Drug Addiction

1. Drug Addiction

2. The History of Drug Abuse • Societies around the world have used drugs ceremonially, recreationally, and medicinally since prehistoric times • Opium, Cannabis, and Alcohol are the oldest drugs on record • Psilocybin, mescaline, jimsonweed and other hallucinogenic drugs have been part of Native American religious ceremonies for thousands of years

3. Continues • amanita muscaria has been used ceremonially in Europe since prehistoric times

4. The United States • Before the 20th century, there were few state laws regulating drugs and none at the Federal Level • Chemistry created problems and stronger medicines such as morphine, cocaine and barbiturates. • Many people saw the damaging effects of alcohol and these new chemicals and called for reform.

5. Racism and Morality Chinese Opium Dens were notorious so Opium eventually fell out of favor except for medical purposes Mexican/African American were the main users of marijuana. This led to stories about rapists and killers using marijuana and attacking white people The idea flourished that morally depraved people used alcohol and that the inability to control one’s use was due to moral and character flaws

6. Harrison Tax Act • 1. Prohibited the use of narcotics for nonmedical purposes • 2. Doctors were required to pay tax and keep records • 3. Small amounts of codeine, heroin, opium and cocaine ordered though the mail was still legal. Addiction was not saw as a disease so doctors prescribing to addicts was illegal. This led the way to drug control laws and black market drugs while failing to prohibit alcohol which was seen as the biggest problem

7. Marijuana Tax Act • Due to societal views on marijuana smoking, it became illegal through the tax • However, the law was found unconstitutional in 1969 but was replaced with a much harsher and broader law banning use of all potentially addicting substances.

8. Schedules of Drugs • . Schedule 1- Highly addicting and no medical value • Includes heroin, marijuana, hallucinogenic drugs such as LSD and MDMA Schedule 2- High abuse potential but has medical value • Amphetamines, morphine, opiates without a second substance in it to prevent use, cocaine, PCP, Demerol, certain barbiturates • Schedule 3- Lower abuse potential and medical value • Includes opiates with other analgesics, certain barbiturates • Schedule 4- Low abuse potential • Benzodiazepines, Phenobarbital, chloral hydrate • Schedule 5- Very low abuse potential, sometimes different • between states • narcotics containing cough syrups or anti-diarrhea medicines • States can regulate drugs- propylhexedrine ,salvia divorinum and ephedra are currently all controlled at a state level

9. Problems with Scheduling • LSD, mescaline, DMT, and psilocybin are neither addicting nor very harmful which is the prerequisite for Schedule 1 • These drugs have been used ceremonially for thousands of years which interrupted Native American Rituals until the mid 1990s • Marijuana has therapeutic uses and medicinal qualities. • Ibogaine is a drug that disrupts addiction. It was made Schedule 1 in 1967 even though it has medicinal value and is used in many countries for addiction treatment.

10. Types of addiction • Physical Dependence • The user continues to use to prevent withdrawal symptoms due to biological compensation by the body and brain for drug use • An example is excessive norepinephrine release when an opiate user discontinues use. This creates anxiety and physical symptoms. Opiates also change metabolism of glucose in brain areas (Streel et al., 2006). • Psychological Dependence- • User has strong urges to use drug even if physical withdrawal does not occur

11. DSM-IV • Dependence of a substance has significantly impaired ones life and is causing distress. • Maladaptive pattern of behavior to avoid withdrawal that puts others in danger or self • Substance dependence and abuse are different • Substance abuse causes impairment or distress • If a person fails to fulfill what they have to because they used a substance once within a 12 month period, then a person under the DSM-IV has substance abuse problems.

12. Anyone ever experience a hangover once they turned 21? • Fits the criteria for abuse and dependence • Not showing up for school • Withdrawal or the hangover itself is the alcohol leaving your body and your body compensating biologically

13. Brain Changes Associated with Addiction • adults who used methamphetamine, show enlarged striatal volumes, and changes in metabolism of certain chemicals in the basal ganglia (Alicata, Ernst, Volkow, Nora, 2007). • Study showed significant axonal damage in the brains of poly-drug abusers (Buttner, Rohrmoser, Gita, Randolph 2006). • Increased amounts of the glutamate receptors NMDAR and AMPAR have been shown in drug addicts (Jones, Bonci 2005). • Secondary messenger systems that regulate cAMP increase a chemical that decreases the amount of dopamine released which may be why drug addicts need increasing dosages to have the same “high” (Jones S, Bonci A 2005).

