Cannabinoides
Artículo de Justin L Scharton, investigador independiente
Última actualización 12/19/2024
Los cannabinoides son un grupo diverso de compuestos de origen natural, siendo el tetrahidrocannabinol (THC) y el cannabidiol (CBD) los más reconocidos. Existen al menos 150 cannabinoides diferentes, y cada uno tiene propiedades y beneficios únicos. Estos compuestos interactúan con diversos receptores y vías de señalización del cuerpo humano, influyendo en procesos relacionados con el dolor, la inflamación, el estado de ánimo, el apetito y otros.
La mayoría de los cannabinoides no han sido objeto de muchas investigaciones sobre sus beneficios. Nueve de ellos son los que tienen más investigaciones que muestran muchos beneficios para la salud. Vamos a repasarlos:
CBC - Cannabichromene (Cannabicromeno)
CBD - Cannabidiol
CBDA - Cannabidiolic Acid (Ácido cannabidiólico)
CBDV - Cannabidivarin (Cannabidivarina)
CBG - Cannabigerol
CBN - Cannabinol
THC - Tetrahydrocannabinol
THCA - Tetrahydrocannabinolic Acid (Ácido tetrahidrocannabinólico)
THCV - Tetrahydrocannabivarin
CBC
Cannabichromene (Cannabicromeno)
El CBC es un agonista TRPA1 y un inhibidor de la recaptación de anandamida.(70A)
El Cannabichromene (cannabicromeno) (CBC) es uno de los cannabinoides menos investigados, con información limitada en comparación con compuestos más estudiados como el THC y el CBD. El CBC es un cannabinoide traza que se encuentra en pequeñas concentraciones en las plantas de cannabis. A pesar de la limitada investigación, el CBC ha demostrado su potencial en algunas áreas.
CBC como antiinflamatorio
El CBC es un antiinflamatorio que actúa sobre el inflamasoma NLRP3 y la IL-6/STAT-3, reduciendo la inflamación sin afectar al NF-κB. También puede influir en la edición del ARN.(69B)
CBC como tratamiento de la neurodegeneración
El CBC inhibe la agregación de β-amiloide, lo que lo convierte en un posible tratamiento para la neurodegeneración como la enfermedad de Alzheimer.(56B)
El CBC se oxida en el cannabinoide CBL (cannabiciclol)(77B)
El CBC tiene propiedades anticonvulsivantes a dosis bajas.(55B)
CBD
Cannabidiol
Receptores TRP con los que interactúa el CBD: TRPA1, TRPV1, TRPV2, TRPV3, TRPM8 (2A,3A,4A,19A,54A)
El CBD tiene muchos beneficios, como ser analgésico, anticonvulsivo, relajante muscular, ansiolítico, antipsicótico, neuroprotector, antiinflamatorio y antioxidante..(37B)
Otras acciones del CBD: Supresión de la degradación del triptófano,(32B) inhibidor competitivo de la captación de adenosina,(22B) agonista de 5HT1A,(3B) agonista de PPARy,(10B) modulador de los canales de calcio de tipo T,(7B) modulador alostérico de los receptores opiáceos Mu y Delta,(91A) inhibidor de GPR55,(86A) agonista inverso de CB2, modulador de la fosfolipasa A2.(70A)
El CBD es un agonista inverso del CB2
El CBD es un agonista inverso del CB2 (70A) - Los agonistas inversos actúan como agonistas normales en la forma en que se unen a los receptores, pero tienen el efecto farmacológico opuesto al de un agonista normal.
CBD es un anticonvulsivo y neuroprotector
El CBD actúa como anticonvulsivo y neuroprotector a través de la homeostasis del calcio en las células neuronales. En condiciones normales, el CBD provoca un aumento sutil del calcio en las células del hipocampo. En condiciones de hiperexcitabilidad, el CBD redujo la liberación de calcio e impidió las oscilaciones de calcio. El CBD regula la homeostasis del calcio en las neuronas haciendo que las mitocondrias absorban el calcio extra del citosol (lo que se conoce como “Sink” (sumidero) o liberen calcio extra cuando lo necesitan (lo que se conoce como “Source” (fuente).(38B)
Vasodilatación a través de la liberación del péptido relacionado con el gen de la calcitonina (CGRP)
El CBD puede liberar péptido relacionado con el gen de la calcitonina (CGRP) de forma dependiente de la dosis desde las neuronas DRG. Esta acción no se debe a la interacción con los receptores cannabinoides o TRPV1. La liberación de CGRP inducida por el CBD está parcialmente mediada por la activación del TRPV2.(39B) El CGRP es un vasodilatador muy potente que interviene en el sistema cardiovascular y en la cicatrización de heridas. Se sabe que los antagonistas del CGRP pueden aliviar las migrañas.(40B)
¿El CBD provoca migrañas por la liberación de CGRP?
Las personas reaccionarán a los cannabinoides de forma diferente, pero dado que el CBD puede afectar a otros receptores y acciones, los efectos vasodilatadores del CGRP podrían estar más regulados con pequeñas dosis de CBD. Será necesario realizar investigaciones reales para evaluar los efectos de las diferentes dosis de CBD y las migrañas, especialmente cómo afectan las grandes dosis de CBD aislado a las migrañas. Además, los efectos del CBD se verán alterados si se utiliza THC y ciertos terpenos que afectan a la vasodilatación o la vasoconstricción. Algunas personas con migrañas podrían responder mejor a una variedad Sativa de THC, o a una variedad rica en humuleno que pueda combinarse con CBD para mantener la vasodilatación al mínimo. Hasta ahora, las investigaciones suelen decir que el CBD puede ayudar con las migrañas, dejando las preguntas aún sin respuesta.
CBDA
Cannabidiolic acid (Ácido cannabidiólico)
Receptores con los que interactúa el CBDA: agonista parcial TRPA1, agonista TRPV1, antagonista TRPM8, (3A,19A) inhibidor de la COX-2 (29B)
La CBDA es inestable
El CBDA acabará descarboxilándose en CBD con el tiempo.(51B) Esto dificultará la compra de CBDA, y la gente tendría que cultivarlo por sí misma para tener un suministro fresco frecuente para utilizar ese cannabinoide. La forma más fácil de administrar CBDA es introducir cogollos secos de CBDA en una cápsula vacía. También se puede preparar un té con los cogollos secos, pero parte de la resina se pegará a la taza. Las hojas frescas y los cogollos también pueden servir para preparar té. Remojar los cogollos en un poco de aceite MCT es otra opción, pero puede hacer que los cannabinoides sean propensos a la descarboxilación con el tiempo. Personalmente me gustan las cápsulas, y tengo un mejor efecto con ese método.
CBDA para el tratamiento de la obesidad
En un estudio se estabilizó el CBDA con CBDA-O-metil éster (HU-580, EPM301) para evitar que se descarboxilara por sí solo. EPM301 a 40 mg/kg al día produjo pérdida de peso, aumento de la deambulación y mejora de los perfiles glucémico y lipídico en ratones obesos inducidos por la dieta. EPM301 también previno la disfunción hepática y la esteatosis inducidas por la dieta. En el tratamiento preventivo, el EMP301 inhibió el aumento de peso y la adiposidad. Ese estudio demostró que el EMP301 reducía la obesidad y sus anomalías metabólicas tanto en la obesidad inducida por la dieta como en la inducida genéticamente.(51B)
CBDA para la enfermedad de Alzheimer
El CBDA mejora los déficits de memoria y reduce la patología amiloide-beta y Tau en ratones con enfermedad de Alzheimer.(50B)
CBDV
Cannabidivarin (Cannabidivarina)
Receptores TRP CBDV interactúa con: agonista y desensibiliza TRPA1, TRPV1, y TRPV2 (81B)
El CBDV tiene propiedades antiinflamatorias, antináuseas, antitumorales, anticonvulsivantes, ansiolíticas y neuroprotectoras.(82B)
Propiedades anticonvulsivas
El CBDV tiene propiedades anticonvulsivas. Se utilizó en un estudio de fase 2a controlado con placebo para las convulsiones focales, pero no alcanzó los criterios de valoración primarios allá por febrero de 2018. El CBDV inhibe la diacilglicerol (DAG) lipasa-α, que es la enzima responsable de sintetizar 2-araquidonoilglicerol (2-AG). Se desconoce la importancia clínica de dicha inhibición.(81B)
Síndrome de Rett y autismo
Se demostró que el CBDV reduce las alteraciones motoras y los déficits cognitivos en ratas con síndrome de Rett, que presenta cierto grado de solapamiento con el autismo. En el estudio con ratas se utilizó ácido valproico prenatalmente para inducir esos problemas neurológicos en las ratas, y se utilizó CBDV para aliviar los síntomas. El CBDV restaura la señalización endocannabinoide del hipocampo y la neuroinflamación inducida por la exposición prenatal al VPA.(83B)
Distrofia muscular de Duchenne (DMD)
El CBD, CBDV y THCV promovieron la formación de miotubos a través de la activación de TRPA1. CBD y CBDV diferenciación de células mioblásticas murinas C2C12 en miotubos mediante el aumento de iones de calcio principalmente a través de la activación TRPV1.(84B)
Comportamiento compulsivo
La administración crónica de CBDV en ratas a una dosis de 20 mg/kg normalizó el comportamiento repetitivo.(83B) Será necesario realizar dosis y ensayos en humanos para demostrar cómo puede ayudar a las personas con problemas compulsivos como el TOC.
Variedades de CBDV
Hasta ahora, las variedades con alto contenido en CBDV sólo están disponibles en variedades autoflorecientes. Tendremos que esperar y ver si las versiones fotoperiódicas estarán disponibles en el futuro. Estas son algunas de las variedades CBDV que están disponibles actualmente y que la gente puede cultivar por sí misma.
Auto CBD-Victory de Dutch Passion Seeds
Esta variedad autofloreciente fue creada por Dutch Passion Seeds con un 75% de Sativa y un 25% de Indica. El CBD y el CBDV son del 4-6% cada uno, y el THC está por debajo del 0,3%. El perfil de terpenos se describe como toques de madera, pino y un ligero sabor a vinagre dulce. Estas plantas tardan unas 10 semanas en cosecharse con 20 horas de luz al día (cultivo interior).
Auto CBDV 1:1 by Seedsman
La genética de Seedsman creó esta variedad autofloreciente 1:1 CBD:CBDV que tarda 9-10 semanas en estar lista para cosechar en interior, y apta también para el cultivo en exterior. El nivel de THC es inferior al 0,3%. Es 75% Sativa y 25% Indica con aroma a pino y resina de árbol (bálsamo).
Royal CBDV Automatic by Royal Queen Seeds
Creado por Royal Queen Seeds, esta variedad tiene los padres de Solomatic CBD con Durban Poison con una calificación de 75% de genética sativa, 20% indica, y 5% ruderalis. Estas plantas producen un 5%, niveles de CBD del 5%, y niveles de THC del 0,3%. Tienen terpenos terrosos y de pino, y tardan tan sólo 8 semanas en estar listas para la cosecha después de la germinación.
CBDV Auto by Kannabia Seeds
CBDV Auto tiene un contenido cannabinoide de CBDV y THC es de 25:1 con el THC inferior al 0,2%. Tardan unos 63-70 días en estar listas para la cosecha, y tienen un aroma terroso y especiado, con toques de pimienta.
Sedativa CBDV by Elite Seeds
Sedativa es un híbrido 50/50 con un aroma fresco y floral que recuerda a la lavanda y al jazmín, y un contenido en cannabinoides de CBDV:CBD de proporción 7:8, y un nivel de THC inferior al 0,5%.
