At 11 a.m. this morning, vets, lawyers and activists hope to present a petition to Ned Calonge, Colorado's chief medical officer, asking that post-traumatic stress disorder be added to a list of conditions that can be treated by medical marijuana.

The battle over PTSD and medical marijuana has been going on for months, notes Grimsinger's attorney, Sensible Colorado's Brian Vicente -- and he doesn't expect it to be easily won.

"What has happened in the past is, Dr. Calonge has out of hand rejected any petition that's come his way and not allowed a public hearing," Vicente says. "But we think at the very least this deserves a public hearing. We think the petition shows beyond a shadow of a doubt that certain individuals who have PTSD benefit from medical marijuana, and we hope the state will recognize that."

Also arguing on behalf of this action is Kevin Grimsinger, who's become the Colorado poster child for PTSD and medical marijuana. Grimsinger, an Army veteran who lost parts of both legs to an Afghanistan mine, is the face of the current fight. Earlier this week, he was profiled by Denver Post columnist Susan Greene, and he'll speak at today's rally, which will take place at the health department's offices, at 4300 Cherry Creek Drive South.

According to Vicente, Grimsinger represents plenty of fellow men and women in uniform who feel as he does but are reticent to take a public stand.

"We've been hearing from veterans for years who have been injured in the line of duty protecting our country and have PTSD related to that," he says. "And they're concerned about the lack of veteran access for medical marijuana for PTSD. Currently, veterans face criminal prosecution for possessing or using medical marijuana to alleviate any sort of medical condition, and we just think that's unconscionable. People who have served our country deserve the best access to health care possible, and we want to make sure Kevin and folks like him have that access."

These arguments were marshaled in March, when Boulder Representative Sal Pace presented an amendment to list PTSD among conditions that can be treated by medical marijuana. At the time, the health department actively fought against the amendment, with staffers passing out a document to legislators arguing against this change, which was eventually voted down.

This move chagrined the likes of Wanda James and Drew Milburn, both of whom are dispensary owners and veterans who say they've seen medical marijuana help those suffering from post-traumatic stress disorder. In addition, Sensible Colorado has spent weeks talking to vets about the PTSD issue and gathering data that's part of the petition.

The document "lays out the multitude of research that shows many people finding relief for PTSD symptoms by using medical marijuana," Vicente allows. "There are studies from abroad and studies from the U.S. that show this. And really, the state has a very low bar in that, as per the constitution, they must accept petitions to expand treatable conditions, and the petitioner only has to show that the individual 'might' benefit from the use of medical marijuana. The word 'might' is written in the constitution."

As such, Vicente goes on, petitioners don't have to incontrovertibly prove that medical marijuana is beneficial to everyone with post-traumatic stress disorder -- just that it might help them.

"We feel it's a fairly reasonable standard," he maintains, "and we want to make sure doctors have this possible treatment in their arsenal, and are able to advise patients to use it as necessary -- especially veterans, who are in a very difficult quandary. Most Veterans Administration doctors will not recommend medical marijuana, because it's federally a Schedule 1 controlled substance, which means it has no medical efficacy in the federal government's view."

Thanks to this designation, Vicente says, "we've heard from dozens of veterans that if they choose medical marijuana, and their VA doctor learns about it, they can be taken off all medicine. And we find that incredibly disturbing."

Calonge has not been receptive to such arguments in the past -- so what are the options for Grimsinger and Vicente if he rejects their call for public hearings on the PTSD issue?

"I think they're setting themselves up for a costly lawsuit," Vicente says. "And I also think it's poor public policy and disrespectful of our veterans."

Look below to get more details about this morning's event, as well as to look at a letter from Grimsinger to Calonge and the petition in its entirety:

Sensible Colorado release:

As highlighted in a Denver Post article, a rally will accompany the official submission of the PTSD petition on July 7 at 11am at the Colorado Health Department office. See more details below.

"The brave men and women who have served our country-- and been injured in the line of duty-- deserve access to all available health care treatment options," said Brian Vicente, Executive Director of Sensible Colorado. "Record numbers of veterans are returning from Iraq and Afghanistan with severe mental issues, making this a critical time to amend our state law to reflect emerging science about the role of marijuana in treating PTSD. Colorado should join neighboring states like New Mexico in allowing PTSD sufferers access to this beneficial drug."

