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

NCT ID: NCT05906511

Last Updated: 2025-10-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-17
• Study Completion Date: 2026-08-31

Brief Summary

The overarching goal of this double-blind, placebo-controlled, crossover study is 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. This protocol includes two sub-studies, each randomizing 20 men and women aged 65 years or older to receive two administration routes of THC; oral administration and vaporized administration.

Detailed Description

This is a double-blind, placebo-controlled, crossover study, with two sub-studies each focusing on different routes of THC administration.

Oral THC Sub-Study: 20 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.

Vaporized THC Sub-Study: 20 men and women aged 65 years or older will be randomized to two doses of vaporized THC (2 mg and 4 mg). Across three 8-hour test sessions, participants will receive a random sequence of 3 conditions: 2 mg vaporized THC; 4 mg vaporized THC; and vaporized placebo.

For both the Oral and Vaporized THC Sub-Studies, 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. General adverse, cardiovascular, and cognitive/psychomotor effects of THC will be thoroughly assessed with behavioral, physiological, and neuropsychological methods.

Conditions

Pain, Tolerance; Oral vs Vaporized THC; Abuse Liability

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Dronabinol 5mg

Dronabinol 5 mg

Group Type: ACTIVE_COMPARATOR

Dronabinol 5 MG

Intervention Type: DRUG

Dronabinol 5 mg

Dronabinol 10mg

Dronabinol 10 mg

Group Type: PLACEBO_COMPARATOR

Dronabinol 10 MG

Intervention Type: DRUG

Dronabinol 10mg

Vaporized THC 2mg

Vaporized THC 2mg

Group Type: ACTIVE_COMPARATOR

2mg Purified THC in an ethanolic solution

Intervention Type: DRUG

2mg Purified THC in an ethanolic solution

Vaporized THC 4mg

Vaporized THC 4 mg

Group Type: ACTIVE_COMPARATOR

4mg Purified THC in an ethanolic solution

Intervention Type: DRUG

4mg Purified THC in an ethanolic solution

Placebo

Masked oral placebo or vaporized saline

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral placebo and/or vaporized saline

Interventions

Dronabinol 5 MG

Dronabinol 5 mg

Intervention Type: DRUG

Dronabinol 10 MG

Dronabinol 10mg

Intervention Type: DRUG

2mg Purified THC in an ethanolic solution

2mg Purified THC in an ethanolic solution

Intervention Type: DRUG

4mg Purified THC in an ethanolic solution

4mg Purified THC in an ethanolic solution

Intervention Type: DRUG

Placebo

Oral placebo and/or vaporized saline

Intervention Type: DRUG

Other Intervention Names

"Marinol"; "Marinol"

Eligibility Criteria

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.

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

VA Connecticut Healthcare System

FED

Sponsor Role: collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Joao De Aquino

Assistant Professor of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joao P. De Aquino, M.D.

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

VA Connecticut Healthcare System

West Haven, Connecticut, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Julia Meyerovich, M.S.

Role: CONTACT

julia.meyerovich@yale.edu

203-623-7493

Facility Contacts

Brendan P. Sullivan

Role: primary

brendan.sullivan@va.gov

203-932-5711 ext. 3350

Julia Meyerovich

Role: backup

julia.meyerovich@yale.edu

203-623-7493

References

Kaskie B, Ayyagari P, Milavetz G, Shane D, Arora K. The Increasing Use of Cannabis Among Older Americans: A Public Health Crisis or Viable Policy Alternative? Gerontologist. 2017 Nov 10;57(6):1166-1172. doi: 10.1093/geront/gnw166.

Reference Type: BACKGROUND

PMID: 28077451 (View on PubMed)

Solomon HV, Greenstein AP, DeLisi LE. Cannabis Use in Older Adults: A Perspective. Harv Rev Psychiatry. 2021 May-Jun 01;29(3):225-233. doi: 10.1097/HRP.0000000000000289.

Reference Type: BACKGROUND

PMID: 33660625 (View on PubMed)

Mahvan TD, Hilaire ML, Mann A, Brown A, Linn B, Gardner T, Lai B. Marijuana Use in the Elderly: Implications and Considerations. Consult Pharm. 2017 Jun 1;32(6):341-351. doi: 10.4140/TCP.n.2017.341.

Reference Type: BACKGROUND

PMID: 28595684 (View on PubMed)

Gagliese L. What do experimental pain models tell us about aging and clinical pain? Pain Med. 2007 Sep;8(6):475-7. doi: 10.1111/j.1526-4637.2007.00360.x. No abstract available.

Reference Type: BACKGROUND

PMID: 17716320 (View on PubMed)

Moore AR, Clinch D. Underlying mechanisms of impaired visceral pain perception in older people. J Am Geriatr Soc. 2004 Jan;52(1):132-6. doi: 10.1111/j.1532-5415.2004.52023.x.

Reference Type: BACKGROUND

PMID: 14687328 (View on PubMed)

Lautenbacher S, Kunz M, Strate P, Nielsen J, Arendt-Nielsen L. Age effects on pain thresholds, temporal summation and spatial summation of heat and pressure pain. Pain. 2005 Jun;115(3):410-418. doi: 10.1016/j.pain.2005.03.025.

Reference Type: BACKGROUND

PMID: 15876494 (View on PubMed)

Backonja MM, Attal N, Baron R, Bouhassira D, Drangholt M, Dyck PJ, Edwards RR, Freeman R, Gracely R, Haanpaa MH, Hansson P, Hatem SM, Krumova EK, Jensen TS, Maier C, Mick G, Rice AS, Rolke R, Treede RD, Serra J, Toelle T, Tugnoli V, Walk D, Walalce MS, Ware M, Yarnitsky D, Ziegler D. Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus. Pain. 2013 Sep;154(9):1807-1819. doi: 10.1016/j.pain.2013.05.047. Epub 2013 Jun 3.

Reference Type: BACKGROUND

PMID: 23742795 (View on PubMed)

Griffiths RR, Troisi JR, Silverman K, Mumford GK. Multiple-choice procedure: an efficient approach for investigating drug reinforcement in humans. Behav Pharmacol. 1993 Feb;4(1):3-13.

Reference Type: BACKGROUND

PMID: 11224166 (View on PubMed)

Other Identifiers

1R21DA057240-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2000035354

Identifier Type: -

Identifier Source: org_study_id