Clinical trial NCT05906511: PK/PD of Oral and Vaporized Delta-9-Tetrahydrocannabinol (THC) in Older Adults
Official title: Pharmacokinetics and Pharmacodynamics of Oral and Vaporized Delta-9-Tetrahydrocannabinol (THC) in Older Adults
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Pain, Tolerance
Oral vs Vaporized THC
Abuse Liability
Keywords: Pharmacokinetics THC
Pharmacodynamics THC
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: VA Connecticut Healthcare System
name: National Institute on Drug Abuse (NIDA)
First posted: 2023-06-18
Enrollment: 20
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: OTHER

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. The research will proceed with a sub-study, randomizing 20 men and women aged 65 years or older, to two doses focusing on oral THC administration and a sub-study randomizing 20 men and women aged 65 years or older, to two doses focusing on vaporized THC administration.

Detailed 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: 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.

Primary 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.

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.

Primary outcomes:
measure: Peak concentration (Cmax)
timeFrame: Up to 8 hours
measure: Time to attain Cmax concentration (Tmax)
timeFrame: Up to 8 hours
measure: Area under the plasma concentration-time curve (AUC0-8h)
timeFrame: Up to 8 hours
measure: Nociception
timeFrame: Up to 8 hours
measure: Abuse Liability
timeFrame: Up to 8 hours
Secondary outcomes:
Other outcomes:
Locations:
city: West Haven
country: United States
facility: VA Connecticut Healthcare System
state: Connecticut
Study officials:
affiliation: Yale University
name: Joao P. De Aquino, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.