methylphenidate

AKA

Adhansia XR®, Aptensio XR®, Biphentin®, Concerta®, Cotempla XR-ODT®, Daytrana®, Foquest®, Jornay PM®, Metadate CD®, Methylin®, Methylin ER®, Ritalin®, RitalinLA®, Quillivant ER®, Quillivant XR®, Quillichew ER®, ACT Methylphenidate ER®, Apo-Methylphenidate®, PMS-methylphenidate®, Ratio-methylphenidate®, Sandoz Methylphenidate SR®, Apo-Methylphenidate ER®, and others.

Purpose [+] Anti-ADHD, Treatment of Narcolepsy

HIDE ALL

SHOW ALL

Alcohol

Booze, ethyl or ethanol, adult beverage, brew, brewski, liquor, drink, shot, sauce, rot gut, hooch, giggle juice, moonshine, jello shots, wobbly pop

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Interaction
The CNS effects of methylphenidate may be enhanced by concomitant use of alcohol.

a) Increased energy and euphoria and a decreased sensation of being drunk were cited as the primary reasons for taking methylphenidate with alcohol by 17 subjects. Some subjects also reported occasionally adverse effects such as nausea, insomnia, and jaw clenching.

b) A significant increase in methylphenidate AUC (25%) and peak plasma concentrations (40%) were see in a study of 20 subjects who were given alcohol and methylphenidate; it did not matter whether the dose of alcohol was given 30 minutes before or 30 minutes after the methylphenidate.

c) Methylphenidate and alcohol produce their stimulant-like subjective effects by a shared mechanism: increased rating of stimulant-like subjective effects such as increased heart rate and blood pressure, and improved vigilance performance after dextroamphetamine (a drug similar to methylphenidate), and increased rating of sedative-like subjective effects, increased heart rate and blood pressure and impaired vigilance after alcohol.

Mechanism
b) The mechanism for altered pharmacokinetics of methylphenidate appears to be related to the decreased esterase metabolism of methylphenidate from ethanol or ethylphenidate (the transesterification product of ethanol and methylphenidate).

c) Alcohol is a sedative drug but also has stimulant-like effects. the stimulant-like effects of ethanol are mediated by catecholamines, such as dopamine. Methylphenidate is a dopamine and norepinephrine agonist and reuptake inhibitor. Since stimulant-like effects of both alcohol and methylphendiate are mediated through catecholamine systems, stimulant-like subjective, cognitive, and performance responses of the two drugs should be positively correlated.

Significance
a,b) Alcohol use is not recommended in individuals taking methylphenidate due to potential exacerbation of methylphenidate CNS effects.

c) Patients who experience pronounced stimulant-like effects from alcohol also report greater stimulant effects from related stimulant medication dextroamphetamine. This correlation does not apply with performance measures, such as the DSST (digit symbol substitution test), or vigilance task performance or heart rate, suggesting that these other effects are mediated by a different mechanism.

Serious Risk for Harm

Methylphenidate makes some people feel more awake and alert. If you have been drinking alcohol, taking methylphenidate might fool you into feeling alert enough to drive, or do other activities requiring alertness. This would be false. You may still be impaired, and it would be unsafe to drive.

Think First

Alcohol may increase the levels of methylphenidate in your blood to unsafe levels, potentially causing more unwanted effects such as jittery or irritable feelings, trembling hands, or trouble sleeping.

Think First

If you are depressed, blue, or moody, alcohol is a 'downer' and will make you feel worse.

Tobacco

smokes, butts, cigs, cigars, darts, stogies, cancer sticks, chew, dip

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Interaction
a) 33 smokers with and without ADHD were given moderate doses of methylphenidate (10-40 mg). Methylphenidate did not seem to have an effect on smoking-reinforced responding.

b) In an open-label study of 154 participants, use of extended-release methylphenidate was associated with low rates of smoking in those with ADHD.

c) In a prospective observational study, individuals with ADHD who received methylphenidate increased their tobacco consumption compared to when they were not taking methylphenidate.

Mechanism
a,b) Evidence suggests that individuals with ADHD smoke more than their non-ADHD counterparts, possibly because the effects of nicotine on cognition are similar to the effects of stimulants such as methylphenidate. Therefore, individuals who take stimulants may be less likely to smoke cigarettes, as this may "replace" the desire for the effects of smoking.

