Substance Abuse and Veterans Supporting Veterans and Service Members: A Mental Health and Community Imperative June 28 th, 2013 Jonathan C Fellers, MD

Substance Abuse and Veterans

Supporting Veterans and Service Members: A Mental Health and Community Imperative

June 28th, 2013Jonathan C Fellers, MD

Addiction Psychiatry FellowPortland VA Medical Center & OHSU

Outline

• Definitions• Neurobiology of Reward• Epidemiology• Common Culprits– Alcohol– Cannabis– Opioids

Addiction

• A behavioral pattern of drug use, characterized by:– overwhelming involvement with the use of a drug

(compulsive use)– the securing of the supply– a high tendency to relapse after withdrawal.

Substance Abuse

Substance abuse is defined as a maladaptive pattern of substance use leading to clinically significant impairment or distress as manifested by one (or more) of the following, occurring within a 12-month period: 1. Recurrent substance use resulting in a failure to fulfill major role obligations at work,

school, or home (such as repeated absences or poor work performance related to substance use; substance-related absences, suspensions, or expulsions from school; or neglect of children or household).

2. Recurrent substance use in situations in which it is physically hazardous (such as driving an automobile or operating a machine when impaired by substance use)

3. Recurrent substance-related legal problems (such as arrests for substance related disorderly conduct)

4. Continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance (for example, arguments with spouse about consequences of intoxication and physical fights).

Note: The symptoms for abuse have never met the criteria for dependence for this class of substance. According to the DSM-IV, a person can be abusing a substance or dependent on a substance but not both at the same time.

Substance DependenceSubstance dependence is defined as a maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring any time in the same 12-month period: 1. Tolerance, as defined by either of the following:

a. A need for markedly increased amounts of the substance to achieve intoxication or the desired effect

b. Markedly diminished effect with continued use of the same amount of the substance.2. Withdrawal, as manifested by either of the following:

a. The characteristic withdrawal syndrome for the substanceb. The same (or closely related) substance is taken to relieve or avoid withdrawal

symptoms.3. The substance is often taken in larger amounts or over a longer period than intended.4. There is a persistent desire or unsuccessful efforts to cut down or control substance use.5. A great deal of time is spent in activities necessary to obtain the substance, use the

substance, or recover from its effects.6. Important social, occupational, or recreational activities are given up or reduced because of

substance use.7. The substance use is continued despite knowledge of having a persistent physical or

psychological problem that is likely to have been caused or exacerbated by the substance (for example, current cocaine use despite recognition of cocaine-induced depression or continued drinking despite recognition that an ulcer was made worse by alcohol consumption).

Substance Use DisorderA maladaptive pattern of substance use leading to clinically significant impairment or distress as manifested by two (or more) of the following, occurring within a 12-month period: 1. Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or

home 2. Recurrent substance use in situations in which it is physically hazardous 3. Continued substance use despite having persistent or recurrent social or interpersonal problems

caused or exacerbated by the effects of the substance 4. Tolerance, as defined by either of the following:

a. A need for markedly increased amounts of the substance to achieve intoxication or the desired effect

b. Markedly diminished effect with continued use of the same amount of the substance.5. Withdrawal, as manifested by either of the following:

a. The characteristic withdrawal syndrome for the substanceb. The same (or closely related) substance is taken to relieve or avoid withdrawal symptoms.

6. The substance is often taken in larger amounts or over a longer period than intended.7. There is a persistent desire or unsuccessful efforts to cut down or control substance use.8. A great deal of time is spent in activities necessary to obtain the substance, use the substance, or

recover from its effects.9. Important social, occupational, or recreational activities are given up or reduced because of

substance use.10. The substance use is continued despite knowledge of having a persistent physical or psychological

problem that is likely to have been caused or exacerbated by the substance.11. Craving or a strong desire or urge to use a specific substance.

Brain Stimulation

• In 1953, Olds and Mills discovered that electrodes in certain areas of rat brain served as operant reinforcers:

• Olds, J. & Milner, P. (1954). Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. Journal of Comparative and Physiological Psychology, 47, 419–427.

