1 Understanding Dual Disorders The Brain Chemistry of Addiction and Mental Illness

2 The Complex Human Brain

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7 Individual Brain Cell (neuron)

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10 Individual Brain Cell (neuron)

11 From one brain cell to another...

12 Neurotransmitters  Serotonin regulates sleep and body temperature; also involved in the regulation of sex, aggression, sleep and mood;  Dopamine is involved with voluntary movement and emotional arousal; along with norepinephrine, is known as one of the excitatory neurotransmitters, which can have the effect of elevating a person’s mood;  Endorphins and enkephalins (the body’s “internal opiates”) reduce pain and produce euphoria and a soothing effect, as neuronal pathways associated with pain pass through the limbic system (the seat of emotion).

13 The “3 Rs” of Neurotransmission  Release  Reception  Re-uptake

14 Release Release Release of neurotransmitters can be likened to the flow of water into a bathroom sink...

15 From one brain cell to another...

16 Reception Reception of neurotransmitters across the synaptic cleft (i.e., the space between nerve cells) can be likened to water going down the drain...

17 From one brain cell to another...

18 Re-uptake If water that doesn’t go down the drain were to somehow be sucked back up into the faucet, that is what Re-uptake would be like...

19 From one brain cell to another – and back again...

20 Brain Chemistry and Mental Illness - Thought disorders - Mood disorders

21 Schizophrenia and Brain Chemistry – too much Dopamine?  Dopamine is the neurotransmitter that is decreased to a certain degree by all antipsychotic medications, in an effort to decrease the overabundance of dopamine that is thought to contribute to psychotic symptoms

22 Decreasing Neurotransmission  Medications can DECREASE the effect of a neurotransmitter in two ways  Decrease Release  Block Reception

23 Decreasing Dopamine  Antipsychotic medications seek to DECREASE Dopamine, resulting in less “water going down the drain” Decrease Release, or Block Reception Block Reception

24 Depression and Brain Chemistry – not enough Serotonin?  Serotonin is the neurotransmitter that is increased to a certain degree by many antidepressant medications, in an effort to counteract the shortage that is thought to contribute to depressive symptoms

25 Increasing Neurotransmission  Medications can INCREASE the presence of a neurotransmitter in two ways  Increase Release  Block Re-uptake

26 Increasing Serotonin  Medications can INCREASE the presence of a neurotransmitter in two ways Increase Release, or Block Re-uptake Block Re-uptake

27 SSRI Antidepressants  SSRI stands for S erotonin S erum S erum R e-uptake R e-uptake I nhibitor I nhibitor  This type of medication seeks to increase the action of Serotonin by blocking its Re-uptake, thus resulting in a greater amount of “water in the sink” that is likely to cause more to “go down the drain” (increased Reception)

28 Brain Chemistry and Substance Use - “Uppers” - “Downers” - “All-Arounders” Brain Chemistry and Substance Use - “Uppers” (Stimulants) - “Downers” (Depressants) - “All-Arounders” (Psychedelics)

29 Release Release  Drugs that INCREASE the flow are like turning open the tap all the way...  Drugs that DECREASE the flow are like turning down the faucet until the output is only a trickle...

30 Reception  Some drugs that DECREASE reception are like a washcloth blocking the drain, causing less flow.

31 Re-uptake  Drugs that INCREASE Re-uptake block neurotransmitters (i.e., water) from being received by the next brain cell (i.e., prevent them from going down the drain), thus causing more neurotransmitters to stay in the synaptic cleft (i.e., the sink) and be reabsorbed (i.e., go back “up the faucet”)

32  Drugs that DECREASE re-uptake block neurotransmitters (i.e., the water) from being reabsorbed (i.e., going back up the faucet), and thus lead to a greater amount of neurotransmission to the next brain cell (i.e., flow down the drain) Re-uptake

33 From one brain cell to another – and back again...

34 “Uppers” / (Stimulants)  Cocaine  Amphetamine / Methamphetamine

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36 “Uppers”  Increasing the number of EXCITATORY neurotransmitter molecules (dopamine or norepinephrine) in the synapse will elevate a person’s mood.  Using our analogy, this would mean more “water in the sink”

37 “Uppers”  What are the ways to get more “water in the sink?”  This can occur through INCREASED RELEASE of the excitatory neurotransmitter (as in the case of high-risk behavior), or through DECREASED RE-UPTAKE of excitatory neurotransmitters, which is what occurs with cocaine

38 Post-acute Withdrawal Syndrome  “PAWS” is a condition experienced by many addicts upon achieving abstinence. It can literally take up to two years for the brain and nervous system to heal and “recalibrate” such that pre- use levels of normal neurotransmitter activity are restored

39  During this time, in the case of individuals addicted to stimulants (cocaine, for example), the lower-than-normal amount of dopamine transmission can result in the “under-stimulation” of brain cells, and resulting depressive symptoms. Post-acute Withdrawal Syndrome

40 “Downers” / (Depressants)  Alcohol  Opiates  Heroin, Opium, Morphine, Codeine, Oxycontin, Methadone  Sedatives / Hypnotics / Anxiolytics  Benzodiazapines (Xanax, Valium, Librium, Ativan, Klonopin)  Barbiturates (Seconal, Nembutal, Phenobarbital)  Soma, Methaqualone (Quaaludes)

41 “Downers” / (Depressants)

42 “Downers”  Opiates DECREASE the RELEASE of excitatory neurotransmitters (dopamine, &/or norepinephrine), thus resulting in a soothing, calming effect  However, excessive opiate ingestion can lower neurotransmission to the point at which slowed physical reactions can endanger life.

43 “All-Arounders” / (Psychedelics)  Cannabis  Marijuana, Hashish  Hallucinogens  LSD, Mescaline, Peyote, Mushrooms (Psilocybin)  Ecstasy / “MDMA” / “Foxy” (hallucinogenic stimulants)  Ketamine, Rohypnol, GHB / “Date rape drugs” (hallucinogenic depressants)  Inhalants  Phencyclidine  PCP (hallucinogenic depressant)

44 Nature or nurture, genetics or environment?

45 All-Arounders  Ecstasy deregulates the level of serotonin, the neurotransmitter involved in the regulation of sex, aggression, sleep and mood  High doses of Ecstasy have been known to cause psychotic episodes, and even permanent brain damage in some users

46 References American Psychiatric Association, (1994). Diagnostic and statistical manual of mental disorders, fourth edition. Washington D.C.: Author. Milkman, H., & Sunderwirth, S., (1987). Craving for ecstasy: The consciousness & chemistry of escape. New York: Lexington Books. Volkow, N.D., et al. (2001). Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. American Journal of Psychiatry, 158(3): Volkow, N.D., et al. (2001). Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence. Journal of Neuroscience, 21(23):

47 Other Neurotransmitters and examples of their actions  Acetylcholine - voluntary movement of the muscles; Acetylcholine  Noradrenaline - wakefulness or arousal; Noradrenaline  GABA (gamma aminobutryic acid) - motor behavior; GABA  Glycine - spinal reflexes and motor behavior; Glycine  Neuromodulators - sensory transmission- especially pain Neuromodulators