Significance
a-c) Overall, the effects of methylphenidate of tobacco consumption are conflicting. More studies are needed to draw a conclusion regarding the effects of methylphenidate on smoking.

Think First

If you take methylphenidate you may find you want to smoke cigarettes less often. More information is needed to figure out if the combination of tobacco and methylphenidate is safe.

Caffeine

coffee, java, joe, soda, pop, tea, energy drinks (Red Bull®, Monster®, Rock Star®, Amp®, NOS®, Full Throttle®, 5-hour Energy Drink®, Beaver Buzz®), chocolate, cocoa

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Interaction

Methylphenidate has the potential to enhance the adverse or toxic effects of other sympathomimetics, such as caffeine.

Mechanism

Additive sympathomimetic effects.

Significance

Patients should be monitored for increased sympathomimetic effects such as increased blood pressure or heart rate if these drugs are used concomitantly. Patients should also be counselled to avoid excessive caffeine intake.

Think First

Lots of caffeine could make the side effects of methylphenidate worse. This includes jittery or irritable feelings, trembling hands, or trouble sleeping.

Cannabis/ Hash

Marijuana, mary jane, BC bud, blunt, chronic, J, jay, joint, hemp, pot, grass, herb, 420, dope, THC, weed, reefer, ganja, gangster, skunk, hydro, hash oil, weed oil, hash brownies, grease, boom, honey oil, K2, spice, poppers, shatter, budder

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Interaction

Use of cannabis has the potential to increase the tachycardic effect of methylphenidate.

Mechanism

Additive sympathomimetic effects.

Significance

The clinical significance of this interaction is unclear.

Think First

Using cannabis while taking methylphenidate could make your heart beat too fast.

Cocaine/ Crack

coke, snow, flake, nose candy, blow, lady white, stardust, rock, crystal, bazooka, moon rock, tar

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Interaction

a) In a placebo-controlled study of cocaine users given 60 or 90 mg of methylphenidate, no significant changes were observed in the pharmacokinetics or the physiological effects of cocaine (20 or 40 mg IV). However, a decrease in some of the positive subjective effects was observed.

b) A second study also observed a reduction in positive and reinforcing effects of cocaine when methylphenidate was co-administered.

c) In a 40 year old male with ADHD who sought out help for addiction (cocaine, gambling, and compulsive sexual behaviour), extended-release methylphenidate managed his addictive behaviours, and after 1 year, he was addiction-free.

d) A 43 year old male was diagnosed with ADHD after years of a cocaine addiction, with some bouts of cocaine-induced psychosis. He was given methylphenidate after 2 months of cocaine abstinence. He used cocaine concomitantly with methylphenidate, and experienced a psychotic episode.

e) 73 cocaine dependent individuals in a multi-centre randomized, double-blind, placebo-controlled trial receiving opioid agonist treatment (OAT) received related drug sustained-release (SR) dextroamphetamine or placebo for cocaine use disorder. The dextroamphetamine group had a significantly higher number of cocaine-abstinent days.

f) A large meta-analysis has shown efficacy of high doses and extended-release formulations of prescription psychostimulants in cocaine use disorder.

Mechanism

a,b) The mechanism of this interaction is unclear.

c) Methylphenidate is a CNS stimulant which blocks the dopamine transporter in the brain. The positive reinforcement and reward centers of the brain (which would be dysfunctional in ADHD) are the regions most affected by methylphenidate. This effect by methylphenidate is likely the mechanism for methylphenidate helping with addiction management.

d) Methylphenidate and cocaine are both dopamine agonists, each which alone may cause psychotic episodes. Therefore, the combination of methylphenidate and cocaine may lead to an additive risk of psychosis.

e, f) The mechanism is unclear. Amphetamines/stimulants can mimic the stimulating effects of cocaine, acting as agonists with slower kinetics and a long elimination half-life, which provides stability and less euphoric and discontinuation effects.

