Nalbuphine

An injected mixed agonist-antagonist opioid for moderate to severe pain, and for pain relief before, during and after surgery and in labor.

psilodex.org/m/nalbuphine · 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: ~5 h; Approximate, in adults. Source under Interaction below.

Named in state rules?

Not namedColorado

Not namedOregon

PendingNew Mexico

Cite asPsilodex, “Nalbuphine”, v2026.10.05. psilodex.org/m/nalbuphine

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

What it is used for

FDA status

FDA-approved

Availability

Generic only in US (injection)

FDA-approved for

Pain severe enough to require an opioid when other treatments are inadequate
Supplement to balanced anesthesia
Preoperative and postoperative pain relief
Pain relief during labor and delivery

Sources [1]

Other safety

Boxed warning: addiction, abuse and misuse; life-threatening respiratory depression; and profound sedation, respiratory depression, coma and death when combined with benzodiazepines or other CNS depressants, including alcohol.

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

Sources [1]

01 Interaction with psilocybin

Not studied with psilocybin; it is sedating and its label reports hallucinations, so added effects are possible. Separately, it can trigger opioid withdrawal.

Detail Nalbuphine is an injected opioid that activates kappa opioid receptors and blocks mu opioid receptors. Its sedation adds to that of other CNS depressants (sedating drugs); psilocybin does not depress breathing. Its label reports psychotomimetic (psychosis-like) effects, such as unreality, depersonalization and hallucinations, as less frequent than with pentazocine. The label also reports serotonin syndrome with serotonergic (serotonin-boosting) drugs. There are no psilocybin data. Separately, it may precipitate withdrawal in people taking full opioid agonists. The label also reports severe hypotension (low blood pressure) and more frequent seizures in seizure disorders. Sources [1]

Human data with psilocybin: No psilocybin data; based on how it works and its label
Half-life: ~5 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

7 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]
Opioid: Activates opioid receptors, causing pain relief, sedation and slowed breathing at higher doses. Psilocybin does not slow breathing, but stopping an opioid suddenly can cause withdrawal. Sources [1]
Opioid blocker: Blocks opioid receptors. It can trigger sudden withdrawal in someone taking opioids, and after it wears off, a usual opioid dose can cause overdose. Sources [1]
Lowers seizure threshold or carries seizure risk: Makes a seizure more likely, or has been linked to seizures. Sources [1]
Serotonergic: Increases serotonin activity, for example by blocking its reuptake or releasing it. Psilocybin acts on serotonin receptors, so effects can add together. With antidepressant use, the psilocybin response can be weaker. Sources [1]

03 State rules

Plain-language summary · official text governs

CO4 CCR 755-1

Not named

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

None linked

No condition named in state rules is linked to this medication.

05 Sources

Nalbuphine Hydrochloride Injection (Hospira) · FDA label (DailyMed) — opioid_agonist, opioid_antagonist: Mechanism of Action "Nalbuphine is an agonist at kappa opioid receptors and an antagonist at mu opioid receptors." | Sedating or CNS depressant: Boxed Warning "Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death." | Serotonergic: Precautions, Drug Interactions "The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system" ... "has resulted in serotonin syndrome" | Lowers blood pressure or causes orthostasis: "Nalbuphine Hydrochloride Injection may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients." | Lowers seizure threshold or carries seizure risk: "may increase the frequency of seizures in patients with seizure disorders" | Withdrawal or rebound if stopped abruptly: Withdrawal "When discontinuing Nalbuphine Hydrochloride Injection in a physically-dependent patient, gradually taper the dosage" | Adverse Reactions "The incidence of psychotomimetic effects, such as unreality, depersonalization, delusions, dysphoria and hallucinations has been shown to be less than that which occurs with pentazocine." | "The plasma half-life of nalbuphine is 5 hours"

Record history

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

Report an error in this record →