14. Brain Areas Implicated in Addiction • The mesolimbic system is the brain area mainly associated with drug addiction and the neurotransmitter implicated is dopamine. • Nucleus Accumbens “The pleasure center of the brain” • Ventral Tegmental Area- connected to the Nucleus Accumbens and is involved in dopamine release associated with addiction • Basolateral amygdala- Projects to the Nucleus Accumbens and it is involved in motivation (Floresco , Ghods-Sharifi, 2007). • Hippocampus- alters dopamine firing in VTA and Nucleus Accumbens (Kalivas, Volkow, 2005).

15. Theories of Addiction • Morality theory- Theory that drug use was a failure of drug user • Does not account for susceptibility in genetics and family life • The model does not account for brain changes that create an addiction circuit learned by the brain • Physical Dependence Model • Can still create uncomfortable symptoms such as insomnia, irritability, anxiety, or cravings • A common misconception that physical addiction is worse. Psychological addictions and cravings can be tougher to get rid of since there is no definite time that it will take to get over • The model does not account for those who experience cravings or use years after use has discontinues

16. The Disease Model • Treats drug or alcohol addiction as a disease rather than a moral fault • There is genetic evidence that some genes or altered brain chemistry may play a role in who becomes addicted or not • In 2003, males were almost twice as likely to be classified with substance dependence or abuse as females (12.2 vs. 6.2 percent) (Substance Abuse) • Native Americans have a high rate of alcoholism which may be linked to mutations of the enzyme alcohol dehydrogenase (Wall, Garcia Andrade, Thomasson, Carr, Ehlers, 1997) • Genetic differences can create differences in reactions to drugs (Benios, T. 2007). • Altered sensitivity in receptors • Difference in the metabolism of drugs • An example is rats with less D2 and D3 receptors are more susceptible to addiction and are more impulsive than normal rats (Benios, T. 2007).

17. The Moral Model • The addiction is seen as personal or moral weakness • While still accepted by some, it has widely fallen out of favor

18. Self-Medication Model • Theory states that people use drugs because they have an undiagnosed mental illness or are self-medicating through problems, stress, depression or other illnesses • Comorbidity of mental illness and drug use • The prevalence of a serious mental illness was more than twice as high among those who used an illicit drug during the past year than it was among those who did not (17.1 vs. 6.9 percent). (Substance Abuse) • Benzodiazepines • Animal models do not accurately show that animals self-administer benzodiazepines unless physically addicted. • 1) It is very rare according to studies for someone under a doctors care to abuse benzodiazepines (O'brien 2005). People who abuse the medication are people with substance abuse disorders. It could be hypothesized that using this drug is a coping mechanism for an underlying mental illness much like other drug use can be.

19. Opponent-process model and incentive-sensitization model • Begins with initial drug use, and the positive reinforcement from the pleasure of drug use • Drug use is continued, pleasure is continued but lessens over time • Addiction may occur and repeated attempts at abstinence and failure occur • The main difference is the incentive-sensitization theory focuses on the difference between the brain mechanisms wanting and liking, where as the opponent-process focuses on neuronal processes involved in brain mechanisms that evoked strong feelings of pleasure • The incentive-sensitization theory is built on the foundation that liking and wanting are two different phenomenon separate from eachother and there is a switch in addicts from like to want • The Opponent-process model focuses on strong feelings. Withdrawal or stopping use evoked strong negative feelings where as drug use evokes strong positive feelings. Both contribute to addiction

20. Biopsychosocial Model • Encompasses the social network or “drug culture” that reinforces drug behaviors • Encompasses the biological rewards of drug use and the susceptibility of some to addiction at birth • Encompasses the psychological addiction, wanting, craving, and relief from unpleasant feelings

21. Ibogaine • This alkaloid is found in the plant Tabernathe Iboga (Levant, Pazdernik, 2004). It is found in West Africa, and it has been used for hundreds of years for increased energy, rituals, and increasing positive moods • It was made schedule 1 in 1967 • Multiple studies show effectiveness in treatment of drug addiction and its effect on the mesolimbic system ( Levant, Pazdernik, 2004) • Effects are immediate in alleving withdrawal symptoms associated with cocaine, morphine and other drugs (Alper,. Lotsof, Frenken, Luciano, Bastiaans, 1999) • Brain changes outlast pharmacological effects

22. Ibogaine and Plasticity • It seems ibogaine effects brain plasticity and protein expression in the brain and directly effects the addiction circuit in addicts (Levant, Pazdernik, 2004) • This disruption of the neuronal circuit along with tolerance, withdrawal, and cravings shows a disruption in the learning that had taken place with the drug abuse

23. Ibogaine and Drugs • c. Study used rats who self-administered cocaine, the result was a discontinuation in self-administering of cocaine (Cappendijk, Dzoljic, 1993) • d. Another study has shown that ibogaine interferes with the reward pathway of alcohol and results in a decrease in consumption (Halpern, 2007).

