Marijuana for PTSD Among Veterans? Karen Drexler, MD National Mental Health Program Director-Substance Use Disorders Veterans Health Administration
DISCLOSURES Employed by the Department of Veteran Affairs No financial conflicts of interest July 11, 2017 Drexler-Marijuana as Medicine- NADCP & J4Vets 2
OVERVIEW What is PTSD? What is Marijuana and Cannabis Use Disorder? How might marijuana relieve PTSD symptoms? How might marijuana make PTSD symptoms worse? Summary of known health risks and benefits for PTSD Treatment options for PTSD and CUD July 11, 2017 Drexler-Marijuana as Medicine- NADCP & J4Vets 3
WHAT IS POST TRAUMATIC STRESS DISORDER (PTSD)? A mental health problem that some people develop after experiencing a lifethreatening event. 4 types of PTSD symptoms: Reliving the event Avoiding things that remind you of the event Having more negative thoughts and feelings that before Feeling on edge https://www.ptsd.va.gov/public/understanding_ptsd/booklet.pdf July 11, 2017 Drexler-Marijuana as Medicine- NADCP & J4Vets 4
WHAT IS MARIJUANA? Raw plant product with >100 cannabinoids Delta-9-Tetrahydrocannabinol (THC) Primary intoxicant- FDA approved (dronabinol) to reverse weight loss in AIDS and for chemotherapyinduced nausea- 2.5 mg to 20 mg daily 1960s- concentration ~1.5% 3% (average 10 mg) 2000s- concentration ~15% (average 160 mg) Cannabidiol (CBD) Possible therapeutic benefit; undergoing clinical trials 1995- concentration 0.28% 2014- concentration <0.15% Others July 11, 2017 Drexler-Marijuana as Medicine- NADCP & J4Vets 5
DSM-5 CLASSIFICATION CANNABIS USE DISORDER At least two of the following symptoms within a 12 month period (Mild is used to indicate 2-3 symptoms, moderate indicates 4-5 symptoms, and severe indicates 6 or more symptoms): Taking more cannabis than was intended Difficulty controlling or cutting down cannabis use Spending a lot of time on cannabis use Craving cannabis Problems at work, school and home as a result of cannabis use Continuing to use cannabis despite social or relationship problems Giving up or reducing other activities in favor of cannabis Taking cannabis in high risk situations Continuing to use cannabis despite physical or psychological problems Tolerance to cannabis Withdrawal when discontinuing cannabis.
EPIDEMIOLOGY: CANNABIS USE DISORDER & MENTAL ILLNESS AMONG VETERANS Any psychiatric: 71.41% Depression: 23.21% GAD: 2.96% Panic: 1.86% Social Phobia: 0.43% OCD: 0.56% PTSD: 29.05% Schizophrenia: 6.68% 1.20% 1.00% 0.80% 0.60% 0.40% 0.20% 0.66% 0.39% 0.27% 0.93% 0.49% 0.44% 1.05% 0.58% 0.47% CUD-Overall Cannabis-Disorder Cannabis-Mixed 0.00% 2002 2008 2009 Bonn-Miller, M. O., Harris, A. H. S., & Trafton, J. A. (2012). Prevalence of cannabis use disorder diagnoses among veterans in 2002, 2008, and 2009. Psychological Services, 9, 404-416.
VA PERC, 2015 VHA TRENDS IN SUD DIAGNOSES AMONG VETERANS WITH PTSD
CANNABINOIDS AND FEAR MEMORY EXTINCTION Classical conditioning paradigm Aversive stimulus paired with neutral stimulus Subject then has anxiety/fear-like reaction to neutral stimulus alone Anxiety/fear extinguishes over time as neutral stimulus presented alone Appears to involve amygdalahippocampal-frontal cortex circuitry loop (all areas dense with CB 1 receptors) Fear memory extinction delayed in CB 1 knockouts or in presence of CB 1 antagonists Acute administration of THC, synthetic CB 1 agonists, or drugs that increase endocannabinoid activity enhances fear memory extinction Chronic administration of cannabinoids may interfere with this effect Single dose oral THC 7.5 mg compared to placebo enhanced fear extinction in a single human study of non-psychiatrically ill individuals
CB1 RECEPTORS: ELEVATED IN PTSD PATIENTS VS. TRAUMA EXPOSED AND HEALTHY CONTROLS PTSD n=25 TE n=12 HC n=23 PTSD: lower peripheral anandamide levels Neumeister et al., 2013
IMPACT OF CANNABIS USE AND PTSD ON TREATMENT OUTCOMES Veterans with PTSD using cannabis demonstrate: Increased cravings Greater withdrawal More problems related to cannabis use CUD diagnosis associated with worse treatment outcomes in Veterans receiving residential PTSD treatment N = 260 male combat-exposed Veterans (Boden et al., 2013; Bon-Miller et al., 2013; Bonn-Miller et al., 2011)
CANNABIS AND ANXIETY Cannabis can have anxiolytic and anxiogenic effects depending on: Proportions and concentration of cannabinoids Dose and quantity consumed Frequency of use History of use Environment/context of use Gender Genetic vulnerability Anxiety disorder/symptoms Longer term studies seem to indicate: Initial benefits may dissipate May ultimately result in worsening of symptoms (Crippa et al., 2009; Tambaro & Bortolato, 2012)
