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
As a CNS depressant, trazodone has the potential to enhance the adverse or toxic effects of other CNS depressants, such as alcohol.

In a small study of 6 healthy subjects, trazodone 100 mg resulted in impairment of psychomotor functions, drowsiness, and reduced 'clearheadedness'. Co-administration of alcohol (blood levels were approximately 40 mg%) resulted in a further impairment of manual dexterity; no other parameters appeared to result in increased impairment.

A similar study also found increased psychomotor impairment with concomitant use of trazodone and alcohol.

Mechanism
The exact mechanism of increased CNS depression is unknown, but it appears that the effects are mainly additive.

Significance
While trazodone itself can cause a reduction in psychomotor function, it is important to warn patients of the potential for a further 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

Trazodone can cause sleepiness, dizziness and confusion. Alcohol can make this worse, and make it more dangerous to drive or do activities that require alertness and attention.

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
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

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Interaction
In a randomized, placebo-controlled study where caffeine administration was used to mimic the effects of insomnia, trazodone 100 mg was found to attenuate the caffeine-induced decrease in both total sleep time and sleep efficiency. Concomitant use of trazodone was also associated with an increase in stage 3 sleep, a reduction in the number of awakenings as well as a reduction in spindle density. However, no significant changes were seen in REM sleep.

Mechanism
Opposing CNS effects.

Significance
Trazodone may reduce the wakefulness promoting effects of caffeine.

Think First

Taking large amounts of caffeine may cause shaking hands, fast heart beat, trouble sleeping at night, edgy or irritable feelings. If you are taking trazodone to help with sleep or anxiety, this may work against the helpful effects of trazodone.

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
As a CNS depressant, trazodone has the potential to enhance the adverse or toxic effects of other CNS depressants, such as cannabis.

Mechanism
The exact mechanism of increased CNS depression is unknown, but it appears that the effects are mainly additive.

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 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

Trazodone can cause sleepiness, dizziness and confusion. Cannabis can make this worse, and make it more dangerous to drive or do activities that require alertness and attention.

Cocaine/ Crack

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

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Interaction
a) There is a case of priapism which occurred following trazodone overdose in an individual actively using cocaine.

b) The stimulatory effects of cocaine may directly counteract the hypnotic effects of trazodone.

c) There is an increased risk of serotonin syndrome if cocaine is combined with trazodone.

Mechanism
b) Opposing CNS effects.

c) Cocaine binds to the serotonin receptor and has the potential to block the re-uptake of serotonin. Trazodone also blocks the re-uptake of serotonin. The combination can lead to a drastic increase in serotonin.

Significance
a) Since trazodone is commonly employed as a hypnotic and often chosen for polysubstance abusers due to its low abuse potential, clinicians should be aware of the possible additive risk of priapism in this patient population.

b) Cocaine use should be avoided in patients with insomnia who use trazodone.

c) There is a risk of serotonin syndrome when trazodone is combined with other serotonergic agents. The combination should be avoided if possible. If not possible, monitoring for serotonin syndrome (e.g. agitation, myoclonus, increased sweating, tachycardia, etc) is advised.

Serious Risk for Harm

There is a medical report of a guy taking trazodone and cocaine, and getting something called 'priapism'. Priapism is a prolonged, painful erection that won't go away. This type of erection is an emergency, because if it goes on too long, the penis can be permanently damaged. If you experience a prolonged, painful erection lasting 4 or more hours, see a doctor right away.

Serious Risk for Harm

If you are taking trazodone, using cocaine may increase the risk for side effects from both drugs and you could get: very high fever, really sick, dangerously high blood pressure, a very fast heart beat, heart problems and even die. This is called ‘serotonin syndrome’.

Think First

If you are using trazodone for sleep, cocaine can work against the helpful effects of trazodone.

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

b) DEXTROMETHORPHAN, FENTANYL, MEPERIDINE, METHADONE, TRAMADOL: There is a risk of serotonin syndrome if trazodone is combined with serotonergic opioids: dextromethorphan, fentanyl, meperidine, methadone, and tramadol.

Mechanism
a) ALL OPIOIDS:The exact mechanism of increased CNS depression is unknown, but it appears that the effects are mainly additive.

b) DEXTROMETHORPHAN, FENTANYL, MEPERIDINE, METHADONE, TRAMADOL: The serotonergic opioids inhibit the neuronal reuptake of serotonin. Trazodone also blocks the re-uptake of serotonin. The combination can lead to a drastic increase in serotonin.

Significance
a) ALL 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.

b) DEXTROMETHORPHAN, FENTANYL, MEPERIDINE, METHADONE, TRAMADOL:The combination of trazodone and serotonergic opioids could lead to serotonin syndrome and therefore should be avoided if possible. If not possible, monitoring for serotonin syndrome (e.g. agitation, myoclonus, increased sweating, tachycardia, etc) is advised.

