Drug Cocktails

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

Learn more about this substance »

Interaction
a) A 0.5 g/kg dose of alcohol resulted in an average increase of 16% in lithium carbonate serum levels in 9 out of 10 healthy men. A 25% increase was seen in 4 of the subjects. However, the increased serum levels did not appear to be clinically relevant.

b) Co-administration of lithium appeared to antagonize some of the effects of alcohol in a study of 20 healthy subjects. Co-administration resulted in poorer performance on psychomotor tests when compared to the use of either drug alone. Lithium did not appear to affect alcohol's blood levels.

c) In a placebo-controlled study, 35 alcohol dependent patients rated themselves as less intoxicated when lithium was co-administered. Improvements were seen in 3 out of 6 cognitive tests; however co-administration did not improve skills related to driving. Lithium did not appear to affect alcohol blood levels.

Significance
It is important to warn patients of the potential for a reduction in psychomotor function when these drugs are taken concurrently. They may or may not be aware of their deterioration in skill level and response will vary between individuals. They may experience a deterioration in their abilities to operate a vehicle and/or carry out tasks that require mental alertness.

Serious Risk for Harm

Mixing lithium and alcohol will reduce alertness and attention more than alcohol by itself. It will be more dangerous to drive if you mix alcohol and lithium. Taking lithium and alcohol together may increase the amount of lithium absorbed by your body, by about 20%. This would be like taking too much lithium.

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

Learn more about this substance »

Interaction
No information currently available.

Unknown Dangers

Unknown dangers.

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

Learn more about this substance »

Interaction

There is conflicting evidence regarding the interaction between caffeine and lithium.

a) Increased urinary clearance of lithium was observed in a single-dose study when subjects were co-administered caffeine.

b) A second single-dose study found no significant reductions in urinary clearance of lithium in 6 subjects who were given 200 mg caffeine four times a day.

c) An average of a 24% increase in serum lithium levels was observed when coffee consumption was discontinued in 8 out of 11 patients taking lithium (600 to 1200 mg daily). No changes in lithium levels were observed in the 3 remaining patients. These patients had been consuming 4-8 cups of coffee (70-120 mg caffeine per cup) on a regular basis prior to its withdrawal.

d) Two patients experienced worsening of their lithium-induced tremors upon elimination of coffee from their diet. One patient experienced a 50% increase in lithium levels which prompted a reduction in the daily lithium dose from 1500 mg to 1200 mg daily.

e) A case report describes a 54-year-old man who experienced decreased levels of lithium with excessive caffeine intake. When caffeine intake was reduced, the patient’s lithium concentrations increased.

Mechanism

e) The mechanism for this interaction is unclear.

Significance

While patients do not have to avoid caffeine consumption when taking lithium, it is recommended to only consume low to moderate amounts. If a patient wishes to decrease caffeine intake, it is recommended to proceed cautiously and to lower the lithium dose if required. This is especially important in patients receiving high lithium doses due to the increased risks of lithium toxicity.

In addition, if a patient chooses to decrease or stop consuming caffeine, it is important to keep in mind that caffeine-withdrawal symptoms (e.g. headache, fatigue) may worsen some psychiatric disorders which are treated with lithium.

Serious Risk for Harm

Using lots of caffeine (like 4 or more coffees or colas per day) can speed up the removal of lithium from your body. This means lithium may not work as well as it should and this could cause your symptoms to return. Try to stick to just one or two caffeine drinks (or less) per day.

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

Learn more about this substance »

Interaction

a) One case report found that lithium levels were significantly raised to toxic levels during a period when cannabis was smoked, but dropped again when cannabis use ceased.

b) A case report describes a 13-year old male who experienced symptoms of lithium toxicity after receiving concomitant lithium with cannabidiol (CBD) 10 mg/kg/day.

Mechanism

a) Cannabis and lithium are excreted by completely different mechanisms so it appears unlikely that cannabis caused this effect (this patient had a complex psychiatric history with fluctuating lithium levels). One hypothesis is that cannabis may slow gastrointestinal transit and increase lithium absorption. However, this is unlikely as lithium is usually absorbed rapidly and completely.

b) Although the mechanism is not fully understood, it is thought that CBD-induced renal dysfunction may be a factor.

Significance

These case reports emphasize the important of monitoring signs and symptoms of lithium toxicity if there is concomitant CBD administration.

Serious Risk for Harm

Using marijuana may increase the amount of lithium absorbed by your body, by quite a lot. This is like taking too much lithium. This could cause side effects like confusion, slurred speech or make you really shaky. If you have these effects, get checked by a doctor right away.

Cocaine/ Crack

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

Learn more about this substance »

Interaction
a) QTc interval prolongation has been observed with lithium. Concomitant use with cocaine may result in an arrhythmia with the potential to develop Torsades de Pointes.

b) Lithium (and other mood stabilizers) may reduce the high that cocaine users experience. In one report, 4 patients stated they were unable to get high on cocaine while taking lithium.