CANNABIS AND SLEEP THC and CBD may have either sedating or arousing effect THC may decrease slow wave sleep and increase stage 2 Among individuals (N=170) at a medical MJ dispensary n=75 (44.1%) had PTSD Checklist (PCL) > 30 More likely to use cannabis for sleep and coping than were individuals with PCL 30 (Bonn-Miller et al., 2014) Individuals (N=20) using cannabis on average 4X daily Ad lib cannabis use periods separated by abstinence periods Crossed over from placebo to zolpidem during abstinence Polysomnography conducted (See next slide) (Vandrey et al., 2011)
EFFECTS OF CANNABIS WITHDRAWAL ON SLEEP (VANDREY ET AL., 2011)
DSM-5 CANNABIS INTOXICATION COMPARED TO PTSD Cannabis Intoxication Behavioral or Psychological Changes impaired coordination euphoria anxiety slowed time sense impaired judgment social withdrawal Two or more of following: conjunctival injection increased appetite dry mouth tachycardia Specify if with Perceptual Disturbances hallucinations auditory, visual, or tactile illusions PTSD Reliving the event (dissociative reactions) Avoiding reminders of the event Feeling on edge (marked alterations in arousal and reactivity)
DSM-5 CANNABIS WITHDRAWAL COMPARED TO PTSD Cannabis Withdrawal PTSD Irritability, anger, aggression Nervousness or anxiety Sleep difficulty (insomnia, disturbing dreams) Decreased appetite or weight loss Restlessness Depressed mood At least one physical symptom: abdominal pain shakiness/tremors sweating fever chills headache Reliving the event (recurrent distressing dreams) Feeling on Edge: Irritable behavior/angry outbursts Intense psychological distress Sleep disturbance Marked physiological arousal Having more negative feelings than before
POSSIBLE CYCLE BETWEEN PTSD AND CANNABIS USE Patient conflates PTSD and cannabis withdrawal Sleep and physiologic disturbance, irritability Tolerance, withdrawal cannabis use reduces symptoms Symptom relief encourages more frequent use
VA-DOD CLINICAL PRACTICE GUIDELINE FOR PTSD DATE DOCUMENT TYPE/STATUS 18
EVIDENCE HIERARCHY Metaanalyses of RCTs Randomized Controlled Trials Observational Studies Non Analytical Studies Expert Opinion Recommendations are explicitly linked to the supporting evidence and graded according to the strength of that evidence
GRADE SYSTEM Four Domains to Assess Strength of Recommendation Balance of desirable and undesirable outcomes Values and preferences Confidence in the quality of the evidence Other implications, e.g.: Resource Use Equity Acceptability Feasibility Subgroup considerations Andrews J, et al: Grade guidelines The significance and presentation of recommendations. J Clin Epidemiol. Jul 2013;66(7):719-725.
VA- DOD CLINICAL PRACTICE GUIDELINE FOR PTSD We recommend against treating PTSD with cannabis or cannabis derivatives due to the lack of evidence for their efficacy, known adverse effects, and associated risks. July 11, 2017 Drexler-Marijuana as Medicine- NADCP & J4Vets 21
MARIJUANA AS MEDICINE? Differences between marijuana plant and medicine: THC (not the marijuana plant) received FDA approval dronabinol (Marinol ) Legitimate medicine has well-defined and measurable ingredients consistent from one dose to the next Marijuana plant contains hundreds of chemical compounds that vary from plant to plant Most people are not using the specific cannabinoid that may have shown positive effects (e.g., CBD)
NADCP STATEMENT- MARIJUANA AS MEDICINE Selected Premises Several states have passed voter initiative declaring marijuana as medicine AMA and most major health organizations oppose marijuana legalization Smoked marijuana is not an FDAapproved medicine and has not passed standards of safety and efficacy The IOM concluded that smoked marijuana should generally not be recommended for medical use The future of marijuana as medicine lies in development of its individual components delivered in a safe, uninhaled manner 2017 Update 29 states have passed medical marijuana laws; 8 states and DC have legalized recreational use. 1 AMA remains opposed to state marijuana laws, advocates for Schedule II status to support research. No change National Academies (2017) report did not address delivery method. Calls for better quality research on health effects. 1 No change DATE DOCUMENT TYPE/STATUS 23
