The Challenge for IDARS Scientists:  Combating Global Stimulant Abuse

What is IDARS?
“IDARS” is an acronym for the International Drug Abuse Research Society. The purposes of IDARS are scientific, educational and charitable. The Society seeks to promote excellence in: 1) advancing the understanding of drug abuse, substance abuse, and addiction, 2) bringing together scientists of varying backgrounds and disciplines within the field of drug abuse research, 3) integrating drug abuse research directed at all levels of biological organization to improve prevention and treatment efforts, 4) promoting education in the addiction sciences, 5) informing the general public about the results and implications of current research in the addiction sciences.

Who are the members of IDARS?
Members of IDARS are research scientists and clinicians from around the world. The current president of IDARS is Dr. Michael J. Kuhar, Professor of Pharmacology, at the Yerkes National Primate Center of Emory University, in Atlanta, GA. The Executive Officer is Dr. Syed F. Ali, Head, Neurochemistry Laboratory, Division of Neurotoxicology, at the National Toxicological Research Center, Food and Drug Administration, in Jefferson, AR.

IDARS has 3 categories of membership.
Regular Members: Any credentialed research scientist or health professional working in the field of substance abuse may be considered for Regular Membership. Annual dues are $50.
Student and Post-Doctoral Fellow Members: Any post-baccalaureate student matriculated in an advanced degree program, or anyone participating in a post-doctoral training program, in a field related to drug abuse research, may be considered for this category of membership. Annual dues are $20.
Emeritus Members: Upon retirement, any member of IDARS may apply for Emeritus status. In some cases, distinguished scientists will be nominated for Emeritus membership. There are no annual dues for Emeritus members.

The current IDARS Board of Directors:
Peter Dodd, Brisbane, Australia
Francesco Fornai, Pisa, Italy
Carlos Jimenez-Rivera, San Juan, Puerto Rico
Timothy Maher, Boston, MA, USA
Deborah Mash, Miami, FL, USA
Jerrold Meyer, Amherst, MA, USA
Sakire Pogun, Izmir, Turkey
Marcus Rattray, London, UK
Susan Schenk, Wellington, NZ
George Uhl, Baltimore, MD, USA

When does IDARS meet?
IDARS will have annual meetings, where members and non-members alike can share their most recent research data. IDARS plans to hold its first meeting in Spring 2006 in Washington, DC. This year, many members of IDARS will attend a scientific conference entitled, “Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity: Cocaine, GHB and Substituted Amphetamines”, which will take place from August 16-19, in Venice, Italy. The Venice conference is an official Pre-Satellite meeting of the 20th Biennial meeting of the International Society for Neurochemistry (ISN), held jointly with the European Society for Neurochemistry (ESN).

Worldwide Stimulant Abuse – An Emerging Health Crisis
“Stimulant” drugs produce a spectrum of effects that includes increased energy, cardiovascular stimulation, heightened mood and decreased need for sleep. After high doses or long periods of use, stimulants can produce a range of medical complications including heart attacks, strokes, psychotic episodes and seizures. From a molecular perspective, most stimulants interact with monoamine transporter proteins found on nerve cells. Stimulant drugs can be divided into two classes based on their transporter-mediated mechanisms of action: monoamine transporter blockers (i.e., cocaine) and substrate-type monoamine releasers (i.e., amphetamines) [reviewed in Baumann and Rothman, 2003]. It is noteworthy that many stimulants are useful medications with long histories of safety and efficacy, whereas others are highly addictive substances associated with considerable morbidity and mortality. Illicit stimulants are some of most commonly abused drugs worldwide – during the year 2000, it is estimated that 34.3 million people used amphetamines, 14.1 million used cocaine, and 7.7 million used the amphetamine analog, 3,4,-methylenedioxymethamphetamine (MDMA) [UNODC, 2003]. Such evidence supports the emergence of stimulant abuse as global health crisis.