Sensible Colorado is filing this petition on behalf of Denver resident Kevin Grimsinger, an Army Sergeant (ret) and veteran on Kosovo, Operation Desert Storm, and Afghanistan. Mr Grimsinger suffers from PTSD related to stepping on a landmine in Afghanistan. His PTSD causes insomnia, nightmares, suicidal thoughts, and depression which he believes may be relieved by marijuana. Under current Colorado law, those suffering from PTSD face criminal penalties for using medical marijuana to alleviate their symptoms.

SOUTH DENVER, CO -- On Wednesday, July 7, at the Colorado Health Department Office, Sensible Colorado, the state's leading medical marijuana advocacy non-profit, will join with veterans of the U.S. Armed Services in filing a petition to add Post Traumatic Stress Disorder (PTSD) to the list of conditions for which doctors can recommend medical marijuana under Colorado law.

Letter from Kevin Grimsinger to Ned Calonge:

For myself, for veterans, and for other fellow Coloradans who suffer daily from the debilitating nature of life with PTSD, I respectfully submit this petition to add PTSD to the list of debilitating conditions that qualify for the use of marijuana as part of a recommended treatment from a physician that may have a beneficial effect.

From personal experience and as stated in the petition with the support of scientific evidence, the use of marijuana to treat PTSD symptoms has been effective. I am not alone in this experience, researchers have estimated that veterans returning from our current wars in Afghanistan and Iraq have an 18.3% percent incidence rate for PTSD. In addition there are the millions of other people that the National Institute of Mental Health (NIMH) estimate to suffer with PTSD in the United States every year.

I look forward to further recovery physical recovery, but a serious concern I have is that once my physical pains are deemed to no longer be debilitating by my physicians, I will lose access to the medicine that makes life bearable dealing with my PTSD from that day in Kandahar. Someday I may be completely free from pain from my injuries but I will most likely never be free from the sleepless nights, constant memories, suicidal thoughts, and depression that plague those diagnosed with PTSD.

I submit this petition to you as a veteran who faces an uncertain future when it comes to my ability to access my medicine. My name is Kevin Grimsinger. I have served our country in Kosovo, Operation Desert Storm, and Afghanistan. In 2003, I stepped on a landmine in Kandahar, losing parts of both of my legs as well as sustaining severe injuries throughout my internal organs. I was in the hospital for two years before I was released, and to this day I still suffer from my injuries. The pain makes it difficult to eat, to sleep, and to function in my day-to-day life. I was recommended medical marijuana in 2005 and have been using marijuana along with a number of other prescriptions to fight the pain.

On behalf of the state of Colorado's sick, disabled, and dying veterans, please consider this an official petition to add Post Traumatic Stress Disorder (PTSD) to the list of conditions for which doctors may recommend to their patients the use of medical marijuana as treatment under the provisions of the Colorado Constitution, Article 18, Section 14. This petition is submitted in accordance with 5 CCR 1006-2, Regulation 6(D), which states that the Board of Health will consider "whether there is scientific evidence that treatment with marijuana may have a beneficial effect." [emphasis added] The following petition provides ample proof that the use of marijuana as treatment for PTSD is based on scientific evidence and should be added to the list of debilitating conditions kept by the department.

PTSD petition:

The Use of Medical Cannabis to Treat Post Traumatic Stress Disorder

I. Introduction

Currently, there are approximately 500 suicides a month in patients with Post Traumatic Stress Disorder (PTSD) and over three hundred thousand backlogged disability claims involving PTSD and depression. n1. Those suffering from PTSD also have a reduced quality of life, an increased number of hospitalizations, high frequency of depressions and alcohol drug abuse, and suffer in social, family, and work life. n2. For patients who are treated, many have poor responses to psychotherapy and pharmacological treatment and often turn to alcohol and drugs. n3.