Mechanism
a) Both lithium and cocaine can cause QTc interval prolongation. When used together, these effects may be additive.

b) Mechanism is unknown.

Significance
a) Due to increased risk of QTc interval prolongation, it is recommended to avoid concomitant use of cocaine and lithium.

Serious Risk for Harm

Both cocaine and lithium can cause abnormal heart rhythm. Mixing these two medications could make the chance of having a deadly abnormal heart beat more likely, so this cocktail should be avoided.

Think First

Some medical reports shows that lithium may make the cocaine high 'milder'.

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

Learn more about this substance »

Interaction
OPIOIDS: As a CNS depressant, lithium has the potential to enhance the adverse or toxic effects of other CNS depressants, such as opioids.

DEXTROMETHORPHAN: Concomitant use of lithium with serotonergic opioids may increase a patient's risk of serotonin syndrome.

FENTANYL: Concomitant use of lithium with serotonergic opioids may increase a patient's risk of serotonin syndrome.

LOPERAMIDE: QTc prolongation has been observed with lithium. Concomitant use with high-dose loperamide (>100 mg/day) may result in an arrhythmia with the potential to develop Torsades de Pointes.

METHADONE:a) Concomitant use of lithium with serotonergic opioids may increase a patient's risk of serotonin syndrome.

b) QTc prolongation has been observed with lithium. Concomitant use with methadone may result in an arrhythmia with the potential to develop Torsades de Pointes.

MEPERIDINE: Concomitant use of lithium with serotonergic opioids may increase a patient's risk of serotonin syndrome.

TRAMADOL: Concomitant use of lithium with serotonergic opioids may increase a patient's risk of serotonin syndrome.

Mechanism
OPIOIDS: Additive CNS depression.

DEXTROMETHORPHAN: Additive serotonergic activity.

FENTANYL: Additive serotonergic activity.

LOPERAMIDE: Both lithium and high dose loperamide can cause QTc interval prolongation. When used together, these effects may be additive.

METHADONE: a) Additive serotonergic activity.

b) Both lithium and methadone can cause QTc interval prolongation. When used together, these effects may be additive.

MEPERIDINE: Additive serotonergic activity.

TRAMADOL: Additive serotonergic activity.

Significance
OPIOIDS: It is important to warn patients of the potential for a reduction in psychomotor function when these drugs are taken concurrently. They may or may not be aware of their deterioration in skill level and response will vary between individuals. They will likely experience a deterioration in their abilities to operate a vehicle and/or carry out tasks that require mental alertness.

DEXTROMETHORPHAN: Patients should be monitored closely for signs and symptoms of serotonin syndrome (e.g. agitation, myoclonus, increased sweating, tachycardia, etc.) if lithium and dextromethorphan are used concurrently.

FENTANYL: Patients should be monitored closely for signs and symptoms of serotonin syndrome (e.g. agitation, myoclonus, increased sweating, tachycardia, etc.) if lithium and fentanyl are used concurrently.

LOPERAMIDE: Due to increased risk of QTc interval prolongation, it is recommended to avoid concomitant use of high-dose loperamide (>100 mg/day) and lithium.

METHADONE:a) Patients should be monitored closely for signs and symptoms of serotonin syndrome (e.g. agitation, myoclonus, increased sweating, tachycardia, etc.) if lithium and methadone are used concurrently.

b) Due to increased risk of QTc interval prolongation, it is recommended to avoid concomitant use of methadone and lithium.

MEPERIDINE: Patients should be monitored closely for signs and symptoms of serotonin syndrome (e.g. agitation, myoclonus, increased sweating, tachycardia, etc.) if lithium and meperidine are used concurrently.

TRAMADOL: Patients should be monitored closely for signs and symptoms of serotonin syndrome (e.g. agitation, myoclonus, increased sweating, tachycardia, etc.) if lithium and tramadol are used concurrently.

Serious Risk for Harm

OPIOIDS: Lithium can cause sleepiness, dizziness and confusion. Opioids can make this worse, and make it more dangerous to drive or do activities that require alertness and attention.

Serious Risk for Harm

LOPERAMIDE: Use of both lithium and very high doses of loperamide (more than 100 mg in one day) can cause abnormal heart rhythm. Mixing these two medications could make the chance of having a deadly abnormal heart beat more likely, so this cocktail should be avoided.

METHADONE: Both lithium and methadone can cause abnormal heart rhythm. Mixing these two medications could make the chance of having a deadly abnormal heart beat more likely, so this cocktail should be avoided.

When lithium is combined with methadone you could get: very high fever, really sick, dangerously high blood pressure, heart problems and even die. This is 'serotonin syndrome'.

