PK/PD of Oral and Vaporized Delta-9-Tetrahydrocannabinol (THC) in Older Adults

Yale University

Status and phase: Enrolling; Early Phase 1

Conditions: Abuse Liability; Pain, Tolerance; Oral vs Vaporized THC

Treatments: Drug: Placebo; Drug: Dronabinol 5 MG; Drug: 2mg Purified THC in an ethanolic solution; Drug: 4mg Purified THC in an ethanolic solution; Drug: Dronabinol 10 MG

Study type: Interventional

Funder types: Other; Other U.S. Federal agency; NIH

Identifiers

NCT05906511

1R21DA057240-01 (U.S. NIH Grant/Contract)

2000035354

Details and patient eligibility

About

This double-blind, placebo-controlled, crossover study aims to characterize the pharmacokinetic (PK) and pharmacodynamic (PD) effects of the main analgesic and psychoactive constituent of cannabis, delta-9 tetrahydrocannabinol (THC), among older adults - the fastest growing population of cannabis consumers, and the most likely age cohort to use cannabinoids to relieve pain.

Full description

This is a double-blind, placebo-controlled, crossover study, commencing with an oral THC Sub-Study. Following the completion of this sub-study, the Primary Study will commence.

Oral THC Sub-Study: 10 men and women aged 65 years or older, will be randomized to two doses of oral THC (5 mg and 10 mg). Across three, 8-hour test sessions, participants will receive a random sequence of 3 conditions: 5 mg oral THC; 10 mg oral THC; oral placebo.

Primary Study: 20 men and women aged 65 years or older will be randomized to two doses of oral THC (5 mg and 10 mg) and vaporized THC (2 mg and 4 mg). Across six 8-hour test sessions, participants will receive a random sequence of 6 conditions: 5 mg oral THC; 10 mg oral THC; oral placebo; 2 mg vaporized THC; 4 mg vaporized THC; and vaporized placebo.

For both the sub-study and primary study, blood samples will be regularly collected from an intravenous line, up to 8 hours post-dose, and at 24 hours post-dose, to assess the PK of THC and its phase I and II metabolites. PD effects of THC on pain will be measured with Quantitative Sensory Testing (QST), a psychophysical technique used to reliably measure pain sensitivity and investigate pain modulatory mechanisms. The abuse liability of THC will be measured using an established drug reinforcement paradigm.

Enrollment: 30 estimated patients

Sex: All

Ages: 65+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Healthy male and female participants aged 65 ≥ years old
2. Prior exposure to THC or cannabis least once in the last 10 years; 1-10 times in the last 20 years; or more than 20 times in their lifetime
3. Capable of providing informed consent in English.

Exclusion criteria

1. Meeting DSM-5 criteria for psychiatric/substance use disorders (SUD) other than tobacco use disorder, within the last year
2. Current use of cannabinoid products, as evidenced by a urine drug screen
3. Having a history of treatment for cannabis use disorder
4. History of intent or current intent of abstaining from cannabis use
5. Clinically significant medical disorders (e.g. liver/kidney dysfunction, immunosuppressing conditions, history or presence of epilepsy, seizures, head trauma with loss of consciousness)
6. Medical conditions that increase the risk of respiratory problems (e.g. COPD, asthma, recuring bronchitis, reactive airway disorder)* (does not apply to the Oral THC Sub-Study)
7. History of environmental sensitivities (e.g. bronchospastic allergies, multiple chemical sensitivities) or other airway sensitivities that require the use of an epi pen*(does not apply to the Oral THC Sub-Study)
8. Neurological conditions that may change the response to nociceptive stimuli (e.g., stroke, neuropathy), or that lead to loss of balance, evidenced by a neuro-sensory exam
9. Contraindications for exposure to nociceptive stimuli, such as untreated hypertension
10. Current regular use of drugs known to affect pain, or that are prominent inducers or inhibitors of CYP2C9, CYP3A4, or UGTA19 (e.g., carbamazepine, valproate, fluvoxamine, and paroxetine)
11. Major neurocognitive disorders precluding participation, evidenced by a clinical exam
12. Abnormal EKG, arrythmia, vasospastic disease, chronic heart failure, or presence of a pacemaker
13. Elevation of liver enzymes (ALT, AST) 2x the normal limit or higher
14. Personal or family history of primary psychotic disorders, or mood disorders with psychotic features
15. Current suicidal ideation
16. Allergy or serious adverse reactions to sesame oil, THC, or cannabis
17. Having received any drug as part of a research study within 30 days prior to receiving the study medication in the current study.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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30 participants in 5 patient groups, including a placebo group

Dronabinol 5mg

Active Comparator group

Description:

Dronabinol 5 mg

Treatment:

Drug: Dronabinol 5 MG

Dronabinol 10mg

Placebo Comparator group

Description:

Dronabinol 10 mg

Treatment:

Drug: Dronabinol 10 MG

Vaporized THC 2mg

Active Comparator group

Description:

Vaporized THC 2mg

Treatment:

Drug: 2mg Purified THC in an ethanolic solution

Vaporized THC 4mg

Active Comparator group

Description:

Vaporized THC 4 mg

Treatment:

Drug: 4mg Purified THC in an ethanolic solution

Placebo

Placebo Comparator group

Description:

Masked oral placebo or vaporized saline

Treatment:

Drug: Placebo