Nucleus accumbens

Ventral tegmental area

Medial forebrain bundle

Brain Stimulation

• In 1963, Heath demonstrated in humans that stimulation is pleasure producing

• “During these sessions, B-19 stimulated himself to a point that he was experiencing an almost overwhelming euphoria and elation, and had to be disconnected, despite his vigorous protests"

• Moan, C.E., & Heath, R. G. (1972). Septal stimulation for the initiation of heterosexual behavior in a homosexual male. Journal of Behavior Therapy and Experimental Psychiatry, 3, 23–30.

Intracranial Stimulation

Nucleus accumbens



Reward Circuitry

• Activation of these brain areas associated with novelty, rather than pleasure– Increases the “salience” of objects– Increases the motivation to approach a gratifying

object• Dopamine is the main neurotransmitter• “The final common pathway of reinforcement

and reward in the brain is hypothesized to be the mesolimbic dopamine pathway”

Mesocorticolimbic Pathways


Frontal lobe

Amygdala & hippocampus


Nucleus accumbens

Epidemiology

• Substance Abuse and Mental Health Services Administration, Office of Applied Studies. (November 1, 2007). The NSDUH Report: Serious Psychological Distress and Substance Use Disorder among Veterans. Rockville, MD.

84.4%

7.0%

7.1%

1.5%Prevalence of Substance Abuse and Mental Illness in Veterans

None

Serious Psychological Distress

Substance Use Disorder

Dual Diagnosis

Epidemiology

Serious Psychological Distress Substance Use Disorder Dual Diagnosis0%

2%

4%

6%

8%

10%

12%

14%

16%Sex Prevalence of Substance Abuse and Mental Illness in Veterans

Male

Female


Epidemiology

Aged 18 to 25 Aged 26-54 Aged 55 or Over0%

5%

10%

15%

20%

25%

30%

Age Prevalence of Substance Abuse and Mental Illness in Veterans

Serious Psychological Distress

Substance Use Disorder

Dual Diagnosis


Epidemiology

18-25 26-35 36-45 46-64 All Ages0%

5%

10%

15%

20%

25%

30%

Standardized Comparisons of Civilians and All Services, Heavy Alcohol Use by Age Group, 2008

MilitaryCivilian

Age Group

Perc

enta

ge

• Bray RM, Pemberton MR, Lane ML, Hourani LL, Mattiko MJ, Babeu LA. (2010). Substance use and mental health trends among US military active duty personnel: key findings from the 2008 DoD health behavior survey. Mil Med. 175:6, 390.

Epidemiology

• Bonn-Miller MO, Harris AHS, Trafton JA. (2012). Prevalence of cannabis use disorder diagnoses among veterans in 2002, 2008, and 2009. Psych Svs, 9(4): 404.

2002 20090.0%

0.2%

0.4%

0.6%

0.8%

1.0%

1.2%

Prevalence of Cannabis Use Disorders Among Veterans 2002-2009

Any CUDOnly CUD

Perc

enta

ge

Epidemiology

• Bray RM, Pemberton MR, Lane ML, Hourani LL, Mattiko MJ, Babeu LA. (2010). Substance use and mental health trends among US military active duty personnel: key findings from the 2008 DoD health behavior survey. Mil Med. 175:6, 390.

2001 2002 2003 2004 2005 2006 2007 2008 20090%

2%

4%

6%

8%

10%

12%

Misuse of Prescription Drugs by Military Personnel

Prescription

Illicit

Year

Perc

enta

ge

Epidemiology

Alcohol Heroin Other Opiates Cannabis Methamphetamine Cocaine/Crack0%

10%

20%

30%

40%

50%

60%

50.7%

9.0%12.2% 12.2%

6.2% 6.3%

34.4%

16.8%

12.0%

17.6%

7.6% 7.2%

Primary Substance of Abuse in Treatment Admissions Aged 21 to 39, by Veteran Status: 2010

Veterans

Non-veterans

• Substance Abuse and Mental Health Services Administration (SAMHSA) Treatment Episode Data Set (TEDS), 2010, based on data received through October 10, 2011.