Recent studies demonstrate the potential benefits of the use of cannabis for PTSD. These studies confirm that extinction of aversive memories and the adaptation to stress responses are in part, controlled by endocannabinoids. n4. There are two cannabinoid receptors in the brain, CB1 and CB2. These receptors are activated by: endocannabinoids, which are synthesized internally in the body, cannabinoids derived from the cannabis plant (such as THC), and synethic cannabinoids that are synthesized in a laboratory. This natural system works much like our natural GABA system. Just as we produce our own endocannabinoids, we produce our own internal GABA, and we use synthetic benzodaizapines that bind to the receptors. Likewise, we have cannabinoid receptors, and we should be using cannabis to modulate them. Cannabinoids can act as a therapeutic target for the treatment of diseases associated with the inappropriate retention of aversive memories, such as PTSD. n5 Furthermore, because of the effects of the cannabis on the stress response, it is likely that potential patients treated with cannabinoids may also benefit from the stress-reversing effects of the drug. n6

While the state of Colorado has acknowledged and approved the use of cannabis for many physical illnesses such as multiple sclerosis and chronic pain, it has failed to acknowledge the use of cannabis for psychological disorders such as PTSD, in which the medical benefits of cannabis are scientifically proven. This reflects unfounded discrimination on mental illness and psychological disorders. As Nancy Pelosi stated in a recent address on health care, "Illness of the brain must be treated just like illness anywhere else in the body." n7. Recently, the federal government has expressly acknowledged this in its passage of the Mental Health Parity and Equalization Act of 2008, mandating that health care providers provide equal treatment for mental disorders/substance abuse disorders as it does for any other physical illness. n8 The stereotype that psychological illnesses are any less debilitating or credible than physical illnesses is unacceptable and has no basis in science or reality. In both cases people are sick and need care; in both cases there are treatments that can relieve them of pain. When people receive the necessary treatment, people have the potential to get better and be productive and independent citizens. n9.

Hundreds of recent studies indicate that cannabis is an effective treatment for PTSD. Considering the high suicide rate associated with PTSD (50-100 suicides a month for veterans alone) n10, and that accepted psychotherapeutic and pharmacological treatments are often ineffective, n11, it is imperative that PTSD patients have access to another option that is effective, natural, safe, and can be regulated by a doctor. These are people, often veterans, whose chronic psychological trauma, depression, insomnia, and accompanying symptoms cannot be relived by conventional therapy or psychothearaputics and is worsened by alcohol. n12. In fact, since the U.S. sent more than 1.6 million men and women into combat in Iraq and Afghanistan in 2001, 18.3% of those returning have PTSD or major depression. n13. These patients have fought for our country and are now plagued with horrible memories. Their health and quality of life should be of top priority, and studies show and patients have testified that cannabis is an effective, alternative treatment. Cannabis can help relieve these patients of psychological trauma, it can stop horrible nightmares and stress related sleep disorders, and it can provide them with a better quality of life. n14

II. The Effectiveness of Cannabis as a treatment for PTSD.

a) The endocannabinoid system reverses enhancing effects of stress and helps with retention of aversive memories.

Over the past few years, remarkable advances have been made in our understanding of the endocannabinoid system and its molecular and physiological functions. n15. The potential therapeutic value of cannabinoid modulation is highlighted by the dense expression of the cannabinoid CB1 receptor in regions known to be significant for anxiety and emotional learning, particularly the basolateral amygdala (BLA). n16.

The endocannabinoid system has specific involvement in the habituation component of fear extinction and mediates habituation to repeated stress, suggesting that augmentation of endocannabinoid signaling is a good target for the treatment of affective disorders. n18, n19. The endocannabinoid system has a direct effect on the natural brain's function of dealing with information and can in fact aid the brain in discarding unneeded information. n20.

The functions of the endocannabinoid system are especially relevant to the treatment of conditions associated with retention of aversive memories and stress related disorders, such as PTSD. A recent study examining the cannabinoid receptor activation in the BLA found that it reverses the enhancing effects of environmental stress on inhibitory avoidance (IA) conditioning and its impairing effects on extinction. n21. The study tested rats, known for their love of dark places, who were given electric shots when entering the darkened region of their cage. Shortly thereafter, the rats became afraid of the dark area and began to remain in the brighter part of the cage. The researchers then stopped giving the electric shock treatment and the rats returned to the dark area. The length of time between the shocks stopping and the rats returning was measured. In the next phase of the study, a new group of rats were used. These rats were shocked as they entered the dark area of the cage and were placed on an elevated grid. (Most animals, including rats, avoid walking over elevated grids as they find the distressing). It took longer for this group of rats to trust the dark region again. The researchers then tested a third group of rats, who were treated in the same way as the second group, except in this group a synthetic THC-like compound was injected into a the BLA, the region of their brains associated with fear. This medical-marijuana receiving group of rats returned just as quickly to the dark spot in the cage as the rats in group one. n22.

