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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
a) The pharmacokinetics of bupropion 100 mg and alcohol were not affected by each other in single dose studies.

b) There are case reports of reduced alcohol tolerance in patients taking bupropion.

c) Taking bupropion while undergoing abrupt withdrawal from sustained heavy alcohol use increases the risk of seizures.

Mechanism
c) Abrupt alcohol withdrawal is a risk factor for seizures. Seizures are a dose-related adverse effect of bupropion.

Significance
Due to seizure risk, the manufacturer recommends minimal or no alcohol consumption with bupropion, and contraindicates the use of bupropion during abrupt alcohol withdrawal. They also recommend caution in patients who abuse alcohol.

Serious Risk for Harm

Drinking too much alcohol, or stopping alcohol suddenly after drinking large amounts for several days, can trigger a seizure. Taking bupropion can increase the risk of seizure in these situations.

Think First

Mixing bupropion with small amounts of alcohol doesn't seem to change the level of impairment from drinking alcohol. This means, your usual dose of bupropion and 1 or 2 drinks.

Remember, 1 drink = 1 beer, 1 glass of wine or 1 shot of liquor

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) Bupropion has been studied in randomized trials as an aide to smoking cessation. It is often taken for a period of time before smoking cessation is attempted.

b) Smoking does not appear to affect bupropion concentrations when bupropion is taken in a dose of 150 mg daily. There was no information on doses higher than 150 mg daily.

c) The combination of bupropion and nicotine replacement therapy may increase the risk of hypertension.

Mechanism
a) Nicotine activates central nervous system pathways to release norepinephrine, dopamine, and other neurotransmitters and elevates dopamine levels in areas of the brain associated with the reinforcement of the effects of amphetamines, cocaine, and opiates.

Bupropion is a weak inhibitor of the neuronal uptake of norepinephrine and dopamine but has no effect on serotonin. Its dopaminergic and noradrenergic activities could be responsible for its efficacy in smoking cessation, with the dopaminergic activity affecting areas of the brain having to do with the reinforcement properties of addictive drugs and the noradrenergic activity affecting nicotine withdrawal.

Significance
a) Bupropion is an approved treatment for smoking cessation, with cessations rates superior to those with placebo, and comparable to those with transdermal nicotine patch use. Combination use of bupropion and nicotine transdermal patch results in cessations rates superior to either treatment alone.

b) Bupropion doses do not need to be altered in patients who smoke cigarettes.

Think First

Bupropion does not seem to change the risk of smoking cigarettes.

Bupropion is commonly prescribed to help reduce cigarette cravings in people who are trying to quit smoking.

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
No information currently available.

Think First

Caffeine may make the side effects of bupropion worse, for example, shaking hands, pounding heart, trouble sleeping at night, edgy or irritable feelings.

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
No information currently available.

Think First

Cannabis use, especially in large amounts, or if you do not use cannabis regularly can give you anxiety. This could make the side effects of bupropion worse, because bupropion can also cause or worsen anxiety.

Cocaine/ Crack

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

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Interaction

a) Following inadvertent injection of a mixture of cocaine and bupropion into his vertebral artery, an emergency MRI showed that the man's brain stem and spinal cord were turning “to mush.” As the neurological havoc began to permanently shut down the patient’s body, he remained conscious and aware. The man was taken off life support, and died soon after.

b) One case study of a male with a history of cocaine abuse developed paroxysms of psychosis following a 150 mg dose of bupropion.

Another case report describes a 67 year old man who developed paranoid ideations after starting bupropion 150 mg daily. His paranoia resolved after stopping bupropion. It was later discovered that he had a similar psychotic experience 8 years previously when he was taking bupropion and using cocaine concomitantly.

c) The use of cocaine with bupropion increases the risk of seizures.

d) Two previous cocaine users reported experiencing cocaine-like sensations after taking bupropion. This did not cause any cravings for cocaine.

e) Bupropion was effective in treating depressed bipolar disorder type 1 patients with comorbid cocaine dependence without increasing scores on the Young mania rating scale (YMRS).

Mechanism

a) Bupropion appears to have the typical stimulant action of causing blood vessels to spasm and clamp shut, and heightens the same effects in cocaine, potentially causing anoxic injury to the brain (stroke) and other parts of the body. Tissue destruction may also occur following injection of the non-medicinal ingredients contained in the tablets.

b) Cocaine binds to dopaminergic transporter at higher levels but with shorter occupancy (>50% for less than 20 minutes) than bupropion (25% for more than 24 hours). These cases show the temporal relationship between emergence of psychotic symptoms with expected peak plasma levels of bupropion (about 2-3 hours). In addition, the paroxysms stopped upon discontinuation of bupropion. Similar to cocaine, chronically administered bupropion given to rats results in sensitization of behavioral and dopaminergic response. Cocaine psychosis, characterized by acute fear, paranoid delusions, and a lack of major perceptual disturbances has been studied in the context of sensitization.

c) Cocaine and bupropion can both lower the seizure threshold or cause seizures.

