Question 1

Can you take psilocybin mushrooms with lithium?

Accepted Answer

Documented serious harm, or a well-founded risk of it. Do not combine. Seizures, in people with no seizure history. In the same reports, many people sought medical attention. Not established in humans. In rats, lithium pretreatment turned a normally non-convulsant dose of a 5-HT2 agonist into a seizure-causing one, and a 5-HT2 blocker prevented this, which suggests lithium amplifies signalling downstream of the receptor psilocin acts on. Lithium toxicity can also cause seizures on its own. The human evidence comes from user reports and case reports, not trials. Don't combine, this is the one real 'no' in the list. Don't stop your lithium to get around it either: it treats conditions where stopping risks a manic or depressive episode. If you want to explore psychedelics, that's a conversation with whoever manages your lithium.

Question 2

Can you take psilocybin mushrooms with maois (irreversible)?

Accepted Answer

Documented serious harm, or a well-founded risk of it. Do not combine. Unpredictable. User reports describe stronger and longer effects than expected, and a published case describes a hypertensive emergency after psilocybin mushrooms in a man taking tranylcypromine together with an amphetamine. Because the size of any effect is not predictable, a dose someone has taken safely before can behave very differently. Psilocin is cleared mainly by glucuronidation and by conversion to 4-HIAA. In lab studies MAO-A, CYP2D6 and CYP3A4 all contribute, but MAO-A alone produced only small amounts of 4-HIAA, so how much an MAOI changes psilocin levels in people is unknown. The better-documented hazard is blood pressure: irreversible MAOIs can cause hypertensive crisis with certain foods and drugs, and mushrooms contain other amines besides psilocybin. Treat as a hard no unless you are working with a prescriber who knows both drugs. Irreversible MAOIs take about two weeks to wash out after the last dose, so 'I stopped yesterday' does not clear this. Don't stop an MAOI on your own; they're usually prescribed for treatment-resistant depression, and stopping has its own risks.

Question 3

Can you take psilocybin mushrooms with tramadol?

Accepted Answer

Documented serious harm, or a well-founded risk of it. Do not combine. Raised seizure risk. Seizures are a recognised adverse effect of tramadol: common in overdose, and also reported in prescribed use, usually alongside other risk factors. Tramadol is an opioid that also inhibits serotonin and noradrenaline reuptake. Its label warns that seizures can occur within the recommended dose range, that other drugs can raise that risk, and that serotonin syndrome can occur, particularly with other serotonergic drugs. The concern with psilocybin rests on these properties rather than on any reported case. Avoid the combination. If you are on tramadol for pain, ask your prescriber about the interaction rather than skipping doses of a drug that may also cause withdrawal.

Question 4

Can you take psilocybin mushrooms with moclobemide and other rimas?

Accepted Answer

A real mechanism for harm exists. Stronger and longer effects than expected, to a lesser degree than with an irreversible MAOI. Moclobemide reversibly inhibits MAO-A, about 80% at a 300 mg dose, and the inhibition lasts at most about 24 hours. MAO-A plays only a small part in breaking down psilocin in lab work, so any change to psilocin levels is likely smaller than with irreversible MAOIs, but it has not been measured in people. The antibiotic linezolid and intravenous methylene blue are also reversible inhibitors of monoamine oxidase, according to their FDA labels (linezolid is nonselective, and the methylene blue label bases this on literature reports); no study of either with psilocybin is cited here. Assume any dose will hit harder than it did the last time you took it without this. Not a reason to stop your medication.

Question 5

Can you take psilocybin mushrooms with harmala alkaloids?

Accepted Answer

A real mechanism for harm exists. Substantially amplified and extended effects, plus additive nausea. The dose of the harmala is usually unmeasured, so the multiplier is unknowable. Harmine and harmaline are potent, reversible, competitive inhibitors of MAO-A, the same mechanism as moclobemide. Peganum harmala seeds contain several percent of these alkaloids by weight, so plant material can carry a large and variable dose. How much this changes psilocin levels in people has not been measured. If you are doing this deliberately, the relevant fact is that you cannot predict the multiplier, so the only safe approach is a fraction of a dose you already know. Note that harmala MAOIs also carry the dietary tyramine problem.

Question 6

Can you take psilocybin mushrooms with bupropion?

