Drug Cocktails

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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) According to the manufacturer, there are post-marketing reports of patients experiencing increased alcohol intoxication while taking varenicline. There are also some reports of unusual and aggressive behaviour, often accompanied by amnesia.

b) Alternatively, some studies show that varenicline 2 mg daily can reduce alcohol consumption and craving in patients with alcohol use disorders. Another study found that varenicline with alcohol increased dysphoria and reduced alcohol liking ratings.

c) A randomized control trial found varenicline decreased alcohol consumption in alcohol-dependent or abusing tobacco smokers. Another randomized control trial confirmed varenicline’s safety and effectiveness in alcohol-dependent tobacco smokers. Additionally, a systematic review found varenicline to be superior to placebo in reducing alcohol consumption over a period of time.

d) However, other studies found varenicline was not superior to placebo for reduction of alcohol intake.

Mechanism

b,c) The mechanism of varenicline lowering alcohol cravings is still unclear, but it is hypothesized to be related to varenicline acting on nicotinic receptors and inhibitory effects on nACh, reducing the cravings for alcohol.

Significance

a) The manufacturer recommends that patients be warned that drinking alcohol while taking varenicline may increase the risk of psychiatric adverse effects.

b,c) Varenicline may be an potentially effective treatment for alcohol use disorder.

Serious Risk for Harm

You may have a lower alcohol tolerance while taking varenicline. This means that you could feel more "drunk" or intoxicated from the same amount of alcohol you normally drink.

There are also medical reports of people having unusual or aggressive behaviour after drinking alcohol while taking varenicline.

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) Varenicline is a smoking cessation agent which can be initiated while the patient is still smoking.

b) When varenicline was used with nicotine replacement therapy there was a decrease in blood pressure on the final day of the study. There was also an increase in nausea, vomiting, headache, dizziness, dyspepsia, and fatigue with the combination compared to nicotine replacement therapy alone.

c) A randomized controlled trial evaluated varenicline (control arm) versus varenicline with 2 mg NRT lozenges (maximum 15/day). Biochemically verified prolonged abstinence at 6 months or longer was found to not be statistically significant between the two groups. Self-reported prolonged abstinence at 6 months favored the combined varenicline/NRT arm, but was not statistically significant. There was no additional risk of adverse effects from combination therapy compared to monotherapy.

Mechanism

Varenicline is a partial agonist at the a4B2 nicotinic acetylcholine receptor. It prevents nicotine binding and has less agonist activity than nicotine.

Significance

a) Patients who are taking varenicline should have a quit date set or should be decreasing their amount of smoking.

b) It is not believed that co-administration of varenicline and nicotine replacement therapy would have additional benefits to varenicline alone, and the combination could increase adverse effects.

c) The significance of this interaction is unclear and requires additional studies to evaluate effectiveness in smoking cessation.

Think First

Varenicline is usually prescribed to help you quit smoking. If you are taking varenicline you should talk to your doctor about setting a date to quit smoking, or about how to cut back on your smoking while taking varenicline.

Think First

Nicotine replacement therapies like nicotine gum, sprays, inhalers or patches appear safe to use together with varenicline, but don't seem to improve your chances of quitting 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.

Unknown Dangers

Unknown dangers.

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.

Unknown Dangers

Unknown dangers.

Cocaine/ Crack

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

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Interaction
Varenicline has been studied for cocaine use disorder and in one study was shown to be associated with lower cocaine use and decreased rates of cocaine reward. However, in another study of varenicline for treatment of cocaine and tobacco dependence in methadone maintained patients, varenicline was not more effective than placebo for increasing cocaine abstinence.

Significance
Varenicline may be effective for use in cocaine use disorder, but results are conflicting and more data is needed.

Unknown Dangers

Unknown dangers.

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

A study investigating the use of varenicline in opioid-dependent smokers with psychiatric comorbidities who were receiving methadone treatment found few documented adverse effects (no suicidal ideation, cardiac, or vascular events within 6 months of varenicline prescription). Another study found similar results.

Significance

The authors of both studies concluded that patients maintained on methadone may benefit from varenicline therapy for smoking cessation.

Think First

METHADONE: It appears varenicline can safely be used to help people quit smoking while they are taking methadone for treatment of opioid dependence.

Think First

METHADONE: Smoking cigarettes speeds up the clearance of methadone from your body. Tell your doctor if you smoke, or if you start or quit smoking, because the dose of methadone may need to be changed for you. On-and-off cigarette smoking could make the effects of methadone for pain control or prevention of opioid withdrawal inconsistent.

Unknown Dangers

OTHER OPIOIDS: Unknown dangers.

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) A study in non-treatment seeking methamphetamine-dependent volunteers found that varenicline 2 mg twice daily reduced rations of drug effect and stimulation and attenuated the high, drug liking, and positive effects of methamphetamine 30 mg. No serious adverse effects occurred.

b) A case report describes an 18 year old male receiving amphetamine-dextroamphetamine for ADHD who was prescribed varenicline for smoking cessation. He quit smoking on day 7 of therapy and remained smoke free for the next 17 days. On day 4-12 of varenicline therapy he took only half of his prescribed dose of amphetamine-dextroamphetamine. He then further reduced his dose to one-quarter of the prescribed dosage on days 13 and 14, and on day 15 his supply of dextroamphetamine-amphetamine was depleted. On day 23 he filled a new prescription for dextroamphetamine-amphetamine at the prescribed dosage, and he began smoking again within 48 hours. Rechallenge with varenicline resulted in similar results.

c) A study in non-treatment seeking methamphetamine-dependent patients found that varenicline 1 mg daily improved reaction time but not working memory, episodic memory, or attention.