Significance

a) As the neurological havoc began to permanently shut down the patient’s body, he remained conscious and aware. The man was taken off life support, and died soon after.

b) Some patients with a history of cocaine use may be unable to use bupropion without becoming paranoid. Use bupropion with caution in individuals with a history of cocaine abuse associated with psychosis.

c) The manufacturer recommends extreme caution when prescribing bupropion to patients known to use cocaine.

Serious Risk for Harm

Both bupropion and cocaine can make blood vessels clamp shut, shut off oxygen to parts of the body, and result in tissue damage, stroke or death. There is a report of a man who died shortly after injecting a mixture of bupropion and cocaine into an artery in his neck.

Serious Risk for Harm

Taking bupropion and cocaine together could cause you to have a seizure.

Think First

There are medical reports of bupropion being used to treat patients with cocaine addiction. These people had no harmful effects from the combination of bupropion and cocaine. If you have ever experienced psychosis (very unusual or paranoid thoughts or hallucinations) while using cocaine, taking bupropion may make these symptoms more likely to return if you use cocaine.

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
OPIOIDS: a) There is some concern that smoking cessation therapies may be less effective in patients taking opioids. A study found that in patients stabilized on buprenorphine or methadone, bupropion did not result in significantly greater abstinence rates than placebo.

CODEINE: Concomitant administration of bupropion with codeine may result in decreased analgesia.

DEXTROMETHORPHAN: a) A 43-year-old patient with a history of depression and post-traumatic stress disorder (PTSD) developed serotonin syndrome during treatment with bupropion and dextromethorphan.

b) Bupropion appears to reduce the metabolism of dextromethorphan, a CYP2D6 substrate. In one study, 13 patients who were CYP2D6 extensive metabolizers received bupropion 150 mg daily for 3 days then 150 mg twice daily x 14 days and a 30 mg dose of dextromethorphan. Six of these subjects had a metabolic ratio of dextromethorphan that resembled that of a poor metabolizer. The 8 subjects who received placebo did not show any such change.

TRAMADOL: a) Bupropion may reduce the therapeutic effects of tramadol.

b) Concomitant use of bupropion and tramadol may increase the risk of developing serotonin syndrome.

c) Taking tramadol with bupropion can increase your risk of having seizures.

Mechanism
CODEINE: Bupropion is a strong CYP2D6 inhibitor. Concomitant administration with codeine, a CYP2D6 substrate may result in decreased conversion of codeine to the active analgesic morphine.

DEXTROMETHORPHAN: a) Serotonin syndrome is a dose-related response to the use of serotonergic drugs, often in combination. Genetic polymorphism in CYP2D6 function leads to differences in the ability to metabolize dextromethorphan which may explain the differences in clinical experiences reported by those who abuse dextromethorphan for its dissociative effects. While bupropion mainly inhibits noradrenaline and dopamine reuptake, dopaminergic neurons can have mild effects on serotonergic transmission.

b)Bupropion inhibits CYP2D6 which metabolizes dextromethorphan.

TRAMADOL: a) Concomitant administration of bupropion with tramadol (a CYP2D6 substrate) may result in decreased conversion of tramadol to the active metabolite (O-desmethyl-tramadol) responsible for its opioid-like effects. The analgesic effects of tramadol are due to two separate mechanisms - a) agonism of the opioid receptor and b) via inhibition of serotonin and norepinephrine reuptake. The (+) enantiomer of O-desmethyl-tramadol, formed via O-demethylation by CYP2D6, is the primary opioid agonist. If CYP2D6 is inhibited, this leads to reduced agonism at opioid receptors. However, some analgesic effect does remain due to inhibition of serotonin and norepinephrine reuptake.

b) While bupropion mainly inhibits noradrenaline and dopamine reuptake, dopaminergic neurons can have mild effects on serotonergic transmission, with additive effects on serotonergic transmission, since tramadol has effects of inhibition of serotonin and norepinephrine reuptake.

Significance
CODEINE: Patients who are co-administering these two drugs are at increased risk of poor pain control. If used concurrently, it is recommended to monitor for decreased analgesic response. If an inadequate response is observed, consider an alternative analgesic that does not require metabolic activation via CYP2D6.

DEXTROMETHORPHAN: a) Patients should be monitored for symptoms of serotonin syndrome when bupropion and dextromethorphan are used concurrently.

b) Use caution when initiating, discontinuing, or changing the dose of bupropion when patients are taking dextromethorphan. However, dextromethorphan is considered to have a wide therapeutic index and it is unlikely that this interaction will be clinically significant.

