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

NCT05906511 | Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: 20000353541R21DA057240-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Pain, Tolerance; Oral vs Vaporized THC; Abuse Liability

Keywords

Pharmacokinetics THC; Pharmacodynamics THC

Outcome Measures

Primary Outcomes (5)

• Peak concentration (Cmax)

  Serial blood samples will be collected for plasma levels of THC; its phase I metabolite 11-hydroxy-THC (OH-THC); phase II metabolite 11-nor-9-carboxy-THC (THC-COOH); and THC-COOH glucuronide. For THC and all other analytes, the peak concentration (Cmax) will be derived using a linear noncompartmental analysis.

  Up to 8 hours

• Time to attain Cmax concentration (Tmax)

  Serial blood samples will be collected for plasma levels of THC; its phase I metabolite 11-hydroxy-THC (OH-THC); phase II metabolite 11-nor-9-carboxy-THC (THC-COOH); and THC-COOH glucuronide. For THC and all other analytes, the time to attain Cmax concentration (Tmax) will be derived using a linear noncompartmental analysis.

  Up to 8 hours

• Area under the plasma concentration-time curve (AUC0-8h)

  Serial blood samples will be collected for plasma levels of THC; its phase I metabolite 11-hydroxy-THC (OH-THC); phase II metabolite 11-nor-9-carboxy-THC (THC-COOH); and THC-COOH glucuronide. For THC and all other analytes, the area under the plasma concentration-time curve (AUC0-8h) will be derived using a linear noncompartmental analysis.

  Up to 8 hours

• Nociception

  Multimodal quantitative sensory testing (QST) will be used ensure that various types of afferent fibers are engaged, so that the analgesic efficacy of THC can be comprehensively investigated. A composite pain sensitivity measure as a Z-score (ranging from -1 to +1) will be derived from the QST battery, with greater scores indicating a higher sensitivity to pain.

  Up to 8 hours

• Abuse Liability

  A modified Multiple-Choice Procedure (MPC) will be used to measure abuse liability. The MCP was developed and validated by Roland Griffiths to efficiently assess drug reinforcement - including cannabinoid-induced reinforcement. In each of the 6 experimental sessions, participants will choose between forfeiting or receiving escalating sums of money, on a scale of values between -$20.00 and $20.00; or re-receiving the study medication assigned for that day. The primary outcome will be the crossover point, the value at which the participant chooses money rather than the study medication, which will be determined for each session.

  Up to 8 hours

Study Arms (5)

Dronabinol 5mg

ACTIVE COMPARATOR

Dronabinol 5 mg

Drug: Dronabinol 5 MG

Dronabinol 10mg

PLACEBO COMPARATOR

Dronabinol 10 mg

Drug: Dronabinol 10 MG

Vaporized THC 2mg

ACTIVE COMPARATOR

Vaporized THC 2mg

Drug: 2mg Purified THC in an ethanolic solution

Vaporized THC 4mg

ACTIVE COMPARATOR

Vaporized THC 4 mg

Drug: 4mg Purified THC in an ethanolic solution

Placebo

PLACEBO COMPARATOR

Masked oral placebo or vaporized saline

Drug: Placebo

Interventions

4mg Purified THC in an ethanolic solution DRUG

4mg Purified THC in an ethanolic solution

Vaporized THC 4mg

Dronabinol 5 MG DRUG

Dronabinol 5 mg

Also known as: "Marinol"

Dronabinol 5mg

Dronabinol 10 MG DRUG

Dronabinol 10mg

Also known as: "Marinol"

Dronabinol 10mg

2mg Purified THC in an ethanolic solution DRUG

2mg Purified THC in an ethanolic solution

Vaporized THC 2mg

Placebo DRUG

Oral placebo and/or vaporized saline

Placebo

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Healthy male and female participants aged 65 ≥ years old
• 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
• Capable of providing informed consent in English.

You may not qualify if:

• Meeting DSM-5 criteria for psychiatric/substance use disorders (SUD) other than tobacco use disorder, within the last year
• Current use of cannabinoid products, as evidenced by a urine drug screen
• Having a history of treatment for cannabis use disorder
• History of intent or current intent of abstaining from cannabis use
• Clinically significant medical disorders (e.g. liver/kidney dysfunction, immunosuppressing conditions, history or presence of epilepsy, seizures, head trauma with loss of consciousness)
• 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)
• 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)
• 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
• Contraindications for exposure to nociceptive stimuli, such as untreated hypertension
• 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)
• Major neurocognitive disorders precluding participation, evidenced by a clinical exam
• Abnormal EKG, arrythmia, vasospastic disease, chronic heart failure, or presence of a pacemaker
• Elevation of liver enzymes (ALT, AST) 2x the normal limit or higher
• Personal or family history of primary psychotic disorders, or mood disorders with psychotic features
• Current suicidal ideation

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): collaborator
• Yale University: lead
• VA Connecticut Healthcare System: collaborator

Study Sites (1)

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

RECRUITING

Related Publications (8)

• 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.

  PMID: 28077451 BACKGROUND

• 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.

  PMID: 33660625 BACKGROUND

• 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.

  PMID: 28595684 BACKGROUND

• 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.

  PMID: 17716320 BACKGROUND

• 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.

  PMID: 14687328 BACKGROUND

• 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.

  PMID: 15876494 BACKGROUND

• 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.

  PMID: 23742795 BACKGROUND

• 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.

  PMID: 11224166 BACKGROUND

MeSH Terms

Conditions

Pain

Interventions

Dronabinol

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Joao P. De Aquino, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julia Meyerovich, M.S.

CONTACT

203-623-7493; julia.meyerovich@yale.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Study medication will be prepared by study pharmacy.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry

Model Details: This is a double-blind, placebo-controlled, crossover study, randomizing 20 men and women aged 65 years or older to two doses of oral THC and vaporized THC.

Study Record Dates

• First Submitted: May 25, 2023
• First Posted: June 18, 2023
• Study Start: October 17, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)