CBG
Cannabigerol
Receptores TRP con los que interactúa el CBG: TRPA1 y TRPV1 agonista, TRPM8 antagonista.(70A)
Otras acciones del CBG: agonista parcial de CB1 y CB2, inhibidor de la recaptación de anandamida, modulador/inhibidor de la fosfolipasaA2,(70A,56B) inhibe la COX-1, COX-2 y 12/15-LOX.(56B)
El CBG se encuentra en el cannabis y en el Helichrysum umbraculigerum.(70B) Los nombres comunes del Helichrysum umbraculigerum incluyen woolly umbrella helichrysum o umbrella everlasting en inglés, y kerriekruie en afrikaans, que hace referencia a su aroma parecido al curry.(71B,72B)
El CBG actúa como estimulante del apetito, agente antiinflamatorio, agente antibacteriano, agente neuroprotector y antioxidante. Es un fitocannabinoide y un miembro de los resorcinoles.(70B)
CBG para la ansiedad, psoriasis, protección gástrica y más
El CBG reduce la ansiedad y el estrés y puede mejorar la memoria sin intoxicación, deterioro o efectos subjetivos de la droga.(73B)
El CBG es un inhibidor de la cPLA2, la COX-1, la COX-2 y la 12/15-LOX.(74B) El CBG también protege contra la mucositis gástrica,(56B) por lo que la inhibición de la COX-1 probablemente no causaría ningún problema en la mucosa gástrica por los beneficios protectores del CBG.
El CBG reduce la inflamación de la piel,(75B) lo que podría ser útil contra afecciones como la psoriasis, el eccema o la dermatitis.
CBG para la neurodegeneración
El CBG inhibe la agregación de β-amiloide, lo que lo convierte en un posible tratamiento para la neurodegeneración, como la enfermedad de Alzheimer.(56B)
CBG para el tratamiento del SARS-CoV-2 (COVID)
Tanto el CBG como el CBL ( cannabicyclol) son eficaces contra el virus Covid, con una EC(50) del cannabigerol de 5,5 µM y del cannabicyclol de 10,8 µM. Bloquean la fusión celular del SARS-CoV-2.(76B) El CBL se forma cuando el CBC oxida.(77B)
CBG para el tratamiento del adenocarcinoma ductal pancreático (PDAC)
El CBG es un tratamiento anticancerígeno eficaz para las líneas celulares PANC-1 y MIAPaCa-2 de adenocarcinoma ductal pancreático (PDAC) mediante la modulación de las vías asociadas a EGFR-RAS.(78B)
¿Es malo el CBG para el embarazo?
El CBG y el CBDV pueden influir negativamente en el embarazo al aumentar la expresión del TRPV1, lo que puede alterar la angiogénesis y aumentar el riesgo de complicaciones en el embarazo, como el retraso del crecimiento intrauterino y la preeclampsia.(79B)
Variedades CBG
Las variedades CBG están disponibles en los fotoperiodos que se incluyen a continuación. También están disponibles algunas versiones autoflorecientes. Es posible que los tricomas claros tengan más CBG que los tricomas blancos, pero eso no se indica en ninguna de las descripciones de semillas que se encuentran en línea.
CBG-Force de Dutch Passion Seeds
CBG-Force es una variedad CBG de fotoperiodo con un porcentaje de THC inferior al 0,15%. Esta variedad sólo tarda unas 7 semanas en estar lista para la cosecha. No hay un olor fuerte, ni muchos terpenos en esta variedad.
CBG Zerodue by Seedstockers
CBG Zerodue es un cruce entre CBD Critical XXL e Italian Research Genetics. Se puede esperar que tenga niveles de THC por debajo del 0,2% y niveles de CBG tan altos como 9,18% y tarda unos 70 días en estar lista para la cosecha. Esta variedad es de fotoperíodo.
Eboshi CBG by Medical Seeds
Eboshi CBG es una fotoperiodo que puede alcanzar hasta un 15% de CBG y tanto THC como CBD por debajo del 0,2%. Tiene sabor y aroma a toques cítricos con matices afrutados y a tierra húmeda.
CBG 1 by Seedsman
CBG 1 es un fotoperíodo con niveles de CBG del 16,9%, mientras que el THC es del 0,25%. Los sabores son picantes, del terpeno limoneno, con notas de bayas, y tarda unas 12 semanas en estar lista para la cosecha.
Pure CBG by Philosopher Seeds
Pure CBG es una fotoperiódica con niveles de CBG de hasta el 12%, y una concentración de THC inferior al 0,3%. Tarda unos 55 días en estar lista para la cosecha, y tiene terpenos cítricos y dulces.
CBN
Cannabinol
Receptores TRP con los que interactúa el CBN: TRPA1 agonista, TRPM8 antagonista.(52B)
El CBN es un agonista parcial débil CB1 y CB2.(70A)
¿El CBN ayuda a dormir?
Un estudio mostró que el CBN a una dosis de 10 mg/kg inicialmente redujo el sueño REM, pero 4 horas después de su administración, el REM aumentó significativamente. Esto podría indicar que el CBN puede reducir los despertares después del inicio del sueño.(53B)
Hubo un ensayo clínico sobre la eficacia del uso de CBN para dormir que se completó el 9-5-2023. Se trataba de una comparación de 30 mg y 300 mg de CBN. Los resultados de ese estudio no están disponibles en el momento de escribir esto (10-24-2024), que es más de 1 año desde el final de ese estudio. Tendremos que esperar hasta que esté disponible en ClinicalTrials.gov ID NCT05344170.
CBN para aliviar el dolor
El CBN inhibe los canales de sodio dependientes de voltaje (Nav1.7) y las neuronas del ganglio de la raíz dorsal (GDR), lo que sugiere que podría ser útil para reducir el dolor neuropático. Las mutaciones del Nav1.7 se asocian a trastornos dolorosos como el dolor oftálmico, y el CBN podría ser útil para reducir ese dolor. El CBN es ligeramente menos potente en la inhibición de los canales Nav1.7 que el CBD o el CBG.(52B)
El CBN es antiinflamatorio al inhibir el inflamasoma NF-κB y NLRP3, pero actúa de forma diferente al THCV sobre vías específicas como STAT-3.(54B)
CBN para el tratamiento de la neurodegeneración
El CBN inhibe la agregación de β amiloide, lo que lo convierte en un posible tratamiento para la neurodegeneración como la enfermedad de Alzheimer.(56B)
El CBN tiene propiedades anticonvulsivantes a dosis bajas.(55B)
¿Cómo se forma el CBN?
Las investigaciones afirman que el CBN es THC oxidado. El CBN aumenta a medida que el THC se degrada durante el almacenamiento.(70A) Los cultivadores de marihuana tienden a fijarse en los tricomas ámbar como fuente de CBN. Esto se puede conseguir dejando que la planta madure más tiempo antes de cosecharla, y observando los tricomas bajo aumento con una lupa de joyero. Los tricomas ámbar también aparecen tras el curado al agua de las flores de cannabis. El curado en agua consiste en sumergir los cogollos de cannabis recién cosechados en agua durante 3-7 días, cambiando el agua todos los días. La imagen de arriba es de un curado en agua de 3 días de CBD Lemon Skunk. No hay pruebas de laboratorio disponibles para mostrar la conversión a CBN de curado en agua.
THC
Tetrahydrocannabinol
Receptores TRP con los que interactúa el THC: TRPA1 y TRPV2 (2A,3A,4A,54A,19A)
Otras acciones del THC: supresión de la degradación del triptófano,32B agonista PPARy,10B agonista indirecto del canal de calcio tipo T,7B modulador alostérico de los receptores opiáceos Mu y Delta,91A agonista GPR55,86A modulador de la fosfolipasa A2,70A agonista parcial CB1 y CB2.(41B)
El Δ9-THC es el principal cannabinoide psicoactivo de la planta de marihuana. Se utiliza habitualmente para estimular el apetito en el tratamiento de la pérdida de peso en pacientes con SIDA. También es eficaz para reducir las náuseas y los vómitos asociados al tratamiento del cáncer con quimioterapia.(41B)
Metabolitos de Δ9-THC
11-Hydroxytetrahydrocannabinol (11-OH-THC)
Este metabolito suele denominarse 11-hydroxy-THC. Se produce en el hígado con la enzima citocromo CYP2C9. Se asocia sobre todo con el metabolismo de la ingestión de THC comestible.42B El 11-hydroxy-THC es varias veces más potente que el Δ9-THC.(43B)
11-Nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid (THC-COOH)
El THC-COOH es el metabolito inactivo que permanece en el cuerpo durante semanas y es el objetivo de las pruebas de detección de drogas.(42B)
Medicamento análogo al THC
Marinol (Dronabinol) es una sustancia controlada de la Lista 2 de la DEA que es una forma sintética de Δ9-THC. (41B)
Déficits cognitivos por consumo de THC
El consumo crónico de THC puede provocar déficits cognitivos, entre los que se incluyen: un deterioro de la capacidad para centrar la atención y filtrar información irrelevante.(44B) Este deterioro puede persistir durante al menos 7 días después de dejar de consumir THC, mientras que algunas personas podrían verse afectadas hasta un mes después de haber dejado de consumir THC.(45B)
Es posible que el consumo de suficiente CBD pueda prevenir este deterioro cognitivo gracias a los beneficios neuroprotectores del CBD, y a cómo este cannabinoide modula la forma en que el THC actúa sobre el receptor CB1. La proporción entre CBD y THC necesaria para evitarlo podría variar de una persona a otra, y el tipo de terpenos que se utilicen. El uso crónico de cepas con a-pineno probablemente sería más neuroprotector, ya que ese terpeno actúa como inhibidor de la acetilcolinesterasa. Mientras que la disminución de acetilcolina del linalool podría tener el efecto contrario.
Delta 8 THC
El THC Delta 8 es un agonista CB1 (44E)
Delta 8 THC tiene menos investigación disponible en comparación con Delta 9 THC. Es menos psicoactivo que el THC Delta 9. La investigación hasta ahora muestra que Delta 8 THC podría tener los beneficios de ser un antiemético, ansiolítico, estimulante del apetito, analgésico, y la actividad neuroprotectora.(46B)
Algunos de los efectos adversos del Delta 8 THC son: alucinaciones, vómitos, temblores, ansiedad, mareos, confusión, pérdida de conciencia e incluso la muerte de un niño. Los comestibles como brownies y gomitas infundidos con Delta 8 THC fueron responsables del 68% de los efectos adversos notificados.(47B)
THCA
Tetrahydrocannabiorcolic acid (Ácido tetrahidrocannabinólico)
Receptores TRP con los que interactúa el THCA: Agonista parcial TRPA1, agonista TRPV2, antagonista TRPM8. (3A19A)
Otras acciones del THCA: agonista de PPARy48B Δ9-THCA activa PPARy más fuerte que el THC.(49B)
El THCA ofrece neuroprotección y es un posible tratamiento para la enfermedad de Huntington y la neurodegeneración
El Δ9-THCA tiene potentes efectos neuroprotectores a través de la activación de PPARγ, lo que mejora la función mitocondrial, previene la citotoxicidad, protege contra la degeneración estriatal y reduce la neuroinflamación. El conjunto de estas funciones sugiere que el Δ9-THCA podría ser una valiosa opción terapéutica para la enfermedad de Huntington y otros trastornos neurodegenerativos.(49B)
El THCA mejora los déficits de memoria y reduce la patología amiloide-beta y Tau en ratones con enfermedad de Alzheimer.(50B)
THCA para la inhibición de TRPM8
El THCA es más estable que el CBDA durante la descarboxilación a lo largo del tiempo, lo que lo convierte en una buena opción como antagonista del TRPM8 fácil de obtener. Rellenar una cápsula vacía con flores secas de cannabis es un método eficaz para administrar THCA. Moler primero los cogollos puede exponer los tricomas a la oxidación, convirtiendo potencialmente algunos en CBN o desencadenando una descarboxilación parcial. Desde mi experiencia, el cannabis molido en una cápsula se siente más sedante en comparación con el cannabis sin moler. Otra opción es remojar el cannabis en aceite MCT, pero se descarboxilará naturalmente con el tiempo. En mi experiencia, el método de la cápsula ha sido la mejor opción para mantener el contenido de THCA.
