[Opgelost] Amitriptaline and psychedelics

Amitriptyline is a tricyclic antidepressant (TCA). At Triptherapie, we take the use of TCAs very seriously because of their complex interaction with psychedelics such as psilocybin truffles, LSD analogues, ketamine, and MDMA.

1. Serotonin system interaction

Amitriptyline increases serotonin levels by blocking reuptake, but it does so in a less selective way than SSRIs. Combining TCAs with serotonergic psychedelics (psilocybin, LSD, DMT) introduces a theoretical risk of serotonin syndrome, particularly at higher doses. While the risk is lower than with SSRI + MAOI combinations, it remains significant enough that professional providers like Triptherapie treat it as a contraindication.

2. Blunted psychedelic effects

Reports and user experiences show that TCAs can blunt or weaken the effects of psychedelics. People often describe their psilocybin or LSD trips as being noticeably muted while on amitriptyline. This means that, even if no dangerous interaction occurs, the therapeutic depth of the session may be lost.

3. Cardiovascular effects

Amitriptyline can increase heart rate, raise blood pressure, and lower the seizure threshold. Psychedelics — especially ketamine or high-dose tryptamines — also put strain on the cardiovascular system. The combination therefore raises the risk of arrhythmias, hypertension, or seizures, particularly in people with pre-existing heart conditions.

4. Ketamine and amitriptyline

Research on ketamine + TCAs is limited, but both act on the central nervous system and can affect blood pressure and heart rhythm. Potential risks include sedation, confusion, or sudden blood pressure changes. While not as well documented as psilocybin or MDMA interactions, caution is warranted.

5. MDMA and amitriptyline (strong contraindication)

The combination of amitriptyline and MDMA is strongly discouraged. Both substances rely on the CYP2D6 enzyme for metabolism. Taken together, they can slow each other’s breakdown, leading to elevated levels in the bloodstream. Risks include:

1. Serotonin syndrome
2. Cardiac arrhythmias and hypertension
3. Overheating, neurotoxicity, or even medical emergencies

On the Triptherapie forum, amitriptyline is listed among the antidepressants that should never be combined with MDMA or its analogues. This makes it a clear contraindication for MDMA therapy sessions.

6. Half-life and washout considerations

The half-life of amitriptyline ranges from 10 to 28 hours, and its active metabolite nortriptyline has a half-life of 18 to 44 hours. This means that it takes several days for the drug to clear the system. In clinical practice, at least 5 to 7 days are needed for a safe washout, sometimes longer depending on dosage and duration of use.

Therefore, even if you discontinue amitriptyline, you should allow a sufficient washout period before considering a psychedelic session — and always under medical guidance.

7. Ayahuasca, psilohuasca, and Caapi exclusion

It’s also important to note that combining amitriptyline with Banisteriopsis Caapi (ayahuasca or psilohuasca) is extremely risky. Caapi is a strong MAOI and can dangerously amplify serotonergic activity, making serotonin syndrome far more likely. For this reason, Triptherapie excludes ayahuasca and psilohuasca sessions altogether, even for those not on medication.

Conclusion

If you are currently using amitriptyline, participating in a psychedelic session at Triptherapie is not allowed. The main reasons are:

1. Low Risk of serotonin syndrome when combined with psilocybin or LSD.

2. HIGH Risk of serotonin syndrome when combined with MDMA.

3. Potential cardiovascular strain from overlapping side effects.

4. Blunted psychedelic effects, reducing therapeutic value.

5. Serious and documented dangers with MDMA.

6. Additional risk if combined with MAOIs like Caapi in ayahuasca or psilohuasca.

The professional guideline is that you must first taper off amitriptyline safely under supervision of your prescribing doctor, allow a proper washout period, and then undergo intake screening to evaluate whether a psychedelic session is suitable for you.