Psilocybin as a Treatment for Chronic Pain in Smokers

Inclusion Criteria: * Veterans aged 21 to 65 years, who have been smoking tobacco cigarettes daily cigarettes for at least a year (confirmed with urine cotinine strips indicating smoking status (28) * not seeking treatment at the time of the study for tobacco use. * endorsement of bothersome or high-impact chronic non-cancer pain per the Graded Pain Scale - Revised (29); * in good health as verified by medical history, screening examination, and screening laboratory tests; and * body mass index (BMI) between 18 to 35 because there is limited information on the safety of psilocybin in individuals outside this range. * for women, not pregnant as determined by pregnancy screening, nor breastfeeding, and using acceptable birth control methods (e.g., oral contraceptives). Exclusion Criteria: * History of major medical disorders (e.g., diabetes, epilepsy, kidney or liver diseases, heart rhythm problems, heart failure, hypertension with BP greater than 140/90mmHg, history of cerebrovascular problems, severe asthma, etc.). * lifetime history of schizophrenia, bipolar disorder, dissociative disorders, or borderline personality disorder, current major depressive episode, or PTSD. * first- or second-degree relatives with a history of bipolar disorder or schizophrenia. * suicide attempt or ideation in the past year. * regular use of certain psychotropic medications (antidepressants, antipsychotics, mood stabilizers or anxiolytics) that are deemed to have the potential for adverse effects or drug reactions with psilocybin including SSRIs and MAO inhibitors. * current untreated moderate or severe substance use disorder for any other recreational or prescription drugs other than nicotine. * known sensitivity or intolerability to psilocybin.