Substance Related Disorders Lecture Notes PDF

Substance Related, Addictive, and Impulse-Control Disorders  The nature of opiates and opioids Opiate:  compound derived naturally from the opium poppy plant (’Papaver somniferum’)  Include alkaloids such as morphine and codeine, harvested from the plant's sap Opioids:  a broader term encompassi...

Substance Related, Addictive, and Impulse-Control Disorders  The nature of opiates and opioids Opiate:  compound derived naturally from the opium poppy plant (’Papaver somniferum’)  Include alkaloids such as morphine and codeine, harvested from the plant's sap Opioids:  a broader term encompassing all compounds: , natural, synthetic, or semi-synthetic, that bind to opioid receptors and produce effects similar to those of opiates  Include the natural opiates, as well as synthetic (e.g., fentanyl, methadone) and semisynthetic opioids (e.g., heroin, which is derived from morphine), and oxycodone, which is derived from thebaine Analgesic (pain-killing) and sedative properties; highly addictive  Effects of opioids Exert their effects by binding to specific opioid receptors  (especially ’mu’ receptors, which are involved in pain relief and reward) – co-opt your body’s endorphin network Interrupt pain signaling, reduce excitability of neurons involved in pain signaling, increase inhibitory neurotransmitters Activate reward centers Inhibit brainstem areas associated with wakefulness and alertness Low doses induce euphoria, drowsiness, and slowed breathing High doses can be fatal Withdrawal symptoms can be lasting and severe Mortality rates are high for opioid addicts High risk for HIV infection due to shared needles  See how this recently impacted a small Indiana community Figure 1. National Drug-Involved Overdose Deaths*, Number Among All Ages, by Gender, 1999-2021 120,000 100,000 Total Female Male There were 106,699 drug-involved overdose deaths reported in the U.S. in 2021; 69% of cases occurred among males. 91,799 80,000 60,000 106,699 70,630 52,404 40,000 20,000 0 *Includes deaths with underlying causes of unintentional drug poisoning (X40–X44), suicide drug poisoning (X60–X64), homicide drug poisoning (X85), or drug poisoning of undetermined intent (Y10–Y14), as coded in the International Classification of Diseases, 10th Revision. Source: Centers for Disease Control and Prevention, National Center for Health Statistics. Multiple Cause of Death 1999-2021 on CDC WONDER Online Database, released 1/2023. Figure 2. National Drug-Involved Overdose Deaths*, Number Among All Ages, 1999-2021 100,000 Synthetic Opioids other than Methadone (primarily fentanyl) Psychostimulants with Abuse Potential (primarily methamphetamine) Cocaine 80,000 2021 2020 2019 2018 2017 2016 2008 2007 2006 2005 2004 2003 2002 2001 2000 0 1999 20,000 2015 40,000 2014 Antidepressants 2013 Heroin 60,000 2012 Synthetic opioids other than methadone (primarily fentanyl) were the main driver of drug overdose deaths with a nearly 7.5-fold increase from 2015 to 2021 2011 2010 Benzodiazepines 2009 Prescription Opioids (natural & semi-synthetic opioids & methadone) *Includes deaths with underlying causes of unintentional drug poisoning (X40–X44), suicide drug poisoning (X60–X64), homicide drug poisoning (X85), or drug poisoning of undetermined intent (Y10–Y14), as coded in the International Classification of Diseases, 10th Revision. Source: Centers for Disease Control and Prevention, National Center for Health Statistics. Multiple Cause of Death 1999-2021 on CDC WONDER Online Database, released 1/2023. Figure 3. National Overdose Deaths Involving Any Opioid*, Number Among All Ages, by Gender, 1999-2021 100,000 Total Female Male 80,000 60,000 Drug overdose deaths involving any opioid―prescription opioids (including natural and semi-synthetic opioids and methadone), other synthetic opioids other than methadone (primarily fentanyl), and heroin―continued to rise through 2021 with 80,411 deaths. More than 70% of deaths occurred among 47,600 males 80,411 68,630 40,000 21,089 20,000 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 0 *Among deaths with drug overdose as the underlying cause, the “any opioid” subcategory was determined by the following ICD-10 multiple cause-of-death codes: natural and semi-synthetic opioids (T40.2), methadone (T40.3), other synthetic opioids (other than methadone) (T40.4), or heroin (T40.1). Source: Centers for Disease Control and Prevention, National Center for Health Statistics. Multiple Cause of Death 1999-2021 on CDC WONDER Online Database, released 1/2023. Figure 4. National Overdose Deaths Involving Prescription Opioids*, Number Among All Ages, 1999-2021 25,000 20,000 Total Prescription Opioids in Combination with Synthetic Opioids other than Methadone 15,000 From 2020 to 2021, the number of deaths involving prescription opioids remained steady 17,029 16,706 14,139 