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RX + Party Drug Combos Hormones & Birth Control Mental Health Meds SSRI/SNRI Combos Wellbutrin + Stimulants Benzos + Depressants ADHD Meds + Stimulants Antipsychotics + Mood Stabilizers Sleep Aids & Other Meds Recreational Combos Golden Rules Interaction Checker

RX + Party Drug Combos

Understanding polydrug risks that aren't discussed enough in the community.

SSRI/SNRI + Party Drugs

  • + MDMA/Molly: Dulls the high → redosing → serotonin syndrome
  • + LSD/Shrooms: Flat visuals or erratic tripping
  • + Cocaine/Adderall: Anxiety spike, heart risk

Wellbutrin + Stimulants

  • + MDMA/Coke: Lowers seizure threshold
  • + Alcohol: Blackouts, impulsivity, seizures

Benzos + Depressants

  • + Opiates: Breathing stops → fatal risk
  • + Alcohol: Respiratory depression
  • + K/GHB: Memory loss, vomit risk

ADHD Meds + Stimulants

  • + MDMA/Coke/Meth: Overheating, heart stress
  • + Alcohol: Blackouts, impaired judgment
  • + Psychedelics: Heightened confusion

Hormones, Birth Control & Club Drugs

Why it matters: Most rave drug info isn't made with AFAB folks in mind.

Estrogen + Stimulants

Higher estrogen levels can intensify effects of MDMA and other stimulants, increasing risk of overheating, serotonin syndrome, or comedown crash.

Hormones + Psychedelics

Hormonal shifts can change how you experience shrooms, LSD, or DMT. Some report stronger visuals or more emotional depth around ovulation or during PMS.

Birth Control + Liver Enzymes

Some substances compete for liver enzymes. Hormonal BC can slow or intensify metabolization—meaning unpredictable roll length or strength.

Research Gap

Clinical drug trials often exclude AFAB folks or don't study interactions with HRT/BC. That means DIY harm reduction matters more than ever.

Mental Health Meds + Party Drugs

Mixing psychiatric medications with recreational substances requires special caution.

SSRIs + Stimulants

Increased risk of serotonin syndrome — symptoms include agitation, rapid heart rate, sweating, confusion, and in severe cases, seizures or death.

Benzos + Depressants

Combining benzos with alcohol or opioids causes compounded sedation and respiratory depression, potentially leading to unconsciousness or fatal overdose.

Mood Stabilizers & Antipsychotics

Many of these meds alter metabolism of party drugs, making effects unpredictable. Can cause heart issues or severe anxiety when mixed with stimulants.

Harm Reduction Tips

  • Talk with your prescriber about your drug use
  • Avoid mixing stimulants and SSRIs
  • Carry naloxone if using opioids or benzos
  • Have a trusted sober friend aware of your meds
  • Test your substances whenever possible

SSRI / SNRI + Party Drugs

(Lexapro, Zoloft, Prozac, Effexor, Cymbalta)

+ MDMA / Molly / Ecstasy

  • Dulls the high
  • People redose = serotonin syndrome
  • Can still overheat or seize, even if you "don't roll hard"

+ LSD / Shrooms / DMT

  • Often flattens visuals/emotion
  • Some people feel nothing; others trip hard anyway
  • Risk of redosing or combining more drugs to "feel something"

+ Cocaine or Adderall

  • Increased anxiety, overstimulation
  • High blood pressure, heart risk
  • May worsen depression long-term

Wellbutrin (Bupropion) + Stimulants

(Adderall, Vyvanse, Ritalin, Coke, MDMA)

+ MDMA or Coke

  • Seizure threshold drops
  • Anxiety, paranoia spike
  • Risk of panic attacks, overstimulation

+ Alcohol

  • Lowers seizure threshold further
  • May increase aggression or impulsivity
  • Blackout risk is higher than usual

Warning

Avoid this combo if you've ever had a seizure—even once.

Benzos (Xanax, Klonopin, Ativan) + Depressants

(Opiates, Alcohol, Ketamine, GHB)

+ Opiates (Percocet, Fentanyl, Heroin)

  • One of the deadliest combos
  • Slows or stops breathing
  • You will not feel how high you are, until it's too late

+ Alcohol

  • Common, normalized, but incredibly dangerous
  • Both slow your nervous system
  • Overdose while "just sleeping"

+ Ketamine or GHB

  • Complete disassociation, memory loss
  • Loss of control, high assault risk
  • Can vomit while unconscious and choke

Xanax + Alcohol

Two downers = one very real chance of never waking up. They depress your nervous system—together, they can stop your breathing in your sleep.