The beneficial effects of cannabinoids in the BA are extremely significant. Specifically, the study found that: 1) cannabinoid receptor activation in the BA blocks the effects of stress on the conditioning and extinction of inhibitory avoidance (IA); 2); cannabinoid receptor stimulation in the BLA reduces stress-induced elevations in corticosterone levels (this is significant because most people with PTSD show a high secretion of cortisol), n23; and (3) the CB1 receptor has an extremely important role in the BLA in the extinction of avoidance behavior because the receptor antagonist impairs IA extinction. n24. These findings show that cannabinoid receptor activation can act to reverse the effects of stress on memory. These results support a wide therapeutic application for the cannabis cannabinoids in the treatment of conditions in which patients suffer from aversive memories and stress. PTSD patients should be entitled to a treatment that can have such a profound beneficial effect on relieving traumatic memories.

b) Cannabinoids are effective in cessation of nightmares and a reduction in nightmare intensity

The disruption of sleep is often one of the most debilitating parts of PTSD and patients are often unable to find relief through pharmaceutical treatment. n25. Particularly, nightmares and sleep disorders are frequent symptoms of PTSD, with some patients experiencing even more severe problems such as violent or injurious behaviors during sleep, sleep paralysis, and hypnagogic and hypnopompic hallucinations. n26, n27.

Recent studies have shown that cannabis is effective in cessation of nightmares and reduction of nightmare intensity. In a study evaluating the effects of an endocannabinoid receptor agonist on treatment-resistant nightmares in patients diagnosed with PTSD, patients who had continued nightmares despite treatment with conventional anti-depressants and hypnotics were reviewed after treatment with nabilone, an endocannabinoid receptor agonist. n28. A large majority (72%) of patients experienced either cessation of nightmares or a significant reduction in nightmare intensity. n29. Furthermore, patients noted improvement in sleep time, the quality of sleep, and the reduction of daytime flashbacks and night sweats. n30.

These findings are extremely significant because they not only illustrate the many benefits of cannabis on PTSD symptoms, but also that cannabis can be an effective option for patients who are unable to find relief with the currently accepted treatments. Dr. Tod Mikuriya, psychiatrist, author, and former marijuana research for the National Institute of Health, emphasized the importance of treating sleep deficits in those with PTSD when he explained, "PTSD often involves irritability and inability to concentrate, which is aggravated by sleep deficit. Cannabis use enhances the quality of sleep through modulation of emotional reactivity. It eases the triggered flashbacks and accompanying emotional reactions, including nightmares. The importance of restoring circadian rhythm of sleep cannot be overestimated in the management of PTSD." n31.

c) Cannabinoids promote neurogenesis and produce anxiolytic and antidepressant like effects.

The hippocampus is able to generate new neurons (neurogenesis) throughout the lifespan of mammals. n32. Studies teach us that newborn hippocampal neurons are functionally integrated into the existing circuitry and are positively correlated with learning and memory processes and the developmental mechanisms of stress and mood disorders. n33. Recent studies have shown that chronic treatment with synthetic cannabinoids produces antidepressant and anxiolyic effects. The anxiolytic effects are achieved by promoting hippocampal neurogenesis, which is in turn promoted by cannabinoids. n34. By finding that embryonic and adult rat hippocampal neural stem/progenitor cells are immunoreactive for CB1 cannabinoid receptors, studies demonstrate that cannabinoids can act on CB1 receptors to regulate neurogenesis. n35. This is further corroborated by findings that cannabinoids promote proliferation, but not differentiation, of embryonic hippocampal neural stem/progenitor cells via activation of CB1 receptors combined with G proteins and ERK signaling. n36.