10,000 5,000 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 0 *Among deaths with drug overdose as the underlying cause, the prescription opioid subcategory was determined by the following ICD-10 multiple cause-of-death codes: natural and semi-synthetic opioids (T40.2) or methadone (T40.3). Source: Centers for Disease Control and Prevention, National Center for Health Statistics. Multiple Cause of Death 1999-2021 on CDC WONDER Online Database, released 1/2023. Figure 5. National Overdose Deaths Involving Heroin*, by other Opioid Involvement, Number Among All Ages, 19992021 25,000 All Heroin Heroin in Combination with Synthetic Opioids other than Methadone Heroin without any Other Opioid 20,000 10,000 Nearly 75% of overdose deaths in 2021 involving heroin also involved synthetic opioids other than methadone (primarily fentanyl) 2002 15,000 2001 Overdose deaths involving heroin have trended down since 2016 with 9,173 deaths reported in 2021 5,000 15,482 13,165 9,173 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2000 1999 0 *Among deaths with drug overdose as the underlying cause, the heroin category was determined by the T40.1 ICD-10 multiple cause-of-death code. Source: Centers for Disease Control and Prevention, National Center for Health Statistics. Multiple Cause of Death 1999-2021 on CDC WONDER Online Database, released 1/2023. Figure 6. National Overdose Deaths Involving Stimulants (Cocaine and Psychostimulants*), by Opioid Involvement, Number Among All Ages, 1999-2021 60,000 Stimulants 53,495 Stimulants in Combination with Synthetic Opioids other than Methadone Stimulants without any Opioid 40,643 50,000 40,000 30,000 20,000 Drug overdose deaths involving stimulants, cocaine, or psychostimulants with abuse potential (primarily methamphetamine) have significantly increased since 2015 from 12,122 to 53,495 in 2021 12,122 10,000 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 0 *Among deaths with drug overdose as the underlying cause, the psychostimulants with abuse potential (primarily methamphetamine) category was determined by the T43.6 ICD-10 multiple cause-of-death code. Abbreviated to psychostimulants in the bar chart above. Source: Centers for Disease Control and Prevention, National Center for Health Statistics. Multiple Cause of Death 1999-2021 on CDC WONDER Online Database, released 1/2023. - 87% of people with Opioid Use Disorder (OUD) do not receive evidence-based treatments - Utilization of medications for OUD, esp. buprenorphine, has risen across most states over past decade, but cannot keep pace with need/use Source: Krawczyk et al., 2022; Intl J Drug Pol. OPIOID USE DISORDERS - - From 1999–2018, almost 450,000 people died from an overdose involving any opioid, including prescription and illicit opioids. - This rise in opioid overdose deaths can be outlined in 3 distinct waves The first wave began with increased prescribing of opioids in the 1990s, with overdose deaths involving prescription opioids (natural and semi-synthetic opioids and methadone) increasing since at least 1999  FIRST WAVE -- 1990’s Doctors became increasingly aware of the burden of chronic pain Pharma saw an opportunity and began to heavily market opioids  Misled doctors about the safety and efficacy of drugs such as OxyContin (produced by Purdue Pharma; not related to Purdue University!) The drugs proliferated, making America the world’s leader in opioid prescriptions - CDC: enough opioids prescribed in 2015 to medicate every American around the clock for 3 weeks  As a result, the pills were often diverted: To teens rummaging through parents’ medicine cabinets Family members Friends ….black market  Roughly 21-29% of patients prescribed opioids for chronic pain misuse them  Between 8-12% develop an opioid use disorder OPIOID USE DISORDERS - - From 1999–2018, almost 450,000 people died from an overdose involving any opioid, including prescription and illicit opioids. - This rise in opioid overdose deaths can be outlined in 3 distinct waves - The first wave began with increased prescribing of opioids in the 1990s, with overdose deaths involving prescription opioids (natural and semi-synthetic opioids and methadone) increasing since at least 1999 - - The second wave began in 2010, with rapid increases in overdose deaths involving heroin - - New cheap heroin supply flooded the US in 2000’s in response to opioid demand.  Over time, especially as prescription opioids became more scarce, opioid users began moving towards more potent opioid derivatives Approx. 