Significance

a) Based on the limited data available, stimulant medications should be used with caution in patients taking cocaine. The authors of the first study above suggested that 60 or 90 mg doses of methylphenidate may be safely used in patients who use cocaine. The authors of the second study concluded that sustained release formulations (40 and 60 mg) appeared safe to use in cocaine abusers.

b) While concomitant use of methylphenidate did increase the cardiovascular effects of cocaine, the increase was not clinically significant in this study.

c) Methylphenidate may be helpful in managing addiction in individuals with ADHD.

d) Individuals who use cocaine while taking methylphenidate may be at higher risk of psychosis and should be monitored. More studies are required to draw a conclusion.

e, f) Dextroamphetamine SR and other mixed amphetamine salts may be beneficial in reducing cocaine use. Further larger studies are required to confirm this use.

Serious Risk for Harm

Cocaine and methylphenidate have some things in common, like the way they can affect your heart and blood pressure if you have too much. Taken together, we think the risk is greater. You could get a dangerously fast heart beat, or too high blood pressure. There is a risk of you getting heart damage, seizures, or even a stroke.

Think First

Using cocaine while you are taking methylphenidate may cause you to have a milder high.

Think First

Some doctors may prescribe medical amphetamines or stimulants to reduce the desire (often called "cravings") to use cocaine. This is done very carefully with close monitoring.

Opioids

codeine, Tylenol #3®, cody, meperidine, Demerol®, DXM, dextromethorphan, robo, skittles, morphine, morph, monkey, methadone, bupe, sub, or dollies, oxycodone, Oxycontin®, hillbilly heroin, OxyNeo®, OC, oxy, roxy, percs, fentanyl, Sublimaze®, Duragesic®, china white, hydrocodone, Hycodan®, Vicodin®, suboxone®, buprenorphine, vike, heroin, H, horse, junk, smack, brown sugar, black tar, down, china white, purple drank, W18, carfentanil, elephant tranquilizer, loperamide, lope, lean

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Interaction

In a study of 32 patients with advanced cancer and chronic pain, methylphenidate administration (10 mg with breakfast and 5 mg with lunch) augmented the analgesic effect of opioids (hydromorphone, levorphanol, morphine and oxycodone) and decreased opioid-induced drowsiness.

Significance

Concurrent administration of methylphenidate and opioids may allow for a lower opioid dose to be used in patients on long-term opioid treatment.

Unknown Dangers

Unknown dangers.

Think First

Sometimes doctors prescribe methylphenidate for patients taking opioids, but this is done carefully, with close monitoring.

Amphetamines/ Stimulants

uppers, ecstasy, E, X, Molly, mesc, XTC, love drug, MDA, MDE, Eve, MDMA, adam, disco biscuit, bennies, black beauties, Dexedrine®, Adderall®, dexies, Ritalin®, speed, crystal, meth, ice, glass, crank, tweak, cat, qat, kat, khat, bath salts, Ivory Wave, Vanilla Sky, Cloud 9

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Interaction
a) As a sympathomimetic, methylphenidate has the potential to enhance the adverse or toxic effects of other sympathomimetics, such as amphetamines.

b) 56 individuals with methamphetamine-dependence received methylphenidate. Patients who were given methylphenidate had less amphetamine-positive urine tests and less cravings for methamphetamine. There were no significant differences in adverse drug reactions between methamphetamine-dependent individuals who received methylphenidate or placebo.

c) 16 individuals were given methylphenidate in combination with MDMA. There were no significant changes in psychotropic effects when the two drugs were combined, but the adverse hemodynamic response (increased blood pressure and heart rate) and other adverse events were higher with the combination.

Mechanism
a) there is direct overlap of the mechanism of action between methylphenidate and amphetamines or other stimulants, since all increase CNS dopamine and norepinephrine activity.

b) The mechanism for this may be due to that methylphenidate antagonizes the effects of methamphetamine in vitro, or that methylphenidate acts as a “replacement” to methamphetamine.

c) The mechanism is likely pharmacodynamic in nature.

Significance
a,c) Patients should be monitored for increased sympathomimetic effects such as increased blood pressure or heart rate if these drugs are used concomitantly. Patients should also be counselled on avoidance of amphetamine use while taking methylphenidate.

b) Methylphenidate may be useful in managing methamphetamine-dependence.

Serious Risk for Harm

Methylphenidate and amphetamines have some things in common, kind of like cousins in the 'chemical family'. Taking methylphenidate and street amphetamines together could put you at risk of severe side effects. It could cause dangerous heart problems, high blood pressure, or even seizures. It would be like taking too much amphetamine.

