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

Официальное название

Pharmacokinetics and Pharmacodynamics of Oral and Vaporized Delta-9-Tetrahydrocannabinol (THC) in Older Adults

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Dronabinol 5 MG
  Dronabinol 5 mg
• Препарат Dronabinol 10 MG
  Dronabinol 10mg
• Препарат 2mg Purified THC in an ethanolic solution
  2mg Purified THC in an ethanolic solution
• Препарат 4mg Purified THC in an ethanolic solution
  4mg Purified THC in an ethanolic solution
• Препарат Placebo
  Oral placebo and/or vaporized saline

Первичные конечные точки

• Peak concentration (Cmax) [Срок оценки: Up to 8 hours]
• Time to attain Cmax concentration (Tmax) [Срок оценки: Up to 8 hours]
• Area under the plasma concentration-time curve (AUC0-8h) [Срок оценки: Up to 8 hours]
• Nociception [Срок оценки: Up to 8 hours]
• Abuse Liability [Срок оценки: Up to 8 hours]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Двойное слепое

Основная цель

Другое

Центры проведения

США · 1 центр

• VA Connecticut Healthcare System — West Haven

Публикации

• 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
• 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
• 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
• 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
• 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
• 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
• 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): PMID 23742795
• 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

Идентификаторы

NCT: NCT05906511 · 2000035354 · 1R21DA057240-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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