Istradefylline

An adenosine A2A receptor antagonist, FDA-approved as add-on treatment to levodopa/carbidopa for "off" episodes in adult Parkinson's disease.

psilodex.org/m/istradefylline · data v2026.10.05

Clinical contraindication: None listed; No label contraindication covering psilocybin was found. This is not a finding that the combination has been shown to be without risk.
Psilocybin evidence: No psilocybin data
Half-life: ~83 h; Approximate, in adults. Source under Interaction below.

Named in state rules?

Not namedColorado Condition rules (3)

Not namedOregon

PendingNew Mexico

Cite asPsilodex, “Istradefylline”, v2026.10.05. psilodex.org/m/istradefylline

Clinical data and state rules are separate facts. Both are shown; neither is a decision.

What it is used for

FDA status

FDA-approved

FDA-approved for

Parkinson's disease "off" episodes (add-on to levodopa/carbidopa)

Sources [1]

01 Interaction with psilocybin

Its label reports hallucinations, which may add to psilocybin's perceptual effects (not studied with psilocybin).

Detail There are no psilocybin data for istradefylline. It is an adenosine A2A receptor antagonist (blocker). Its label reports hallucinations and psychotic behavior, which may add to psilocybin's perceptual effects. At 40 mg it raises levels of drugs processed by CYP3A4 (a liver enzyme). Psilocin is eliminated mainly by glucuronidation and conversion to 4-HIAA, with a minor CYP3A4 role in lab studies (Thomann 2024). Its terminal half-life is about 83 hours. Sources [1][2]

Human data with psilocybin: No psilocybin data; based on how it works and its label
Half-life: ~83 h (FDA label, checked 2026-10-04)

Evidence types on this record

No psilocybin dataNo psilocybin data: no human data with psilocybin or another classic psychedelic; the text draws on the medication's own pharmacology and its label or reference facts

02 Pharmacology relevant to psilocybin

1 listed · counted on reports

Psychiatric reactions: The label or source warns of psychiatric effects such as psychosis, mania, hallucinations, suicidal thoughts or severe mood or behavior changes. Psilocybin can also bring up strong emotions, so these warnings are relevant to screening. Sources [1]

03 State rules

Plain-language summary · official text governs

CO4 CCR 755-1

Not namedCondition rules (3)

No provision names this medication or its class.

Colorado · checked 2026-10-04

OROAR 333-333

Not named

No provision names this medication or its class.

Oregon · checked 2026-10-04

NM7.35.3 NMAC (proposed)

Pending

New Mexico's clinical rules (proposed 7.35.3 NMAC) are not final. No provision naming this medication has been found.

New Mexico · checked 2026-10-04

04 Conditions to ask about

Screening items in state rules

This medication is usually taken for a condition. State rules screen for some conditions directly, so the medication is a prompt to ask about them. Confirm with the participant; never assume a condition from the medication.

Parkinson's disease (severe chronic illness)
- CO 2.5(A)(2) · Clinical Facilitator licensees
- CO 6.16(F)(2)(a) · Facilitators without a clinical facilitator license
- CO 6.16(F)(1) · All licensees

05 Sources

NOURIANZ (istradefylline) tablets (Kyowa Kirin) · FDA label (DailyMed) — Psychiatric reactions: 5.2 "Because of the potential risk of exacerbating psychosis, patients with a major psychotic disorder should not be treated with NOURIANZ." | 7 "Monitor for an increase in adverse reactions of concomitant drugs that are CYP3A4 substrates when coadministering with NOURIANZ 40 mg." | 12.3 "The mean terminal half-life (t1/2) for istradefylline at steady-state is approximately 83 hours."
Thomann J, Kolaczynska KE, Stoeckmann OV, et al. In vitro and in vivo metabolism of psilocybin’s active metabolite psilocin. Front Pharmacol 2024;15:1391689. — Abstract: "recombinant CYP2D6 and CYP3A4 enzymes metabolized nearly 100% and 40% of psilocin, respectively." "MAO-A transformed psilocin into minimal amounts of 4-HIAA and 4-HTP." "In conclusion, MAO-A, CYP2D6, and CYP3A4 are involved in psilocin's metabolism." Introduction: "Around 33% of a psilocybin dose is renally excreted as 4-HIAA."

Record history

v2026.10.02First published.
2026-10-04Last reviewed against its sources.

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