NADCP STATEMENT- MARIJUANA AS MEDICINE Selected premises Non-smoked cannabinoid preparations have been developed (Sativex, Marinol, Nabilone) The vast majority of medical recommendations are not based on medical necessity, an accurate or complete diagnosis, or consideration of appropriate alternatives Few of those seeking medical marijuana have cancer, HIV/AIDS, glaucoma or multiple sclerosis 2017 update Cannabidiol is in clinical trials for epilepsy 1 FSMB Statement on Medical Board Expectations for Physicians Recommending Marijuana (2016) 2 State approved indications have expanded to include seizures, pain, PTSD, ALS, chorea, sickle cell disease, and others DATE DOCUMENT TYPE/STATUS 24
BE IT RESOLVED THAT NADCP. Opposes legalization of raw or smoked marijuana Opposes efforts to approve any medicine, including marijuana, outside the FDA process. Supports continued research into medically safe, non-smoked delivery of marijuana components for medical purposes Supports reasonable prohibitions in Drug Courts against the use of smoked or raw marijuana by participants and the imposition of suitable consequences, consistent with evidence-based practices, for positive drug tests or other evidence of illicit marijuana consumptions Recommends Drug Courts require convincing and demonstrable evidence of medical necessity presented by a competent physician with expertise in addiction psychiatry or addiction medicine before permitting the use of smoked or raw marijuana by participants for ostensibly medicinal purposes Supports a balanced policy approach to marijuana-related offenses, which does not emphasize either legalization of marijuana or incarceration for marijuana use, but rather offers an evidence-based combination of treatment and behavioral interventions to achieve long-term recovery from marijuana abuse and addiction. DATE DOCUMENT TYPE/STATUS 25
NASEM 2017 REPORT- SUBSTANTIAL EVIDENCE OF Harm: Respiratory symptoms and bronchitis (long term smoking) Increased risk of motor vehicle crashes Schizophrenia & psychosis (dose response) Cannabis use disorder- risk increases with lower age of first use, dose and duration. Low birth weight in infants Limited evidence of worsening anxiety and PTSD Benefit Chronic pain Chemotherapy-induced nausea & vomiting Spasticity due to multiple sclerosis Fair evidence-single small trial of nabilone for PTSD DATE 26
TREATMENT FOR CANNABIS USE DISORDER AND PTSD July 11, 2017 Drexler-Marijuana as Medicine- NADCP & J4Vets 27
TREATMENT OF CANNABIS USE DISORDER 4 Primary options Pharmacotherapy (insufficient evidence to date) Motivational Enhancement (brief & helps ambivalence) Cognitive-Behavioral Therapy (breaks down thoughts and behaviors that lead to use) Contingency Management (monetary reinforcement of abstinence) These are often used in combination (e.g., Motivational Enhancement & Cognitive- Behavioral Therapy)
CONCURRENT TREATMENT OF PTSD & SUBSTANCE USE DISORDERS USING PROLONGED EXPOSURE COPE- combines two evidence-based treatments for patients with SUD & PTSD 12 weeks of concurrent prolonged exposure treatment for PTSD combined with CBT for SUD (alcohol and drugs) Brief, individual sessions can be applied to any type of traumatic event Appropriate for men & women, veterans & others Positive results for both alcohol and drug use disorders, and among childhood and adult traumas.
www.ptsd.va.gov/apps/decisionaid
FOR EVERY 100 PEOPLE WHO RECEIVE THE TREATMENT, HOW MANY WILL NO LONGER HAVE PTSD AFTER 3 MONTHS? 53 20 CPT/PE/EM DR SSRIs SIT 42 9 No Treatment Harik, J. M., Hamblen, J. L., Grubbs, K. G., & Schnurr, P. P. Will it work for me? A meta-analysis of loss of PTSD diagnosis after evidence-based treatment. Manuscript in preparation.
CONCLUSIONS Cannabis use is common among Veterans with PTSD VA and DoD Guideline for PTSD strongly recommends against cannabis to treat PTSD symptoms Effective treatments are available for PTSD, for cannabis use disorder and for treating both simultaneously 34
ACKNOWLEDGEMENTS NADCP Department of Veteran Affairs: National Center for PTSD (Sonya Norman, PhD, Nancy Bernardy, PhD, Paula Schnurr, PhD, Todd McKee, PhD, and Juliet Harik, PhD) Seattle CESATE (Andy Saxon, MD & Kendall Brown, PhD) Philadelphia CESATE (Marcel Bonn-Miller, PhD) Program Evaluation and Resource Center (Jodie Trafton PhD) July 11, 2017 Drexler-Marijuana as Medicine- NADCP & J4Vets 35
PTSDconsult@va.gov (866) 948-7880 www.ptsd.va.gov/consult
Questions 37
SUPPLEMENTAL SLIDES July 11, 2017 Drexler-Marijuana as Medicine- NADCP & J4Vets 38