THCV
Tetrahydrocannabivarin
Receptores TRP activados por THCV: TRPA1, TRPV1, TRPV2, TRPV3, TRPV4, y antagoniza TRPM8.(3A,19A,20A,21A)
Otros receptores y acciones: Antagonista CB1, agonista parcial CB2.69A70A71A Pequeñas dosis de THCV actúan como antagonista CB1, mientras que grandes dosis de THCV actúan como agonista CB1.(57B)
Las áreas en las que el THCV puede influir a través de la activación del TRPV4 incluyen cardiomiocitos, células endoteliales, células musculares lisas, pulmón, condrocitos, neuronas, astrocitos y esperma.(58B,59B,60B,61B,62B)
Activación del TRPV4 por el THCV en el sistema inmunitario
THCV activación de TRPV4 en el sistema inmunológico TRPV4 activación en los macrófagos son necesarios para la fagocitosis eficaz, y la secreción de citoquinas anti-inflamatorias. Se descubrió que TRPV4 protege el pulmón de lesiones tras una neumonía por infección con P. aeruginosa a través de la señalización MAPK.(63B)
¿Puede el THCV causar problemas respiratorios en la EPOC?
El polimorfismo TRPV4 se encuentra en la enfermedad pulmonar obstructiva crónica (EPOC). Los agonistas del TRPV4 pueden causar broncoconstricción, mientras que los antagonistas del TRPV4 la revierten.(64B) Existe la posibilidad de que el THCV también pueda causar constricción de las vías respiratorias, especialmente cuando se fuma o se inhala, debido a su posible agonismo del TRPV4, que podría exacerbar el estrechamiento de las vías respiratorias.
¿Cómo puede actuar el THCV como estimulante?
Los agonistas del TRPV4 aumentan la liberación de trifosfato de adenosina (ATP).64B El potencial del THCV para aumentar la liberación de ATP puede contribuir a sus efectos estimulantes y activar potencialmente el sistema nervioso simpático, provocando una respuesta estimulante.
¿El THCV provoca una supresión o un aumento del apetito?
La activación del TRPV4 aumentará la secreción de la hormona grelina. El THCV es un agonista del TRPV4. Ese receptor está sobreexpresado en los estómagos de las personas obesas, y se produce un aumento de la secreción de grelina cuando se estira el estómago.(65B)
El THCV es un antagonista del CB1. (71A) Cuando se activa el CB1 con un agonista, aumenta el apetito. El bloqueo de CB1 con un antagonista disminuye el apetito. (66B) El THCV se conoce normalmente como un supresor del apetito, pero a algunas personas les da hambre con el THCV.
¿El THCV provoca palpitaciones?
El TRPV4 se regula al alza en afecciones como: fibrosis cardiaca, hipertrofia, lesiones por isquemia-reperfusión, insuficiencia cardiaca, infarto de miocardio, arritmia,(58B) fibrosis quística, frecuencia de latidos ciliares, broncoconstricción, enfermedad pulmonar obstructiva crónica, hipertensión pulmonar, lesión pulmonar aguda, síndrome de dificultad respiratoria aguda y tos.(59B)
Si el TRPV4 está sobreexpresado en el corazón, su activación podría aumentar la excitabilidad del músculo cardíaco y contribuir a las palpitaciones. La liberación adicional de ATP por la acción del THCV podría amplificar aún más los efectos estimulantes sobre el corazón, aumentando la posibilidad de palpitaciones.
El THCV también activa el TRPV3. La activación del TRPV3 puede causar una vasodilatación que podría contribuir a las palpitaciones a través de la taquicardia refleja. La activación del TRPV3 también aumenta la liberación de ATP..(42A,43A)
Cómo puede afectar al corazón el exceso de ATP
Una paciente de 68 años se sometió a una infusión de ATP para una prueba diagnóstica. Tenía taquicardia y un complejo QRS ancho. Tras la infusión de ATP, entró en fibrilación ventricular probablemente debido a una sobrecarga simpática secundaria a la infusión de ATP. (67B) El THCV provocará la liberación de ATP. (64B)
¿El THCV provoca contracciones de la vejiga o un aumento de la micción?
El TRPV4 en la vejiga es responsable de dar la sensación de vejiga llena a través de la activación de esos receptores por el estiramiento de la vejiga. (68B) El THCV activando el TRPV4 en la vejiga podría dar a las personas esa sensación de que la vejiga está llena cuando realmente no lo está, e incluso provocar contracciones de la vejiga.
THCV como antiinflamatorio
El THCV reduce la inflamación inhibiendo el NF-κB y las vías de producción de citoquinas, incluido el P2X7 y el ensamblaje del inflamasoma NLRP3. También bloquea las vías que contribuyen a las tormentas de citoquinas (inflamación excesiva).(69B)
El THCV reduce la glucemia de los diabéticos de tipo 2
El THCV puede aumentar la sensibilidad a la insulina y disminuir la glucosa plasmática mediante el aumento de la actividad de las células b pancreáticas, la adiponectina y las concentraciones de Apo A. El THCV fue más eficaz para reducir la glucemia que el CBD.(57B)
Los diabéticos de tipo 1 podrían notar que el azúcar en sangre disminuye más con la administración conjunta de THCV e insulina en comparación con la insulina sin THCV debido a un aumento de las concentraciones de adiponectina y Apo A.
THCV para reducir el pánico
No existen investigaciones que expliquen por qué el THCV puede reducir el pánico. Podría deberse a los efectos estimulantes del THCV que insensibilizan el sistema nervioso a la respuesta de nuestro cuerpo a la secreción de adrenalina.
¿El THCV provoca ansiedad?
No existen investigaciones que expliquen por qué esto puede ocurrirle a algunas personas. Dado que el THCV actúa como un estimulante, las personas que sufren ansiedad con estimulantes como la cafeína o los picos de adrenalina en el cuerpo probablemente sufrirían ansiedad con el THCV.
Referencias
1A. Alvarado MG, Thakore P, Earley S. Transient Receptor Potential Channel Ankyrin 1: A Unique Regulator of Vascular Function. Cells. 2021 May 11;10(5):1167. doi: 10.3390/cells10051167. PMID: 34064835; PMCID: PMC8151290.
2A. Watanabe H., Vriens J., Prenen J., Droogmans G., Voets T., Nillus B. (2003). Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature 424, 434–438. 10.1038/nature01807
3A. Muller C, Morales P, Reggio PH. Cannabinoid Ligands Targeting TRP Channels. Front Mol Neurosci. 2019 Jan 15;11:487. doi: 10.3389/fnmol.2018.00487. PMID: 30697147; PMCID: PMC6340993.
4A. De Petrocellis L., Orlando P., Moriello A. S., Aviello G., Stott C., Izzo A. A., et al.. (2012a). Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation. Acta Physiol. 204, 255–266. 10.1111/j.1748-1716.2011.02338.x
5A. Hu F, Song X, Long D. Transient receptor potential ankyrin 1 and calcium: Interactions and association with disease (Review). Exp Ther Med. 2021 Dec;22(6):1462. doi: 10.3892/etm.2021.10897. Epub 2021 Oct 20. PMID: 34737802; PMCID: PMC8561754.
6A. Cordero-Morales, J. F., Gracheva, E. O., & Julius, D. (2011). Cytoplasmic ankyrin repeats of transient receptor potential A1 (TRPA1) dictate sensitivity to thermal and chemical stimuli. Proceedings of the National Academy of Sciences, 108(46), E1184-E1191. https://doi.org/10.1073/pnas.1114124108
7A. Bang S, Kim KY, Yoo S, Kim YG, Hwang SW. Transient receptor potential A1 mediates acetaldehyde-evoked pain sensation. Eur J Neurosci. 2007 Nov;26(9):2516-23. doi: 10.1111/j.1460-9568.2007.05882.x. Epub 2007 Oct 23. PMID: 17970723.
8A. Macpherson LJ, Xiao B, Kwan KY, Petrus MJ, Dubin AE, Hwang S, Cravatt B, Corey DP, Patapoutian A. An ion channel essential for sensing chemical damage. J Neurosci. 2007 Oct 17;27(42):11412-5. doi: 10.1523/JNEUROSCI.3600-07.2007. PMID: 17942735; PMCID: PMC6673017.
9A. McNamara CR, Mandel-Brehm J, Bautista DM, Siemens J, Deranian KL, Zhao M, Hayward NJ, Chong JA, Julius D, Moran MM, Fanger CM. TRPA1 mediates formalin-induced pain. Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13525-30. doi: 10.1073/pnas.0705924104. Epub 2007 Aug 8. PMID: 17686976; PMCID: PMC1941642.
10A. Taylor-Clark TE, McAlexander MA, Nassenstein C, Sheardown SA, Wilson S, Thornton J, Carr MJ, Undem BJ. Relative contributions of TRPA1 and TRPV1 channels in the activation of vagal bronchopulmonary C-fibres by the endogenous autacoid 4-oxononenal. J Physiol. 2008 Jul 15;586(14):3447-59. doi: 10.1113/jphysiol.2008.153585. Epub 2008 May 22. PMID: 18499726; PMCID: PMC2538817.
11A. Andersson DA, Gentry C, Moss S, Bevan S. Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. J Neurosci. 2008 Mar 5;28(10):2485-94. doi: 10.1523/JNEUROSCI.5369-07.2008. PMID: 18322093; PMCID: PMC2709206.
12A. Hinman A, Chuang HH, Bautista DM, Julius D. TRP channel activation by reversible covalent modification. Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19564-8. doi: 10.1073/pnas.0609598103. Epub 2006 Dec 12. PMID: 17164327; PMCID: PMC1748265.
13A. Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ, Patapoutian A. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron. 2004 Mar 25;41(6):849-57. doi: 10.1016/s0896-6273(04)00150-3. PMID: 15046718.
14A. GeneCards. (n.d.).TRPA1 Gene - GeneCards | The Human Gene Database. Retrieved 9/26/2024 from https://www.genecards.org/cgi-bin/carddisp.pl?gene=TRPA1&keywords=TRPA1
15A. Terada Y, Yamashita R, Ihara N, Yamazaki-Ito T, Takahashi Y, Masuda H, Sakuragawa S, Ito S, Ito K, Watanabe T. Human TRPA1 activation by terpenes derived from the essential oil of daidai, Citrus aurantium L. var. daidai Makino. Biosci Biotechnol Biochem. 2019 Sep;83(9):1721-1728. doi: 10.1080/09168451.2019.1611405. Epub 2019 May 10. PMID: 31072263.
16A. Molot J, Sears M, Anisman H. Multiple chemical sensitivity: It's time to catch up to the science. Neurosci Biobehav Rev. 2023 Aug;151:105227. doi: 10.1016/j.neubiorev.2023.105227. Epub 2023 May 10. PMID: 37172924.
17A. Faris P, Rumolo A, Pellavio G, Tanzi M, Vismara M, Berra-Romani R, Gerbino A, Corallo S, Pedrazzoli P, Laforenza U, Montagna D, Moccia F. Transient receptor potential ankyrin 1 (TRPA1) mediates reactive oxygen species-induced Ca2+ entry, mitochondrial dysfunction, and caspase-3/7 activation in primary cultures of metastatic colorectal carcinoma cells. Cell Death Discov. 2023 Jul 1;9(1):213. doi: 10.1038/s41420-023-01530-x. PMID: 37393347; PMCID: PMC10314907.
18A. Zhai K, Liskova A, Kubatka P, Büsselberg D. Calcium Entry through TRPV1: A Potential Target for the Regulation of Proliferation and Apoptosis in Cancerous and Healthy Cells. Int J Mol Sci. 2020 Jun 11;21(11):4177. doi: 10.3390/ijms21114177. PMID: 32545311; PMCID: PMC7312732.
19A. De Petrocellis L., Ligresti A., Moriello A. S., Allarà M., Bisogno T., Petrosino S., et al.. (2011b). Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br. J. Pharmacol. 163, 1479–1494. 10.1111/j.1476-5381.2010.01166.x
20A. Lowin T., Straub R. H. (2015). Cannabinoid-based drugs targeting CB1 and TRPV1, the sympathetic nervous system, and arthritis. Arthritis Res. Ther. 17:226. 10.1186/s13075-015-0743-x
21A. Petrosino S., Schiano Moriello A., Cerrato S., Fusco M., Puigdemont A., De Petrocellis L., et al.. (2016). The anti-inflammatory mediator palmitoylethanolamide enhances the levels of 2-arachidonoyl-glycerol and potentiates its actions at TRPV1 cation channels. Br. J. Pharmacol. 173, 1154–1162. 10.1111/bph.13084
22A. Taylor-Clark TE, McAlexander MA, Nassenstein C, Sheardown SA, Wilson S, Thornton J, Carr MJ, Undem BJ. Relative contributions of TRPA1 and TRPV1 channels in the activation of vagal bronchopulmonary C-fibres by the endogenous autacoid 4-oxononenal. J Physiol. 2008 Jul 15;586(14):3447-59. doi: 10.1113/jphysiol.2008.153585. Epub 2008 May 22. PMID: 18499726; PMCID: PMC2538817.