Alcohol

• Most commonly abused substance

• Yeast produce ethanol through the anaerobic enzymatic process

• Fermentation can produce alcohol contents of up to 16%

Alcohol

• Distillation can then “spirit” off alcohol to achieve up to 96% concentration (limit of ethanol-water azeotrope)

Acute EffectsBAC Effects

0.02 – 0.03 slightly light headed; inhibitions are loosened

0.05 – 0.06 warm and relaxed; behavior may become exaggerated

0.08 – 0.09 legally drunk, start to slur speech, sense of balance is probably off; motor skills are becoming impaired

0.10 – 0.12 euphoric, but lack coordination and balance; motor skills are markedly impaired, as are judgment and memory.

0.14 – 0.17 euphoric feelings may give way to unpleasant feelings; difficulty talking, walking, or even standing; judgment and perception are severely impaired

0.20 confused, dazed, or otherwise disoriented, nausea and/or vomiting, blackouts are likely

0.25 all mental, physical, and sensory functions are severely impaired; increased risk of asphyxiation from choking on vomit and of seriously injuring self by falling or other accidents

0.30 little comprehension of where you are; may suddenly pass out

0.35 level of surgical anesthesia; may stop breathing

0.40 probably in a coma; the nerve centers controlling heartbeat and respiration are slowing down.

Alcohol Dose-Response

Alcohol and PTSD

• The estimated prevalence of alcohol use disorders in individuals with PTSD is higher than the prevalence in the general population

• In individuals with both PTSD and substance use disorders, the symptoms of PTSD tend to be more severe, particularly in the avoidance and hyperarousal clusters

• There is evidence that they are more prone to substance use relapse than non co-morbid individuals

• Co-morbidity of PTSD and substance use is associated with a higher rate of psychosocial and medical problems and higher utilization of inpatient hospitalization

• McCarthy E, Petrakis I. (2010). Epidemiology and management of alcohol dependence in individuals with post-traumatic stress disorder. CNS Drugs. 24(12): 997-1007.

Cannabis

• Several species:– Cannabis sativa – Cannabis indica – Cannabis ruderalis

• Psychoactive components thought to be produced to defend the plant from predators

• Most concentrated in the flowers of the female plant

Cannabis

• Major psychoactive ingredient Δ9-tetrahydrocannabinol (THC)

• Several other cannabinoids including cannabidiol (CBD), cannabinol (CBN), tetrahydrocannabivarin (THCV)

THC CBD

Cannabis

• Modern cannabis production– Selective breeding for yield and

potency– Manipulation of growing

conditions• Hydroponic gardening with

control of light cycle, nutrients, CO2

• “Sinsemilla” technique to enhance resin production

Cannabis

• Burgdorf JR, Kilmer B, & Pacula RL. (2011). Heterogeneity in the composition of marijuana seized in California. Drug Alc Dep. 117 (1), 59-61.

1994 1996 1998 2000 2002 2004 2006 2008 20100%

5%

10%

15%

20%

THC Levels in Seized Samples in California

% T

HC

by W

eigh

t

Medicinal Cannabinoids

• Dronabinol (Marinol®)– FDA approved for treatment of anorexia in AIDS

patients, and for refractory nausea and vomiting of patients undergoing chemotherapy

– CN-III controlled substance

THC

Medicinal Cannabinoids

• Nabilone (Cesamet®)– FDA approved for treatment of chemotherapy-

induced nausea and vomiting– C-II controlled substance

Nabilone

Cannabicyclohexanol

Artificial Cannabinoids

• Many research chemicals and analogues of THC have been created

• “Legal” substitutes for cannabis: “Spice,” “K2”• Most common: cannabicyclohexanol, JWH-018

JWH-018

Mechanism of Action

• Endocannabinoid system– CB1 (CNS)

– CB2 (periphery)

• Endogenous ligands – Anandamide– 2-arachidonoyl

glycerol Anandamide

Acute Effects

• Mild euphoria• Relaxation• Perceptual alterations– Time distortion– Intensification of normal experiences

• Increased sociability and laughter• Increase in appetite• Loss of short-term memory

Cannabis and PTSD

• Links between PTSD and:– Using cannabis to cope– Severity of cannabis withdrawal– Craving

• Boden MT, Babson KA, Vujanovic AA, Short NA, Bonn-Miller MO. (2013). Posttraumatic stress disorder and cannabis use characteristics among military veterans with cannabis dependence. Am J Addict. 22(3):277-84.