“Super Coke” In Colombia – It’s the Real Thing!
The abuse of cocaine continues to be a problem in the US and other nations around the world. Colombia remains the number one producer of marketable cocaine hydrochloride and provides more than 80% of global supply. Figure 1 shows the explosive growth in Colombian cocaine production in the past few years. Cocaine alkaloid is extracted from the coca plant, Erythroxylaceae coca, which is cultivated throughout the Andean region (see Figure 2). Recently, anti-drug operatives in Colombia have identified genetically-modified (GM) coca plants that produce yields of cocaine much greater than normal. The “super coke” plants grow to heights of 7-9 ft whereas typical coca plants grow to heights of 3-4 ft. Furthermore, the GM plants are resistant to herbicides and produce up to 5-times more cocaine alkaloid than normal plants. The discovery of transgenic coca plants adds a troubling new dimension to the spread of cocaine abuse.

Few treatments options are available for cocaine-dependent patients, and the development of medications to combat cocaine addiction is a major challenge for biomedical research. IDARS scientists have discovered novel approaches for treating cocaine dependence. Christian Heidbreder and colleagues at Glaxo-Smith-Kline have identified and tested the selective dopamine D3 receptor antagonist, SB277011A as a potential treatment for cocaine dependence [reviewed in Heidbreder and Hagan, 2005]. In animal models, SB277011A blocks the ability of cocaine and stress to induce reinstatement of cocaine-seeking behavior [Xi et al., 2004]. Moreover, SB277011A appears to reduce drug-seeking behavior in general, suggesting that D3 antagonists could have anti-addictive efficacy in the treatment of nicotine, opioid and stimulant dependence.

“Ya-Ba” Da-Ba Doom in Thailand
Similar to the cocaine crisis, the abuse of methamphetamine is increasing in the US and abroad. One of worst epidemics of methamphetamine abuse is occurring in Thailand, where 70% of drug addicts, or 2.5 million people, are dependent upon methamphetamine. Most users ingest a tablet formulation of methamphetamine known as “Ya-Ba”, meaning “crazy medicine”. Figure 3 depicts the typical appearance of Ya-Ba tablets. Nearly all Ya-Ba confiscated in Thailand is produced in the neighboring country of Burma, by the drug-trafficking insurgent group, the United Wa State Army (USWA). USWA and other such groups pose a significant threat to the national security of countries in South East Asia and elsewhere. It is estimated that Burmese methamphetamine production exceeds 800 million tablets per year. Figure 4 shows Thai police prepared to destroy large quantities of confiscated Ya-Ba tablets.

The long-term effects of methamphetamine abuse in humans are not well studied, but in rodents, methamphetamine causes depletions of dopamine and serotonin in the brain. Methamphetamine-induced loss of monoamines could underlie depression and suicidal ideation that often accompany drug withdrawal. Members of IDARS have shown that methamphetamine can cause neurotoxic effects. Francesco Fornai and colleagues at the University of Pisa, in Italy, demonstrated that mice treated with methamphetamine display abnormal dopamine cells in the brain [Fornai et al., 2004a]. The affected cells have intracellular inclusions which resemble those found in Parkinson’s disease and other neurodegenerative disorders. Methamphetamine produces similar inclusions in cultured PC12 cells. While the clinical relevance of these data is uncertain, they suggest that methamphetamine abuse could predispose individuals to neurodegenerative disorders [Fornai et al., 2004b].

Ecstasy in the UK and Beyond: It’s Nothing to Rave About!
The “rave” scene continues to be major source of drug abuse in the UK, throughout Europe, and in the US. In particular, the substituted amphetamine MDMA (Ecstasy, or E) is commonly abused at all night dance parties, or raves. Users often take multiple doses of MDMA at once (i.e., “stacking”) or take supplemental doses of the drug repeatedly during the party (i.e., “bumping”). Figure 5 shows some examples of MDMA tablets. US statistics show that medical complications associated with MDMA use have risen exponentially – MDMA-related emergency room visits increased from 253 in 1994 to 4026 in 2002. Young people continue to experiment with MDMA despite the risk of adverse effects including depression, cognitive disturbances and memory problems. Figure 6 depicts a popular DVD program, “Generation E”, that describes the rave culture and criticizes attempts by the US government to criminalize rave-related activities.