23A. GeneCards. (n.d.).TRPV1 Gene - GeneCards | The Human Gene Database. Retrieved 9/26/2024 from https://www.genecards.org/cgi-bin/carddisp.pl?gene=TRPV1
24A. Brito R, Sheth S, Mukherjea D, Rybak LP, Ramkumar V. TRPV1: A Potential Drug Target for Treating Various Diseases. Cells. 2014 May 23;3(2):517-45. doi: 10.3390/cells3020517. PMID: 24861977; PMCID: PMC4092862.
25A. Munjuluri S, Wilkerson DA, Sooch G, Chen X, White FA, Obukhov AG. Capsaicin and TRPV1 Channels in the Cardiovascular System: The Role of Inflammation. Cells. 2021 Dec 22;11(1):18. doi: 10.3390/cells11010018. PMID: 35011580; PMCID: PMC8750852.
26A. Omari SA, Adams MJ, Geraghty DP. TRPV1 Channels in Immune Cells and Hematological Malignancies. Adv Pharmacol. 2017;79:173-198. doi: 10.1016/bs.apha.2017.01.002. Epub 2017 Mar 21. PMID: 28528668.
27A. Chen K, Neu A, Howard AL, Földy C, Echegoyen J, Hilgenberg L, Smith M, Mackie K, Soltesz I. Prevention of plasticity of endocannabinoid signaling inhibits persistent limbic hyperexcitability caused by developmental seizures. J Neurosci. 2007 Jan 3;27(1):46-58. doi: 10.1523/JNEUROSCI.3966-06.2007. PMID: 17202471; PMCID: PMC6672287.
28A. Gibson HE, Edwards JG, Page RS, Van Hook MJ, Kauer JA. TRPV1 channels mediate long-term depression at synapses on hippocampal interneurons. Neuron. 2008 Mar 13;57(5):746-59. doi: 10.1016/j.neuron.2007.12.027. PMID: 18341994; PMCID: PMC2698707.
29A. MalaCards. (n.d.) Pulpitis. Human Disease Database. Retrieved 9/26/2024 from https://www.malacards.org/card/pulpitis
30A. MalaCards. (n.d.) Cystinosis, Nephropathic. Human Disease Database. Retrieved 9/26/2024 from https://www.malacards.org/card/cystinosis_nephropathic
31A. GeneCards. (n.d.).TRPV1 Gene - GeneCards | The Human Gene Database. Retrieved 9/26/2024 from https://www.genecards.org/cgi-bin/carddisp.pl?gene=TRPV1
32A. GeneCards. (n.d.).TRPV2 Gene - GeneCards | The Human Gene Database. Retrieved 10/08/2024 from https://www.genecards.org/cgi-bin/carddisp.pl?gene=TRPV2#:~:text=GeneCards%20Summary%20for%20TRPV2%20Gene,Renal%20Pelvis%20Transitional%20Cell%20Carcinoma.
33A. Kojima I, Nagasawa M. TRPV2. Handb Exp Pharmacol. 2014;222:247-72. doi: 10.1007/978-3-642-54215-2_10. PMID: 24756709.
34A. Siveen KS, Nizamuddin PB, Uddin S, Al-Thani M, Frenneaux MP, Janahi IA, Steinhoff M, Azizi F. TRPV2: A Cancer Biomarker and Potential Therapeutic Target. Dis Markers. 2020 Dec 10;2020:8892312. doi: 10.1155/2020/8892312. PMID: 33376561; PMCID: PMC7746447.
35A. Santoni G, Farfariello V, Liberati S, Morelli MB, Nabissi M, Santoni M, Amantini C. The role of transient receptor potential vanilloid type-2 ion channels in innate and adaptive immune responses. Front Immunol. 2013 Feb 14;4:34. doi: 10.3389/fimmu.2013.00034. PMID: 23420671; PMCID: PMC3572502.
36A. Kalinovskii AP, Utkina LL, Korolkova YV, Andreev YA. TRPV3 Ion Channel: From Gene to Pharmacology. Int J Mol Sci. 2023 May 11;24(10):8601. doi: 10.3390/ijms24108601. PMID: 37239947; PMCID: PMC10218142.
37A. Su W, Qiao X, Wang W, He S, Liang K, Hong X. TRPV3: Structure, Diseases and Modulators. Molecules. 2023 Jan 12;28(2):774. doi: 10.3390/molecules28020774. PMID: 36677834; PMCID: PMC9865980.
38A. Sherkheli MA, Benecke H, Doerner JF, Kletke O, Vogt-Eisele AK, Gisselmann G, Hatt H. Monoterpenoids induce agonist-specific desensitization of transient receptor potential vanilloid-3 (TRPV3) ion channels. J Pharm Pharm Sci. 2009;12(1):116-28. doi: 10.18433/j37c7k. PMID: 19470296.
39A. Vogt-Eisele AK, Weber K, Sherkheli MA, Vielhaber G, Panten J, Gisselmann G, Hatt H. Monoterpenoid agonists of TRPV3. Br J Pharmacol. 2007 Jun;151(4):530-40. doi: 10.1038/sj.bjp.0707245. Epub 2007 Apr 10. PMID: 17420775; PMCID: PMC2013969.
40A. GeneCards. (n.d.).TRPV3 Gene - GeneCards | The Human Gene Database. Retrieved 9/26/2024 from https://www.genecards.org/cgi-bin/carddisp.pl?gene=TRPV3&keywords=TRPV3
41A. Xu H, Delling M, Jun JC, Clapham DE. Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels. Nat Neurosci. 2006 May;9(5):628-35. doi: 10.1038/nn1692. Epub 2006 Apr 16. PMID: 16617338.
42A. Murphy TV, Kanagarajah A, Toemoe S, Bertrand PP, Grayson TH, Britton FC, Leader L, Senadheera S, Sandow SL. TRPV3 expression and vasodilator function in isolated uterine radial arteries from non-pregnant and pregnant rats. Vascul Pharmacol. 2016 Aug;83:66-77. doi: 10.1016/j.vph.2016.04.004. Epub 2016 Apr 9. PMID: 27073026.
43A. Martin LS, Josset-Lamaugarny A, El Jammal T, Ducreux S, Chevalier FP, Fromy B. Aging is associated with impaired triggering of TRPV3-mediated cutaneous vasodilation: a crucial process for local heat exposure. Geroscience. 2024 Aug;46(4):3567-3580. doi: 10.1007/s11357-023-00981-5. Epub 2023 Oct 19. PMID: 37855862; PMCID: PMC11226586.
44A. GeneCards. (n.d.).TRPV4 Gene - GeneCards | The Human Gene Database. Retrieved 10/09/2024 from https://www.genecards.org/cgi-bin/carddisp.pl?gene=TRPV4
45A. Chaigne S, Barbeau S, Ducret T, Guinamard R, Benoist D. Pathophysiological Roles of the TRPV4 Channel in the Heart. Cells. 2023 Jun 17;12(12):1654. doi: 10.3390/cells12121654. PMID: 37371124; PMCID: PMC10296986.
46A. Baratchi S, Keov P, Darby WG, Lai A, Khoshmanesh K, Thurgood P, Vahidi P, Ejendal K, McIntyre P. The TRPV4 Agonist GSK1016790A Regulates the Membrane Expression of TRPV4 Channels. Front Pharmacol. 2019 Jan 23;10:6. doi: 10.3389/fphar.2019.00006. PMID: 30728775; PMCID: PMC6351496.
47A. Kumar H, Lim CS, Choi H, Joshi HP, Kim KT, Kim YH, Park CK, Kim HM, Han IB. Elevated TRPV4 Levels Contribute to Endothelial Damage and Scarring in Experimental Spinal Cord Injury. J Neurosci. 2020 Feb 26;40(9):1943-1955. doi: 10.1523/JNEUROSCI.2035-19.2020. Epub 2020 Jan 23. PMID: 31974206; PMCID: PMC7046444.
48A. Dunn KM, Hill-Eubanks DC, Liedtke WB, Nelson MT. TRPV4 channels stimulate Ca2+-induced Ca2+ release in astrocytic endfeet and amplify neurovascular coupling responses. Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):6157-62. doi: 10.1073/pnas.1216514110. Epub 2013 Mar 25. PMID: 23530219; PMCID: PMC3625327.
49A. Liao J, Yang ST, Lu K, Lu Y, Wu YW, DU YM. [Oral administration of TRPV4 inhibitor improves atrial calcium handling abnormalities in sterile pericarditis rats]. Sheng Li Xue Bao. 2022 Apr 25;74(2):188-200. Chinese. PMID: 35503066.
50A. Liao J, Wu Q, Qian C, Zhao N, Zhao Z, Lu K, Zhang S, Dong Q, Chen L, Li Q, Du Y. TRPV4 blockade suppresses atrial fibrillation in sterile pericarditis rats. JCI Insight. 2020 Dec 3;5(23):e137528. doi: 10.1172/jci.insight.137528. PMID: 33119551; PMCID: PMC7714415.
51A. Everaerts W, Nilius B, Owsianik G. The vanilloid transient receptor potential channel TRPV4: from structure to disease. Prog Biophys Mol Biol. 2010 Sep;103(1):2-17. doi: 10.1016/j.pbiomolbio.2009.10.002. Epub 2009 Oct 14. PMID: 19835908.
52A. Darby WG, Grace MS, Baratchi S, McIntyre P. Modulation of TRPV4 by diverse mechanisms. Int J Biochem Cell Biol. 2016 Sep;78:217-228. doi: 10.1016/j.biocel.2016.07.012. Epub 2016 Jul 15. PMID: 27425399.
53A. Scheraga RG, Southern BD, Grove LM, Olman MA. The Role of TRPV4 in Regulating Innate Immune Cell Function in Lung Inflammation. Front Immunol. 2020 Jun 26;11:1211. doi: 10.3389/fimmu.2020.01211. PMID: 32676078; PMCID: PMC7333351.
54A. De Petrocellis L., Starowicz K., Moriello A. S., Vivese M., Orlando P., Di Marzo V. (2007). Regulation of transient receptor potential channels of melastatin type 8 (TRPM8): effect of cAMP, cannabinoid CB1 receptors and endovanilloids. Exp. Cell Res. 313, 1911–1920. 10.1016/j.yexcr.2007.01.008
55A. GeneCards. (n.d.).TRPM8 Gene - GeneCards | The Human Gene Database. Retrieved 10/09/2024 from https://www.genecards.org/cgi-bin/carddisp.pl?gene=TRPM8
56A. Borrelli F, Pagano E, Romano B, Panzera S, Maiello F, Coppola D, De Petrocellis L, Buono L, Orlando P, Izzo AA. Colon carcinogenesis is inhibited by the TRPM8 antagonist cannabigerol, a Cannabis-derived non-psychotropic cannabinoid. Carcinogenesis. 2014 Dec;35(12):2787-97. doi: 10.1093/carcin/bgu205. Epub 2014 Sep 30. PMID: 25269802
57A. Liu Y, Leng A, Li L, Yang B, Shen S, Chen H, Zhu E, Xu Q, Ma X, Shi P, Liu Y, Liu T, Li L, Li K, Zhang D, Xiao J. AMTB, a TRPM8 antagonist, suppresses growth and metastasis of osteosarcoma through repressing the TGFβ signaling pathway. Cell Death Dis. 2022 Mar 31;13(3):288. doi: 10.1038/s41419-022-04744-6. PMID: 35361751; PMCID: PMC8971393.