24. Ibogaine mechanisms • While it also seems to have a stimulatory effect on brain metabolism, it also inhibited the serotonin transporter SERT (Jacobs, Zhang, Campbell, Rudnick, 2007) • This mechanism may explain how this alkaloid effected rat’s self-administration of cocaine • Another mechanism is its effect on glial cell line-derived neurotrophic factor or GDNF • The amount of GDNF is increased • This has been shown to be a possible candidate for why it interferes with alcohol consumption (Halpern, 2007). • In high dosages, it can be neurotoxic and cause neuronal death in the prefrontal cortex. However, it does not appear in therapeutic dosages to cause problems

25. Drawbacks • Has been shown to be neurotoxic in higher levels • While it does interupt the tolerance and addiction circuit, it could pose a problem • Person just uses to decrease the amount they use which may lead to an increase of overdosages if abstinance is not maintained Not fully understood, but studies around the world are looking at the effectiveness and determining if this will be the future of the treatment of drug-addiction

26. Treatments • Opiate maintenance has the highest success rating of other drug abuse programs with as high as an 80% abstinence rate • Methadone • Full mu agonist that provides steady supply of opiate in blood • Prevents withdrawal symptoms for 24 hours which allows addicts to function • Limited high • tolerance to other opiates develops-decreases pleasure of other opiates • Has to be administered daily by clinic • Opiates have few damaging effects on organ systems so long-term use is possible

27. Buprenorphine • Parial mu opiate receptor agonist • Can be prescribed at doctors which allows for minimum visits and allows for a normal work schedule • It is mixed with the opiate antagonist nalaxone. This does not disrupt normal sublingual dosaging. However, it does prevent using an I.V. to administer the drug • The drug blocks the action of other opiates. Therefore it prevents addicts from being able to administer other opiates in conjunction • If opiate medication is taken, buprenenorphine is competitive and will displace the other drug leaving the person in a state of withdrawal

28. Drawbacks to opiate maintanince • Side-effects include sexual problems, drowsiness, increased sweating, anxiety • However, some may just be because of the use of these weaker opiates • It does cause discontinuation symptoms but are considerably milder than other opiates and can be avoided by gradual reduction

29. C. Drug Abuse Programs • Alcoholics anonymous and narcotics anonymous • 12 steps to sobriety • Requires abstinence from all drugs and alcoholics • There is models of this using cognitive-behavior therapy

30. Bupropion • . Atypical antidepressant that prevents the reuptake of serotonin, dopamine and norepinephrine • It is a stimulant antidepressant with low abuse potential • It has been abused in animal models but when a group of amphetamine addicts were asked to use this once, they stated it did not give them an amphetamine like high or pleasure. • Being tested experimentally to help alleviate those who quit cocaine • Buproprion effects dopamine in a similar way to cocaine which provides relief from cravings and other symptoms of discontinuing cocaine use (Tella, Ladenheim,Cadet 1997).

31. Drawbacks • Side-effects include weight-loss, insomnia, anxiety, depression, and nausea • Has been shown to have mild abuse potential and cause false positive drug tests for amphetamines • It has discontinuation symptoms

32. Drawbacks • An opiate addicts risk of death by anything increases by discontinuing maintanence • Some people oppose because of the idea that the drug addict should not receive this drug- its just a trade off • Brain changes show that opiate users brains years after use is discontinued is still wired differently and can cause cravings and difficulty in maintaining abstinence • While it is a trade-off, the rate of IV use of drugs and drug use decreases as well as the person learns skills to become a more functional part of society

33. Phenibut • Derived from neurotransmitter GABA • Has shown a clear anxiolytic effect in rats • It has been used to treat alcohol addiction and withdrawal, anxiety, menstrual pains, chronic headaches, and insomnia in various countries