The long-term consequences of MDMA abuse in humans are not well understood, and there is disagreement concerning the reinforcing properties of MDMA in animals and humans. IDARS scientists are exploring the potential addictive properties of MDMA. Susan Schenk and colleagues at University of Wellington, in New Zealand, have developed a novel paradigm where rats learn to self-administer MDMA [Schenk et al., 2003]. Their work shows that MDMA is a positive reinforcer in rats, and prior experience with cocaine engenders more rapid acquisition of MDMA intake. Dopamine appears to be involved in the addictive properties of MDMA, since D1 dopamine receptor antagonists reduce self-administration of the drug [Daniela et al., 2004]. These findings may have implications for the development of treatments for MDMA addiction.

New “Legal Highs” in New Zealand
A number of non-amphetamine designer drugs have appeared on internet websites where they are marketed as “legal Ecstasy”. In particular, the substituted piperazine analogs 1-benzylpiperazine (BZP, or ‘A2’) and 1-(m-trifluoromethylphenyl)piperazine (TFMPP, or ‘Molly’) are increasingly trafficked in the US, Europe, and elsewhere. BZP produces amphetamine-like stimulant effects in humans, suggesting the potential for abuse. Figure 7 shows BZP tablets confiscated by US authorities. The US DEA has moved swiftly to place BZP in Schedule 1 of the Controlled Substances Act, making possession of this substance a criminal offense. In other places, however, BZP is legally available. A significant level of BZP abuse is occurring in New Zealand, where BZP is widely sold over the internet and at “party pill” shops. Figure 8 depicts the Rave.Net.NZ website, a popular site for sharing information about the rave scene in New Zealand.

The pharmacology of BZP, and other substituted piperazines, is not well characterized, but available data suggest that BZP has stimulant properties. Members of IDARS are examining the neurobiological effects of BZP in animal models. Michael Baumann and colleagues at the NIDA IRP have shown BZP interacts with monoamine transporters to release dopamine and serotonin from brain tissue in vitro [Baumann et al., 2005]. Microdialysis studies in rats show that BZP causes elevations in extracellular monoamines that are similar to the effects of methamphetamine. Likewise, self-administration studies in monkeys demonstrate that BZP is a powerful reinforcer with significant abuse liability [Fantegrossi et al., 2005]. The long-term effects of BZP are unexplored and warrant further investigation.

Michael H. Baumann, Ph.D., Staff Scientist, IRP, NIDA, NIH, Baltimore, MD, USA
Chairman, Membership Committee, International Drug Abuse Research Society (IDARS)

References
Baumann MH, Clark RD, Budzynski AG, et al. (2005) Neuropsychopharmacology 30: 550-560.
Daniela E, Brennan K, Gittings D, et al. (2004) Pharmacol Biochem Behav 77: 745-750.
Fantegrossi WE, Winger G, Woods JH, et al. (2005) Drug Alcohol Depend 77: 161-168.
Fornai F, Lenzi P, Gesi M (2004a) J Neurochem 88: 114-123.
Fornai F, Lenzi P, Gesi M (2004b) Ann N Y Acad Sci 1025: 162-170.
Heidbreder CA, Hagan JJ (2005) Curr Opin Pharmacol 5:107-118.
Rothman RB, Baumann MH (2003) Eur J Pharmacol 479: 23-40.
Schenk S, Gittings D, Johnstone M, et al. (2003) Psychopharmacology 169: 21-27.
UNODC (2003) Global Illicit Drug Trends, New York, NY, United Nations Office on Drugs and Crime.
Xi Z, Gilbert J, Campos AC, et al. Psychopharmacology 176: 57-65.

