3-HO-PCP

Pre-existing cardiovascular disease (hypertension, coronary artery disease, arrhythmias) increases risk from sympathomimetic cardiovascular effects documented in the PCP analog class.

Any pre-existing compromise of respiratory function (COPD, sleep apnea, neuromuscular respiratory weakness) is an absolute contraindication due to the compound's intrinsic opioid-mediated respiratory depression.

3-HO-PCP's potent NMDA antagonism (Ki ≈ 30 nM) carries high psychotomimetic risk. Personal or family history of schizophrenia, schizoaffective disorder, or other psychotic disorders is an absolute contraindication.

Risk of precipitating manic, hypomanic, or mixed episodes. Relative contraindication; risk is elevated but not absolute.

Hepatic impairment may lead to elevated and prolonged plasma concentrations. CYP enzyme involvement is inferred by class analogy (CYP2B6, CYP3A4) and not compound-specific.

Absolutely contraindicated in pregnancy and breastfeeding by precautionary principle. No reproductive safety data exist. Opioid agonism carries specific risk of neonatal abstinence syndrome with repeated exposure.

Concurrent use of any opioid agonist (prescription or illicit) is absolutely contraindicated. The WHO ECDD review noted all serious cases involved co-present opioids, benzodiazepines, or stimulants.

All documented serious 3-HO-PCP adverse events involved co-present benzodiazepines. While benzodiazepines are used therapeutically for PCP-analog agitation, unsupervised co-use carries substantial risk.

Persons with current or prior opioid dependence face elevated risk of relapse and re-establishment of physical dependence due to 3-HO-PCP's intrinsic MOR agonist activity.