Transcript Substance Abuse and Veterans Supporting Veterans and Service Members: A Mental Health and Community Imperative June 28th, 2013 Jonathan C Fellers, MD Addiction Psychiatry Fellow Portland.

Substance Abuse and Veterans
Supporting Veterans and Service Members: A Mental Health and
Community Imperative
June 28th, 2013
Jonathan C Fellers, MD
Addiction Psychiatry Fellow
Portland VA Medical Center & OHSU
Outline
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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 Dependence
Substance 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 substance
b. 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 Disorder
A 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 substance
b. 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:

Nucleus accumbens

Ventral tegmental area

Medial forebrain bundle
• 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.
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
Medial forebrain
bundle
Ventral tegmental area
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
Nucleus accumbens
Frontal lobe
Amygdala &
hippocampus
Medial forebrain
bundle
Ventral tegmental area
Epidemiology
Prevalence of Substance Abuse and Mental Illness in Veterans
1.5%
7.1%
7.0%
None
Serious Psychological Distress
Substance Use Disorder
Dual Diagnosis
84.4%
• 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.
Epidemiology
Sex Prevalence of Substance Abuse and Mental Illness in Veterans
16%
14%
Male
12%
Female
10%
8%
6%
4%
2%
0%
Serious Psychological Distress
Substance Use Disorder
Dual Diagnosis
• 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.
Epidemiology
Age Prevalence of Substance Abuse and Mental Illness in Veterans
30%
Serious Psychological Distress
25%
Substance Use Disorder
20%
Dual Diagnosis
15%
10%
5%
0%
Aged 18 to 25
Aged 26-54
Aged 55 or Over
• 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.
Epidemiology
Standardized Comparisons of Civilians and All Services,
Heavy Alcohol Use by Age Group, 2008
30%
Military
Percentage
25%
Civilian
20%
15%
10%
5%
0%
18-25
26-35
36-45
Age Group
46-64
All Ages
• 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
Prevalence of Cannabis Use Disorders Among Veterans 2002-2009
1.2%
Any CUD
1.0%
Only CUD
Percentage
0.8%
0.6%
0.4%
0.2%
0.0%
2002
2009
• 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.
Epidemiology
Misuse of Prescription Drugs by Military Personnel
12%
10%
Prescription
Percentage
8%
Illicit
6%
4%
2%
0%
2001
2002
2003
2004
2005
Year
2006
2007
2008
2009
• 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
Primary Substance of Abuse in Treatment Admissions
Aged 21 to 39, by Veteran Status: 2010
60%
50.7%
Veterans
50%
Non-veterans
40%
34.4%
30%
20%
17.6%
16.8%
12.2% 12.0%
12.2%
9.0%
10%
6.2%
7.6%
6.3%
7.2%
0%
Alcohol
Heroin
Other Opiates
Cannabis
Methamphetamine
Cocaine/Crack
• 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 Effects
BAC
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 Δ9tetrahydrocannabinol (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
THC Levels in Seized Samples in California
20%
% THC by Weight
15%
10%
5%
0%
1994
1996
1998
2000
2002
2004
2006
2008
2010
• Burgdorf JR, Kilmer B, & Pacula RL. (2011). Heterogeneity in the composition of marijuana seized in California. Drug Alc Dep. 117 (1), 5961.
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 chemotherapyinduced nausea and vomiting
– C-II controlled substance
Nabilone
Artificial Cannabinoids
• Many research chemicals and analogues of THC
have been created
• “Legal” substitutes for cannabis: “Spice,” “K2”
• Most common: cannabicyclohexanol, JWH-018
Cannabicyclohexanol
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
Brain Cannabinoid CB1 Receptor Availability by PET
1.6
* p = 0.001
1.4
[11C]OMAR VT values
1.2
1
0.8
0.6
0.4
0.2
0
HC
TC
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.
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
Codeine
Thebaine
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 bloodbrain 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): 149153.
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
Mood
Drug Effect
Dysphoria
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
Thalamus
Neocortex
Cerebellum
Hypothalamus
Spinal cord
Temporal lobe
Locus coeruleus
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.