BioPsychoSocial Approaches to Addiction

1. CSAM-SCAM Fundamentals BioPsychoSocial Approaches to Addiction Presentation by: Kathryn J. Gill PhD -Associate Professor, Psychiatry Department, McGill University -Psychotherapist and Researcher, Addictions Unit, McGill University Health Centre

2. Disclosures/Warnings

3. Fundamentals: BioPsychoSocial Approaches to Addiction • No current funding from pharmaceutical or medical device companies • Psychotherapist at the Addictions Unit, McGill University Health Centre, and in private practice • Tenured professor, McGill University with undergraduate, graduate and post-graduate teaching duties • Addiction research funded by Canadian Institutes of Health Research https://muhc.ca/addictions_unit/profile/addictions-unit kathryn.gill@mcgill.ca

4. Overview • Alcohol, drugs, new psychoactive substances • Addiction –What are the signs and symptoms? How does it develop? • What are the effects of drugs/alcohol on the brain? What are the implications for treatment? • Vulnerability to addiction - the roles of genetics andenvironment

7. http://www.emcdda.europa.eu/ 6 new substances — 25I-NBOMe, AH-7921, methoxetamine, MDPV, 4,4′-DMAR and MT-45 are currently undergoing risk assessment

8. Harms related to substance use disorders (SUD) Social Effects • family violence/child neglect • isolation/lack of social support • job loss, legal issues, poverty • increased emergency room visits Physical/Brain Effects • HIV, HCV • liver toxicity, sleep problems • neurocognitive & brain deficits (decrease in receptors, neurotransmitters) • increased depression, anxiety, psychosis (Keil et al., 2015; Goldstein et al., 2011; McClure et al., 2009

9. Costs of SUD in Primary Care (Quebec) (Gill et al., 2016) Average annual per patient RAMQ costs (± SEM) for medical services (a) and pharmaceuticals (b) at two time points over a 3 year period for SU-RC and SUD+ groups N=2794

10. Addiction – What are the signs and symptoms?

11. How many started the day with a cup of coffee or tea this morning? • What drug did you consume? • Xanthines – caffeine and/or theophylline • Do you think coffee and tea are addictive? • regular use leads to subjective sensation of needing a lift/energy/break + preference for caffeinated forms • strong pharmacological effects - increases alertness, energy, concentration via brain adenosine receptors • produces physical dependence. Withdrawal symptoms (headache, fatigue, nausea, poor concentration, irritability, increased muscle tension begin 12–24 hours after stopping; peak by 20–48 hours)

12. Reinforcing complex - coffee • Warmth • Colour, smell, taste • Taking a break • Pick me up – stimulant • Reduction in withdrawal – fatigue, headache conditioned cues

13. Tobacco Smoking Single largest preventable cause of illness and mortality in the world

14. Many of you have patients that are current smokers

15. What drug are they consuming?

16. nicotine + • harmane/norharmane(known to inhibit brain enzymes that regulate the level of the neurotransmitters dopamine and serotonin • acetaldehyde (effects neurotransmitter release) • preservatives, pesticides, mould retardants, humectants, polycyclic aromatic hydrocarbons (carcinogens)

17. Why can’t they just stop?

18. Pleasure and Reward

19. Reinforcing Complex - tobacco • smell, taste • sound (lighter or match) • cigarette shape & colour • cigarette package • oral sensations, inhalation/exhalation (calming) • pharmacological effects of tobacco smoke • time out, taking a break • relief from withdrawal (anxiety, fatique) conditioned cues

20. Rewarding Effects of Tobacco

22. Physical Dependence - Withdrawal Discomfort

24. Why is it difficult to quit? "He stated he could give up smoking with ease, and in fact had done so hundreds of times"(Mark Twain)

25. Why it is Difficult to Quit High Availability – Legal, relatively socially acceptable cheap, readily available - difficult to avoidcues, non-intoxicating– no deficits in performance Conditioning - Exposure to conditioned cues repeatedhundreds of times per day (oral stimulation, inhalation, exhalation), associated with many activities Complex Pharmacological Effects short duration of action, rapid acute tolerance – promotes repeated self-administration, strong physiological dependence with unpleasant withdrawal long delay to negative medical consequences(lung, larynx, stomach, pancreatic cancers), cardiovascular disease

26. Extrapolate to other drugs of abuse (alcohol, cocaine, heroin, cannabis) • Many of the factors that make smoking a difficult habit to quit apply equally to other drugs of abuse • + + strong intoxication and/or euphoria • + ++ cortical suppression after chronic use (impaired control of impulsivity, decision making, planning)

27. What are the effects of drugs/alcohol on the brain? The brain is hard-wired to respond to drugs of abuse

29. Drugs of abuse resemble/activate or disrupt natural neurotransmitters in the brain

30. Anandamide is an endogenous cannabinoid with a much shorter half-life, as well as lower efficacy and binding affinity for CB1 receptors in the brain compared to exogenous THC