Mechanism
b) Amphetamine may negate the partial agonism of varenicline. Varenicline prevents dopamine release secondary to nicotine-induced stimulation of a4B2 nicotinic acetylcholine receptors. Amphetamine increases mesolimbic dopamine levels and may thus decrease varenicline efficacy.

Significance
a) Varenicline may be a treatment option for methamphetamine dependence; more data is required.

b) The significance of this case report is unclear. Varenicline may not be effective for smoking cessation in patients taking amphetamines.

c) Varenicline may improve reaction time in methamphetamine-dependent patients; more data is required.

Think First

There are medical reports of varenicline not working as well as expected to help people quit smoking if they were also taking amphetamines.

Ketamine/ Phencyclidine

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)

Learn more about this substance »

Interaction
No information currently available.

Unknown Dangers

Unknown dangers.

References

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Bejczy A, Lof E, Walther L, et al. Varenicline for Treatment of Alcohol Dependence: A Randomized, Placebo-Controlled Trial. Alcohol Clin Exp Res. 2015; 39: 2189-99.

Childs E, Roche D, King A, et al. Varenicline Potentiates Alcohol-Induced Negative Subjective Responses and Offsets Impaired Eye Movements. Alcohol Clin Exp Res. 2012; 36: 906-14.

Hurt RT, Ebbert JO, Croghan IT, et al. Varenicline for tobacco-dependence treatment in alcohol-dependent smokers: A randomized controlled trial. Drug Alcohol Depend 2018; 184: 12-17.

Kalechstein A, Mahoney J, Verrico C, et al. Short-term, low-dose varenicline administration enhances information processing speed in methamphetamine-dependent users. Neuropharmacology 2014; 85: 493-8.

Lexi-Comp ONLINE, Lexi-Comp ONLINE Interaction Analysis, Hudson, Ohio: Lexi-Comp, Inc.; 2026; Mar 28, 2026.

Nahvi S, Ning Y, Segal K, et al. Varenicline efficacy and safety among methadone maintained smokers: a randomized placebo-controlled trial. Addiction 2014; 109: 1554-63.

Nahvi S, Wu B, Richter K, et al. Low incidence of adverse events following varenicline initiation among opioid dependent smokers with comorbid psychiatric illness. Drug Alcohol Depend 2013;132:47-52.

Oon-Arom A, Likhitsathain S, Srisurapanont M. Efficacy and acceptability of varenicline for alcoholism: A systematic review and meta-analysis of randomized-controlled trials. Drug Alcohol Depend 2019; 205: 1-9.

Pfeifer P, Fehr C. Efficacy of Varenicline in Patients With Severe Alcohol Dependence: A Pilot Double-Blind Randomized and Controlled Study. J Clin Psychopharmacol 2019; 39: 398-402.

Phimarn W, Sakhancord R, Paitoon P et al. Efficacy of Varenicline in the Treatment of Alcohol Dependence: An Updated Meta-Analysis and Meta-Regression. Int J Environ Res Public Health 2023;20:4091.

Plebani J, Lynch K, Yu Q, et al. Drug Alcohol Depend 2012; 121: 163-6.

Poling J, Rounsaville B, Gonsai K, et al. The Safety and Efficacy of Varenicline in Cocaine Using Smokers Maintained on Methadone: A Pilot Study. Am J Addict. 2010; 19: 401-8.

Preston CL (Ed), Stockley’s drug interactions. 12th ed. London: Pharmaceutical Press; 2019. 2090 p. (Accessed Mar 28, 2026).

Therapeutic Research Center. Natural Medicines [Internet]. Somerville (MA): Varenicline; [cited July 24, 2021].

Verplaetse T, Pittman B, Shi J, et al. Effect of Lowering the Dose of Varenicline on Alcohol Self-administration in Drinkers With Alcohol Use Disorders. J Addict Med 2016; 10: 166-73.

Verrico C, Mahoney J, Thompson-Lake D, et al. Safety and efficacy of varenicline to reduce positive subjective effects produced by methamphetamine in methamphetamine- dependent volunteers. Int J Neuropsychopharmacol 2014; 17: 223-33.

Weeks GR, Gobarani RK, Abramson MJ et al. Varenicline and Nicotine Replacement Therapy for Smokers Admitted to Hospitals. JAMA Netw Open 2024;7:e2418120.

Whitley H, Moorman K. Interference with Smoking-Cessation Effects of Varenicline After Administration of Immediate-Release Amphetamine-Dextroamphetamine. Pharmacotherapy 2007; 27: 1440-5.

Zawertailo L, Ivanova A, Ng G, et al. Safety and Efficacy of Varenicline for Smoking Cessation in Alcohol-Dependent Smokers in Concurrent Treatment for Alcohol Use Disorder: A Pilot, Randomized Placebo-Controlled Trial. J Clin Psychopharmacol 2020; 40: 130-6.

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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varenicline

References

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