HISTORY MPH PHARMACOLOGY METHYLPHENIDATE HYDROCHOLORIDE- RITALIN. RITALIN ADDICTION PAOLA ROSCA Head Depart. for the Treatment of Substance Abuse

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1 METHYLPHENIDATE HYDROCHOLORIDE- RITALIN RITALIN ADDICTION PAOLA ROSCA Head Depart. for the Treatment of Substance Abuse Ministry of Health December 2013 HISTORY Ritalin was synthesized in 1944 by the chemist Andrea Pezzolan at Ciba-Geigy The name Ritalin comes from his wife Margherita`s nick name- Rita who suffered from low blood pressure and used Ritalin to increase it. It was first used for ADHD in 1955 Its use highly increased in the 90s due to increased ADHD detection and diagnosis It is indicated for the medical treatment of ADHD and narcolepsy. It is sometimes used to increase alertness, energy, mood. A PSYCHO-STIMULANT DRUG OF THE PHENETYL-AMINE CLASS His formula is C14H19NO2 DA re-uptake inhibitor and a weaker NE re-uptake inhibitor and increases the levels of these neuro-transmitters in the brain. It is on the list of substances banned from sports competitions by the World Anti-Doping Agency In the Us is classified as Schedule II controlled substance because of its potential for misuse and addiction The risk to develop dependence is relatively low for ADHD subjects In Israel it is scheduled as an addictive drug in the Bill for Dangerous Drugs

Its therapeutic effect on cognition is exerted by increasing the level of catecholamines in the pre-frontal cortex, and the cortical and sub-cortical regions projecting to it thus improving cognition

These effects are active in different systems such as the attention system. The psychological effects are mediated by N.

2 Its therapeutic effect on cognition is exerted by increasing the level of catecholamines in the pre-frontal cortex, and the cortical and sub-cortical regions projecting to it thus improving cognition and behavior in ADHD subjects. It primarily inhibits the re-uptake of DA by pre-synaptic neurons thus leaving more DA in the synapse to interact with post-synaptic neurons. These effects are active in different systems such as the attention system. The psychological effects are mediated by N. Acc, Ventral Striatum, and the reward system thus creating euphoria with a potential for addiction IMMEDIATE DANGERS: Panic attacks Serious heart attacks Over-dose SIDE-EFFECTS Headache Decreased appetite Increased heart rate Insomnia, restlessness, anxiety Paranoia or worsening of previous psychotic condition Euphoria, manic reaction Weight loss Growth consequences Rebound Epilepsy, Tics Long-term side effects Tolerance Dependence Non-prescription use Diversion Its physical effects include activation of the sympathetic system-( fight\flight response) producing increased heart rate and blood pressure. Its main route of metabolism is hepatic trough CYTP450 Its main route of administration is oral- immediate and slow release preparations(concerta) It can be misused by snorting- it can be dangerous because it creates vaso-constriction in the mucosa of the nose and prolonged misuse can cause septum necrosis or erosion. It can be injected- easy over-dose, rush and permanent artery and vein damage and infections. There exists a trans-dermal preparation- DAYTRANAreducing misuse and improving therapeutic effect especially in children.

MISUSE OF MPH AMONG HIGH-RISK POPULATIONS High-risk populations are more prone to misuse MPH and develop dependence Lesbian,Gay and Bi-sexual high risk adolescents were found more prone to MPH misuse