The anti-depressant and anxiolytic effects of cannabis are important as anxiety and depression are frequent symptoms of PTSD and can be very debilitating. n37. It is well-founded that cannabis and its major psychoactive component, (-)-trans-Δ9-tetrahydrocannabinol, have profound effects on mood and can modulate anxiety and mood states. n38. Thus, stimulating the endogenous cannabinoid system with natural cannabinoids could be a major therapeutic target for the treatment of anxiety-related and mood disorders. n39. In a study that looked at treating anxiety with cannabinoids, blocking the CB1 receptor resulted in the rats having more fear, demonstrating that modulation may be useful treatment for blocking fear, as seen in the blockade mice. n40. These results indicate that the endocannabinoid system can be modulated to enhance emotional learning and that endocannabinoid modulators may be therapeutically useful for exposure based psychotherapies such as those used to treat PTSD and other anxiety disorders. n41.

Based on its efficacy alone, cannabis should be considered an acceptable treatment for PTSD. As Dr. Mikuriya said "Cannabis relieves pain, enables sleep, normalizes gastrointestinal function and restores peristalsis. Fortified by improved digestion and adequate rest, the patient can resist being overwhelmed by triggering stimuli. There is no other psychotherapeutic drug with these synergistic and complementary effects." n42. Dr. Mikuriya also emphasizes that cannabis can relieve many other symptoms of PTSD such as physical pain, fatigue, and sleep deficit. Furthermore, restorative exercise and diet are requisite components of PTSD treatment and depression treatment, and cannabis, unlike some analgesics, sedatives, and benzodiazepines, does not leave the patient too immobile to exercise. n43.

III. PTSD and substance abuse

Many PTSD patients have poor responses to psychotherapy and often turn to alcohol and drugs. n44. Moreover, many suffer from chronic pain and become addicted to opiate pain medications. n45. Due to continuous problems such as depression, anxiety, secondary alcoholism, and substance abuse that PSTD patients suffer from and the numerous poor responses to pharmacological and psychological treatments, alternative treatments such as cannabis are imperative.

While many studies, and the Colorado Department of Health, cite cannabis use as substance abuse in PTSD patients, they ignore the positive effects of cannabis on the brain and the reality that patients may not be abusing cannabis, but using it as an alternative, effective treatment. Abuse can occur with any drug, including medically prescribed Oxycontin or Vicodin as well as an over the counter drug like Tylenol. But the possibility that these drugs can be abused does not make them illegal. The possibility that some people might abuse cannabis should not make it illegal, when, like these other drugs, it is scientifically proven to effectively treat a condition. In fact, "it is generally appreciated that the use of cannabinoids is related to their positive modulatory effects on brain-rewarding processes along with their ability to positively influence emotional states and remove stress responses." n46.

The differing effects of cannabis and other drugs of abuse on the brain highlight the difference between using a drug as an effective treatment versus substance abuse. Chronic administration of the major drugs of abuse including opiates, alcohol, nicotine, and cocaine has been reported to suppress hippocampal neurogenesis in rats. n47. Unlike these major drugs that inhibit neurogenesis, studies demonstrate that cannibas promotes hippocampal neurogenesis. n48. This suggests a role of hippocampal neurogenesis in the initiation, maintenance, and treatment of drug addiction.

The specific effect of the cannabinoid system on the fear response is significant and suggests the potential for long-term relief. n49. Current acceptable treatments such as behavior therapy, on the other hand, are ineffective for many. While behavior therapy for human anxiety disorders is often effective, extinction-like treatments require repeated cue exposures and are vulnerable to reversal by a number of environmental factors, particularly stress. n50. Thus, cannabis has the potential to be an effective alternative to often-ineffective behavior therapy and extinction treatment. n51.

The ineffectiveness of currently acceptable treatments leads to substance abuse. Patients unable to find relief seek it elsewhere, with substances that are not regulated or monitored by a physician. Moreover, psychiatrist-advised use of medical marijuana can actually help PTSD patients reduce their alcohol intake. Marijuana addiction potential is a fraction of that of alcohol (3% vs. 10%). n52. Dr. Christopher Ficthner, section chief for PTSD at Hines V.A. Hospital in Illinois, explained that the use of medical cannabis can reduce the physical and psychological harm for those who self-medicate with alcohol. n53.

IV. New Mexico: Taking the lead in treating PTSD with cannabis.

New Mexico has taken the lead in explicitly allowing people with PTSD to have access to marijuana under its medical marijuana law. PTSD accounts for more patients than any other of the state's 16 eligible debilitating conditions approved for medical marijuana treatment. n54. After a review of the evidence of the effectiveness of marijuana in treating PTSD, health professionals in New Mexico agreed that medical marijuana could be beneficial for patients with PTSD. On the other hand, health officials in Colorado are denying veterans and other patients suffering from PTSD a legitimate, safe, treatment alternative.

