Cannabidiol, Morphine, Pain

The purpose of the proposed study is to investigate the interaction of cannabidiol (CBD) and morphine effects on pain sensitivity. Cannabidiol is a cannabinoid (similar to cannabis, or marijuana) present in marijuana that alters some of the effects of marijuana.

Eligible participants will be asked to participate in a total of three experimental sessions with each session day separated by at least one week. Each session day will last approximately 6-7 hours.

In the morning of each of the three study sessions, participants will be asked to complete baseline assessments which include self-report questionnaires (answering questions about how they feel), vital sign measurements (blood pressure, heart rate, oxygen saturation, temperature, and pupillometry) will be taken using a non-invasive (external) vitals monitor, and lastly thermal (heat and cold) and mechanical sensitivity testing will be done.

Participants will be asked to take an oral morphine capsule.

Participants will participate in 2 smoking sessions where they will be asked to smoke cigarettes or a vaporizer balloon containing either cannabidiol or a placebo (a blank).

Participants will be asked to complete the same battery assessments mentioned above, which include self-report questionnaires (answering questions about how they feel); vital sign measurements (blood pressure, heart rate, oxygen saturation, temperature, and pupillometry) will be taken using a non-invasive (external) vitals monitor; and lastly thermal (heat and cold) and mechanical stimulation will be administered to test pain sensitivity.

Participants will be asked to complete subjective questionnaires and have vital signs (blood pressure, heart rate, oxygen saturation, temperature, and pupillometry) measured multiple times throughout the visit; these measurements will be monitored for reasons such as safety.

After completing the second round of smoking and battery assessments, participants will be provided with lunch and can relax, watch television, listen to music, or read.

Once vital signs and questionnaire ratings have returned to baseline levels; participants can leave the laboratory.

Eligibility Criteria:
Inclusion Criteria:

* Participants must report having smoked a cigarette (nicotine or marijuana) AND having taken an opioid on 3 or more occasions in their lifetime.
* Participants must be in good health to participate; those with certain contraindications will be excluded.
* All participants will undergo psychiatric evaluation and will be asked to report their substance use history by interview and structured questionnaire methods.
* Participants will undergo medical evaluations using medical history, physical exam, standard lab tests (complete blood chemistry, urinalysis, urine pregnancy test for females), and 12-lead ECG.

Exclusion Criteria:

* Serious psychiatric illness (e.g. psychotic or bipolar disorder, recent suicide attempts; severe depression)
* Substance Use Disorders other than Nicotine Use Disorder and Mild Cannabis Use Disorder
* Neurological diseases; cardiovascular problems (e.g. systolic BP \>140 or \<95 mmHg, diastolic BP \>90 mmHg, abnormal ECG); pulmonary diseases; systemic diseases (e.g. liver, renal, inflammatory)
* Cognitive impairment (\<80 IQ)
* Past-month medications that increase study risk
* Women who are pregnant (urine HCG), lactating (self-report), or if heterosexually active and not using (self-report) medically approved birth control (oral or depot contraception, IUD, condom/foam, sterilization, tubal ligation)
* Individuals unable to give informed consent will be excluded.