4-6% of people who misuse prescription opioids transition to heroin About 80% of people who use heroin first misused prescription opioids  Increased supply heroin supply and decreased painkiller Prescription opioid painkiller deaths have leveled off (more associated with suicide risk) while fentanyl (especially) and synthetic opioid deaths have increased  Heroin (diacetylmorphine) is processed from morphine and is substantially more potent  Heroin is available medically in some circumstances, particularly in Europe and Canada. - Originally synthesized by English chemist C.R. Alder Wright in 1874 Heinrich Dreser at Bayer Labs continued to test heroin - Bayer marketed it as an analgesic and cough suppressant in 1898; when its addictive potential was recognized Bayer ceased production in 1913 OPIOID USE DISORDERS - - - - From 1999–2018, almost 450,000 people died from an overdose involving any opioid, including prescription and illicit opioids. - This rise in opioid overdose deaths can be outlined in 3 distinct waves The first wave began with increased prescribing of opioids in the 1990s, with overdose deaths involving prescription opioids (natural and semi-synthetic opioids and methadone) increasing since at least 1999 The second wave began in 2010, with rapid increases in overdose deaths involving heroin. - The third wave began in 2013, with significant increases in overdose deaths involving synthetic opioids, particularly those involving illicitly manufactured fentanyl - Fentanyl dispersion continues to change; found in combination with heroin, counterfeit pills, cocaine Wave 3  Heroin and meth cut with more potent synthetic opioids: Fentanyl – 80-100x more potent than morphine Carfentanil – 10,000x more potent than morphine; 100x more potent than fentanyl  Only 2 mg of fentanyl is considered a potentially lethal dose; it’s particularly dangerous for someone who does not have a tolerance to opioids  Cheap to produce  Substantial death rate increases nationwide, particularly in Midwest (esp. WV, OH) Tranq Dope: Animal Sedative Mixed With Fentanyl Brings Fresh Horror to U.S. Drug Zones A veterinary tranquilizer called xylazine is infiltrating street drugs, deepening addiction, baffling law enforcement and causing wounds so severe that some result in amputation. (NY Times, 1/8/23) Tranq dope is an ever-fluctuating blend of xylazine, a sedative, and usually an opioid, with each type of drug binding to different brain receptors Reversing an overdose where xylazine was involved is tricky -- A dose of the overdose-halting medicine naloxone, which blocks or reverses opioids’ effect on brain receptors, will address the fentanyl but still won’t rouse a victim sedated with xylazine A study published in June detected xylazine in the drug supply in 36 states and the District of Columbia. Desperate rescuers may try a second or third dose. But too much naloxone can put someone into withdrawal, vomiting and writhing. More than 90 % of Philadelphia’s lab-tested dope samples were positive for xylazine In November, the Food and Drug Administration issued a nationwide four-page xylazine alert to clinicians.  Cannabis One of world’s most widely used psychoactive substances Most frequently used psychotropic drug in the U.S. after alcohol  Proportion of young adults who reported past-year marijuana use = 43% in 2021, a significant increase from 34% in 2016  Marijuana use in the past month = 29% of young adults in 2021 vs. 21% in 2016 See map about states that have enacted medical and recreational marijuana legalization  Cannabis Cannabis sativa/indica (marijuana and hemp are two varieties) contains over 450 different chemical compounds  100 different cannabinoids, which interact with the body’s own endogenous (internal) cannabinoid system  2 widely studied:  9-Tetrahydrocannabinol (THC)  Cannabidiol (CBD)  THC’s analgesic effects modulated by activating CB1 and CB2 receptors  In contrast, CBD does not activate CB1 or CB2 – acts at multiple receptor types While THC is classified as a mild hallucinogen, its effects are quite variable  May include euphoria, mood swings, time slowing, paranoia, hallucinations, reduced concentration – all dose dependent  Cannabis Use Disorder (CUD) Is cannabis addictive?  If we define addiction as an acquired, chronic, relapsing disorder that is characterized by a powerful motivation to continually use the substance despite persistent negative consequences, then the answer is a clear YES  However, the addictive potential for cannabis is lower than for alcohol, cocaine, and tobacco  Much of the addictive process involved in cannabis use disorder relates to psychological processes associated with craving as well as physiological processes associated with reward processes (i.e., the dopamine system) Can you overdose on cannabis?  