[Solved] Bisoprolol and hydrochlorothiazide during psilocybin session (truffles)

At psilocybin and truffle sessions In practice, we see two different blood pressure responses: a brief rise during the peak of the trip and often a drop in the aftermath (this is not mentioned in scientific studies). Combining this with blood pressure medication is therefore not necessarily dangerous, but it must be used with due consideration. Below you will find a full explanation for your situation.

How does bisoprolol work in combination with psilocybin?

Bisoprolol is a beta-blocker that slows the heart rate and lowers blood pressure. During a psilocybin experience, mild sympathetic activation usually occurs, causing blood pressure to rise temporarily.

In practice, we see:

• Bisoprolol partially prevents the peak in heart rate and blood pressure during the trip.
• This is not dangerous, provided there are no serious heart or rhythm problems.
• It does not inhibit the psychedelic experience because it does not act on serotonin receptors.

The main risk lies not in the peak, but in the phase after the session. Psilocybin can lower blood pressure at the end of the session or afterwards. If someone also has a dose of bisoprolol in their system at that moment, the blood pressure can descend too far, which leads to dizziness, instability, or fainting.

How does hydrochlorothiazide work in combination with psilocybin?

Hydrochlorothiazide is a diuretic (water tablet) that affects fluids and electrolytes.

In combination with psilocybin, we pay particular attention to:

• Possible blood pressure drop in the hours after the session.
• Chance of dehydration and electrolyte shifts, especially if someone drinks too little or sweats too little during the session.
• It can the trailing decline strengthen.

No direct pharmacological interaction with serotonin, so it does not strengthen or weaken the trip effect, but it does change the blood pressure profile.

What is the biggest risk, then?

The greatest risk is hypotension in the aftermath of the psilocybin experience, especially if both substances are still active in the body.

Therefore, at Triptherapie we usually recommend:

Stop both medications before approximately 5 times the half-life, unless there are medical reasons not to do so.. Do this only in consultation with your doctor!

Half-lives:
• Bisoprolol: ± 10–12 hours → 5× ≈ 50–60 hours (stop 2–3 days in advance). If a mild reduction in blood pressure is desired, stopping 1-2 days in advance may be sufficient.
• Hydrochlorothiazide: ± 6–15 hours → 5× ≈ stop 2–3 days in advance. For some, stopping for 1-2 days may be sufficient.

Most people do not resume taking their blood pressure medication until the day after the session, unless blood pressure rises in the meantime. In that case, it may be taken earlier after consultation.

Is a truffle session possible?

Yes, in most cases a truffle session is possible, provided that:

• There are no serious heart or rhythm diseases.
• The blood pressure is normal or mildly elevated.
• Bisoprolol and hydrochlorothiazide (if feasible) are temporarily stopped under supervision.
• We closely monitor blood pressure before, during, and after the session.

In practice, we regularly guide clients with this combination, with good and safe results, as long as the preparation is correct.

When is it actually a contraindication?

• Severe heart disease, recent heart attacks or unstable rhythms.
• Impossible to safely temporarily stop medication.
• Blood pressure that becomes too high without medication (e.g. > 170/100).

Extra tips

1. Always consult your treating physician before scheduling a session. Ask if stopping the medication for 1-3 days is possible and whether a slight increase in blood pressure could be problematic, or if a drop in blood pressure after the session could pose a risk.

2. Consider following a blood pressure-lowering diet with plenty of potassium-rich vegetables and less salt to potentially reduce your medication use.

3. Avoid alcohol and other stimulants in the two weeks prior to the session.

Bisoprolol is a cardioselective β₁-blocker that lowers heart rate and contractility, resulting in reduced cardiac oxygen consumption and blood pressure reduction. Hydrochlorothiazide is a thiazide diuretic that reduces extracellular volume, resulting in a drop in blood pressure but also in fluid and electrolyte loss (hypokalemia, hyponatremia). Psilocybin is a psychedelic substance (prodrug of psilocin) with strong agonism at 5-HT₂A serotonin receptors in the brain and also at 5-HT₄ receptors in cardiac tissue. Activation of 5-HT₄ in the heart produces positive inotropic and chronotropic effects (increase in contractile force and heart rate). Under controlled conditions, psilocybin causes relatively mild autonomic responses; however, high doses can increase systolic blood pressure (>140 mmHg) and heart rate.

