Butorphanol

A mixed agonist-antagonist opioid pain medicine, given as a nasal spray or injection, also used before surgery and during labor.

psilodex.org/m/butorphanol · 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: ~4.7 h; Approximate, in adults. Source under Interaction below.

Named in state rules?

Not namedColorado Condition rules (3)

Not namedOregon

PendingNew Mexico

Cite asPsilodex, “Butorphanol”, v2026.10.05. psilodex.org/m/butorphanol

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

FDA-approved for

Pain severe enough to require an opioid when other treatments are inadequate
Before surgery or anesthesia, and as a supplement to balanced anesthesia (injection)
Pain during labor (injection)

Sources [1][2]

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

Its label reports possible unpleasant dreamlike mental effects, which may add to psilocybin's. Stopping it suddenly after regular use can cause withdrawal.

Detail Butorphanol is a mixed agonist-antagonist opioid: it partly activates mu opioid receptors and fully activates kappa opioid receptors. Its label states it may produce unpleasant psychotomimetic (psychosis-like) effects, which may add to psilocybin's perceptual and emotional effects; it has not been studied with psilocybin. Its sedation adds to other CNS depressants (sedating drugs); psilocybin does not depress breathing. Also, labels also report serotonin syndrome with serotonergic drugs, rare low blood pressure (hypotension) with fainting, and more frequent seizures in seizure disorders. In people taking full opioid agonists, it may trigger withdrawal; stopping it after regular use can also cause withdrawal. Sources [1]

Human data with psilocybin: No psilocybin data; based on how it works and its label
Half-life: ~4.7 h (6.6 h in older adults) (FDA label, checked 2026-10-04) Nasal spray; active metabolite hydroxybutorphanol about 18 h.

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

8 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]
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]
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 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.

Chronic pain
- 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

Butorphanol Tartrate Nasal Spray (Hikma) · FDA label (DailyMed) — Opioid: Mechanism of Action "Butorphanol is a partial opioid agonist at the mu opioid receptor and a full agonist at the kappa opioid receptor." | Psychiatric reactions: Pharmacodynamics "may produce unpleasant psychotomimetic effects in some individuals" | 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: Precautions, General "Hypotension associated with syncope during the first hour of dosing with Butorphanol Tartrate Nasal Spray has been reported rarely" | Lowers seizure threshold or carries seizure risk: "may increase the frequency of seizures in patients with seizure disorders" | Opioid blocker: Withdrawal "in patients who are receiving a full opioid agonist analgesic may reduce the analgesic effect and/or precipitate withdrawal symptoms" | Withdrawal or rebound if stopped abruptly: "Do not rapidly reduce or abruptly discontinue butorphanol tartrate nasal spray in a patient physically dependent on opioids." | "Elimination half-life is increased in the elderly (6.6 hours as opposed to 4.7 hours in younger subjects)." "The elimination half-life of hydroxybutorphanol is about 18 hours"
Butorphanol Tartrate Injection (Hospira) · FDA label (DailyMed) — Indications: "as a preoperative or pre-anesthetic medication" "for the relief of pain during labor"

Record history

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

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