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

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WHAT IS POST TRAUMATIC STRESS DISORDER (PTSD)?

A mental health problem that some people develop after experiencing a life-threatening 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

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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 chemotherapy-induced 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

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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%

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.

0.66%

0.93%

1.05%

0.27%

0.49%

0.58%

0.39%

0.44%0.47%

0.00%

0.20%

0.40%

0.60%

0.80%

1.00%

1.20%

2002 2008 2009

CUD-Overall

Cannabis-Disorder

Cannabis-Mixed

VHA TRENDS IN SUD DIAGNOSES AMONG VETERANS WITH PTSD

VA PERC, 2015

• 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 amygdala-hippocampal-frontal cortex circuitry loop (all areas dense with CB1 receptors)

• Fear memory extinction delayed in CB1 knockouts or in presence of CB1 antagonists

• Acute administration of THC, synthetic CB1 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

CANNABINOIDS AND FEAR MEMORY EXTINCTION

CB1 RECEPTORS: ELEVATED IN PTSD PATIENTS VS. TRAUMA EXPOSED AND HEALTHY CONTROLS

Neumeister et al., 2013

PTSD n=25

TE n=12

HC n=23

PTSD: lower

peripheral

anandamide levels

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)

• 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

• Reliving the event (dissociative reactions)

• Avoiding reminders of the event

• Feeling on edge (marked alterations in arousal and reactivity)

DSM-5 CANNABIS INTOXICATIONCOMPARED TO PTSD

Cannabis Intoxication 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

DSM-5 CANNABIS WITHDRAWALCOMPARED TO PTSD

• Cannabis Withdrawal • PTSD

POSSIBLE CYCLE BETWEEN PTSD AND CANNABIS USE

Sleep and physiologic

disturbance, irritability

cannabis use reduces

symptoms

Symptom relief encourages

more frequent use

Tolerance, withdrawal

Patient conflates PTSD

and cannabis withdrawal

VA-DOD CLINICAL PRACTICE GUIDELINE FOR PTSD

DATE DOCUMENT TYPE/STATUS 18

Meta-

analyses

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

EVIDENCE HIERARCHY

GRADE SYSTEM

Four Domains to Assess Strength of Recommendation

Balance of desirable and undesirable outcomes

Confidence in the quality of the evidence

Values and preferences Other implications, e.g.:Resource UseEquityAcceptabilityFeasibilitySubgroup 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.

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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 2017 Update

Several states have passed voter initiative declaring marijuana as “medicine”

29 states have passed medical marijuana laws; 8 states and DC have legalizedrecreational use.1

AMA and most major health organizations oppose marijuana legalization

AMA remains opposed to state marijuana laws, advocates for Schedule II status to support research.

Smoked marijuana is not an FDA-approved medicine and has not passed standards of safety and efficacy

No change

The IOM concluded that smoked marijuana should generally not be recommended for medical use

National Academies (2017) report did not address delivery method. Calls for better quality research on health effects.1

The future of marijuana as medicine lies in development of its individual components delivered in a safe, uninhaled manner

No change

DATE DOCUMENT TYPE/STATUS 23

NADCP STATEMENT- MARIJUANA AS MEDICINE

Selected premises 2017 update

Non-smoked cannabinoid preparations have been developed (Sativex®, Marinol®, Nabilone)

Cannabidiol is in clinical trials for epilepsy1

The vast majority of medical recommendations are not based on medical necessity, an accurate or complete diagnosis, or consideration of appropriate alternatives

FSMB Statement on Medical Board Expectations for PhysiciansRecommending Marijuana (2016)2

Few of those seeking medical marijuana have cancer, HIV/AIDS, glaucoma or multiple sclerosis

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:

Benefit

DATE 26

• Chronic pain

• Chemotherapy-induced nausea & vomiting

• Spasticity due to multiple sclerosis

• Fair evidence-single small trial of nabilone

for PTSD

• 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

TREATMENT FOR CANNABIS USE DISORDER AND PTSD

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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?

CPT/PE/EM

DR

53 2042 9SSRIs 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.

SIT

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

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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)

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(866) 948-7880

PTSDconsult@va.gov

www.ptsd.va.gov/consult

Questions

37

SUPPLEMENTAL SLIDES

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