Levoketoconazole

A cortisol synthesis inhibitor related to ketoconazole, FDA-approved for high cortisol in adults with Cushing's syndrome when surgery is not an option or not curative.

psilodex.org/m/levoketoconazole · 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: 4–6 h; Approximate, in adults. Source under Interaction below.Effect duration: Cortisol suppression may persist beyond the 4–6 hour half-life after stopping

Named in state rules?

Not namedColorado Condition rules (3)

Not namedOregon

PendingNew Mexico

Cite asPsilodex, “Levoketoconazole”, v2026.10.05. psilodex.org/m/levoketoconazole

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

What it is used for

FDA status

FDA-approved

Sources [1]

FDA-approved for

Endogenous hypercortisolemia in adults with Cushing's syndrome when surgery is not an option or has not been curative

Sources [1]

Other safety

The label reports adrenal insufficiency in 7% of patients; low cortisol can cause nausea, fatigue, dizziness and low blood pressure. It is contraindicated with other drugs that prolong the QT interval.

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

Sources [1]

01 Interaction with psilocybin

It may slow how the body clears psilocybin (not studied with psilocybin). Also, it can cause liver injury, heart-rhythm (QT) effects and low cortisol.

Detail Levoketoconazole inhibits CYP3A4 (a liver enzyme), which metabolized psilocin in lab studies (Thomann 2024). So psilocin levels may rise, though psilocin is removed mainly by glucuronidation and conversion to 4-HIAA. There are no psilocybin data. Also, its label carries boxed warnings for liver injury and dose-related QT prolongation (a heart-rhythm change). Lowered cortisol can cause dizziness and low blood pressure. Sources [1][2][3]

Human data with psilocybin: No psilocybin data; based on how it works and its label
Effect duration: Cortisol suppression may persist beyond the 4–6 hour half-life after stopping Sources [1]
Half-life: 4–6 h (multiple doses); 3–4.5 h single dose (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

2 listed · counted on reports

Liver injury: The label or source warns of liver injury, from raised liver enzymes to liver failure. Liver disease also affects how the body clears psilocin. Sources [1]
QT-prolonging: Lengthens the QT interval on an ECG, a measure of the heart’s electrical recovery between beats. A long QT raises the risk of a dangerous heart rhythm, more so with other QT-prolonging drugs or low potassium or magnesium. 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.

Cushing's syndrome (only indication; 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

RECORLEV (levoketoconazole) tablets (Xeris; NDA214133) · FDA label (DailyMed) — revised 2026-03-10 | "treatment of endogenous hypercortisolemia in adult patients with Cushing's syndrome for whom surgery is not an option or has not been curative" | Liver injury: "Serious hepatotoxicity has been reported in patients receiving RECORLEV" | QT-prolonging: "RECORLEV is associated with dose-related QT interval prolongation." | "half-life of 3 to 4.5 hours after a single dose and 4 to 6 hours after multiple doses" | "cortisol suppression may persist beyond the 4- to 6- hour half-life of RECORLEV" | "Adrenal insufficiency was observed in 7% of patients"
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. — psilocin clearance mainly by UGT glucuronidation and MAO | 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."
Manevski N, Kurkela M, Höglund C, et al. Glucuronidation of psilocin and 4-hydroxyindole by the human UDP-glucuronosyltransferases. Drug Metab Dispos 2010;38(3):386–395. — psilocin clearance mainly by UGT glucuronidation and MAO

Record history

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

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