Serious Risk for Harm

ALL OPIOIDS:Trazodone 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

DEXTROMETHORPHAN, FENTANYL, MEPERIDINE, METHADONE, TRAMADOL: If you are taking trazodone, using one of these opioids may increase the risk for side effects from both drugs and you could get: very high fever, really sick, dangerously high blood pressure, a very fast heart beat, heart problems and even die. This is called ‘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

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Interaction
a) Stimulants may decrease the sedative effects of trazodone.

b) There is an increased risk of serotonin syndrome if amphetamines or stimulants are combined with trazodone.

Mechanism
a) Stimulant wakefulness-promoting effect opposes sedative effects of trazodone.

b) Additive effects of serotonin reuptake inhibition by psychostimulants (amphetamine derivatives or methylphenidate) and increased serotonin levels by trazodone could contribute to an increased risk of serotonin syndrome.

Significance
a) Amphetamines/stimulants should be avoided in patients with insomnia who use trazodone.

b) There is a risk of serotonin syndrome when trazodone is combined with other serotonergic agents. The combination should be avoided if possible. If not possible, monitoring for serotonin syndrome (e.g. agitation, myoclonus, increased sweating, tachycardia, etc) is advised.

Serious Risk for Harm

If you are taking trazodone, using amphetamines or stimulants, especially in 'street' doses, may increase the risk for side effects from both drugs and you could get: very high fever, really sick, dangerously high blood pressure, a very fast heart beat, heart problems and even die. This is called ‘serotonin syndrome’.

Think First

If you are using trazodone for sleep, taking amphetamines or stimulants can work against the helpful effects of trazodone.

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: As a CNS depressant, trazodone 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: Trazodone 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

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Interaction
Chronic administration of trazodone subjectively decreases the response to LSD and may even eliminate its effects. 88% (28 out of 32) of subjects in a retrospective study found that their responses to LSD were either reduced or eliminated if they had taken trazodone or an SSRI for more than 3 weeks prior to the LSD dose.

Mechanism
The mechanism of this interaction is not clear. However, taking into account that LSD causes a rise in serotonin levels in the brain, it is hypothesized that there is increased stimulation of 5-HT1 and 5-HT2 receptors when re-uptake of serotonin is blocked. Serotonin reuptake blockade is part of the mechanism of action of trazodone.

Significance
The significance of this interaction is unknown.

Serious Risk for Harm

This cocktail can cause a bad trip, or can bring feelings of terror. Or it can cause a trip that goes on and on and seems like it will never end. And sometimes, people have very 'mild' trips on LSD when they are taking trazodone.

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
As a CNS depressant, trazodone has the potential to enhance the adverse or toxic effects of other CNS depressants, such as benzodiazepines.

Mechanism
The exact mechanism of increased CNS depression is unknown, but it appears that the effects are mainly additive.

Significance
While the additive effects may be clinically appropriate, monitoring of the patient is advised.

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

Mixing trazodone with benzodiazepines may result in increased side effects like severe sleepiness, dizziness, and confusion. It will make it more dangerous to drive or do activities that require alertness and attention.

Think First

Doctors will sometime give small amounts of medical benzodiazepines to patients taking trazodone to help treat certain illnesses, but this is done very carefully.

Think First

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

References

[+]

Baxter K, ed. Stockley's Drug Interactions. [online] London: Pharmaceutical Press. 2021; May 31, 2021.

Bonson KR, Buckholtz JW, Murphy DL. Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans. Neuropsychopharmacology 1996; 14: 425-36.

Falls BA, Gurrera RJ. Serotonin syndrome in a patient on tramadol, bupropion, trazodone, and oxycodone. Psychosomatics 2014; 55: 305-9.

Lexi-Comp ONLINE, Lexi-Comp ONLINE Interaction Analysis, Hudson, Ohio: Lexi-Comp, Inc.; 2021; May 31, 2021.

McCue RE, Joseph M. Venlafaxine- and trazodone-induced serotonin syndrome. Am J Psychiatry 2001; 158: 2088-9.

Myrick H, Markowitz JS, Henderson S. Priapism following trazodone overdose with cocaine use. Ann Clin Psychiatry 1998; 10: 81-3.

Paterson LM, Nutt DJ, Ivarsson M et al. Effects on sleep stages and microarchitecture of caffeine and its combination with zolpidem or trazodone in healthy volunteers. J Psychopharmacol 2009; 23: 487-94.

Warrington SJ, Ankier SI, Turner P. Evaluation of possible interactions between ethanol and trazodone or amitriptyline. Neuropsychobiology 1986; 15: 31-7.

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

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.

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trazodone

References

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