3 MISUSE OF MPH AMONG HIGH-RISK POPULATIONS High-risk populations are more prone to misuse MPH and develop dependence Lesbian,Gay and Bi-sexual high risk adolescents were found more prone to MPH misuse in the USA compared to unisex adolescents. They showed earlier age of misuse of stimulants Earlier misuse of other substances and a trend to inject opioids Among the predictors: Sexual and physical abuse during childhood Drug availability, own prescription and presence of the drug in the house-hold. Misuse of Prescription drugs among high-risk young adults in LA and NY THE RESEARCH WAS CONDUCTED ON A SAMPLE OF 509 YOUNG ADULTS YEARS OLD- WITH MISUSE OF PRESCRIPTION DRUGS DURING THE PAST 90 DAYS 3 GROUPS : IDUs, homeless and poly-drug users were interviewed Results: Initiation of prescription stimulants initiated before illicit stimulants Combining prescription and illicit stimulants occurred frequently during drug using events Misuse of Prescription drugs among highrisk young adults in LA and NY Prescription drugs are primary substances of abuse alongside illicit drugs during the past 10 years in the US It is increasingly viewed as a public health concern as it is associated with risk practices- sexual risk behavior, poly-drug use, injection drug use, negative health outcomes-dependence and overdose. Stimulants were prescribed at earlier ages followed by tranquillizers and opioids A significantly greater percentage in LA was prescribed stimulants compared to NY where more opioid medications were prescribed. Misuse of Prescription drugs among high risk young adults in NY and LA Adderall was the most frequently misused stimulant, followed by Ritalin,Concerta and Dexedrine. NY participants were misusing much more. They misused them in different modalities such as snorting, injecting and smoking. One-quarter ever injected the stimulants. Combining drugs during a single event was the most common practice They misused at least one prescription drug during the last 90 days NY participants reported more frequent co-use of stimulants and cocaine.

-Misuse of prescription drugs in high-risk young adults in LA & NY Life-time history of receiving a prescription for a stimulant was high -88% and they were prescribed them much earlier than the age

Initiation of prescription drugs started in the early-mid teens, after marijuana and before illicit drugs They may serve as a pathway to the use of illicit stimulants in some cases.

4 -Misuse of prescription drugs in high-risk young adults in LA & NY Life-time history of receiving a prescription for a stimulant was high -88% and they were prescribed them much earlier than the age of first misuse- participants used them as prescribed long-time before they started misusing them. Initiation of prescription drugs started in the early-mid teens, after marijuana and before illicit drugs They may serve as a pathway to the use of illicit stimulants in some cases. The pattern of misuse in the different cities appear to conform to the differences in the local black market Misuse and Diversion of stimulants prescribed for ADHD Do ADHD patients misuse and divert their medication? Prospective longitudinal studies show that ADHD per se is a risk factor for subsequent drug abuse ADHD pharmacotherapy in childhood reduces the risk for substance use disorder Misuse and diversion of prescribed stimulants occur in a minority of ADHD patients, especially those with conduct disorder or previous substance use disorder Long-acting stimulants seem to be less likely abused or diverted. Lankenau et al, J. Pub Health Res,2012;1(1): Faraone,Wilens, J Clin Psych 2007, 68 Suppl 11: Misuse and Diversion of stimulants used for ADHD A systematic review of the literature identified 21 studies on 113,104 subjects Rates of non-prescribed stimulant use range 5%-9% among high-school age children, and 5%-35% among college students. Life-time range of diversion ( give, sell or trade their medication) among students- 16%-29% The profile of at risk subjects for diversion and misuse: Whites Members of fraternities or sororities Misuse and Diversion of stimulants used for ADHD Individuals with lower grades Immediate release versus extended release medication users Subjects with severe ADHD symptoms Reported reasons for misuse and diversion of stimulants include : to better concentrate, improve alertness, get high, lose weight or to experiment. Wilens et al, J Am Acad Child Adolesc Psychiatry, 2008; 47(1):21-31.

Patterns and predictors of diversion and misuse in adult prescribed MPH Medication misuse, diversion and level of compliance appear to be interrrelated and associated with concurrent substance abuse

in a ADHD support group The use of prescription stimulants by normal healthy people to enhance cognition is on the rise and it has become a major issue The practice is common among college and

smart pills Smart pill definition - a drug increasing the cognitive ability of anyone taking it whether the user is normal or cognitively impaired.