The chief medical officer of the Colorado health department said, "There is no evidence of efficacy of marijuana for treatment of PTSD in the medical literature." n50. This statement is outright false, inconsistent with evidence-based medicine and demonstrates ignorance of the hundreds of medical studies on the efficacy of marijuana for PTSD treatment. To deny the enormous body of medical literature is outrageous and offensive to the suffering PTSD patients who are now the victims of the health department's ignorance. Dr. Eve Elting, a New Mexico physician, emphasized the offensiveness of the Colorado Health Department when she said, "It's bad enough they have something that makes life so challenging. On top of that they're discriminated against, made to feel like they're doing something wrong." n55.

New Mexico is not alone in recognizing cannabis as an effective treatment for PTSD. In Canada, the government pays for medical marijuana for their veterans, acknowledging that for many, its is more effective than available alternatives, with fewer side effects. n56. In Israel, the Ministry of Health is currently granting licenses for people who have PTSD to use medical marijuana. n57

Even Croatia acknowledges cannabis as a treatment for PTSD. In 2009, Croatia's Supreme Court threw out a jail sentence given to a veteran who used marijuana for his PTSD. n58. This ruling is extremely significant considering Croatia's "zero tolerance" drug policy. In its ruling, the court noted that "the defendant suffers from PTSD, and marijuana relaxes him and helps him to overcome psychological problems." n59.

V. Conclusion

To deny those with PTSD suffering from psychological trauma and terrifying flashbacks access to a natural herb that is scientifically proven to provide them with relief is simply outrageous. By allowing PTSD to be treated with medical marijuana, physicians can help patients treat their condition with cannabis and assist the patient in using cannabis in a manner that is safe and most effective for the particular patient. Physicians can be re-assured that there is an ample body of medical literature that supports the beneficial use of cannabinoids. Studies teach us that we have our own cannabinoid receptors in our internal cannabinoids, and these should be modulated as they are proven to reverse effects of stress and help with retention of aversive memories, promote neurogenesis, and can reduce nightmares, fear, anxiety, mood disorders and other PTSD symptoms. The importance of the endocannabinoid system and the large body of medical literature supporting the beneficial use of cannabis should be acknowledged. Without the acceptance of cannabis to treat PTSD, patients who cannot find relief with pharmaceuticals and psychotherapy are forced to turn to the streets to have access to cannabis. They are denied the very important role of the doctor in helping them treat their condition. These patients will often turn to substance abuse and many turn to suicide.

We are sending millions of our citizens to Iraq and Afghanistan, and many are coming back afflicted with PTSD and other psychological trauma. n60. We should give them all of the tools available to regain their health. The enormous volume of scientific research and data proves that the use of medical marijuana for PTSD is safe and effective. To deny patients access to a treatment whose efficacy is well founded with scientific evidence is callous and discriminatory at best.

Footnotes

n1 Fred Gardner, Marijuana As a Treatment for PTSD. CounterPunch (US Web). 26 May 2008. http://www.mapinc.org/drugnews/v08.n532.a02.html

n2 Hovhannisyan LP, Mkrtchyan GM, Sukiasian SH, Boyajyan AS.. Alterations in the complement cascade in post-traumatic stress disorder. Allergy Asthma Clin Immunol. 2010 Feb 21;6(1):3.

n3. Leeies M, Pagura J, Sareen J, Bolton JM . The use of alcohol and drugs to self-medicate symptoms of posttraumatic stress disorder. Depress Anxiety. 2010 Feb 23.