The IDARS reception held at the NIDA International Forum is generously supported by the following sponsors:

Bio-Rad Laboratories
C.A.R.E., Inc., Addiction Treatment Center
G & G Holistic Addiction Treatment, Inc.
Geller and Geller, P.A., Attorneys at Law
Luis and Stavroula Mendez
Novoneuron, Inc., Miami, FL.
Ocean Drive Magazine
Tango Technology

Source: www.idars.org/docs/IDARS-Final.doc

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How does Ritalin work? What will it do for me?

Methylphenidate belongs to the family of medications known as stimulants. It is used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy (uncontrollable need to sleep) in children over 6 years old and adults. It helps to increase attention and decrease restlessness in children and adults who have been diagnosed with ADHD. Other measures (e.g., psychological, educational, and social therapies) are used along with methylphenidate as part of an overall treatment program for ADHD. This medication also helps to stimulate people with narcolepsy so that they do not fall asleep at inappropriate times.

Your doctor may have suggested this medication for conditions other than the ones listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.
How should I use Ritalin?

The dose of methylphenidate needs to be individualized according to the needs of the person taking the medication. The dose is usually started low and increased gradually to the dose that works best for the person. The usual starting dose for this medication is 5 mg to 10 mg two or three times daily. Doses above 60 mg daily are not recommended. If symptoms worsen or if side effects occur, contact your doctor for further instruction. In many cases for children, the medication does not need to be continued after puberty.

Take methylphenidate with or shortly after a meal or snack.

If you are taking the SR tablets, swallow the medication whole and do not crush or split the tablets.

Many things can affect the dose of medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones above, do not change the way that you are taking the medication without consulting your doctor.

It is important that this medication be taken exactly as prescribed by your doctor. If you miss a dose, take it as soon as possible and continue on with your regular schedule. If it is almost time for your next dose, skip the missed dose and continue on with your regular dosing schedule. Do not take a double dose to make up for a missed one.

This medication is available under multiple brand names and in several different forms. Any specific brand name of this medication may not be available in all of the forms listed here. The forms available for the specific brand you have searched are listed under “What form(s) does this medication come in?”

What form(s) does Ritalin come in?

10 mg
Each pale blue, round, flat-faced, beveled-edged tablet, scored and imprinted “AB” on one side with “CIBA” on the other, contains methylphenidate HCl 10 mg. Nonmedicinal ingredients: cornstarch, FD&C Green No. 3, lactose, magnesium stearate, polyethylene glycol, sugar and talc.

20 mg
Each pale yellow, round, flat-faced, beveled-edged tablet, scored and imprinted “PN” on one side with “CIBA” on the other, contains methylphenidate HCl 20 mg. Nonmedicinal ingredients: D&C Yellow No. 10, lactose, magnesium stearate, polyethylene glycol, sugar, tragacanth and talc.
Some medications may have other generic brands available. Always ask your doctor or pharmacist about the safety of switching between brands of the same medication.
Who should NOT take Ritalin?

Methylphenidate should not be taken by anyone who:
is allergic to methylphenidate or to any of the ingredients of the medication
is taking an monoamine oxidase (MAO) inhibitor (e.g., phenelzine, tranylcypromine) or has taken one in the last 14 days
has advanced hardening of the arteries
has an overactive thyroid gland
has anxiety, tension, or agitation
has glaucoma (increased pressure in the eye)
has heart disease
has moderate-to-severe high blood pressure
has motor tics, Tourette’s syndrome, or a family history of Tourette’s syndrome
has pheochromocytoma (a condition that causes excess production of epinephrine and norepinephrine hormones)

What side effects are possible with Ritalin?