Phencyclidine/ Ketamine

PCP, angel dust, PeaCe Pill, rocket fuel, love boat, embalming fluid, elephant tranquilizer, hog, illy, wet, wet stick, dipper, toe tag, cadillac, snorts, or surfer, Special K, vitamin K, CVR, cat tranquilizer, cat valium, jet, kit kat, Ketalar®

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Interaction

KETAMINE: a) A 6-year-old boy taking methylphenidate 5 mg twice daily for ADHD was given midazolam 20 mg orally for a procedure requiring sedation. After 20 minutes, he was only mildly sedated and would not lie still. He was given an additional 10 mg oral dose of midazolam mixed with ketamine 60 mg orally but remained alert and uncooperative. Sedation was then successfully achieved with intravenous glycopyrrolate and midazolam over 5 minutes. His recovery was uneventful, but he experienced nausea, vomiting and lethargy after discharge.

b) In an attempt to speed recovery, methylphenidate (20 mg IV) was given to 30 patients after a short urologic procedure requiring sedation with ketamine. No improvement in recovery scores were seen and patients experienced a higher incidence of vomiting, excessive talking and limb movement.

PHENCYCLIDINE: No information available.

Mechanism

KETAMINE: a) it was thought that the methylphenidate antagonized the sedative effects of midazolam and ketamine. It was also hypothesized that methylphenidate delayed both the absorption and elimination of the drugs.

Significance

KETAMINE: a) The significance of this interaction is unclear due to the limited data available.

Unknown Dangers

Unknown dangers.

LSD/ Hallucinogens

acid, blotter, cartoon acid, hit, purple haze, trip, white lightning, raggedy ann, sunshine, window-pane, microdot, boomers, buttons, mesc, peyote, salvia, morning glory seeds, flying saucers, licorice drops, pearly gates, magic mushrooms, shrooms

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Interaction
No information currently available.

Unknown Dangers

Unknown dangers.

Benzodiazepines

benzos, downers, tranquilizers, tranks, Ativan®, Halcion®, Klonopin®, Rivotril®, Restoril®, Serax®, Valium®, Xanax®, Rohypnol® (roofies, rope, the forget or date rape pill)

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Interaction
a) A 6-year-old boy taking methylphenidate 5 mg twice daily for ADHD was given midazolam 20 mg orally for a procedure requiring sedation. After 20 minutes, he was only mildly sedated and would not lie still. He was given an additional midazolam 10 mg orally mixed with ketamine 60 mg orally but remained alert and uncooperative. Sedation was then successfully achieved with intravenous glycopyrrolate and midazolam over 5 minutes. His recovery was uneventful, but he experienced nausea, vomiting and lethargy after discharge.

b) The sedative effects of benzodiazepines may counteract the stimulating effects of methylphenidate.

Mechanism
a) It was thought that the methylphenidate antagonized the sedative effects of midazolam and ketamine. It was also hypothesized that methylphenidate delayed both the absorption and elimination of the drugs.

b) Opposing CNS effects.

Significance
a,b) Benzodiazepines should be avoided when the stimulatory effects of methylphenidate are required.

Serious Risk for Harm

Methylphenidate makes some people feel more awake and alert. If you have been using benzodiazepines, taking methylphenidate might fool you into feeling alert enough to drive, or do other activities requiring alertness. This would be false. You may still be impaired, and it would be unsafe to drive.

Think First

Benzodiazepines may reduce the stimulant effects of methylphenidate.

Think First

Doctors sometimes prescribe benzodiazepines to patients taking methylphenidate to help treat some illnesses, but this is done very carefully.

Benzodiazepines are 'downers'. If you are depressed, blue, or moody, benzodiazepines can make this worse.

References

[+]

Attalah MM, Saied MM, Yahya R, et al. Ketamine anesthesia for short transurethral urologic procedures. Middle East J Anesthesiol 1993; 12: 123-33.

Barkla XM, McArdle PA, Newbury-Birth D. Are there any potentially dangerous pharmacological effects of combining ADHD medication with alcohol and drugs of abuse? A systematic review of the literature. BMC Psychiatry 2015; 1: 207-12

Barrett SP, Pihl RO. Oral methylphenidate-alcohol co-abuse. J Clin Psychopharmacol 2002; 22: 633-4.