Interactions and cardiovascular effects

No specific pharmacokinetic interactions have been described between psilocybin and bisoprolol or hydrochlorothiazide. Psilocybin is primarily metabolized to psilocin by phosphatase enzymes and subsequently degraded via monoamine oxidase, a pathway not known to compete with the hepatic or renal elimination of bisoprolol or HCTZ. Psilocybin induces sympathetic activity (↑ catecholamines), leading to an increase in blood pressure and heart rate. Bisoprolol will dampen psilocybin-induced tachycardia through β₁-blockade, causing the heart rate to rise less sharply than without a beta-blocker. This can be beneficial in the occurrence of palpitations, but theoretically, insensitivity to the sympathetic response leads to stronger vasoconstriction via α-receptors. Hydrochlorothiazide reduces blood volume and lowers blood pressure, which can influence the combined effect of psilocybin in an unpredictable direction.

1. Blood pressure: Psilocybin can transiently increase blood pressure. In clinical studies, one study reported that 76% of the participants had elevated blood pressure at a therapeutic dose (21 mg), and 34% even had a systolic peak >160 mmHg at high dose. However, these increases were generally transient and not severe; patients under treatment (such as in control groups or at low doses) showed similar increases. Bisoprolol can moderate these blood pressure peaks by reducing cardiac output, whereas HCTZ reduces basal blood volume and thus blood pressure may tend towards hypotension, especially in cases of dehydration.

2. Heart rate and heart rhythm: The most common cardiovascular effect of psilocybin is tachycardia. A meta-analysis of clinical studies found that heart rate was elevated in approximately 76% of the participants after psilocybin. In practice, these elevations were usually moderate and resolved spontaneously within 24 hours. Patients on bisoprolol will largely be spared from this tachycardia due to reduced catecholamine response. However, the risk of cardiac arrhythmias due to electrolyte disturbance must be taken into account: thiazide diuretics can cause hypokalemia, which predisposes to ventricular arrhythmias such as Torsade de pointes. Psilocybin itself has no known additional arrhythmia threshold-lowering effect, but potassium deficiency caused by HCTZ, together with sympathetic activation, can increase the risk of arrhythmia. It has also been reported that very high doses of psilocybin can cause QT interval prolongation, which should be noted in the presence of existing QT-prolonging medication (not in this case).

3. Other cardiovascular effects: In rare case reports, stress cardiomyopathy (takotsubo) has been described following psychedelic use, possibly due to strong sympathetic stimulation. There are indications that psilocybin can cause very high doses and cognitive stress on the myocardium, but these are exceptional cases. In general, classic psychedelics are considered relatively safe in healthy participants, with only mild, temporary stimulation of the cardiovascular system.

Neurological and other effects

Psilocybin induces strong changes in perception and mood via 5-HT₂A activation in the cortex. Bisoprolol can (rarely) cause neurological side effects such as nightmares or hallucinations, which could theoretically enhance or disrupt the subjective effect of psilocybin. Hydrochlorothiazide itself has no direct psychotropic effect, but can cause dizziness or fatigue at high doses. The combination does not result in any known central pharmacodynamic interaction, but one should be alert to exacerbation of orthostatic hypotension or accelerated neuropsychological symptoms when combining antihypertensives and psychedelics.

Clinical data and guidelines

There is very little specific literature regarding the combination of psilocybin with bisoprolol or HCTZ. Psilocybin studies often exclude participants with untreated or unstable hypertension. Registered safety data in health-selected subjects show no serious risks, but practical research with this drug combination is lacking. Health guidelines emphasize monitoring vital signs during psilocybin administration and avoiding patients with cardiovascular instability. There are no pharmacology or interaction tables reporting a contraindication for bisoprolol or thiazides with psychedelics, but the combination of substances with opposing effects on blood pressure requires caution. Consultation with a specialist (cardiologist or clinical pharmacologist) may be advisable regarding interactions not described in the literature.

Conclusion and recommendations

There are no documented dangerous interactions between psilocybin, bisoprolol, and hydrochlorothiazide. However, theoretically, opposing blood pressure and heart rate effects should be taken into account: psilocybin can activate the sympathetic nervous system (slightly increased blood pressure and heart rate), whereas bisoprolol/HCTZ actually lowers these parameters. Bisoprolol will likely suppress psilocybin-induced tachycardia, but HCTZ can cause fluid loss and (ortho)static hypotension. Furthermore, hypokalemia caused by HCTZ can increase the risk of arrhythmia under sympathetic stress. Clinically, vital functions should be monitored; serious cardiovascular complications appear to be rare with use under medical supervision. Consultation with the treating physician and education regarding possible changes in blood pressure and heart rhythm are recommended with this medication combination.