Cannabis and PTSD

• Neumeister A et al. (2013). Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study. Mol Psychiatry. Advance online publication 14 May 2013.

HC TC PTSD1.05

1.1

1.15

1.2

1.25

1.3

1.35

1.4

1.45

1.5* p = 0.001

Brain Cannabinoid CB1 Receptor Availability by PET

[11C

]OM

AR

VT v

alue

s

Opioids

• Opium poppy– Papaver somniferum

• Opioid alkaloids concentrated in the sap of developing seed pods

• Raw form called opium• In 2007, 93% of the world’s

illicit opiates from Afghanistan

• United Nations Office on Drugs and Crime. Afghanistan Opium Survey 2007.

Opioids

• Major psychoactive ingredients are morphine and codeine

• Several other important alkaloids including thebaine

Morphine ThebaineCodeine

Medicinal Opioids

• Synthetic variants of morphine and codeine

Parent Compound Reduced Ketone Oxidized Ketone

Morphine (MS Contin) Hydromorphone (Dilaudid) Oxymorphone (Opana, Numorphan)

Codeine (Tylenol #3) Hydrocodone (Vicodin) Oxycodone (Percocet, OxyContin)

Heroin

• Heroin is diacetylated morphine• Acetyl groups create highly lipophilic

compound that rapidly crosses the blood-brain barrier and accumulates in the CNS

Heroin

Mechanism of Action

• Opioid system– μ receptor

• Brain, spinal cord and intestinal tract• Analgesia, euphoria, miosis, physical dependence, respiratory

depression, decreased GI motility

– κ receptor• Brain, spinal cord• Analgesia, anticonvulsant effects, dissociative & deliriant effects,

dysphoria, miosis

– δ receptor• Brain• Analgesia, antidepressant effects, convulsant effects, physical

dependence

Mechanism of Action

• Endogenous ligands • Small peptide neurotransmitters– Endorphins

• Bind to μ receptor• “Natural pain relievers,” “runner’s high”

– Dynorphins• Bind to κ receptor• Modulators of pain response, maintain homeostasis through

appetite control and circadian rhythm, weight control and regulation of body temperature

– Enkephalins• Bind to δ receptor

• Koneru A, Satyanarayana S, Rizwan S. (2009). Endogenous opioids: their physiological role and receptors. Global J Pharmacol. 3(3): 149-153.

Acute Effects

• Euphoria• Decreased pain perception• Sedation• Nausea, vomitting• Respiratory depression• Decreased GI motility• Miosis

Opioid Withdrawal

• Tolerance– After repeated opioid use, the body establishes a

new homeostasis for the presence of opioids

Euphoria

Dysphoria

Moo

d

Drug Effect

Baseline Mood

Withdrawal Symptoms

Early to Moderate Moderate to Advanced

Anxiety, dysphoria, irritability Broken sleep

Fatigue, headache, restlessness, craving Muscle and bone pain

Yawning, lacrimation, rhinorrhea, Myoclonus

Perspiration, piloerection Vasomotor symptoms

Tachypnea Hypertension, tachycardia, hyperthermia

Anorexia Abdominal cramps, nausea, vomiting

Mild mydriasis Severe mydriasis

Norepinephrine Pathways

Locus coeruleus

Thalamus

Hypothalamus

Neocortex

Temporal lobe

Cerebellum

Spinal cord

Opioids and PTSD

• Use of morphine soon after injury associated with a reduced risk of PTSD (odds ratio, 0.47; p<0.001)

• Among US veterans of Iraq and Afghanistan, PTSD associated with:– Prescriptions for opioids– High-risk use– Adverse clinical outcomes

• Holbrook TL, Galarneau MR, Dye JL, Quinn K, Dougherty AL. (2010). Morphine use after combat injury in Iraq and post-traumatic stress disorder. N Engl J Med. 362(2): 110-7.

• Seal KH, Shi Y, Cohen G, Cohen BE, Maguen S, Krebs EE, Neylan TC. (2012). Association of mental health disorders with prescription opioids and high-risk opioid use in US veterans of Iraq and Afghanistan. JAMA. 307(9): 940-7.

Documents

Substance Abuse and Veterans Supporting Veterans and Service Members: A Mental Health and Community Imperative June 28 th, 2013 Jonathan C Fellers, MD