Accepted Answer

A real mechanism for harm exists. Raised seizure risk, particularly at higher bupropion doses, in the immediate-release formulation, or where there is any additional risk factor such as an eating disorder history or alcohol withdrawal. Bupropion is a weak noradrenaline and dopamine reuptake inhibitor that does not inhibit serotonin reuptake or MAO, so serotonin toxicity is not the concern. Its label states it can cause seizures, with dose-related risk that also depends on patient factors and other medications. Worth genuine caution, especially at 300 mg and above. Unlike SSRIs, bupropion does not blunt psychedelic effects much, so people are more likely to take a full dose on it.

Question 7

Can you take psilocybin mushrooms with tricyclic antidepressants?

Accepted Answer

A real mechanism for harm exists. Reports of intensified effects. Additive cardiovascular strain, psilocybin already produces a modest rise in heart rate and blood pressure. Unlike SSRIs, chronic tricyclic use was linked to stronger LSD effects in a very small study, possibly through changes in serotonin or dopamine receptor sensitivity. Tricyclics also have anticholinergic effects and can cause arrhythmias and slowed cardiac conduction, especially at high doses. Clomipramine inhibits serotonin reuptake and has a notable seizure risk of its own. Expect more effect than you planned for, not less. If you have any cardiac history, the additive cardiovascular load is the part to take seriously.

Question 8

Can you take psilocybin mushrooms with st john's wort?

Accepted Answer

A real mechanism for harm exists. Unpredictable. Reported both to blunt effects and to leave them unchanged. The main documented hazard of St John's Wort is what it does to other prescribed drugs. St John's Wort induces CYP3A4 and P-glycoprotein, lowering blood levels of many drugs, and it counts as a serotonergic drug in medicine labels. CYP3A4 is one of several enzymes that metabolise psilocin in lab work, so a change in psilocin levels is possible in theory but has not been measured. Treat as an unknown quantity rather than as safe because it is sold in a health-food shop. If you take other medication, St John's Wort is already interacting with it.

Question 9

Can you take psilocybin mushrooms with stimulants?

Accepted Answer

A real mechanism for harm exists. Higher heart rate and blood pressure than either alone. Anxiety and panic are markedly more likely, and a panic reaction during the come-up is the most common route to a bad experience. Additive load on the heart and circulation. Prescription stimulants raise blood pressure and heart rate modestly on average, and psilocybin raises autonomic measures moderately; together the effects add. Higher psilocybin doses also increase anxiety. Prescribed ADHD stimulants are widely combined without disaster, but they reliably make the come-up worse. Cocaine is a different question and belongs nowhere near a psychedelic. Any pre-existing cardiac condition moves this into the do-not category.

Question 10

Can you take psilocybin mushrooms with antipsychotics?

Accepted Answer

A real mechanism for harm exists. Usually a blunted or absent experience. With typical antipsychotics, sometimes intensified dysphoria and agitation instead. Many antipsychotics, such as risperidone, block 5-HT2A, the receptor psilocin acts on, and blunt the experience in proportion to dose. Haloperidol, which mainly blocks dopamine D2, did not block psilocybin in a controlled study; it reduced some effects but increased anxiety. If you are prescribed an antipsychotic, the underlying reason matters more than the interaction. Classical psychedelics can precipitate or worsen psychosis in vulnerable people, and that's the real thing to weigh here, not the pharmacology. Don't stop an antipsychotic to take mushrooms.

Question 11

Can you take psilocybin mushrooms with triptans?

Accepted Answer

Not studied. Treated as caution. No characteristic reported interaction. The concern is theoretical and mostly cardiovascular. Triptans act at 5-HT1B/1D receptors on blood vessels and nerves and can narrow arteries, which is why they are contraindicated in coronary disease. Psilocin acts mainly at 5-HT2A but also binds 5-HT1A with moderate to high affinity. Any additive effect on blood vessels is theoretical. Low practical concern for most people, higher if you have cardiovascular disease. Worth knowing that a bad experience can produce a headache you then want to treat.

Question 12

Can you take psilocybin mushrooms with dextromethorphan?

Accepted Answer

A real mechanism for harm exists. At cough-suppressant doses, little. At recreational doses, additive serotonergic load and a confusing, disorienting combination. DXM is an NMDA antagonist and sigma-1 agonist with serotonergic activity. CYP2D6 is its major metabolic route, so CYP2D6 poor metabolisers (about 7 to 10% of white people) and people on CYP2D6 inhibitors such as fluoxetine or paroxetine reach much higher levels. Serotonin syndrome cases involve high DXM doses plus an SSRI or MAOI, not psilocybin. A normal dose of cough medicine is not the issue. Taking DXM recreationally on top of mushrooms is a different and worse drug experience than either alone.

