RIPAC: Medical Marijuana in Rhode Island

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Rhode Island Patient Advocacy Coalition

Post-Traumatic Stress Disorder (PTSD)

**NOTE: The RI Medical Marijuana Program does not currently list PTSD as a debilitating medical condition for which medical practitioners may recommend medical marijuana to patients.**
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Post-Traumatic Stress Disorder (PTSD) is an anxiety disorder that affects people who have been through traumatic events. Symptoms can include re-experiencing the trauma (intrusive memories, flashbacks, and nightmares), avoidance of reminders of the trauma, feeling numb or detached, and hyperarousal (hypervigilance, exaggerated startle, sleep disturbance, irritability/anger discontrol, distractability). For thousands of years, humans have used cannabis for its physical effects, but also for its mental effects, including relaxation and relief of depression and anxiety. Humans are born with a natural system of neuroreceptors called the endocannabinoid system. The endocannabinoid system has many functions in the body, some of which are known, including the regulation of pain, appetite, and mood. The cannabis plant contains 70+ active chemical compounds called cannabinoids, with multiple receptor effects. When these cannabinoids are taken into the human body, cannabis effects the body by binding with the endocannabinoid receptors. In 1999, the Institute of Medicine at the National Academy of Sciences published Marijuana and Medicine: Assessing the Science Base, which concludes in part, "The psychological effects of cannabinoids, such as anxiety reduction, sedation, and euphoria can influence their potential therapeutic value."

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The Use of a Synthetic Cannabinoid in the Management of TreatmentResistant Nightmares in Posttraumatic Stress Disorder (PTSD). CNS Neurosci Ther. 2009 Winter;15(1):84-8. Fraser GA. This is the report of an open label clinical trial to evaluate the effects of nabilone, an endocannabinoid receptor agonist, on treatment-resistant nightmares in patients diagnosed with posttraumatic stress disorder (PTSD). Methods: Charts of 47 patients diagnosed with PTSD and having continuing nightmares in spite of conventional antidepressants and hypnotics were reviewed after adjunctive treatment with nabilone was initiated. These patients had been referred to a psychiatric specialist outpatient clinic between 2004 and 2006. The majority of patients (72%) receiving nabilone experienced either cessation of nightmares or a significant reduction in nightmare intensity. Subjective improvement in sleep time, the quality of sleep, and the reduction of daytime flashbacks and nightsweats were also noted by some patients. The results of this study indicate the potential benefits of nabilone, a synthetic cannabinoid, in patients with PTSD experiencing

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poor control of nightmares with standard pharmacotherapy. This is the first report of the use of nabilone (Cesamet; Valeant Canada, Ltd., Montreal, Canada) for the management of treatment-resistant nightmares in PTSD. (Nabilone is a relatively weak compound; the authors note that the whole cannabis plant would likely have a more potent effect.) Distinct effects of 9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch Gen Psychiatry. 2009 Jan;66(1):95-105. Fusar-Poli P, et al. CONTEXT: Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown. OBJECTIVE: To investigate the effects of 2 main psychoactive constituents of Cannabis sativa (Delta9-tetrahydrocannabinol [Delta9-THC] and cannabidiol [CBD]) on regional brain function during emotional processing. DESIGN: Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10 mg of Delta9-THC, 600 mg of CBD, or a placebo in a double-blind, randomized, placebocontrolled design. PARTICIPANTS: Fifteen healthy, English-native, right-handed men who had used cannabis 15 times or less in their life. MAIN OUTCOME MEASURES: Regional brain activation (blood oxygenation level-dependent response), electrodermal activity (skin conductance response [SCR]), and objective and subjective ratings of anxiety. RESULTS: Delta9Tetrahydrocannabinol increased anxiety, as well as levels of intoxication, sedation, and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD. The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of Delta9-THC but decreased following administration of CBD. Cannabidiol attenuated the blood oxygenation level-dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations. Delta9Tetrahydrocannabinol mainly modulated activation in frontal and parietal areas. CONCLUSIONS: Delta9-Tetrahydrocannabinol and CBD had clearly distinct effects on the neural, electrodermal, and symptomatic response to fearful faces. The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of Delta9-THC may be related to effects in other brain regions. Modulation of fear and anxiety by the endogenous cannabinoid system. CNS spectrums, 3/2007, 211-220. Chhatwal JP, Ressler KJ. The last decade has witnessed remarkable progress in the understanding of the mammalian cannabinoid system, from the cloning of the endogenous cannabinoid receptor to the discovery of new pharmacologic compounds acting on this receptor. Current and planned studies in humans include compounds with effects ranging from direct antagonists to inhibitors of reuptake and breakdown. This progress has been accompanied by a much greater understanding of the role of the cannabinoid system in modulating the neural circuitry that mediates anxiety and fear responses. This review focuses on the neural circuitry and pharmacology of the cannabinoid system as it relates to the acquisition, expression, and extinction of conditioned fear as a model of human anxiety. Preclinical studies suggest that these may provide important emerging targets for new treatments of anxiety disorders. Prescription For A Joint. Maariv, HaMagazin, January 2009. Dan Even. In the nation of Israel, 26 patients receive marijuana for the treatment of PTSD.

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The endogenous cannabinoid system controls extinction of aversive memories. Nature 418, 530-534 (1 August 2002). Marsicano G, et al. Acquisition and storage of aversive memories is one of the basic principles of central nervous systems throughout the animal kingdom1. In the absence of reinforcement, the resulting behavioural response will gradually diminish to be finally extinct. Despite the importance of extinction2, its cellular mechanisms are largely unknown. The cannabinoid receptor 1 (CB1)3 and endocannabinoids4 are present in memory-related brain areas5, 6 and modulate memory7, 8. Here we show that the endogenous cannabinoid system has a central function in extinction of aversive memories. CB1-deficient mice showed strongly impaired short-term and long-term extinction in auditory fear-conditioning tests, with unaffected memory acquisition and consolidation. Treatment of wild-type mice with the CB1 antagonist SR141716A mimicked the phenotype of CB1-deficient mice, revealing that CB1 is required at the moment of memory extinction. Consistently, tone presentation during extinction trials resulted in elevated levels of endocannabinoids in the basolateral amygdala complex, a region known to control extinction of aversive memories9. In the basolateral amygdala, endocannabinoids and CB1 were crucially involved in long-term depression of GABA (gammaaminobutyric acid)-mediated inhibitory currents. We propose that endocannabinoids facilitate extinction of aversive memories through their selective inhibitory effects on local inhibitory networks in the amygdala. Cannabis Eases Post-Traumatic Stress. Dr. Tod Mikuriya, O'Shaughnessy's, Spring 2006. Cannabis as a treatment for PTSD provides effective control and relief of chronic stressors. Its side-effect profile seems especially benign when contrasted with those of the prevailing mainstream treatments. PTSD and Cannabis: A Clinician Ponders Mechanisms of Action. Dr. David Bearman, O'Shaughnessy's, Spring 2006. Ample anecdotal evidence suggests that cannabis enhances ability to cope with PTSD. Many combat veterans suffering from PTSD rely on cannabis to control their anger, nightmares and even violent rage. Recent research sheds light on how cannabis may work in this regard.
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