increased CB1 receptor densities in rat brains. Therefore it appears that changes in the eCB system play a role in the rebound effect. Because THC and anandamide increase sleep in humans and other mammals, Murillo-Rodríguez, et al., 2003, investigated whether or not adenosine, a sleep-inducing nucleoside, might be involved in cannabinoid induced sleep. During the third hour after administration of anandamide, intracellular adenosine levels peaked in rat basal forebrains. Peak adenosine levels were accompanied by a significant increase in slow-wave sleep during the third hour after anandamide administration. Both the induction of sleep and the rise in adenosine levels were blocked by the administration of a CB1 receptor antagonist. Together, these findings led the researchers to suggest that the eCB system may be a pharmacological target of treatment for conditions that produce severe sleep disruption such as PTSD.

 

All these indications that the CB1 receptor and anandamide may play a role in stress and memory has led the Israeli military to start an investigation into treating PTSD in their soldiers with therapeutic cannabis. In 2004 at Jerusalem's Hebrew University, Raphael Mechoulam started studying the effects of orally administered delta9-THC, the active ingredient in cannabis, on 15 Israeli soldiers suffering from PTSD acquired during combat in the Gaza Strip. Although the study is still in progress, Mr Mechoulam stated that, as one might expect based the studies discussed above, cannabis “helps them sleep better, for one thing. These people often wake up from nightmares and experience sweating or hallucinations” (Heller, 2004).

 

Despite the anecdotal evidence to the contrary, most of the experimental studies that have been conducted so far indicate that by and large the administration of exogenous cannabinoids such as vaporizing therapeutic cannabis may not be the most reliable nor effective means of utilizing the eCB system to treat anxiety and aversive memories such as those formed in PTSD. For reliable and truly effective treatment of these conditions it appears that restricting eCB breakdown by way of FAAH inhibition is the best target discovered so far within the eCB system. (The other eCB targets include the two primary receptors CB1/CB2, vanilloid receptors, eCB reuptake, as well as eCB production.) To this end, Kadmus Pharmaceuticals, Inc. has started to express serious interest in marketing a new FAAH inhibitor they have developed, currently code-named KDS-4103. KDS-4103 appears to have a lot of potential from a pharmacological perspective. Even though it produces analgesic, anxiolitic, and anti-depressant effects it otherwise does not produce a classic cannabis-like effect profile and animals easily discriminate between THC and KDS-4103. All this indicates that KDS-4103 does not produce a “high” like THC and other direct CB1 agonists. KDS-4103 is orally active in mammals and fails to elicit a systemic toxicity even at repeated dosages of 1,500mg/kg body mass. All other available evidence to date also suggests a very high therapeutic margin for KDS-4103. All in all, considering that the kinds of events which usually precipitate PTSD in most individuals often also involve pain, KDS-4103 seems like it may be just about the perfect medication.

 

 

So what should all this mean to the individual? Anecdotal evidence says by and large the use of therapeutic cannabis provides a significant improvement in quality of life both for those suffering from this malady and for their family and friends. Whether or not this is taking the fullest advantage possible of the eCB system in the treatment of PTSD is yet to be seen. Mostly the use of cannabis and THC to treat PTSD in humans appears to provide symptomological relief at best. In and of itself, there is nothing wrong with symptomological relief. That's what taking aspirin for a headache, a diuretic for high blood pressure, opiates to control severe pain, or olanzapine for rapid-cycling mania is all about. We do have the potential, however, to do better than just treating symptoms of PTSD via activation of the cannabinoid receptors. With the right combination of extinction/habituation therapy and the judicious administration of a FAAH inhibitor like KDS-4103 we have the potential to actually cure many cases of PTSD. For the time being though, symptomological treatments are all we have for more generalized anxiety and depression disorders.

 

If an individual were to want to get the most out of using therapeutic cannabis to improve a PTSD condition they should try to use low to moderate doses with as stable a blood level as possible for general anxiety and depression symptoms. Oral cannabis produces more stable blood levels. Since peak levels will produce the most soporific effect, administration of oral cannabis right before bed should produce the most benefits for improving sleep patterns. If the goal is to use cannabis to facilitate extinction of the response to PTSD triggers than small to moderate doses of cannabis vapors should be administered shortly before planned exposure to the trigger. A series of regular extinction sessions will produce better results than a single session. If cannabis appears to make aversion, fear, or aversive memories worse then the dosage should be lowered. If feelings of fear do not improve with lower dose then discontinue use of cannabis as fear-extinction aide.

 

In light of all evidence currently available, it is striking that the FDA refuses to investigate cannabinoids for the treatment of anxiety disorders like PTSD yet they have approved studies of MDMA, the club drug Ecstasy, for the treatment of PTSD (Doblin, 2002). Even if you do not accept cannabis as the answer itself, it should be hard to accept that by and large we still have not found effective and reliable ways to utilize the eCB system in modern western medicine. After all, the most potent (meaning it takes the least amount to produce a threshold effect) substance know to humans is not LSD as many still assume but is instead a derivative of fentanyl, know as Carfentanil. The threshold dosages for LSD and Carfentanil are 20-30µg (micrograms) and 1µg, respectively (Wikipedia, 2 & 3). This makes Carfentanil 10,000 times more potent than morphine, 100 times more potent than fentanyl, and 20-30 times more potent than LSD. At least up until 2005 and unlike LSD, Carfentanil was(is?) regulated as a Schedule II substance in the US (Erowid). For those that do not know, this means that despite perceived extreme dangers from use or abuse of this drug it is still assumed to have medical value. With the lives and well being of so many veterans AND private citizens at stake, those in the scientific community and police makers alike cannot afford to miss the wake up call. Even a child should be able to see the hypocrisy evident in the relative policies concerning cannabinoids and opiates. It is time to fix this appalling imbalance in our policies concerning the pharmacopia or else be the laughing stock of future generations.

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Edited November 7, 2008 by smokin.moose