PK/PD de delta-9-tetrahidrocannabinol (THC) oral y vaporizado en adultos mayores
Farmacocinética y farmacodinámica del delta-9-tetrahidrocannabinol (THC) oral y vaporizado en adultos mayores
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.
Descripción general del estudio
Estado
Descripción detallada
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.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase temprana 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Connecticut
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West Haven, Connecticut, Estados Unidos, 06516
- VA Connecticut Healthcare System
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Otro
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación cruzada
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Comparador activo: Dronabinol 5mg
Dronabinol 5 mg |
Dronabinol 5 mg
Otros nombres:
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Comparador de placebos: Dronabinol 10mg
Dronabinol 10 mg |
Dronabinol 10mg
Otros nombres:
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Comparador activo: Vaporized THC 2mg
Vaporized THC 2mg |
2mg Purified THC in an ethanolic solution |
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Comparador activo: Vaporized THC 4mg
Vaporized THC 4 mg |
4mg Purified THC in an ethanolic solution |
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Comparador de placebos: Placebo
Masked oral placebo or vaporized saline |
Oral placebo and/or vaporized saline |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Peak concentration (Cmax)
Periodo de tiempo: Up to 8 hours
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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
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Time to attain Cmax concentration (Tmax)
Periodo de tiempo: Up to 8 hours
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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
|
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Area under the plasma concentration-time curve (AUC0-8h)
Periodo de tiempo: Up to 8 hours
|
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
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Nociception
Periodo de tiempo: Up to 8 hours
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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
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Abuse Liability
Periodo de tiempo: Up to 8 hours
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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
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Joao P. De Aquino, M.D., Yale University
Publicaciones y enlaces útiles
Publicaciones Generales
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 2000035354
- 1R21DA057240-01 (Subvención/contrato del NIH de EE. UU.)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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