Pentazocine (with naloxone)

A mixed agonist-antagonist opioid pain medicine, sold in the US as tablets with naloxone, which blocks pentazocine if the tablets are injected.

psilodex.org/m/pentazocine · 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: 3.6 h; Approximate, in adults. Source under Interaction below.

Named in state rules?

Not namedColorado Condition rules (3)

Not namedOregon

PendingNew Mexico

Cite asPsilodex, “Pentazocine (with naloxone)”, v2026.10.05. psilodex.org/m/pentazocine

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 (with naloxone)

FDA-approved for

Pain severe enough to require an opioid when other treatments are inadequate

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; its label reports hallucinations and raised blood pressure, so added perceptual and blood pressure effects are possible.

Detail Pentazocine is a mixed agonist-antagonist opioid (partial mu, full kappa agonist). Its label reports hallucinations (usually visual), disorientation and confusion at therapeutic doses, which could add to psilocybin's perceptual effects. The label also states that pentazocine can elevate blood pressure, which could add to psilocybin's transient rise (no psilocybin data). Its sedation adds to other CNS depressants (sedating drugs); psilocybin does not depress breathing. Separately, it may precipitate withdrawal in people taking full opioid agonists. Labels also report serotonin syndrome with serotonergic (serotonin-boosting) drugs, severe hypotension (low blood pressure) and more frequent seizures in seizure disorders. The naloxone in the tablet has no effect when swallowed. Sources [1]

Human data with psilocybin: No psilocybin data; based on how it works and its label
Half-life: 3.6 h (range 1.5–10 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

9 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]
Raises blood pressure or heart rate: Raises blood pressure or heart rate. Psilocybin raises both for several hours, so the effects can add. 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

Pentazocine and Naloxone Tablets (Lupin) · FDA label (DailyMed) — Opioid: Mechanism of Action "Pentazocine is a partial agonist at the mu opioid receptor and an agonist at the kappa opioid receptor." | Psychiatric reactions: Warnings, Acute CNS Manifestations "Patients receiving therapeutic doses of Pentazocine and Naloxone Tablets have experienced hallucinations (usually visual), disorientation, and confusion" | Raises blood pressure or heart rate: Warnings, Cardiovascular Disease "Pentazocine can elevate blood pressure, possibly through the release of endogenous catecholamines." | 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: "Pentazocine and Naloxone Tablets 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" | Opioid blocker: "may reduce the analgesic effect and/or precipitate withdrawal symptoms" | Withdrawal or rebound if stopped abruptly: "Do not abruptly discontinue Pentazocine and Naloxone Tablets in a patient physically dependent on opioids." | "has no action when taken orally and will not interfere with the pharmacologic action of pentazocine" | "the mean plasma elimination half-life was 3.6 hours (range 1.5 to 10 hours)"

Record history

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

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