TRAMADOL: a) Patients who are co-administering these two drugs are at increased risk of poor pain control. If used concurrently, it is recommended to monitor for decreased analgesic response. If an inadequate response is observed, consider an alternative analgesic that does not require metabolic activation via CYP2D6.

b) Patients should also be monitored for symptoms of serotonin syndrome when tramadol and bupropion are used concurrently.

c) The manufacturer recommends caution when bupropion is used with any other drug that may lower the seizure threshold.

Serious Risk for Harm

DEXTROMETHORPHAN: a) When high doses of dextromethorphan are combined with bupropion, you could get: very high fever, really sick, dangerously high blood pressure, heart problems and even die. This is 'serotonin syndrome'.

b) Bupropion may slow down the removal of dextromethorphan from your body. This could put you at risk of side effects or even an overdose, especially if you are using high doses of dextromethorphan.

CODEINE: Painkillers with codeine may not work as well as expected when you are taking bupropion.

TRAMADOL: When tramadol is combined with bupropion, tramadol is less effective for pain, and you could get: very high fever, really sick, dangerously high blood pressure, heart problems and even die. This is 'serotonin syndrome'.

Taking bupropion together with tramadol, especially in high doses may increase the risk of having a seizure.

Think First

OTHER OPIOIDS: One medical report explains that bupropion has been used to treat people addicted to opioids and other drugs. These people had no harmful effects from the mixture of opioids and bupropion.

Think First

ALL OPIOIDS: If you are taking bupropion to quit smoking, opioids may make bupropion not work as well as expected.

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
MDMA a) Bupropion may reduce the metabolism of methylenedioxymethamphetamine (MDMA).

b) One study found that bupropion reduced MDMA-mediated heart rate increases and plasma norepinephrine elevations. However, plasma MDMA concentrations were increased and subjective effects of MDMA were prolonged. Bupropion concentrations were increased by MDMA.

METHAMPHETAMINE: Bupropion does not appear to increase abstinence rates in methamphetamine-dependent patients who used methamphetamine less than daily. Adherence was a major limitation in this trial.

METHYLPHENIDATE: a) A 16 year old boy taking methylphenidate 30 mg twice daily, bupropion 100 mg twice daily, and erythromycin 1000 mg/day experienced an acute MI.

b) a 14 year-old boy taking methylphenidate 60 mg daily had his bupropion dose increased from 200 mg to 300 mg. 4 weeks after the bupropion was increased the patient experienced a generalized tonic-clonic seizure. Bupropion was discontinued and he remained seizure-free.

Mechanism
MDMA a) Bupropion inhibits CYP2D6, which metabolizes MDMA.

b) Reduced norepinephrine release may be responsible for reduced cardiostimulatory effects of MDMA.

METHYLPHENIDATE: a) Erythromycin may have resulted in increased bupropion levels, which may have combined with the sympathetic effects of methylphenidate to cause excessive vasospasm. However, erythromycin does not inhibit CYP2B6 so it is unclear how it would have increased bupropion concentrations.

Significance
MDMA a) Patients may be more likely to experience an overdose of MDMA while taking bupropion.

b) Taking MDMA while on bupropion may result in higher plasma concentrations of both, as well as increased subjective effects and decreased cardiac effects of MDMA.

METHYLPHENIDATE: a)The significance of this case report is unclear.

b) The combination of bupropion and stimulants may increase the risk of seizure.

Serious Risk for Harm

Taking bupropion together with stimulants (such as amphetamines or methylphenidate) could cause you to have a seizure.

Serious Risk for Harm

MDMA/ECSTASY: Bupropion can slow down the removal of MDMA from your body. This can make you more likely to overdose on MDMA.

Think First

Unknown dangers. Some doctors will give small amounts of medical amphetamines to patients taking bupropion, to help treat certain illnesses, but this is done very carefully.

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
No information currently 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
BENZODIAZEPINES: Bupropion is contraindicated during abrupt withdrawal from benzodiazepines due to the risk of seizures.

DIAZEPAM: A crossover study in 12 healthy subjects demonstrated that the combination of bupropion with diazepam resulted in similar function compared to bupropion alone.

ZOLPIDEM: A case report describes a 17 year old boy taking bupropion 450 mg daily who increased his zolpidem dose from 5-10 mg daily to 60 mg daily and experienced visual hallucinations for 3-4 hours.

Mechanism
ZOLPIDEM: Bupropion is not a known inhibitor of CYP3A4, the major CYP enzyme that metabolizes zolpidem.

Significance
DIAZEPAM: The combination dose not appear to result in decreased psychomotor function.