n4. Eti Ganon-Elazar, and Irit Akirav, Cannabinoid Receptor Activation in the Basolateral Amygdala Blocks the Effects of Stress on the Conditioning and Extinction of Inhibitory Avoidance J. Neurosci. 29: 11078-11088; doi:10.1523/JNEUROSCI.1223-09.2009

n5. Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, Hermann H, Tang J, Hofmann C, Zieglgänsberger W, et al. The endogenous cannabinoid system controls extinction of aversive memories. Nature 2002; 418 : 530-534; see also Motluk, A. Natural High Helps Banish Bad Memories. New Scientist. Nature 418: 530. 31 July 2002;

n6. Haller J, Bakos N, Szirmay M, Ledent C, Freund TF (2002) The effects of genetic and pharmacological blockade of the CB1 cannabinoid receptor on anxiety. Eur J Neurosci 16:1395-1398.; Haller J, Varga B, Ledent C, Freund TF (2004) CB1 cannabinoid receptors mediate anxiolytic effects: convergent genetic and pharmacological evidence with CB1-specific agents. Behav Pharmacol 15:299-304; Onaivi ES, Green MR, Martin BR (1990) Pharmacological characterization of cannabinoids in the elevated plus maze. J Pharmacol Exp Ther 253:1002-1009; Patel S, Hillard CJ. Pharmacological evaluation of cannabinoid receptor ligands in a mouse model of anxiety: further evidence for an anxiolytic role for endogenous cannabinoid signaling. J Pharmacol Exp Ther. 2006;318:304-311; Fabre LF, McLendon D. The efficacy and safety of nabilone (a synthetic cannabinoid) in the treatment of anxiety. J Clin Pharmacol 1981; 21 :377S-382S; Hill MN, Karacabeyli ES, Gorzalka BB 2007. Estrogen recruits the endocannabinoid system to modulate emotionality. Psychoneuroendocrinology 32:350-357.

n7. Nancy Pelosi, Speaker, U.S. H.R., Address at the Families USA Conference: Pelosi Remarks at Families USA Conference. (24 Jan. 2008)

n8. H.R. 1424, 110th Cong. § 512(A) (2008) (enacted)

n9. One Step Closer to Mental Health Parity. 9 Nev. L.J. 646, 662. (2009).

n10. Dr. Phillip Leveque; PTSD Suicides: The Army Can't Explain? Salem-News. 12 Feb. 2009, http://www.salem-news.com/articles/february122009/doc_ptsd_suicides_2-12-09.php

n11. Rodriguez BF, Weisberg RB, Pagano ME, Machan JT, Culpepper L, Keller MB. Mental health treatment received by primary care patients with posttraumatic stress disorder. J Clin Psychiatry. Oct 2003;64(10):1230-6

n12 Tod Mikuriya, MD. Cannabis Eases Post Traumatic Stress; O'Shaughnessy's. Spring 2006. (Tod Mikuriya, MD monitored cannabis use by more than 8500 patients, approximately 8% with PTSD)

n13. supra note 9 at 726

n14. Fraser GA, The use of a synthetic cannabinoid in the management of treatment-resistant nightmares in posttraumatic stress disorder (PTSD); CNS Neurosci Ther. 2009 Winter;15(1):84-8.http://www.ncbi.nlm.nih.gov/pubmed/19228182); see also

n15. Ligresti A, Petrosino S, Di Marzo V. From endocannabinoid profiling to endocannabinoid therapeutics. Current Opinion in Chemical Biology. June 2009; see also Bartolucci G. Nabilone and posttraumatic stress disorder in a user of therapeutic marijuana. Four Zero One Pharma , August 2004.

n16. Freund TF, Katona I, Piomelli D 2003. Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 83:1017-1066.; see also supra note 4.

n17. Id.

n18. Barna I, Zelena D, Arszovszki AC, Ledent C 2004. The role of endogenous cannabinoids in the hypothalamo-pituitary-adrenal axis regulation: in vivo and in vitro studies in CB1 receptor knockout mice. Life Sci 75:2959-2970.; Cannich A, Wotjak CT, Kamprath K, Herman H, Lutz B, Marsicano G 2004. CB1 cannabinoid receptors modulate kinase and phosphatase activity during extinction of conditioned fear in mice. Learn Mem 11:625-632.; Castane A, Maldonado R, Valverde O 2004. Role of different brain structures in the behavioural expression of WIN 55 212-2 withdrawal in mice. Br J Pharmacol 142:1309-1317.; Cota D, Marsicano G, Tschop M, Grubler Y, Flachskamm C, Schubert M, et al. 2003. The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J Clin Invest 112:423-431.; Cota D, Steiner MA, Marsicano G, Cervino C, Herman JP, Grubler Y, et al. 2007. Requirement of cannabinoid receptor type 1 for the basal modulation of hypothalamic-pituitary-adrenal axis function. Endocrinology 148:1574-1581.