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent. The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.
agitation, nervousness, or anxiety
diarrhea
dizziness or drowsiness
dry mouth
headache
heartburn
joint pain
loss of appetite
nausea or vomiting
skin rash or itching (mild)
stomach pain
trouble sleeping

Although most of the side effects listed below don’t happen very often, they could lead to serious problems if you do not seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:
chest pain
confusion
hallucinations (hearing, seeing, or feeling things that are not actually there) or abnormal thoughts or behaviour
increased blood pressure
muscle twitching or tics
palpitations (feeling your heart beat quickly or irregularly)
pinpoint-sized red spots on skin or unusual bruising
prickling or tingling sensations in the hands, arms, feet, or legs
sore throat and fever
sudden high fever
sweating
symptoms of depression (e.g., losing interest in your usual activities, feeling sad, having thoughts of suicide – see below)
symptoms of liver damage (e.g., yellow skin or eyes, abdominal pain, loss of appetite, pale stools, dark urine)
symptoms of Tourette’s syndrome (involuntary, sudden body movements or uncontrolled vocal outbursts)
vision changes

Stop taking the medication and seek immediate medical attention if any of the following occur:
convulsions (seizures)
peeling or blistering of the skin
signs of a serious allergic reaction (difficulty breathing; hives; swelling of the face, lips, eyes, mouth, or throat)
thoughts of suicide or hurting yourself

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.
Are there any other precautions or warnings for Ritalin?

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Behaviour or mood changes: There have been reports of agitation, hallucinations, symptoms of depression, and thoughts of self-harm in people taking this medication. If you experience these types of symptoms while taking methylphenidate, contact your doctor immediately

Blood pressure: This medication may increase blood pressure. People with high blood pressure or heart problems talk to their doctor before taking this medication.

Drowsiness/reduced alertness: Methylphenidate may affect the mental or physical abilities needed to drive or operate machinery. People taking this medication are cautioned against undertaking these and other potentially hazardous activities until they determine if the medication affects them in this way.

Drug dependence: Abuse of methylphenidate is possible by certain individuals. This can lead to high levels of tolerance and psychological dependence, and a wide range of abnormal behaviours. People with a history of drug or alcohol dependence should be carefully monitored by their doctors while using this medication.

Epilepsy: There is some evidence that methylphenidate may increase the risk of seizures for people who have had seizures before.

Exercise: People participating in strenuous exercise or activities should consult their doctor before taking methylphenidate.

Heart problems: This medication can increase heart rate and blood pressure. It may also increase the risk of sudden death for people with heart problems. This medication should generally not be used by people with known heart problems, including an irregular heartbeat, known structural heart abnormalities (such as abnormal size, missing or poorly functioning heart valves, or problems with blood vessels connected to the heart), or a family history of sudden death related to heart disease.

Heart or brain circulation problems: People who have, or have a history of, heart or brain circulation problems should be closely monitored by their doctor while using this medication.

Long-term use: If you will be using this medication for a long period of time, you will need regular heart check-ups and lab tests to check your white blood cell counts.

Stopping the medication: Check with your doctor before stopping this medication.

Suppression of growth: Growth suppression (i.e., less increase in height or weight than usual) has been reported for children using stimulants such as methylphenidate for long periods of time. It is not known if the medication causes the growth suppression. However, children who need long-term therapy should be carefully monitored for growth. Their doctor may also recommend a “drug holiday,” where the medication is not given on weekends or during school holidays.

Vision: Rarely, people taking methylphenidate have experienced vision changes. If you notice any changes in your vision, contact your doctor.

Pregnancy: This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding: It is not known if this medication passes into breast milk. If you are a breast-feeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children: The safety and effectiveness of this medication have not been established for children under 6 years old. Methylphenidate should not be used by children of this age group.
What other drugs could interact with Ritalin?

There may be an interaction between methylphenidate and any of the following:
alcohol
amphetamines (e.g., dextroamphetamine)
antidepressants (e.g., amitriptyline, imipramine, fluoxetine)
appetite suppressants (e.g., phentermine)
carbamazepine
clonidine
guanethidine
monoamine oxidase (MAO) inhibitors (e.g., phenelzine, tranylcypromine)
methyldopa
other medications for ADHD
phenobarbital
phenytoin
primidone
sympathomimetic medications (e.g., epinephrine)
warfarin

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:
stop taking one of the medications,
change one of the medications to another,
change how you are taking one or both of the medications, or
leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

Source: http://bodyandhealth.canada.com/drug_info_details.asp?channel_id=0&relation_id=0&brand_name_id=971&page_no=1

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