ZOLPIDEM: This patient took 6 times the recommended daily dose of zolpidem, which can cause hallucinations on its own. Therefore, it is unclear if an interaction with bupropion is responsible for this case.

Serious Risk for Harm

Using benzodiazepines in high doses or for prolonged periods of time and then stopping suddenly while you are also taking bupropion could make you have a seizure.

Think First

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

References

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Anderson A, Li SH, Markova D, et al. Bupropion for the treatment of methamphetamine dependence in non-daily users: A randomized, double-blind, placebo-controlled trial. Drug Alcohol Depend 2015; 150: 170-4.

Barman R, Kumar S, Pagadala B, et al. Cocaine Abuse, Traumatic Brain Injury, and Preexisting Brain Lesions as Risk Factors for Bupropion-Associated Psychosis. J Clin Psychopharmacol 2017; 37: 459-63.

Doctors warn of potentially deadly ‘zombie’ effects of using anti-depressant Wellbutrin [and cocaine] to get high. Blackwell T. National Post. Accessed July 24, 2013 from http://news.nationalpost.com/2013/07/18/doctors-warn-of-potentially-deadly-zombie-effects-of-using-anti-depressant-wellbutrin-to-get-high/

Hahn M, Hajek T, Alda M et al. Psychosis induced by low-dose bupropion: Sensitization of dopaminergic system by past cocaine abuse? J Psychiatr Pract 2007; 13: 336-8.

Hurt RD, Sachs DP, Glover ED et al. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med 1997; 337: 1195-202.

Jorenby DE, Leischow SJ, Nides MA et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 1999; 340: 685-91.

Lexi-Comp ONLINE, Lexi-Comp ONLINE Interaction Analysis, Hudson, Ohio: Lexi-Comp, Inc.; 2021; Sep 6, 2021.

Miller M, Sigmon S. Are Pharmacotherapies Ineffective in Opioid-Dependent Smokers? Reflections on the Scientific Literature and Future Directions. Nicotine Tob Res 2015; 17: 955-9.

Preston CL (Ed), Stockley’s Interactions Checker. [online] London: Pharmaceutical Press. (accessed on Sep 6, 2021).

Roncero C, Abad AC, Padilla-Mata A, et al. Psychotic Symptoms Associated with the use of Dopaminergic Drugs, in Patients with Cocaine Dependence or Abuse. Curr Neuropharmacol 2017; 15: 315-23.

Schmid Y, Rickli A, Schaffner A, et al. Interactions between Bupropion and 3,4-Methylenedioxymethamphetamine in Healthy Subjects. J Pharmacol Exp Ther 2015; 353: 102-11.

Sepede G, Di lorio G, Lupi M, et al. Clin Neuropharmacol 2014; 37: 17-21.

Steuer A, Schmidhauser C, Tingelhoff E, et al. Impact of Cytochrome P450 2D6 Function on the Chiral Blood Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine (MDMA) and Its Phase I and II Metabolites in Humans. PLoS One 2016; 11: e0150955.

Szakaly B, Strauss R. Serotonin syndrome in the oral and maxillofacial surgery office: a review of the literature and report of a case. J Oral Maxillofac Surg 2008; 66: 1949-52.

Therapeutic Research Center. Natural Medicines [Internet]. Somerville (MA): Bupropion; [cited Sep 6, 2021].

Vento A, Schifano F, Gentili F, et al. Bupropion perceived as a stimulant by two patients with a previous history of cocaine misuse. Ann Ist Super Sanita 2013; 49: 402-5.

The Drug Cocktails website – “Facts for Youth about mixing Medicine, Booze and Street Drugs” (the “Site”) has been developed as a resource for youth and staff within Children’s & Women’s Health Centre of British Columbia Branch (C&W) for Provincial Health Services Authority and its branch agencies (PHSA)(C&W and PHSA together the “Societies”). There are support systems at the Societies which may not exist in other clinical settings and therefore adoption or use of this manual is not the responsibility of the Societies. Agencies other than the Societies should use Cocktails as a guideline for reference purposes only. The contents of this website were current at the time of development in July 2013. The Societies are not responsible for information that has changed after that time, whether incorporated into the Site or not.

The Site contains best practice knowledge, but practice standards may change as more knowledge is gained. Decision making in a specific context remains the responsibility of attending professionals. Nothing on the Site should in any way be construed as being either official or unofficial policy of the Societies.

Contact information and links to websites contained on the Site are provided for convenience only. The Societies cannot guarantee that the information, links or content from these links remain current. Providing a contact or link does not mean that the Societies endorse the views, products or services that may be offered via the link. The Societies assume no responsibility or liability arising from any error in, or omission of, information or from the use of any information, link, contact, opinion, advice or similar, provided on the Site.

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bupropion

References

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