  • Memory blackouts
  • Respiratory depression
  • High risk of death

ADHD Meds (Adderall, Vyvanse, Ritalin) + Stimulants

+ MDMA / Coke / Meth

  • Triple stacking dopamine and norepinephrine
  • Heart stress, overheating, stroke risk
  • Emotional crash can be severe

+ Alcohol

  • Alcohol feels lighter than it is
  • High blackout risk
  • Risky behavior, aggression, impulsivity

+ Psychedelics

  • May intensify or destabilize trip
  • Increased anxiety, agitation, confusion

Adderall + MDMA

Stacking uppers floods your brain with chemicals until it can't keep up. The high may be short, but the damage can be long.

  • Serotonin syndrome
  • Neurotoxicity
  • Major comedown depression

Antipsychotics + Mood Stabilizers Combos

Antipsychotics (Seroquel, Abilify, Risperdal) + Psychedelics

  • Can mute or completely block the trip
  • May cause rebound confusion or panic
  • Higher risk of emotional instability or psychotic episode afterward

Antipsychotics + MDMA

  • Dulls empathy/euphoria
  • People redose to chase the high
  • Risk of serotonin overload or heart issues

Mood Stabilizers (Lamictal, Lithium) + Psychedelics

  • Lamictal can make trips feel emotionally numb or panicky
  • Lithium + psychedelics = NOPE
    • Risk of seizures
    • Documented deaths
    • Completely unpredictable

Lithium + Psychedelics (LSD, mushrooms, DMT)

No sugarcoating this: it's a hard no. People have died or ended up in seizures or psychiatric holds from this combo. Lithium + psychedelics is one of the most dangerous interactions out there.

  • Toxic reactions
  • Uncontrollable seizures
  • Long-term psychological effects

❌ Just don't. This combo kills.

Sleep Aids & Other Medication Combos

Trazodone / Hydroxyzine / Sleep Aids + Alcohol or Downers

  • Super common mix to "relax" or "sleep better"
  • Reality: respiratory suppression, blackout, disorientation
  • Hydroxyzine especially can stack with opiates and increase OD risk

+ Ketamine or GHB

  • Slows reflexes, sedation
  • Can enter full blackouts
  • Vomit and fall risk

Gabapentin / Lyrica + Alcohol or Opiates

  • Often misused to "boost" opiate high
  • Stacks sedation and euphoria
  • High overdose risk especially if tolerance is low
  • Motor control and memory go fast

Recreational Drug Combinations

Coke + Opiates (Speedballs)

  • Cocaine hides how sedated you are, so you use more opiates than your body can handle
  • Cardiac arrest risk
  • OD feels like it "comes out of nowhere"
  • Extremely high fatality rate

MDMA + LSD (Candyflipping)

  • Can be incredible if you're experienced and safe
  • Increased risk of bad trip
  • Can trigger psychosis
  • Trip sitter, water, and grounding tools = non-negotiable

Ketamine + Benzos

  • Heavy sedation. You might forget how to move—or breathe
  • Risk of unconscious vomiting = very real
  • Extreme memory loss
  • Dangerous CNS depression

Weed + Psychedelics

  • Weed can make visuals stronger, but also crank up anxiety and nausea
  • Paranoia and panic
  • Derealization
  • Many bad trips start with one too-big hit

Interaction Checker

For a detailed polydrug interaction checker and additional safety information:

Visit Polydrug Interaction Checker

Golden Rules of Harm Reduction

Essential Guidelines

  • Don't stack downers. (Xanax + alcohol = deadly)
  • Don't stack uppers. (Adderall + coke = cardiac arrest)
  • Psychedelics are not "just visuals"
  • Hydrate smart, not excessive
  • Always have a trusted friend nearby—especially if you're "fine"
  • Just because it's prescribed doesn't mean it's safe to stack
  • Many psych meds change how drugs work—sometimes muting, sometimes multiplying effects
  • You can't "guess" your way through brain chemistry
  • If you're on meds for mental health, your set is already shifted—don't mess with your setting

Unknown Substances

No matter how cool someone seems—if you didn't test it, you don't know what it is. Period.

  • Use test kits
  • Carry Narcan
  • Never snort "just a little" mystery line