Serious Risk for Harm

DEXTROMETHOPRHAN, FENTANYL, MEPERIDINE, TRAMADOL:When lithium is combined with one of these opioids you could get: very high fever, really sick, dangerously high blood pressure, heart problems and even die. This is 'serotonin syndrome'.

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

Learn more about this substance »

Interaction
a) Two small studies suggested that lithium can prevent the euphoriant effects of amphetamines.

b) In 3 different case reports, patients reported a lack of effect from amphetamines while taking lithium.

c) A study in 9 depressed patients found that lithium attenuated the stimulant effects of dextroamphetamine or levoamphetamine in 7 of the 9 patients.

d) A significant reduction in the stimulatory effects of dextroamphetamine was also observed in a study of 17 schizophrenic patients receiving lithium.

e) In contrast, a number of other studies have reported variable responses in subjects receiving lithium along with dextroamphetamine and one study found no attenuation of dextroamphetamine stimulatory effects.

f) Concomitant use of psychostimulants (amphetamine derivatives or methylphenidate) and lithium may increase a patient's risk of serotonin syndrome.

Mechanism
a-e) The mechanism for the interaction is unknown; however, it has been proposed that amphetamines and lithium antagonize each other's pharmacological actions on dopamine and noradrenaline release and uptake at adrenergic neurons.

f) Additive serotonergic effects.

Significance
a-e) Due to conflicting data, the interaction risk is not clear. It is recommended to monitor patients for any decrease in the therapeutic effect of amphetamines if patients are also receiving lithium.

f) Patients should be monitored closely for signs and symptoms of serotonin syndrome (e.g. agitation, myoclonus, increased sweating, tachycardia, etc) if psychostimulants are used concurrently with lithium.

Serious Risk for Harm

When lithium is combined with amphetamines or methylphenidate you could get: very high fever, really sick, dangerously high blood pressure, heart problems and even die. This is 'serotonin syndrome'.

Think First

Doctors sometimes prescribe medical amphetamines to patients taking lithium to help treat some illnesses, but this is done very carefully.

Think First

There is conflicting information. Some medical reports show that lithium may make the amphetamine high 'milder'.

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®

Learn more about this substance »

Interaction
KETAMINE: As a CNS depressant, lithium has the potential to enhance the adverse or toxic effects of other CNS depressants, such as ketamine.

PHENCYCLIDINE: No information currently available.

Mechanism
KETAMINE: Additive CNS depression.

Significance
KETAMINE: It is important to warn patients of the potential for a reduction in psychomotor function when these drugs are taken concurrently. They may or may not be aware of their deterioration in skill level and response will vary between individuals. They will likely experience a deterioration in their abilities to operate a vehicle and/or carry out tasks that require mental alertness.

Serious Risk for Harm

KETAMINE: Lithium can cause sleepiness, dizziness and confusion. Ketamine can make this worse, and make it more dangerous to drive or do activities that require alertness and attention.

Unknown Dangers

PHENCYCLIDINE: 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

Learn more about this substance »

Interaction
Chronic administration of lithium may subjectively increase the physical, hallucinatory and psychological responses to LSD.

Mechanism
Lithium induced alterations in response to LSD most likely involve differential changes in central serotonin and dopamine receptor systems.

Serious Risk for Harm

The LSD high can be changed by lithium. This cocktail can cause a bad trip, or a trip that goes on an on and seems like it will never end. The trip can last so long it gets really boring, or can bring on feelings of terror.

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
ALPRAZOLAM: An 8% increase was seen in lithium AUC when alprazolam was co-administered to 10 healthy subjects. Renal elimination was also decreased from 94% to 78%. Researchers concluded that this is unlikely to be a clinically relevant interaction.

BROMAZEPAM: A patient taking lithium carbonate 900 mg daily experienced increased lithium levels (1.1 mmol/L to 1.4 mmol/L) 4 days after bromazepam 18 mg was added to his daily regimen. His lithium levels returned to their previous level after his daily lithium dose was decreased (by 45%) to 500 mg.

CLONAZEPAM: A retrospective study of patients receiving lithium (900 mg to 2400 mg daily) for the treatment of bipolar disorder found 5 patients who had experienced reversible neurotoxic symptoms (e.g. ataxia, dysarthria, drowsiness, confusion) when clonazepam (2 to 16 mg daily) was started. All 5 patients experienced increased lithium levels; moreover, the interaction resulted in toxic levels in 2 of these patients.

DIAZEPAM: A patient with significant mental retardation experienced intermittent episodes of hypothermia (below 35°C) when using concomitant lithium and diazepam, but not when receiving either drug alone. The clinical significance of this case report is unknown.

Mechanism
It has been suggested that the neurotoxic effects may be due to synergistic toxicity or increased CNS sensitivity.