Question 13

Can you take psilocybin mushrooms with 5-htp and l-tryptophan?

Accepted Answer

Not studied. Treated as caution. No characteristic interaction reported with psilocybin alone. 5-HTP and L-tryptophan are serotonin precursors that increase serotonin synthesis. Psilocin acts directly as a 5-HT2A agonist and does not rely on the serotonin transporter or on releasing serotonin, so the additive serotonin load from psilocybin is likely small. The serotonin syndrome risk with these supplements comes mainly from stacking them with drugs that raise serotonin, such as SSRIs, SNRIs or MAOIs. Common advice to take 5-HTP the day after to 'replenish serotonin' rests on a misunderstanding of how psilocybin works. It does not deplete serotonin the way MDMA is thought to. If you are on an SSRI or MAOI, do not add 5-HTP for any reason.

Question 14

Can you take psilocybin mushrooms with ssris?

Accepted Answer

Blunts or blocks the experience. Often a weaker experience than the dose would normally produce, sometimes much weaker. People then redose, which is where the actual risk sits: the second dose can arrive as the first is still climbing. The usual explanation is that weeks of SSRI treatment reduce the number or responsiveness of 5-HT2A receptors, which psilocin needs, though this has not been confirmed directly in humans. Psilocin is a direct receptor agonist, not a serotonin releaser, so the classic SSRI-plus-MDMA serotonin syndrome mechanism does not transfer cleanly. In a two-week trial escitalopram did not change psilocin blood levels. Expect a weaker experience and plan for the redosing trap rather than the serotonin syndrome one. Fluoxetine is the outlier for washout: its active metabolite has a half-life of one to two weeks, so it lingers far longer than the others. Do not taper or stop an antidepressant to take mushrooms without your prescriber, discontinuation syndrome is real, and paroxetine and venlafaxine are particularly unpleasant to stop.

Question 15

Can you take psilocybin mushrooms with snris?

Accepted Answer

Blunts or blocks the experience. Blunted effects, as with SSRIs. Venlafaxine carries a little more risk than the rest of the class. SNRIs block reuptake of both serotonin and noradrenaline, and the blunting is thought to work as with SSRIs, through adaptation of 5-HT2A receptors over weeks. Psilocin is a direct receptor agonist, so a classic serotonin-release interaction is not expected. Venlafaxine has a separate seizure warning: seizures have been reported during treatment and are among the more commonly reported events in overdose. Same redosing trap as the SSRIs. Venlafaxine's seizure-threshold effect makes it the one in this class to be more careful with. Do not stop it abruptly, venlafaxine has one of the worst discontinuation syndromes of any antidepressant.

Question 16

Can you take psilocybin mushrooms with mirtazapine?

Accepted Answer

Blunts or blocks the experience. Blocks the experience almost entirely, more completely than an SSRI does. Taken during an experience it will substantially reduce it, along with heavy sedation. Mirtazapine is an antagonist at 5-HT2 and 5-HT3 receptors as well as alpha-2 adrenergic receptors, and it also blocks histamine H1 receptors, which accounts for its sedation. Because psilocybin's effects depend on 5-HT2A activation, a 5-HT2 antagonist would be expected to reduce them, as other 5-HT2A blockers do in human studies. If you are on mirtazapine, a dose will most likely be wasted. Some people keep it on hand for that reason, though a benzodiazepine is the better-understood rescue option.

Question 17

Can you take psilocybin mushrooms with trazodone?

Accepted Answer

Blunts or blocks the experience. Blunts the experience and adds heavy sedation. Trazodone has dose-dependent actions: at low hypnotic doses it blocks 5-HT2A, histamine H1 and alpha-1 adrenergic receptors, and at higher doses it also blocks the serotonin transporter. Because psilocybin's effects depend on 5-HT2A activation, a 5-HT2A antagonist is expected to reduce them. Its label also carries a general serotonin syndrome warning when combined with other serotonergic drugs. Commonly prescribed for insomnia rather than depression, so people forget they are on a 5-HT2A antagonist at all.

Question 18

Can you take psilocybin mushrooms with benzodiazepines?

Accepted Answer

Blunts or blocks the experience. Reduced anxiety and intensity, drowsiness, and patchy memory of the period afterwards. This is why it is the standard rescue medication in clinical research. Benzodiazepines enhance GABA-A signalling and cause sedation and reduced anxiety without acting on 5-HT2A, so they dampen distress rather than reverse psilocin's receptor action. No controlled study has measured how much they reduce psilocybin's perceptual effects. The most useful thing on this page for someone having a hard time. Worth knowing about before you need it. Benzodiazepines are themselves dependence-forming and dangerous to stop abruptly after regular use, so this is an occasional rescue, not a routine pairing.