n19. Patel S, Roelke CT, Rademacher DJ, Cullinan WE, Hillard CJ 2004. Endocannabinoid signaling negatively modulates stress-induced activation of the hypothalamic-pituitary-adrenal axis. Endocrinology 145: 5431-5438; see also; Ligresti A, Cascio MG, Di Marzo V 2005. Endocannabinoid metabolic pathways and enzymes. Curr Drug Targets CNS Neurol Disord 4:615-623.

n20. Fride, E., and Mechoulam, R. 2003. New advances in the identification and physiological roles of the components of the endogenous cannabinoid system. In Molecular biology of drug addiction. R. Maldonado, editor. Humana Press. Totowa, New Jersey, USA. 173-179; see also; Hampson RE, Deadwyler SA 1998. Role of cannabinoid receptors in memory storage. Neurobiol Dis 5:474-482; Hill MN, Froc DJ, Fox CJ, Gorzalka BB, Christie BR 2004. Prolonged cannabinoid treatment results in spatial working memory deficits and impaired long-term potentiation in the CA1 region of the hippocampus in vivo. Eur J Neurosci 20:859-863.

n21. see supra note 4.

n22. Id.

n23. Mason JW, Giller EL, Kosten TR, Harkness L (1988). Elevation of urinary norepinephrine/cortisol ratio in posttraumatic stress disorder. J Nerv Ment Dis. 176 (8): 498-502. See also: Rodríguez de Fonseca F, Carrera MR, Navarro M, Koob GF, Weiss F (1997) Activation of corticotropin-releasing factor in the limbic system during cannabinoid withdrawal. Science 276:2050-2054; Devane WA, Dysarz FA III, Johnson MR, Melvin LS, Howlett AC. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 1988; 34 :605-613; Drew WG, Slagel DE 1973. Delta 9-THC: selective impairment of corticosterone uptake by limbic structures of the rat. Neuropharmacology 12:909-914.

n24. see supra note 4.

n25. Id.

n26. Diagnostic and statistical manual of mental disorders, DSM-IV-TR . Washington, DC: American Psychiatric Association, 2000.

n27. Ohayon M, Shapiro C. Sleep disturbances and psychiatric disorders associated with posttraumatic stress disorder in the general population. Compr Psychiatry 2000; 41 :469-478; see also Krakow B, Schrader R, Tandberg D, Hollifield M, Koss MP, Yau CL, Cheng DT. Nightmare frequency in sexual assault survivors with PTSD. J Anxiety Disord 2002; 16 :175-190

n28. see supra note 14

n29. Id.

n30. Id.

n31. . Post traumatic stress disorder and Veterans for Medical Marijuana Access. Santa Cruz County Drug Policy Examiner. 1 July 2009. http://www.examiner.com/x-14883-Santa-Cruz-County-Drug-Policy-Examiner~y2009m7d1-Post-traumatic-stress-disorder-and-Veterans-for-Medical-Marijuana-Access

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n52. The Associated Press. VA doctors prohibited from prescribing medical pot. 1 Apr. 2010. http://hamptonroads.com/2010/03/va-doctors-prohibited-prescribing-medical-pot

n53. Christopher Glenn Fichtner, M.D. Cannabinomics: The Marijuana Policy Tipping Point (Well Mind Books, 2010).

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n55. Dan Frosch. States Differ on Marijuana for PTSD. The New York Times. 24 Mar 2010. http://www.nytimes.com/2010/03/25/us/25pot.html

n56. The Canadian Press. Canada to Pay for Military Veterans Medical Marijuana. 15 May 2009. http://www.cannabisculture.com/v2/content/canada-pay-military-veterans-medical-marijuana

n57. Marijuana/PTSD Protocol Drafted; MAPS Tries Again to Overcome PHS/NIDA Obstacles. 21 May 2010. http://www.maps.org/mmj/mmjfacility.html>

n58. Europe: Croatia Supreme Court Throws Out Jail Sentence in Veteran's Use of Medical Marijuana for PTSD. The Drug War Chronicle. 19 Jun. 2009. http://stopthedrugwar.org/chronicle/590/croatia_supreme_court_medical_marijuana_PTSD

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