Significance
Patients should be monitored for the appearance of adverse drug effects and counselled on avoidance, unless clinically necessary, of benzodiazepines while on lithium therapy. Monitoring of lithium levels would be recommended upon initiation, discontinuation or during dose adjustments of a benzodiazepine.

Serious Risk for Harm

Taking lithium and some benzodiazepines together may increase the amount of lithium absorbed by your body. This would be like taking too much lithium. This could cause side effects like confusion, slurred speech or make you really shaky. If you have these effects, get checked by a doctor right away.

Doctors sometimes prescribe lithium and benzodiazepines together, but this is done carefully, with close monitoring.

Think First

Taking lithium and benzodiazepines together can cause sexual problems in about 50% of people (like trouble getting an erection, or trouble having an orgasm).

Think First

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

References

[+]

Angrist B, Gershon S. Variable attenuation of amphetamine effects by lithium. Am J Psychiatry 1979; 136: 806-10.

Anton RF, Paladino JA, Morton A, et al. Effect of acute alcohol consumption on lithium kinetics. Clin Pharmacol Ther 1985; 38: 52-5.

Bell EC, Willson MC, Wilman AH, et al. Lithium and valproate attenuate dextroamphetamine-induced changes in brain activation. Hum Psychopharmacol 2005; 20: 87-96.

Bonson KR, Murphy DL. Alterations in responses to LSD in humans associated with chronic administration of tricyclic antidepressants, monoamine oxidase inhibitors or lithium. Behav Brain Res 1996; 73: 229-33.

Cronson AJ, Flemenbaum A. Antagonism of cocaine highs by lithium. Am J Psychiatry 1978;135:856-7.

Drivers WE, Baxter K, ed. Stockley's Herbal Medicines Interactions. London: Pharmaceutical Press; 2009; 102.

Evans RL, Nelson MV, Melethil S, et al. Evaluation of the interaction of lithium and alprazolam. J Clin Psychopharmacol 1990; 10: 355-9.

Flemenbaum A. Does lithium block the effects of amphetamine? A report of three cases. Am J Psychiatry 1974; 131: 820-1.

Ghadirian AM, Annable L, Bélanger MC. Lithium, benzodiazepines, and sexual function in bipolar patients. Am J Psychiatry 1992; 149: 801-5.

Jefferson JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. J Clin Psychiatry 1988; 49: 72-3.

Judd LL, Huey LY. Lithium antagonizes ethanol intoxication in alcoholics. Am J Psychiatry 1984; 141: 1517-21.

Koczerginski D, Kennedy SH, Swinson RP. Clonazepam and lithium--a toxic combination in the treatment of mania? Int Clin Psychopharmacol 1989; 4: 195-9.

Kunitake Y, Mizoguchi Y, Sogawa R, et al. Effect of Excessive Coffee Consumption on the Clinical Course of a Patient With Bipolar Disorder: A Case Report and Literature Review. Clin Neuropharmacol 2017;40: 160-162.

Lexi-Comp ONLINE, Lexi-Comp ONLINE Interaction Analysis, Hudson, Ohio: Lexi-Comp, Inc.; 2021; July 14, 2021.

Mester R, Toren P, Mizrachi I, et al. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry 1995; 37: 348-50.

Naylor GJ, McHarg A. Profound hypothermia on combined lithium carbonate and diazepam treatment. Br Med J 1977; 2 :22.

Preston CL (Ed), Stockley’s Interactions Checker. [online] London: Pharmaceutical Press. (accessed on July 14, 2021).

Silverstone PH, Pukhovsky A, Rotzinger S. Lithium does not attenuate the effects of D-amphetamine in healthy volunteers. Psychiatry Res 1998; 79: 219-26.

Singh RK, Dillon B, Tatum DA, et al Drug-Drug Interactions Between Cannabidiol and Lithium. Child Neurol Open 2020;7: 1-4.

Turkoglu S. Serotonin syndrome with sertraline and methylphenidate in an adolescent. Clin Neuropharmacol 2015; 38: 65-6.

van Kammen DP, Docherty JP, Marder SR, et al. Lithium attenuates the activation-euphoria but not the psychosis induced by d-amphetamine in schizophrenia. Psychopharmacology (Berl) 1985; 87: 111-5.

Van Kammen DP, Murphy DL. Attenuation of the euphoriant and activating effects of d- and l-amphetamine by lithium carbonate treatment. Psychopharmacologia 1975; 44: 215-24.

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

Willson MC, Bell EC, Dave S, et al. Valproate attenuates dextroamphetamine-induced subjective changes more than lithium. Eur Neuropsychopharmacol 2005; 15: 633-9.

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.

Copyright © 2025. All rights reserved. Children’s & Women's Health Centre of British Columbia. Materials on this website may be copied and used for personal non-commercial purposes.

lithium

References

Which version would you like to print?