5 Patterns and predictors of diversion and misuse in adult prescribed MPH Medication misuse, diversion and level of compliance appear to be interrrelated and associated with concurrent substance abuse MPH misuse associated with the use of illicit stimulants such as amphetamine and cocaine Diversion associated with age and age at first MPH prescription Compliance was associated with participation in a ADHD support group The use of prescription stimulants by normal healthy people to enhance cognition is on the rise and it has become a major issue The practice is common among college and university students The cognitive effects of stimulants on healthy subjects are not definitely clear despite the volume of research conducted The question remains whether prescription stimulants are smart pills Smart pill definition - a drug increasing the cognitive ability of anyone taking it whether the user is normal or cognitively impaired. In 1960 Corneliu Giurgea, a romanian neuro-scientist was the first proposing that smart pills should be developed to increase the intelligence of the general population Among smart substances also caffeine and nicotine are included. Prescription stimulants used to treat ADHD have become recently popular among healthy people to increase performance at school or at work PRESCRIPTION STIMULANTSD AS In 2008 Nature magazine conducted a poll among its readers concerning their cognitive- enhancing habits. Hundreds of them responded and about 1/5 reported using drugs to enhance cognition and among them particularly RITALIN Novak et al, surveyed a sample of more than 4000 subjects from the Harris Poll On-line Panel and found that 4.3% between had used prescription stimulants non-medically during the past year and 1.3% between College students compared to non-students of the same age were more likely to use prescription stimulants non-medically

6 Frequency of use: Most studies showed sporadic use. Most students turned to stimulants at exam time only or under pressure to study for multiple exams Motivations for use The most common reason for use was cognitive enhancement, with top reasons: CONCENTRATION and ATTENTION Other reasons: memorize, study, improve academic grades, alertness, performance Other reasons included: stay awake, get high, be able to drink and party longer without feeling drunk, lose weight, experiment, for recreational purposes. Do they enhance learning? Most of the studies showed some improvement on longterm effects on learning and consolidation of declarative memory and not on immediate effects. Do they improve working memory? Mixed results. Greater improvement for less able participants. Do they improve cognitive control? Mixed results. In a placebo- controlled study effect on cognitive control was greater for people with poor placebo effect, COMT genotype associated with poor executive functions and more impulsive in their life. Do they improve executive functions? Mixed results.1/3 showed no effects on healthy nonelderly subjects. One hypothesis is that they exert a true effect, showed by brain activation in brain imaging studies, but it is too small to be detected in many studies Results vary depending on genetics, individual characteristics, ability, personality, dosage and task characteristics. Effect on motivation Students reports show that prescription stimulants make school work more interesting, thus affecting performance Risk of Dependence It is estimated that 1/20 non medical users of prescription stimulants are addicted or abusers. Ethical issues Use in elementary school children who perform better with stimulants. Un-equal chances at school or work More studies required on cognitive enhancement at work Smith, Farah, Psychol Bull 2011,137(5):

Prescription Stimulants Cognitive effects Studies in non-adhd adults suggest that stimulants do not improve acquisition of new information, might improve retention of information, facilitate memory

7 Prescription Stimulants Cognitive effects Studies in non-adhd adults suggest that stimulants do not improve acquisition of new information, might improve retention of information, facilitate memory consolidation They may impair performance on tasks requiring adaptation, flexibility and planning It is still not clear whether enhancement occurs only when there is a baseline deficit They might influence cognition by their effects on physiological arousal No conclusive evidence that stimulants are cognitive enhancers. Thanks for your attention!!! Advokat C, Neurosci Behav Rev, 2010, 34(8):

1 STUDYING THE STUDY DRUG: ADDERALL. iaddiction.com

1 STUDYING THE STUDY DRUG: ADDERALL Societal Impact of the Drug A stimulant often prescribed for attention deficit hyperactivity disorder (ADHD) and narcolepsy, Adderall has become a drug of choice for