Yes, but it doesn’t necessarily mean death  Ingesting cannabis can lead to severe and life-threatening health consequences for children  For adolescents and adults, an overdose looks like a more severe and unpleasant version of cannabis intoxication (e.g., confusion, paranoia, anxiety/panic, fast heart rate, delusions, hallucinations, nausea, vomiting)  these can land people in the ER, or can dangerously interact with preexisting health problems – more often though it just leads to a bad time  Cannabis Use Disorder (CUD) 12-month prev. rate = 2.54%; lifetime = Prevalence of 12-Month DSM-5 Cannabis Use Disorder in the United States, by Severitya 6.27% (Hasin et al., 2016) CUD risk higher among younger than older age groups, with striking differences between those age 18–29 and those ≥45 Those with lowest incomes had higher odds of CUD  Outcomes are related to income disparities in distal and proximal forms, including: early exposure to disadvantaged environments, low parental SES, family history of addiction, and residence in high-unemployment neighborhoods Those w/ CUD experienced considerable disability across many different domains  Level of disability, esp. among those with severe CUD, was consistent with the very frequent cannabis use reported (252.2 and 310.4 days per year among those with 12-month and lifetime severe cannabis use disorders)  These disability and use patterns attest to the severity of the disorder, which clearly is not a benign or harmless condition.  Disability levels were greater than the corresponding levels associated with alcohol use disorder Prevalences reflect numbers adjusted for nonresponse and weighted to represent the U.S. population based on the 2012 American Community Survey. Total, N=36,309; males, N=15,862; females, N=20,447; age 18–29, N=8,126; age 30–44, N=10,135; age ≥45, N=5,806. a  Cannabis Withdrawal Disorder Well-recognized – affects 33% of daily users and 50-95% of heavy users in treatment upon cessation of use  begins 1-2 days after cessation, peaks at 2-6 days; remits at 1-2 weeks Defined in DSM-5-TR as 3 or more of the following:  Substance-Related and Addictive Disorders Stimulants Other hallucinogens  Gambling Disorder  Other Impulse-control disorders  For your review  The nature of drugs in this class Sedatives – calming (e.g., barbiturates) Hypnotic – sleep inducing Anxiolytic – anxiety reducing (e.g., benzodiazepines)  Effects are similar to large doses of alcohol Combining such drugs with alcohol is synergistic  All exert their influence via the GABA neurotransmitter system  DSM-5 criteria for this class of disorders Same as for other classes of drugs (i.e., significant interference or distress accompanied by problems such as reduced activities or tolerance)  Nature of stimulants Most widely consumed drug in the United States Such drugs increase alertness and increase energy Examples include amphetamines, cocaine, nicotine, and caffeine  DSM-5 criteria for stimulant intoxication Recent stimulant use leading to significant impairment or psychological changes  Accompanied by physical changes (e.g., change in HR/BP, dilated pupils, weight loss, vomiting, weakness, chills)  Effects of amphetamines Produce elation, vigor, reduce fatigue Such effects are usually followed by extreme fatigue and depression  Amphetamines stimulate CNS by Enhancing release of norepinephrine and dopamine Reuptake is subsequently blocked Some ADHD drugs are mild stimulants – E.g., Adderall, Ritalin Ecstasy and crystal meth – Amphetamine effects, but without the crash – Both drugs have a high risk of dependence A. A pattern of amphetamine-type substance, cocaine, or other stimulant use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period: (1) the stimulant is often taken in larger amounts or over a longer period than was intended, (2) there is a persistent desire or unsuccessful efforts to cut down or control stimulant use, (3) a great deal of time is spent in activities necessary to obtain the stimulant, use the stimulant, or recover from its effects, (4) craving, or a strong desire or urge to use the stimulant, (5) recurrent stimulant use resulting in a failure to fulfill major role obligations at work, school, or home, (6) continued stimulant use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the stimulant, (7) important social, occupational, or recreational activities are given up or reduced because of stimulant use, 8) recurrent stimulant use in situations in which it is physically hazardous, (9) stimulant use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the stimulant, (10) tolerance, as defined by either (a) a need for markedly increased amounts of the stimulant to achieve intoxication or desired effect or (b) a markedly diminished effect with continued use of the same amount of the stimulant, (11) withdrawal, as manifested by either (a) the characteristic withdrawal syndrome for the stimulant or (b) the stimulant (or a closely related substance) is taken to relieve or avoid withdrawal symptoms. Specify current severity: Mild: Presence of 2 to 3 symptoms Moderate: Presence of 4 to 5 symptoms Severe: Presence of 6 or more symptoms Effects of cocaine – Short lived sensations of elation, vigor, reduce fatigue – Effects result from blocking the