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

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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

  • 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.

Exclusion criteria

  • 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
  • Allergy or serious adverse reactions to sesame oil, THC, or cannabis
  • 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

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

Trial contacts and locations

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Central trial contact

Julia Meyerovich, M.S.

Data sourced from clinicaltrials.gov

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