58A. Xu Q, Kong N, Zhang J, Bai N, Bi J, Li W. Expression of transient receptor potential cation channel subfamily M member 8 in gastric cancer and its clinical significance. Exp Ther Med. 2021 Apr;21(4):377. doi: 10.3892/ etm.2021.9808. Epub 2021 Feb 19. PMID: 33680099; PMCID: PMC7918222.
59A. Lan X, Zhao J, Song C, Yuan Q, Liu X. TRPM8 facilitates proliferation and immune evasion of esophageal cancer cells. Biosci Rep. 2019 Oct 30;39(10):BSR20191878. doi: 10.1042/BSR20191878. PMID: 31519770; PMCID: PMC6822499.
60A. Okamoto Y, Ohkubo T, Ikebe T, Yamazaki J. Blockade of TRPM8 activity reduces the invasion potential of oral squamous carcinoma cell lines. Int J Oncol. 2012 May;40(5):1431-40. doi: 10.3892/ijo.2012.1340. Epub 2012 Jan 20. PMID: 22267123.
61A. Mergler S, Derckx R, Reinach PS, Garreis F, Böhm A, Schmelzer L, Skosyrski S, Ramesh N, Abdelmessih S, Polat OK, Khajavi N, Riechardt AI. Calcium regulation by temperature-sensitive transient receptor potential channels in human uveal melanoma cells. Cell Signal. 2014 Jan;26(1):56-69. doi: 10.1016/j.cellsig.2013.09.017. Epub 2013 Sep 29. PMID: 24084605.
62A. Kijpornyongpan T, Sereemaspun A, Chanchao C. Dose-dependent cytotoxic effects of menthol on human malignant melanoma A-375 cells: correlation with TRPM8 transcript expression. Asian Pac J Cancer Prev. 2014;15(4):1551-6. doi: 10.7314/apjcp.2014.15.4.1551. PMID: 24641366.
63A. Li Q, Wang X, Yang Z, Wang B, Li S. Menthol induces cell death via the TRPM8 channel in the human bladder cancer cell line T24. Oncology. 2009;77(6):335-41. doi: 10.1159/000264627. Epub 2009 Dec 2. PMID: 19955836.
64A. Klumpp D, Frank SC, Klumpp L, Sezgin EC, Eckert M, Edalat L, Bastmeyer M, Zips D, Ruth P, Huber SM. TRPM8 is required for survival and radioresistance of glioblastoma cells. Oncotarget. 2017 Sep 30;8(56):95896-95913. doi: 10.18632/oncotarget.21436. PMID: 29221175; PMCID: PMC5707069.
65A. Valero ML, Mello de Queiroz F, Stühmer W, Viana F, Pardo LA. TRPM8 ion channels differentially modulate proliferation and cell cycle distribution of normal and cancer prostate cells. PLoS One. 2012;7(12):e51825. doi: 10.1371/journal.pone.0051825. Epub 2012 Dec 14. PMID: 23251635; PMCID: PMC3522609.
66A. Tsavaler L, Shapero MH, Morkowski S, Laus R. Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. Cancer Res. 2001 May 1;61(9):3760-9. PMID: 11325849.
67A. Fakih D, Baudouin C, Réaux-Le Goazigo A, Mélik Parsadaniantz S. TRPM8: A Therapeutic Target for Neuroinflammatory Symptoms Induced by Severe Dry Eye Disease. Int J Mol Sci. 2020 Nov 19;21(22):8756. doi: 10.3390/ ijms21228756. PMID: 33228217; PMCID: PMC7699525. https://www.ncbi.nlm.nih.gov/gene/79054 4/22/2024
68A. Hemida AS, Hammam MA, Heriz NAEM, Shehata WA. Expression of Transient Receptor Potential Channel of Melastatin number 8 (TRPM8) in Non- Melanoma Skin Cancer: A Clinical and Immunohistochemical study. J Immunoassay Immunochem. 2021 Nov 2;42(6):620-632. doi: 10.1080/15321819.2021.1918709. Epub 2021 Apr 25. PMID: 33896372.
69A. Reggio PH. Endocannabinoid binding to the cannabinoid receptors: what is known and what remains unknown. Curr Med Chem. 2010;17(14):1468-86. doi: 10.2174/092986710790980005. PMID: 20166921; PMCID: PMC4120766.
70A. Izzo, A. A., Borrelli, F., Capasso, R., Di Marzo, V., & Mechoulam, R. (2009). Non-psychotropic plant cannabinoids: New therapeutic opportunities from an ancient herb. Trends in Pharmacological Sciences, 30(10), 515- 527
71A. Morales P, Hurst DP, Reggio PH. Molecular Targets of the Phytocannabinoids: A Complex Picture. Prog Chem Org Nat Prod. 2017;103:103-131. doi: 10.1007/978-3-319-45541-9_4. PMID: 28120232; PMCID: PMC5345356.
72A. Jha NK, Sharma C, Hashiesh HM, Arunachalam S, Meeran MN, Javed H, Patil CR, Goyal SN, Ojha S. β-Caryophyllene, A Natural Dietary CB2 Receptor Selective Cannabinoid can be a Candidate to Target the Trinity of Infection, Immunity, and Inflammation in COVID-19. Front Pharmacol. 2021 May 14;12:590201. doi: 10.3389/fphar.2021.590201. PMID: 34054510; PMCID: PMC8163236.
73A. Udoh M, Santiago M, Devenish S, McGregor IS, Connor M. Cannabichromene is a cannabinoid CB2 receptor agonist. Br J Pharmacol. 2019 Dec;176(23):4537-4547. doi: 10.1111/bph.14815. Epub 2019 Nov 21. PMID: 31368508; PMCID: PMC6932936.
74A. GeneCards. (n.d.). CNR1 Gene - GeneCards | The Human Gene Database. Retrieved 10/10/2024 from https://www.genecards.org/cgi-bin/carddisp.pl?gene=CNR1&keywords=CB1
75A. GeneCards. (n.d.). CNR2 Gene - GeneCards | The Human Gene Database. Retrieved 10/10/2024 from https://www.genecards.org/cgi-bin/carddisp.pl?gene=CNR2&keywords=CB2
76A. Kaur R, Sidhu P, Singh S. What failed BIA 10-2474 Phase I clinical trial? Global speculations and recommendations for future Phase I trials. J Pharmacol Pharmacother. 2016 Jul-Sep;7(3):120-6. doi: 10.4103/0976-500X.189661. PMID: 27651707; PMCID: PMC5020770.
77A. Kaplan BL. The role of CB1 in immune modulation by cannabinoids. Pharmacol Ther. 2013 Mar;137(3):365-74. doi: 10.1016/j.pharmthera.2012.12.004. Epub 2012 Dec 20. PMID: 23261520.
78A. Aristizábal B, González Á. Innate immune system. In: Anaya JM, Shoenfeld Y, Rojas-Villarraga A, et al., editors. Autoimmunity: From Bench to Bedside [Internet]. Bogota (Colombia): El Rosario University Press; 2013 Jul 18. Chapter 2. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459455/
79A. Gaffal E, Kemter AM, Scheu S, Leite Dantas R, Vogt J, Baune B, Tüting T, Zimmer A, Alferink J. Cannabinoid Receptor 2 Modulates Maturation of Dendritic Cells and Their Capacity to Induce Hapten-Induced Contact Hypersensitivity. Int J Mol Sci. 2020 Jan 11;21(2):475. doi: 10.3390/ijms21020475. PMID: 31940843; PMCID: PMC7013892.
80A. Galiègue S, Mary S, Marchand J, Dussossoy D, Carrière D, Carayon P, Bouaboula M, Shire D, Le Fur G, Casellas P. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem. 1995 Aug 15;232(1):54-61. doi: 10.1111/j.1432-1033.1995.tb20780.x. PMID: 7556170.
81A. Tortora C, Di Paola A, Argenziano M, Creoli M, Marrapodi MM, Cenni S, Tolone C, Rossi F, Strisciuglio C. Effects of CB2 Receptor Modulation on Macrophage Polarization in Pediatric Celiac Disease. Biomedicines. 2022 Apr 9;10(4):874. doi: 10.3390/biomedicines10040874. PMID: 35453624; PMCID: PMC9029516.
82A. Alger BE. Getting high on the endocannabinoid system. Cerebrum. 2013 Nov 1;2013:14. PMID: 24765232; PMCID: PMC3997295.
83A. Lauckner JE, Jensen JB, Chen HY, Lu HC, Hille B, Mackie K. GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2699-704. doi: 10.1073/pnas.0711278105. Epub 2008 Feb 8. PMID: 18263732; PMCID: PMC2268199.
84A. Haley JE, Abogadie FC, Delmas P, Dayrell M, Vallis Y, Milligan G, Caulfield MP, Brown DA, Buckley NJ. The alpha subunit of Gq contributes to muscarinic inhibition of the M-type potassium current in sympathetic neurons. J Neurosci. 1998 Jun 15;18(12):4521-31. doi: 10.1523/JNEUROSCI.18-12-04521.1998. PMID: 9614229; PMCID: PMC6792692.
85A. Dennis SH, Pasqui F, Colvin EM, Sanger H, Mogg AJ, Felder CC, Broad LM, Fitzjohn SM, Isaac JT, Mellor JR. Activation of Muscarinic M1 Acetylcholine Receptors Induces Long-Term Potentiation in the Hippocampus. Cereb Cortex. 2016 Jan;26(1):414-26. doi: 10.1093/cercor/bhv227. Epub 2015 Oct 15. PMID: 26472558; PMCID: PMC4677984.
86A. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008 Jan;153(2):199-215. doi: 10.1038/sj.bjp.0707442. Epub 2007 Sep 10. PMID: 17828291; PMCID: PMC2219532.
87A. Stančić A, Jandl K, Hasenöhrl C, Reichmann F, Marsche G, Schuligoi R, Heinemann A, Storr M, Schicho R. The GPR55 antagonist CID16020046 protects against intestinal inflammation. Neurogastroenterol Motil. 2015 Oct;27(10):1432-45. doi: 10.1111/nmo.12639. Epub 2015 Jul 30. PMID: 26227635; PMCID: PMC4587547.
88A. Liu Q, Yu J, Li X, Guo Y, Sun T, Luo L, Ren J, Jiang W, Zhang R, Yang P, Yang Q. Cannabinoid receptor GPR55 activation blocks nicotine use disorder by regulation of AMPAR phosphorylation. Psychopharmacology (Berl). 2021 Nov;238(11):3335-3346. doi: 10.1007/s00213-021-05949-x. Epub 2021 Oct 14. PMID: 34648060.
89A. Patricio F, Morales Dávila E, Patricio-Martínez A, Arana Del Carmen N, Martínez I, Aguilera J, Perez-Aguilar JM, Limón ID. Intrapallidal injection of cannabidiol or a selective GPR55 antagonist decreases motor asymmetry and improves fine motor skills in hemiparkinsonian rats. Front Pharmacol. 2022 Sep 2;13:945836. doi: 10.3389/fphar.2022.945836. PMID: 36120297; PMCID: PMC9479130.
90A. Dhaliwal A, Gupta M. Physiology, Opioid Receptor. [Updated 2023 Jul 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK546642/
91A. Kathmann M, Flau K, Redmer A, Tränkle C, Schlicker E. Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors. Naunyn Schmiedebergs Arch Pharmacol. 2006 Feb;372(5):354-61. doi: 10.1007/s00210-006-0033-x. Epub 2006 Feb 18. PMID: 16489449.
92A. Theriot J, Sabir S, Azadfard M. Opioid Antagonists. [Updated 2023 Jul 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537079/
93A. Rao VS, Menezes AM, Viana GS. Effect of myrcene on nociception in mice. J Pharm Pharmacol. 1990
Dec;42(12):877-8. doi: 10.1111/j.2042-7158.1990.tb07046.x. PMID: 1983154.
94A. Jordan BA, Gomes I, Rios C, Filipovska J, Devi LA. Functional interactions between mu opioid and alpha 2A-adrenergic receptors. Mol Pharmacol. 2003 Dec;64(6):1317-24. doi: 10.1124/mol.64.6.1317. PMID: 14645661.