reuptake of dopamine – Highly addictive, but addiction develops slowly – 1.9 million report use in US each year Most cycle through patterns of tolerance and withdrawal – Withdrawal characterized by apathy and boredom > leads to desire to use again  Effects of nicotine Stimulates nicotinic acetylcholine receptors in CNS Results in sensations of relaxation, wellness, pleasure Highly addictive Relapse rates equal to those seen with alcohol and heroin  Nicotine users dose themselves to maintain a steady state of nicotine  Smoking has complex relationship to negative affect Appears to help improve mood in short-term Depression occurs more in those with nicotine dependence  After several weeks of daily use, unpleasant symptoms upon stopping or reducing: Insomnia, increased appetite, restlessness, trouble concentrating, anxiety and depression, irritability  Symptoms lead to clinically significant distress or impairment  Effects of caffeine – the “gentle” stimulant Used by over 90% of Americans Found in tea, coffee, cola drinks, and cocoa products Small doses elevate mood and reduce fatigue Regular use can result in tolerance and dependence Caffeine blocks the reuptake of the neurotransmitter adenosine  DSM-5 Criteria for Caffeine Intoxication Recent caffeine consumption, possibly in excess Associated with physical symptoms including restlessness, anxiety, insomnia, flushed face, diuresis, GI disturbance, muscle twitching, rambling thoughts or speech, elevated or irregular heartbeat, excitement, inexhaustibility, motor agitation Symptoms cause clinically significant distress or impairment  Nature of hallucinogens Change the way the user perceives the world May produce  Delusions, paranoia, hallucinations, altered sensory perception  Examples include marijuana, LSD 5-15% of people in Western countries smoke marijuana regularly  LSD and other hallucinogens LSD is most common form of hallucinogenic drug Hallucinogenic effects are much more intense than marijuana Tolerance is rapid and withdrawal symptoms are uncommon Can produce psychotic delusions and hallucinations  Nature of inhalants Substances found in volatile solvents Breathed directly into lungs  Examples Spray paint, hair spray, paint thinner, gasoline, nitrous oxide  Properties and consequences Rapidly absorbed Effects similar to alcohol intoxication Tolerance and prolonged symptoms of withdrawal are common  Nature of anabolic-androgenic steroids Steroids are derived or synthesized from testosterone Used medicinally or to increase body mass Users may engage in cycling or stacking Do not produce a high Can result in long-term mood disturbances and physical problems  Designer drugs Drugs were originally produced by pharmaceutical companies to target diseases; then others began producing for recreational use Cause drowsiness, pain relief and dissociative sensations  Ecstasy  BDMPEA (“nexus”)  Ketamine (“Special K”)  Often heighten auditory and visual perception, sense of taste/touch  Becoming popular in large social recreational gatherings (e.g., nightclubs, raves)  Produce tolerance and dependence  New disorder in DSM-5  Classified under “Addictive Disorders”  Recurrent gambling leading to clinically significant distress or impairment Associated with 4+ symptoms within a year:  Difficulty stopping/reducing gambling  restlessness/irritability when trying to cut back  need to gamble with increasing amounts of money,  frequent preoccupation  gambling when distressed  attempting to “win it back” after a loss  lying about gambling  relying on others for financial support  jeopardizing a significant relationship/job/opportunity Psychosocial treatment similar to substance abuse Treatment is often ineffective Motivation to get better is critical; dropout is high Research is limited, but multipart CBT interventions are under investigation – Scheduling alternative activities, setting financial limits, relapse prevention  Each is characterized by: Impairment of social and occupational functioning Increased tension/anxiety prior to the act A sense of relief following the act  Include: Intermittent explosive disorder Kleptomania Pyromania  Intermittent explosive disorder Rare condition Characterized by frequent aggressive outbursts Leads to injury and/or destruction of property Few controlled treatment studies  Kleptomania Failure to resist urge to steal unnecessary items Seems rare, but it is not well studied Highly comorbid with mood disorders Also co-occurs with substance-related problems  Pyromania Involves having an irresistible urge to set fires Diagnosed in just 3% of arsonists Little etiological and treatment research Treatment usually focuses on identifying urges and practicing incompatible behaviors  Involve impulsive, self-destructive behaviors  Include gambling disorder, intermittent explosive disorder, kleptomania, pyromania  Research remains scarce