31. Animal Studies Drug Exposure has significant effects on: Release of neurotransmitters (DA, glutamate, GABA…) Structure of neurons and circuits (spine density, #synapses) Stress hormones and underlying brain structures Gene expression (striatum and frontal cortex) Epigenetic modification of genes - transgenerational (Vassoler) current research looking at ways to reverse stress and epigenetic effects – focus on neuroplasticity

32. Human Studies -Brain Imaging Positron Emission Tomography - PET

33. striatum hippocampus frontal cortex substantia nigra/VTA nucleus accumbens raphe Dopamine Pathways Serotonin Pathways • Functions • attention, arousal • reward (motivation) • motor function • decision making • Functions • mood • memory processing • sleep • cognition

34. “Theory - drugs produce pleasure via dopamine release, and addiction may result from neurobiological changes to the dopamine system” Dopamine ≠ Pleasure or Euphoria Not all drugs of abuse release dopamine in humans (inconsistent imaging data). DA blockers or depletion do not affect euphoria or the high in humans, no therapeutic value Preclinical studies show that dopamine firing and release become tied to the cues preceding drug use – not the actual drug decreased DA D2 receptors following chronic drug abuse have been found, but not consistently. However Low D2 receptors may predict poor treatment response to behavioural therapy Issues with Dopamine-related Theory of Reward

35. Dopamine and Incentive Motivation • the mesolimbic dopamine pathway, which includes the NAcc, amygdala and hippocampus, is relevant for drug reward and for drug-related memories and conditioned responses • Current hypothesis is that dopamine mediates the ‘incentive motivational’ value of reward • Dopamine neurons label environmental stimuli with appetitive value, predict and detect rewards and signal motivating events leading to increased dopaminergic activity inresponse to salient cues

36. Dopamine receptors (PET) PET images of D2 receptors and glucose metabolism in the brain With chronic cocaine abuse, there is decreased dopamine D2 receptors and decreased activity in the OFC, which is linked to compulsive behaviour and disinhibition (Volkow & Li, 2004)

37. Alcohol-induced suppression of brain activity (PET Scan) Thanos et al., 2008 (Alc Res Health, 31:233-237)

38. Recovery of function in chronic alcoholics Volkow et al. (Am J Psychiatry, 151: 171-183, 1994)

39. Effects of chronic cocaine on the brain - PET High activity Non-user, normal brain Cocaine Abuser (10 days) Low activity Cocaine Abuser (100 days) From Volkow et al. Synapse 14:169-177

40. Drug-induced reduction of activity in the prefrontal (PFC) and orbitofrontal cortex (OFC) have effects on memory, decision making, inhibitory control, judgement, planning and behaviouralcontrol (Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications. Goldstein & Volkow, 2011)

42. 2016

43. Discussion – What are the implications of frontal cortical dysfunction in terms of treatment planning? disorganization cognitive, attentional and memory deficits low motivation less compliant to treatment/medication regimens poor emotional regulation and decision making

44. Diagnostic Criteria for a Substance Use Disorder

45. Fundamentals: BioPsychoSocial Approaches to Addiction Addiction Definition – ASAM + CSAM “Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations. This is reflected in an individual pathologically pursuing reward and/or relief by substance use and other behaviors…”

46. DSM-5 ** Diagnostic Criteria For Substance Use Disorder (SUD) A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by 2 of 11criteria, occurring within a 12 month period • Impaired control, compulsion to obtain and take the substance • Detrimental effects on users and their close relations • Development of tolerance and withdrawal ** Diagnostic and Statistical Manual of Mental Disorders, APA, 5th edition

47. DSM-5 Diagnostic Criteria 1) use of larger amounts or longer period than intended 2) unsuccessful efforts to cut down or control use 3) long time spent obtaining or recovering from effects 4) craving 5) failure to fulfill major role obligations 6) continued use despite persistent social problems caused by the substance 7) social, occupational, or recreational activities given up 8) repeated use in hazardous situations 9) continued use despite persistent physical/ psychological problems caused by the substance 10) tolerance 11) withdrawal

48. Sedative/Hypnotic and Anxiolytic Withdrawal Two (or more) of the following developing after cessation of alcohol use that has been heavy and prolonged • autonomic hyperactivity (e.g., sweating, pulse rate >100), increased hand tremor • psychomotor agitation and/or anxiety • insomnia • nausea or vomiting • transient visual, tactile, or auditory hallucinations or illusions • generalized tonic-clonic seizures

49. Are some people more vulnerable to addiction?

50. Vulnerability – Transition from use to abuse to dependence? USE REGULAR HEAVY ABUSE DEPENDENCE • availability, cultural norms, sources of recreation/pleasure, drug expectancies, same-sex siblings • peer influences, family attitudes (modeling), high risk taking behavior, sensation seeking • family disruption/divorce • familial antisocial personality disorder • familial substance abuse (chaos, shame, violence, poverty, fetal exposure) • familial mental illness (genetic factors, neglect, abuse, poor parental monitoring)