Blanken P, Nuijten M, van den Brink W, et al. Clinical effects beyond cocaine use of sustained-release dexamphetamine for the treatment of cocaine dependent patients with comorbid opioid dependence: secondary analysis of a double-blind, placebo-controlled randomized trial. Addiction 2020; 115: 917-23.

Bron TI, Bijlenga D, Kasander MV et al. Long-term relationship between methylphenidate and tobacco consumption and nicotine craving in adults with ADHD in a prospective cohort study. Eur Neuropsychopharmacol 2013; 23: 542-54.

Bursteler-MacFarland KM, Farronato NS, Strasser J et al. A randomized, controlled pilot trial of methylphenidate and cognitive-behavioral group therapy for cocaine dependence in heroin prescription. J Clin Psychopharmacol 2013;22:104-8.

Collins SL, Levin FR, Foltin RW, et al. Response to cocaine, alone and in combination with methylphenidate, in cocaine abusers with ADHD. Drug Alcohol Depend 2006; 82: 158-67.

Delavenne H, Duarte Garcia F, Lacoste J et al. Psychosis in a cocaine-dependent patient with ADHD during treatment with methylphenidate. Gen Hosp Psychiatry 2013; 35: 7-9.

Forrest WH Jr, Brown BW Jr, Brown CR, et al. Dextroamphetamine with morphine for the treatment of postoperative pain. N Engl J Med 1977; 296: 712-5.

Hammerness P, Joshi G, Doyle R et al. Do stimulants reduce the risk for cigarette smoking in youth with attention-deficit hyperactivity disorder? A prospective, long-term, open-label study of extended-release methylphenidate. J Pediatr 2013;162:22-7.

Hysek CM, Simmler LD, Schillinger N et al. Pharmacokinetic and pharmacodynamics effects of methylphenidate and MDMA administered alone or in combination. Int J Neuropsychopharmacol 2014; 17: 371-81.

Imbert B, Labrune N, Lancon C et al. Use of Extended-Release Methylphenidate (Concerta) in Treatment of Cocaine Dependence in a Patient Presenting With Attention Deficit Hyperactivity Disorder. J Neuropsychiatry Clin Neurosci 2014; 26: 49-50.

Jiang JY, Best BM, Morello CM et al. Evaluation of Concomitant Methylphenidate and Opioid Use in Patients with Pain. J Anal Toxicol 2014; 38: 421-6.

Kollins SH, Schoenfelder E, English JS et al. Methylphenidate Does Not Influence Smoking-Reinforced Responding or Attentional Performance in Adult Smokers With and Without Attention Deficit Hyperactivity Disorder (ADHD). Exp Clin Psychopharmacol 2013; 21: 365-84.

Lexi-Comp ONLINE, Lexi-Comp ONLINE Interaction Analysis, Hudson, Ohio: Lexi-Comp, Inc.; 2021; August 8, 2021.

Patrick KS, Straughn AB, Minhinnett RR, et al. Influence of ethanol and gender on methylphenidate pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 2007; 81: 346-53.

Preston CL (Ed), Stockley’s Interactions Checker. [online] London: Pharmaceutical Press. (accessed on August 8, 2021).

Rezaei F, Emami M, Zahed S et al. Sustained-release methylphenidate in methamphetamine dependence treatment: a double-blind and placebo-controlled trial. Daru 2015; 2-8.

Ririe DG, Ririe KL, Sethna NF, et al. Unexpected interaction of methylphenidate (Ritalin) with anaesthetic agents. Paediatr Anaesth 1997; 7: 69-72.

Tardelli VS, Bisaga A, Arcadepani FB, et al. Prescription psychostimulants for the treatment of stimulant use disorder: a systematic review and meta-analysis. Psychopharmacology (Berl) 2020; 237: 2233-55.

Wills S. Drugs of Abuse, 2nd edition. Great Britain: Pharmaceutical Press 2005.

Winhusen T, Somoza E, Singal BM, et al. Methylphenidate and cocaine: a placebo-controlled drug interaction study. Pharmacol Biochem Behav 2006; 85: 29-38.

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methylphenidate

References

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