95A. Eason MG, Jacinto MT, Liggett SB. Contribution of ligand structure to activation of alpha 2-adrenergic receptor subtype coupling to Gs. Mol Pharmacol. 1994 Apr;45(4):696-702. PMID: 7910371.
96A. Niemi G, Breivik H. Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose infusion of bupivacaine, fentanyl and adrenaline after major surgery. A randomised, double-blind, cross-over study with and without adrenaline. Acta Anaesthesiol Scand. 1998 Sep;42(8):897-909. doi: 10.1111/j.1399-6576.1998.tb05348.x. PMID: 9773133.
97A. Fujita W, Gomes I, Dove LS, Prohaska D, McIntyre G, Devi LA. Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers. Biochem Pharmacol. 2014 Dec 1;92(3):448-56. doi: 10.1016/j.bcp.2014.09.015. Epub 2014 Sep 28. PMID: 25261794; PMCID: PMC4769596.
98A. Kumar R, Viswanath O, Saadabadi A. Buprenorphine. [Updated 2024 Jun 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459126/
99A. Kopecky BJ, Liang R, Bao J. T-type calcium channel blockers as neuroprotective agents. Pflugers Arch. 2014 Apr;466(4):757-65. doi: 10.1007/s00424-014-1454-x. Epub 2014 Feb 25. PMID: 24563219; PMCID: PMC4005039.
1B. Huguenard JR. Block of T -Type Ca(2+) Channels Is an Important Action of Succinimide Antiabsence Drugs. Epilepsy Curr. 2002 Mar;2(2):49-52. doi: 10.1111/j.1535-7597.2002.00019.x. PMID: 15309165; PMCID: PMC320968.
2B. Powell KL, Cain SM, Snutch TP, O'Brien TJ. Low threshold T-type calcium channels as targets for novel epilepsy treatments. Br J Clin Pharmacol. 2014 May;77(5):729-39. doi: 10.1111/bcp.12205. PMID: 23834404; PMCID: PMC4004393.
3B. Ernst ME, Kelly MW. Mibefradil, a pharmacologically distinct calcium antagonist. Pharmacotherapy. 1998 May-Jun;18(3):463-85. PMID: 9620098.
4B. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 60663, Mibefradil. Retrieved October 15, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Mibefradil.
5B. Chen H, Zhang D, Hua Ren J, Ping Chao S. Effects of L-type Calcium Channel Antagonists Verapamil and Diltiazem on fKv1.4ΔN Currents in Xenopus oocytes. Iran J Pharm Res. 2013 Fall;12(4):855-66. PMID: 24523765; PMCID: PMC3920693.
6B. Ge, W., & Ren, J. (2009). Combined L-/T-type calcium channel blockers: Ready for prime time. Hypertension, 53(4). https://doi.org/10.1161/HYPERTENSIONAHA.108.127548
7B. Ross HR, Napier I, Connor M. Inhibition of recombinant human T-type calcium channels by Delta9-tetrahydrocannabinol and cannabidiol. J Biol Chem. 2008 Jun 6;283(23):16124-34. doi: 10.1074/jbc.M707104200. Epub 2008 Apr 7. PMID: 18390906; PMCID: PMC3259625.
8B. Palee S, Chattipakorn S, Phrommintikul A, Chattipakorn N. PPARγ activator, rosiglitazone: Is it beneficial or harmful to the cardiovascular system? World J Cardiol. 2011 May 26;3(5):144-52. doi: 10.4330/wjc.v3.i5.144. PMID: 21666815; PMCID: PMC3110903.
9B. Singh G, Can AS, Correa R. Pioglitazone. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK544287/
10B. O'Sullivan SE, Sun Y, Bennett AJ, Randall MD, Kendall DA. Time-dependent vascular actions of cannabidiol in the rat aorta. Eur J Pharmacol. 2009 Jun 10;612(1-3):61-8. doi: 10.1016/j.ejphar.2009.03.010. Epub 2009 Mar 11. PMID: 19285060.
11B. Tyagi S, Gupta P, Saini AS, Kaushal C, Sharma S. The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases. J Adv Pharm Technol Res. 2011 Oct;2(4):236-40. doi: 10.4103/2231-4040.90879. PMID: 22247890; PMCID: PMC3255347.
12B. Stiedl O, Pappa E, Konradsson-Geuken Å, Ögren SO. The role of the serotonin receptor subtypes 5-HT1A and 5-HT7 and its interaction in emotional learning and memory. Front Pharmacol. 2015 Aug 7;6:162. doi: 10.3389/fphar.2015.00162. PMID: 26300776; PMCID: PMC4528280.
13B. Resstel LB, Tavares RF, Lisboa SF, Joca SR, Corrêa FM, Guimarães FS. 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats. Br J Pharmacol. 2009 Jan;156(1):181-8. doi: 10.1111/j.1476-5381.2008.00046.x. PMID: 19133999; PMCID: PMC2697769.
14B. Banerjee P, Mehta M, Kanjilal B. The 5-HT1A Receptor: A Signaling Hub Linked to Emotional Balance. In: Chattopadhyay A, editor. Serotonin Receptors in Neurobiology. Boca Raton (FL): CRC Press/Taylor & Francis; 2007. Chapter 7. Available from: https://www.ncbi.nlm.nih.gov/books/NBK5212/
15B. Schatzberg AF, Charles D. The Black Book of Psychotropic Dosing and Monitoring. Psychopharmacol Bull. 2018 Jan 15;48(1):64-153. PMID: 29382960; PMCID: PMC5765435.
16B. Montalbano A, Mlinar B, Bonfiglio F, Polenzani L, Magnani M, Corradetti R. Dual inhibitory action of trazodone on dorsal raphe serotonergic neurons through 5-HT1A receptor partial agonism and α1-adrenoceptor antagonism. PLoS One. 2019 Sep 26;14(9):e0222855. doi: 10.1371/journal.pone.0222855. PMID: 31557210; PMCID: PMC6763016.
17B. DrugBank. Serotonin 5HT1A antagonists. Retrieved 10/17/2024 from https://go.drugbank.com/categories/DBCAT005166.
18B. Celada P, Puig M, Amargós-Bosch M, Adell A, Artigas F. The therapeutic role of 5-HT1A and 5-HT2A receptors in depression. J Psychiatry Neurosci. 2004 Jul;29(4):252-65. PMID: 15309042; PMCID: PMC446220.
19B. Chu A, Wadhwa R. Selective Serotonin Reuptake Inhibitors. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554406/
20B. Sabri MA, Saber-Ayad MM. MAO Inhibitors. [Updated 2023 Jun 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557395/
21B. Moraczewski J, Awosika AO, Aedma KK. Tricyclic Antidepressants. [Updated 2023 Aug 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557791/
22B. Carrier EJ, Auchampach JA, Hillard CJ. Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression. Proc Natl Acad Sci U S A. 2006 May 16;103(20):7895-900. doi: 10.1073/pnas.0511232103. Epub 2006 May 3. PMID: 16672367; PMCID: PMC1472541.
23B. Martinez Naya N, Kelly J, Corna G, Golino M, Abbate A, Toldo S. Molecular and Cellular Mechanisms of Action of Cannabidiol. Molecules. 2023 Aug 9;28(16):5980. doi: 10.3390/molecules28165980. PMID: 37630232; PMCID: PMC10458707.
24B. Allahham M, Lerman A, Atar D, Birnbaum Y. Why Not Dipyridamole: a Review of Current Guidelines and Re-evaluation of Utility in the Modern Era. Cardiovasc Drugs Ther. 2022 Jun;36(3):525-532. doi: 10.1007/s10557-021-07224-9. Epub 2021 Jul 10. PMID: 34245446; PMCID: PMC8271326.
25B. Kerndt CC, Nagalli S. Dipyridamole. [Updated 2023 Jul 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554455/
26B. Wolska N, Rozalski M. Blood Platelet Adenosine Receptors as Potential Targets for Anti-Platelet Therapy. Int J Mol Sci. 2019 Nov 3;20(21):5475. doi: 10.3390/ijms20215475. PMID: 31684173; PMCID: PMC6862090.
27B. Lieu HD, Shryock JC, von Mering GO, Gordi T, Blackburn B, Olmsted AW, Belardinelli L, Kerensky RA. Regadenoson, a selective A2A adenosine receptor agonist, causes dose-dependent increases in coronary blood flow velocity in humans. J Nucl Cardiol. 2007 Jul;14(4):514-20. doi: 10.1016/j.nuclcard.2007.02.016. PMID: 17679059.
28B. Hauser RA, Hattori N, Fernandez H, Isaacson SH, Mochizuki H, Rascol O, Stocchi F, Li J, Mori A, Nakajima Y, Ristuccia R, LeWitt P. Efficacy of Istradefylline, an Adenosine A2A Receptor Antagonist, as Adjunctive Therapy to Levodopa in Parkinson's Disease: A Pooled Analysis of 8 Phase 2b/3 Trials. J Parkinsons Dis. 2021;11(4):1663-1675. doi: 10.3233/JPD-212672. PMID: 34486986; PMCID: PMC8609697.
29B. Takeda S, Misawa K, Yamamoto I, Watanabe K. Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis. Drug Metab Dispos. 2008 Sep;36(9):1917-21. doi: 10.1124/dmd.108.020909. Epub 2008 Jun 12. PMID: 18556441.
30B. Cohen B, Preuss CV. Celecoxib. [Updated 2024 Feb 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535359/
31B. Ghlichloo I, Gerriets V. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK547742/
32B. Jenny M, Santer E, Pirich E, Schennach H, Fuchs D. Delta9-tetrahydrocannabinol and cannabidiol modulate mitogen-induced tryptophan degradation and neopterin formation in peripheral blood mononuclear cells in vitro. J Neuroimmunol. 2009 Feb 15;207(1-2):75-82. doi: 10.1016/j.jneuroim.2008.12.004. Epub 2009 Jan 22. PMID: 19167098.
33B. Kałużna-Czaplińska J, Gątarek P, Chirumbolo S, Chartrand MS, Bjørklund G. How important is tryptophan in human health? Crit Rev Food Sci Nutr. 2019;59(1):72-88. doi: 10.1080/10408398.2017.1357534. Epub 2017 Sep 1. PMID: 28799778.
34B. Evans AT, Formukong E, Evans FJ. Activation of phospholipase A2 by cannabinoids. Lack of correlation with CNS effects. FEBS Lett. 1987 Jan 26;211(2):119-22. doi: 10.1016/0014-5793(87)81420-5. PMID: 3803591.
35B. Wang Q, Sun AY, Pardeike J, Müller RH, Simonyi A, Sun GY. Neuroprotective effects of a nanocrystal formulation of sPLA(2) inhibitor PX-18 in cerebral ischemia/reperfusion in gerbils. Brain Res. 2009 Aug 18;1285:188-95. doi: 10.1016/j.brainres.2009.06.022. Epub 2009 Jun 13. PMID: 19527696; PMCID: PMC2742555.
36B. Sun GY, Geng X, Teng T, Yang B, Appenteng MK, Greenlief CM, Lee JC. Dynamic Role of Phospholipases A2 in Health and Diseases in the Central Nervous System. Cells. 2021 Oct 30;10(11):2963. doi: 10.3390/cells10112963. PMID: 34831185; PMCID: PMC8616333.
37B. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 644019, Cannabidiol. Retrieved October 19, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Cannabidiol.
38B. Ryan D, Drysdale AJ, Lafourcade C, Pertwee RG, Platt B. Cannabidiol targets mitochondria to regulate intracellular Ca2+ levels. J Neurosci. 2009 Feb 18;29(7):2053-63. doi: 10.1523/JNEUROSCI.4212-08.2009. PMID: 19228959; PMCID: PMC6666323.
39B. Qin N, Neeper MP, Liu Y, Hutchinson TL, Lubin ML, Flores CM. TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons. J Neurosci. 2008 Jun 11;28(24):6231-8. doi: 10.1523/JNEUROSCI.0504-08.2008. PMID: 18550765; PMCID: PMC6670541.