Question 19

Can you take psilocybin mushrooms with cyproheptadine?

Accepted Answer

Blunts or blocks the experience. Reduces the experience and adds sedation. It is also the drug used to treat serotonin syndrome. Cyproheptadine is a first-generation antihistamine that also blocks serotonin receptors, with anticholinergic and sedative effects. Because psilocybin acts through 5-HT2A receptors, a serotonin antagonist would be expected to blunt it, as ketanserin does in human studies. It is used as an adjunct in treating serotonin syndrome, though evidence that it changes outcomes is limited. Occasionally suggested as a trip terminator. It's not as reliable as people claim.

Question 20

Can you take psilocybin mushrooms with cannabis?

Accepted Answer

Intensifies effects beyond what was planned for. Sharply amplified intensity, often arriving suddenly. A common route from a manageable experience to a frightening one, particularly during the come-up or peak. There is no known direct receptor interaction. Cannabis can on its own cause anxiety, paranoia and perceptual changes, and survey data suggest that taken alongside a psychedelic it increases intensity in a dose-related way. The effect is unpredictable during the come-up and peak. If you are going to use it at all, wait for the come-down. Adding it at the peak is the specific mistake people describe regretting.

Question 21

Can you take psilocybin mushrooms with alcohol?

Accepted Answer

A real mechanism for harm exists. Increased nausea and vomiting risk, worse coordination, and a muddied experience. At higher intakes, a genuine injury risk from impaired judgement in an already-disorienting state. No specific receptor interaction is known. Alcohol impairs judgement and coordination and worsens nausea and dehydration, which compounds the disorientation of a psilocybin experience. Alcohol is often used alongside mushrooms by people who end up seeking emergency care, though cause and effect are not established. Small amounts are sometimes used to take the edge off the come-up. Meaningful drinking is a bad idea for reasons that have nothing to do with pharmacology and everything to do with falling down stairs.

Question 22

Can you take psilocybin mushrooms with mao-b inhibitors?

Accepted Answer

Not studied. Treated as caution. Not documented. No study or report of this pairing is cited here. At usual doses the drug acts mainly on MAO-B, while the lab work on psilocin found only a minor role for MAO-A. Psilocin is cleared mainly by glucuronidation and by conversion to 4-HIAA. In lab studies MAO-A, CYP2D6 and CYP3A4 all contribute, but MAO-A alone produced only small amounts of 4-HIAA. Rasagiline and oral selegiline at usual Parkinson's doses inhibit MAO-B selectively, so a large effect on psilocin is not expected. That selectivity depends on the dose and is lost at higher doses, where MAO-A is inhibited too. Ask the prescriber who manages the Parkinson's treatment before combining anything with this drug. Do not stop it or change the dose on your own. The selegiline skin patch (Emsam) is a different case and is listed under irreversible MAOIs, because at antidepressant doses it inhibits MAO-A as well.

Question 23

Can you take psilocybin mushrooms with lamotrigine?

Accepted Answer

No mechanism and no signal. No characteristic interaction identified. Lamotrigine is an anticonvulsant thought to work by inhibiting voltage-sensitive sodium channels; it does not act at 5-HT2A. It is not expected to change psilocybin's effects or raise seizure risk. The main concern is the underlying diagnosis: psilocybin use in bipolar disorder has been followed by new or worsening manic symptoms in some people. Not the same risk category as lithium. That said, lamotrigine is usually prescribed for bipolar disorder, and a classical psychedelic can trigger mania in bipolar people, the diagnosis is the risk here, not the drug.

Question 24

Can you take psilocybin mushrooms with common non-psychiatric medication?

Accepted Answer

No mechanism and no signal. Nothing characteristic. These drugs share no relevant pharmacology with psilocin. Psilocin is cleared mainly by glucuronidation and conversion to 4-HIAA, with MAO-A, CYP2D6 and CYP3A4 implicated in laboratory work. None of the listed drugs appears on the FDA's list of strong or moderate CYP2D6 or CYP3A inhibitors, and in one study CYP2D6 genotype did not affect psilocin blood levels. Not a concern. If you take something not listed anywhere on this page, the honest answer is that it has not been studied, see the note below the results.

Medication interaction checker

Every medication, one page each

How severity is graded

About serotonin syndrome