Opicapone

A COMT inhibitor, FDA-approved as add-on treatment to levodopa/carbidopa for "off" episodes in Parkinson's disease.

psilodex.org/m/opicapone · 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: 1–2 h; Approximate, in adults. Source under Interaction below.Effect duration: COMT inhibition returns to baseline slowly; more than 35% inhibition remains 5 days after the last dose, well beyond the 1–2 h half-life.

Named in state rules?

Not namedColorado Condition rules (3)

Not namedOregon

PendingNew Mexico

Cite asPsilodex, “Opicapone”, v2026.10.05. psilodex.org/m/opicapone

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]

Other safety

The label contraindicates nonselective MAO inhibitors and pheochromocytoma or other catecholamine-secreting tumors, and warns of arrhythmias and blood pressure changes with drugs metabolized by COMT (e.g., epinephrine, isoproterenol).

About the medication itself, separate from any interaction with psilocybin.

Sources [1]

01 Interaction with psilocybin

Its target enzyme plays no reported role in clearing psilocybin. Also, its label reports sudden sleep, low blood pressure and hallucinations.

Detail Opicapone has not been studied with psilocybin. It is a peripheral COMT inhibitor (it blocks an enzyme outside the brain) that increases levodopa exposure. COMT is not reported in psilocin clearance (Thomann 2024), so a direct effect on psilocin is not expected. Also, its label reports falling asleep during daily activities, hypotension (low blood pressure) or syncope (fainting), and hallucinations. It also reports a hyperpyrexia-confusion syndrome (high fever with confusion) with withdrawal. Nonselective MAO inhibitors are contraindicated with it. Sources [1][2]

Human data with psilocybin: No psilocybin data; based on how it works and its label
Effect duration: COMT inhibition returns to baseline slowly; more than 35% inhibition remains 5 days after the last dose, well beyond the 1–2 h half-life. Sources [1]
Half-life: 1–2 h (FDA label, checked 2026-10-04) COMT inhibition outlasts the half-life.

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

4 listed · counted on reports

Sedating or CNS depressant: Slows the central nervous system: drowsiness, slower reactions and impaired coordination, and slowed breathing at high doses. Effects add with other sedating substances. Sources [1]
Withdrawal or rebound if stopped abruptly: Stopping suddenly can cause withdrawal or a rebound of symptoms. Sources [1]
Lowers blood pressure or causes orthostasis: Lowers blood pressure, or causes a drop on standing (orthostasis) that can bring dizziness or fainting. Sources [1]
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

ONGENTYS (opicapone) capsules (Amneal) · FDA label (DailyMed) — Sedating or CNS depressant: 5.2 "Patients treated with dopaminergic medications and medications that increase levodopa exposure, including ONGENTYS, have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles" | Lowers blood pressure or causes orthostasis: 5.3 "hypotension (orthostatic and non-orthostatic), syncope, and presyncope occurred in 5% of patients treated with ONGENTYS 50 mg compared to 1% of patients who received placebo." | Psychiatric reactions: 5.5 "Patients with a major psychotic disorder should ordinarily not be treated with ONGENTYS because of the risk of exacerbating the psychosis with an increase in central dopaminergic tone." | Withdrawal or rebound if stopped abruptly: 5.7 "A symptom complex resembling neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction" | 12.3 "The mean elimination half-life of opicapone is 1 to 2 hours." | 12.2 "Following termination of treatment, COMT inhibition slowly returns to baseline levels, with >35% inhibition still observed 5 days after the last dose."
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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