40B. Russell FA, King R, Smillie SJ, Kodji X, Brain SD. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev. 2014 Oct;94(4):1099-142. doi: 10.1152/physrev.00034.2013. PMID: 25287861; PMCID: PMC4187032.
41B. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 16078, Dronabinol. Retrieved October 20, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Dronabinol.
42B. Kumar AR, Patilea-Vrana GI, Anoshchenko O, Unadkat JD. Characterizing and Quantifying Extrahepatic Metabolism of (-)-Δ9-Tetrahydrocannabinol (THC) and Its Psychoactive Metabolite, (±)-11-Hydroxy-Δ9-THC (11-OH-THC). Drug Metab Dispos. 2022 Jun;50(6):734-740. doi: 10.1124/dmd.122.000868. Epub 2022 Apr 3. PMID: 35370140; PMCID: PMC9199115.
43B. Indigent Defense Services. (2023). Marijuana impairment FAQ. New York Cannabis Control Board. https://cannabis.ny.gov/system/files/documents/2023/05/5.4.23_guide-to-cannabis-consumption.pdf
44B. Solowij N. Do cognitive impairments recover following cessation of cannabis use? Life Sci. 1995;56(23-24):2119-26. doi: 10.1016/0024-3205(95)00197-e. PMID: 7776840.
45B. Pope HG Jr, Gruber AJ, Hudson JI, Huestis MA, Yurgelun-Todd D. Neuropsychological performance in long-term cannabis users. Arch Gen Psychiatry. 2001 Oct;58(10):909-15. doi: 10.1001/archpsyc.58.10.909. PMID: 11576028.
46B. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 638026, DELTA8-Tetrahydrocannabinol. Retrieved October 21, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/638026.
47B. U.S. Food and Drug Administration. (n.d.). 5 things to know about Delta-8 Tetrahydrocannabinol – Delta-8 THC. Retrieved July 22, 2024 from https://www.fda.gov/consumers/consumer-updates/5-things-know-about-delta-8-tetrahydrocannabinol-delta-8-thc
48B. Palomares B, Ruiz-Pino F, Garrido-Rodriguez M, Eugenia Prados M, Sánchez-Garrido MA, Velasco I, Vazquez MJ, Nadal X, Ferreiro-Vera C, Morrugares R, Appendino G, Calzado MA, Tena-Sempere M, Muñoz E. Tetrahydrocannabinolic acid A (THCA-A) reduces adiposity and prevents metabolic disease caused by diet-induced obesity. Biochem Pharmacol. 2020 Jan;171:113693. doi: 10.1016/j.bcp.2019.113693. Epub 2019 Nov 9. PMID: 31706843.
49B. Nadal X, Del Río C, Casano S, Palomares B, Ferreiro-Vera C, Navarrete C, Sánchez-Carnerero C, Cantarero I, Bellido ML, Meyer S, Morello G, Appendino G, Muñoz E. Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity. Br J Pharmacol. 2017 Dec;174(23):4263-4276. doi: 10.1111/bph.14019. Epub 2017 Nov 2. PMID: 28853159; PMCID: PMC5731255.
50B. Kim J, Choi P, Park YT, Kim T, Ham J, Kim JC. The Cannabinoids, CBDA and THCA, Rescue Memory Deficits and Reduce Amyloid-Beta and Tau Pathology in an Alzheimer's Disease-like Mouse Model. Int J Mol Sci. 2023 Apr 6;24(7):6827. doi: 10.3390/ijms24076827. PMID: 37047798; PMCID: PMC10095267.
51B. Ben-Cnaan E, Permyakova A, Azar S, Hirsch S, Baraghithy S, Hinden L, Tam J. The Metabolic Efficacy of a Cannabidiolic Acid (CBDA) Derivative in Treating Diet- and Genetic-Induced Obesity. Int J Mol Sci. 2022 May 17;23(10):5610. doi: 10.3390/ijms23105610. PMID: 35628417; PMCID: PMC9144717.
52B. Ghovanloo MR, Effraim PR, Tyagi S, Zhao P, Dib-Hajj SD, Waxman SG. Functionally-selective inhibition of threshold sodium currents and excitability in dorsal root ganglion neurons by cannabinol. Commun Biol. 2024 Jan 23;7(1):120. doi: 10.1038/s42003-024-05781-x. PMID: 38263462; PMCID: PMC10805714.
53B. Lavender I, McCartney D, Marshall N, Suraev A, Irwin C, D'Rozario AL, Gordon CJ, Saini B, Grunstein RR, Yee B, McGregor I, Hoyos CM. Cannabinol (CBN; 30 and 300 mg) effects on sleep and next-day function in insomnia disorder ('CUPID' study): protocol for a randomised, double-blind, placebo-controlled, cross-over, three-arm, proof-of-concept trial. BMJ Open. 2023 Aug 23;13(8):e071148. doi: 10.1136/bmjopen-2022-071148. PMID: 37612115; PMCID: PMC10450062.
54B. Gojani EG, Wang B, Li DP, Kovalchuk O, Kovalchuk I. Anti-Inflammatory Effects of Minor Cannabinoids CBC, THCV, and CBN in Human Macrophages. Molecules. 2023 Sep 7;28(18):6487. doi: 10.3390/molecules28186487. PMID: 37764262; PMCID: PMC10534668.
55B. Kollipara R, Langille E, Tobin C, French CR. Phytocannabinoids Reduce Seizures in Larval Zebrafish and Affect Endocannabinoid Gene Expression. Biomolecules. 2023 Sep 16;13(9):1398. doi: 10.3390/biom13091398. PMID: 37759798; PMCID: PMC10526363.
56B. Marsh DT, Sugiyama A, Imai Y, Kato R, Smid SD. The structurally diverse phytocannabinoids cannabichromene, cannabigerol and cannabinol significantly inhibit amyloid β-evoked neurotoxicity and changes in cell morphology in PC12 cells. Basic Clin Pharmacol Toxicol. 2024 Mar;134(3):293-309. doi: 10.1111/bcpt.13943. Epub 2023 Sep 25. PMID: 37697481.
57B. Abioye, A., Ayodele, O., Marinkovic, A. et al. Δ9-Tetrahydrocannabivarin (THCV): a commentary on potential therapeutic benefit for the management of obesity and diabetes. J Cannabis Res 2, 6 (2020). https://doi.org/10.1186/s42238-020-0016-7
58B. Chaigne S, Barbeau S, Ducret T, Guinamard R, Benoist D. Pathophysiological Roles of the TRPV4 Channel in the Heart. Cells. 2023 Jun 17;12(12):1654. doi: 10.3390/cells12121654. PMID: 37371124; PMCID: PMC10296986.
59B. Baratchi S, Keov P, Darby WG, Lai A, Khoshmanesh K, Thurgood P, Vahidi P, Ejendal K, McIntyre P. The TRPV4 Agonist GSK1016790A Regulates the Membrane Expression of TRPV4 Channels. Front Pharmacol. 2019 Jan 23;10:6. doi: 10.3389/fphar.2019.00006. PMID: 30728775; PMCID: PMC6351496.
60B. Kumar H, Lim CS, Choi H, Joshi HP, Kim KT, Kim YH, Park CK, Kim HM, Han IB. Elevated TRPV4 Levels Contribute to Endothelial Damage and Scarring in Experimental Spinal Cord Injury. J Neurosci. 2020 Feb 26;40(9):1943-1955. doi: 10.1523/JNEUROSCI.2035-19.2020. Epub 2020 Jan 23. PMID: 31974206; PMCID: PMC7046444.
61B. Kumar A, Majhi RK, Swain N, Giri SC, Kar S, Samanta L, Goswami C. TRPV4 is endogenously expressed in vertebrate spermatozoa and regulates intracellular calcium in human sperm. Biochem Biophys Res Commun. 2016 May 13;473(4):781-788. doi: 10.1016/j.bbrc.2016.03.071. Epub 2016 Mar 19. PMID: 27003252.
62B. Dunn KM, Hill-Eubanks DC, Liedtke WB, Nelson MT. TRPV4 channels stimulate Ca2+-induced Ca2+ release in astrocytic endfeet and amplify neurovascular coupling responses. Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):6157-62. doi: 10.1073/pnas.1216514110. Epub 2013 Mar 25. PMID: 23530219; PMCID: PMC3625327.
63B. Scheraga RG, Southern BD, Grove LM, Olman MA. The Role of TRPV4 in Regulating Innate Immune Cell Function in Lung Inflammation. Front Immunol. 2020 Jun 26;11:1211. doi: 10.3389/fimmu.2020.01211. PMID: 32676078; PMCID: PMC7333351.
64B. Bonvini SJ, Birrell MA, Grace MS, Maher SA, Adcock JJ, Wortley MA, Dubuis E, Ching YM, Ford AP, Shala F, Miralpeix M, Tarrason G, Smith JA, Belvisi MG. Transient receptor potential cation channel, subfamily V, member 4 and airway sensory afferent activation: Role of adenosine triphosphate. J Allergy Clin Immunol. 2016 Jul;138(1):249-261.e12. doi: 10.1016/j.jaci.2015.10.044. Epub 2016 Jan 11. PMID: 26792207; PMCID: PMC4929136.
65B. Hayakawa S, Tanaka T, Ogawa R, Ito S, Ueno S, Koyama H, Tomotaka O, Sagawa H, Tanaka T, Iwakura H, Takahashi H, Matsuo Y, Mitsui A, Kimura M, Takahashi S, Takiguchi S. Potential Role of TRPV4 in Stretch-Induced Ghrelin Secretion and Obesity. Int J Endocrinol. 2022 Nov 8;2022:7241275. doi: 10.1155/2022/7241275. PMID: 36397882; PMCID: PMC9666045.
66B. Koch M. Cannabinoid Receptor Signaling in Central Regulation of Feeding Behavior: A Mini-Review. Front Neurosci. 2017 May 24;11:293. doi: 10.3389/fnins.2017.00293. PMID: 28596721; PMCID: PMC5442223.
67B. Miyoshi T, Nagai T, Inoue K, Ikeda S, Yamaguchi O. Adenosine triphosphate-induced life-threatening arrhythmia. J Cardiol Cases. 2023 Jun 1;28(4):150-152. doi: 10.1016/j.jccase.2023.05.011. PMID: 37818434; PMCID: PMC10562110.
68B. Janssen DA, Hoenderop JG, Heesakkers JP, Schalken JA. TRPV4 mediates afferent pathways in the urinary bladder. A spinal c-fos study showing TRPV1 related adaptations in the TRPV4 knockout mouse. Pflugers Arch. 2016 Oct;468(10):1741-9. doi: 10.1007/s00424-016-1859-9. Epub 2016 Aug 5. PMID: 27491796; PMCID: PMC5026715.
69B. Gojani EG, Wang B, Li DP, Kovalchuk O, Kovalchuk I. Anti-Inflammatory Effects of Minor Cannabinoids CBC, THCV, and CBN in Human Macrophages. Molecules. 2023 Sep 7;28(18):6487. doi: 10.3390/molecules28186487. PMID: 37764262; PMCID: PMC10534668.
70B. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 5315659, Cannabigerol. Retrieved October 25, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Cannabigerol.
71B. Rob’s Plants. (2017). Helichrysum umbraculigerum. Retrieved October 7, 2024, from http://www.robsplants.com/plantlinks/HelichrysumUmbraculigerum.htm​:contentReference[oaicite:0]{index=0}
72B. SANBI. (n.d.). Helichrysum umbraculigerum - PlantZAfrica.com. Retrieved October 7, 2024, from https://pza.sanbi.org/helichrysum-umbraculigerum​:contentReference[oaicite:1]{index=1}
73B. Cuttler C, Stueber A, Cooper ZD, Russo E. Acute effects of cannabigerol on anxiety, stress, and mood: a double-blind, placebo-controlled, crossover, field trial. Sci Rep. 2024 Jul 13;14(1):16163. doi: 10.1038/s41598-024-66879-0. PMID: 39003387; PMCID: PMC11246434.