34. Theory • Diazapam is a benzodiazapine with GABA-A and GABA-B mechanism of action. • Phenibut theoretically could be used to treat people who wish to discontinue benzodiazapines but are physically addicted and have rebound anxiety • Since phenibut has been used for alcohol withdrawal and anxiety, theoretically it could be used in place of benzodiazapines

35. Drawbacks • It causes sedation, muscle relaxation, and possibly amnesia in larger dosages • It has discontinuation symptoms similar but weaker to that of benzodiazapines-not life-threatening

36. References • Alicata, L.C., Ernst, D., Volkow, T. Nora. (2007). Structural and metabolic brain changes in the striatum associated with methamphetamine abuse. Addiction Supplement. 102, 16-32. • Alper, K.R., Lotsof, H.S., Frenken, G.M., Luciano, D.J., Bastiaans, J., (1999). Treatment of acute opioid withdrawal with ibogaine. American Journal of Addiction. 8, 234–242. • Benios, T. (2007). Presposition for addiction. Scientific American Mind. 18, (3), 13-16. • Buttner, A.. Rohrmoser, K.M., Gita P., Randolph Weis, S. (2006). Widespread axonal damage in the brain of drug abusers as evidenced by accumulation of β-amyloid precursor protein (β-APP): an immunohistochemical investigation. Addiction. 101, (9), 1339-1346 • Cappendijk, S.L., Dzoljic, M.R., 1993. Inhibitory effects of ibogaine on cocaine self-administration in rats. European. Journal of Pharmacology. 241, 261–265. • Eisch, A.J., Harburg, G.C. (2006). "Opiates, psychostimulants, and adult hippocampal neurogenesis: Insights for addiction and stem cell biology". Hippocampus. 16, (3), 271–86.

37. References • Floresco, S.B., Ghods-Sharifi, S. (2007). "Amygdala-prefrontal cortical circuitry regulates effort-based decision making". Cerebral Cortex.17, (2), 251–60. • Halpern, J.H. (2007). Hallucinogens in the treatment of alcoholism and other addictions. Psychedelic medicine: New evidence for hallucinogenic substances as treatments. 2, 1-14. • Jacobs, M.T., Zhang, Y.W., Campbell, S.D., Rudnick, G.. (2007). Ibogaine, a noncompetitive inhibitor of serotonin transport, acts by stabilizing the cytoplasm-facing state of the transporter. Journal of Biological Chemistry. 282. (40), 29441-29447. • Jones S., Bonci, A. (2005). Synaptic plasticity and drug addiction. Current Opinions in Pharmacology. 5, (1), 20–5. • Kalivas, P.W., Volkow, N.D. (2005). The neural basis of addiction: a pathology of motivation and choice. American Journal of Psychiatry. 162, (8), 1403–13. • Levant, B., Pazdernik, T.L., 2004. Differential effects of ibogaine on local cerebral glucose utilization in drug-naive and morphine-dependent rats. Brain Research. 1003, 159–167.

38. References • Meyer, J.S., Quenzer, L.F. (2005). Psychopharmacology: Drugs, The Brain, and Behavior. Sinaur Associates, Inc. • O'brien, C.P. (2005). "Benzodiazepine use, abuse, and dependence". Journal of Clinical Psychiatry. 66, (2) 28–33. • Substance Abuse and Mental Health Services Administration. (2004). Results from the 2003 National Survey on Drug Use and Health: National Findings (Office of Applied Studies, NSDUH Series H–25, DHHS Publication No. SMA 04–3964). Rockville, MD. • Streel, E., Dan, B., Campanella, S., Meyvaert, A., Hanak, C., Pelc, I., Verbanck, P. (2006). A pharmacological modulation of opiate withdrawal using an up-/down-regulation of the noradrenergic system in opiate-dependent rats International Journal of Neuropsychopharmacology. 9, (5), 621-626. • Tella S.R., Ladenheim B., Cadet, J.L. (1997). Differential regulation of dopamine transporter after chronic self-administration of bupropion and nomifensine. Pharmacology and Experimental Therapeutics. 281, (1), 508-513. • Wall, T.L. Garcia-Andrade, C., Thomasson, H.R., Carr, L.G., Ehlers, C.L., (1997). • Alcohol dehydrogenase polymorphisms in native Americans: Identification of the ADH2*3 allele. Alcohol and Alcoholism. 32, (2), 129-132.