74B. Sztolsztener K, Harasim-Symbor E, Chabowski A, Konstantynowicz-Nowicka K. Cannabigerol as an anti-inflammatory agent altering the level of arachidonic acid derivatives in the colon tissue of rats subjected to a high-fat high-sucrose diet. Biomed Pharmacother. 2024 Sep;178:117286. doi: 10.1016/j.biopha.2024.117286. Epub 2024 Aug 11. PMID: 39128189.
75B. Maiocchi A, Fumagalli M, Vismara M, Blanco A, Ciriello U, Paladino G, Piazza S, Martinelli G, Fasano V, Dell'Agli M, Passarella D. Minor Cannabinoids as Inhibitors of Skin Inflammation: Chemical Synthesis and Biological Evaluation. J Nat Prod. 2024 Jul 26;87(7):1725-1734. doi: 10.1021/acs.jnatprod.4c00212. Epub 2024 Jun 18. PMID: 38889235.
76B. Classen N, Pitakbut T, Schöfbänker M, Kühn J, Hrincius ER, Ludwig S, Hensel A, Kayser O. Cannabigerol and Cannabicyclol Block SARS-CoV-2 Cell Fusion. Planta Med. 2024 Aug;90(9):717-725. doi: 10.1055/a-2320-8822. Epub 2024 Jun 17. PMID: 38885660.
77B. GVB Biopharma. ND. What is Cannabicyclol (CBL)? Retrieved 10/25/2024 from https://www.gvbbiopharma.com/what-is-cannabicyclol-cbl/
78B. Zeppa L, Aguzzi C, Morelli MB, Marinelli O, Giangrossi M, Luongo M, Amantini C, Santoni G, Nabissi M. Cannabigerol Induces Autophagic Cell Death by Inhibiting EGFR-RAS Pathways in Human Pancreatic Ductal Adenocarcinoma Cell Lines. Int J Mol Sci. 2024 Feb 7;25(4):2001. doi: 10.3390/ijms25042001. PMID: 38396679; PMCID: PMC10888274.
79B. Alves P, Amaral C, Gonçalves MS, Teixeira N, Correia-da-Silva G. Cannabidivarin and cannabigerol induce unfolded protein response and angiogenesis dysregulation in placental trophoblast HTR-8/SVneo cells. Arch Toxicol. 2024 Sep;98(9):2971-2984. doi: 10.1007/s00204-024-03781-8. Epub 2024 May 15. PMID: 38748041; PMCID: PMC11324689.
80B. Santoni G, Farfariello V, Liberati S, Morelli MB, Nabissi M, Santoni M, Amantini C. The role of transient receptor potential vanilloid type-2 ion channels in innate and adaptive immune responses. Front Immunol. 2013 Feb 14;4:34. doi: 10.3389/fimmu.2013.00034. PMID: 23420671; PMCID: PMC3572502.
81B. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 11601669, Cannabidivarin. Retrieved November 9, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Cannabidivarin.
82B. Voicu V, Brehar FM, Toader C, Covache-Busuioc RA, Corlatescu AD, Bordeianu A, Costin HP, Bratu BG, Glavan LA, Ciurea AV. Cannabinoids in Medicine: A Multifaceted Exploration of Types, Therapeutic Applications, and Emerging Opportunities in Neurodegenerative Diseases and Cancer Therapy. Biomolecules. 2023 Sep 14;13(9):1388. doi: 10.3390/biom13091388. PMID: 37759788; PMCID: PMC10526757.
83B. Zamberletti E, Gabaglio M, Woolley-Roberts M, Bingham S, Rubino T, Parolaro D. Cannabidivarin Treatment Ameliorates Autism-Like Behaviors and Restores Hippocampal Endocannabinoid System and Glia Alterations Induced by Prenatal Valproic Acid Exposure in Rats. Front Cell Neurosci. 2019 Aug 9;13:367. doi: 10.3389/fncel.2019.00367. PMID: 31447649; PMCID: PMC6696797.
84B. Iannotti FA, Pagano E, Moriello AS, Alvino FG, Sorrentino NC, D'Orsi L, Gazzerro E, Capasso R, De Leonibus E, De Petrocellis L, Di Marzo V. Effects of non-euphoric plant cannabinoids on muscle quality and performance of dystrophic mdx mice. Br J Pharmacol. 2019 May;176(10):1568-1584. doi: 10.1111/bph.14460. Epub 2018 Sep 9. PMID: 30074247; PMCID: PMC6487563.
85B. Ashenhurst, James. Stereochemistry and Chirality. Retrieved May 1, 2024 from https://www.masterorganicchemistry.com/2017/01/17/determining-rs-2-the-method-of-dots/
86B. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 440917, Limonene, (+)-. Retrieved May 1, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/4R_-1-methyl-4-prop-1-en-2-ylcyclohexene.
87B. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 439250, Limonene, (-)-. Retrieved May 1, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/4S_-1-methyl-4-prop-1-en-2-ylcyclohexene.
88B. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 22311, Limonene, (+/-)-. Retrieved May 1, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Limonene.
89B. Park HM, Lee JH, Yaoyao J, Jun HJ, Lee SJ. Limonene, a natural cyclic terpene, is an agonistic ligand for adenosine A(2A) receptors. Biochem Biophys Res Commun. 2011 Jan 7;404(1):345-8. doi: 10.1016/j.bbrc.2010.11.121. Epub 2010 Dec 4. PMID: 21134357.
90B. Song Y, Seo S, Lamichhane S, Seo J, Hong JT, Cha HJ, Yun J. Limonene has anti-anxiety activity via adenosine A2A receptor-mediated regulation of dopaminergic and GABAergic neuronal function in the striatum. Phytomedicine. 2021 Mar;83:153474. doi: 10.1016/j.phymed.2021.153474. Epub 2021 Jan 21. PMID: 33548867.
91B. Mori A, Chen JF, Uchida S, Durlach C, King SM, Jenner P. The Pharmacological Potential of Adenosine A2A Receptor Antagonists for Treating Parkinson's Disease. Molecules. 2022 Apr 6;27(7):2366. doi: 10.3390/molecules27072366. PMID: 35408767; PMCID: PMC9000505.
92B. Raja K, Ramrakhia S, Dev K, Shahid W, Sohail H, Memon MK, Memon S. The Risk Factors for the Wearing-Off Phenomenon in Parkinson's Disease. Cureus. 2020 Sep 30;12(9):e10729. doi: 10.7759/cureus.10729. PMID: 33145134; PMCID: PMC7599057.
93B. Choi J, Horner KA. Dopamine Agonists. [Updated 2023 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551686/
94B. Rains CP, Bryson HM, Fitton A. Cabergoline. A review of its pharmacological properties and therapeutic potential in the treatment of hyperprolactinaemia and inhibition of lactation. Drugs. 1995 Feb;49(2):255-79. doi: 10.2165/00003495-199549020-00009. PMID: 7729332.
95B. Ozery M, Wadhwa R. Bromocriptine. [Updated 2022 Nov 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK555948/
96B. Gandhi KR, Saadabadi A. Levodopa (L-Dopa) [Updated 2023 Apr 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482140/
97B. Jia SS, Xi GP, Zhang M, Chen YB, Lei B, Dong XS, Yang YM. Induction of apoptosis by D-limonene is mediated by inactivation of Akt in LS174T human colon cancer cells. Oncol Rep. 2013 Jan;29(1):349-54. doi: 10.3892/or.2012.2093. Epub 2012 Oct 19. PMID: 23117412.
98B. Porter AG, Jänicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999 Feb;6(2):99-104. doi: 10.1038/sj.cdd.4400476. PMID: 10200555.
99B. Avrutsky MI, Troy CM. Caspase-9: A Multimodal Therapeutic Target With Diverse Cellular Expression in Human Disease. Front Pharmacol. 2021 Jul 9;12:701301. doi: 10.3389/fphar.2021.701301. PMID: 34305609; PMCID: PMC8299054.
1C. Li P, Zhou L, Zhao T, Liu X, Zhang P, Liu Y, Zheng X, Li Q. Caspase-9: structure, mechanisms and clinical application. Oncotarget. 2017 Apr 4;8(14):23996-24008. doi: 10.18632/oncotarget.15098. PMID: 28177918; PMCID: PMC5410359.
2C. He Y, Sun MM, Zhang GG, Yang J, Chen KS, Xu WW, Li B. Targeting PI3K/Akt signal transduction for cancer therapy. Signal Transduct Target Ther. 2021 Dec 16;6(1):425. doi: 10.1038/s41392-021-00828-5. PMID: 34916492; PMCID: PMC8677728.
3C. Sarker D, Ang JE, Baird R, Kristeleit R, Shah K, Moreno V, Clarke PA, Raynaud FI, Levy G, Ware JA, Mazina K, Lin R, Wu J, Fredrickson J, Spoerke JM, Lackner MR, Yan Y, Friedman LS, Kaye SB, Derynck MK, Workman P, de Bono JS. First-in-human phase I study of pictilisib (GDC-0941), a potent pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, in patients with advanced solid tumors. Clin Cancer Res. 2015 Jan 1;21(1):77-86. doi: 10.1158/1078-0432.CCR-14-0947. Epub 2014 Nov 4. PMID: 25370471; PMCID: PMC4287394.
4C. Bendell JC, Rodon J, Burris HA, de Jonge M, Verweij J, Birle D, Demanse D, De Buck SS, Ru QC, Peters M, Goldbrunner M, Baselga J. Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2012 Jan 20;30(3):282-90. doi: 10.1200/JCO.2011.36.1360. Epub 2011 Dec 12. PMID: 22162589.
5C. Miyazawa M, Yamafuji C. Inhibition of acetylcholinesterase activity by bicyclic monoterpenoids. J Agric Food Chem. 2005 Mar 9;53(5):1765-8. doi: 10.1021/jf040019b. PMID: 15740071.
6C. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 6654, alpha-PINENE. Retrieved November 17, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/alpha-PINENE.
7C. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 440968, (-)-alpha-Pinene. Retrieved November 17, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/1S_-_-_-alpha-Pinene.
8C. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 82227, (+)-alpha-Pinene. Retrieved November 17, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/1R_-_-alpha-Pinene.
9C. Perry NS, Houghton PJ, Theobald A, Jenner P, Perry EK. In-vitro inhibition of human erythrocyte acetylcholinesterase by salvia lavandulaefolia essential oil and constituent terpenes. J Pharm Pharmacol. 2000 Jul;52(7):895-902. doi: 10.1211/0022357001774598. Erratum in: J Pharm Pharmacol 2000 Dec;52(12):203. PMID: 10933142.
10C. Singh R, Sadiq NM. Cholinesterase Inhibitors. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK544336/
11C. Colović MB, Krstić DZ, Lazarević-Pašti TD, Bondžić AM, Vasić VM. Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol. 2013 May;11(3):315-35. doi: 10.2174/1570159X11311030006. PMID: 24179466; PMCID: PMC3648782.
12C. Khan-Mohammadi-Khorrami MK, Asle-Rousta M, Rahnema M, Amini R. Neuroprotective effect of alpha-pinene is mediated by suppression of the TNF-α/NF-κB pathway in Alzheimer's disease rat model. J Biochem Mol Toxicol. 2022 May;36(5):e23006. doi: 10.1002/jbt.23006. Epub 2022 Feb 17. PMID: 35174932.
13C. Gaweł S, Wardas M, Niedworok E, Wardas P. Dialdehyd malonowy (MDA) jako wskaźnik procesów peroksydacji lipidów w organizmie [Malondialdehyde (MDA) as a lipid peroxidation marker]. Wiad Lek. 2004;57(9-10):453-5. Polish. PMID: 15765761.
14C. Picón-Pagès P, Garcia-Buendia J, Muñoz FJ. Functions and dysfunctions of nitric oxide in brain. Biochim Biophys Acta Mol Basis Dis. 2019 Aug 1;1865(8):1949-1967. doi: 10.1016/j.bbadis.2018.11.007. Epub 2018 Nov 27. PMID: 30500433.
15C. Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL. Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem. 2009 Mar;390(3):191-214. doi: 10.1515/BC.2009.033. PMID: 19166318; PMCID: PMC2756154.
16C. Nandi A, Yan LJ, Jana CK, Das N. Role of Catalase in Oxidative Stress- and Age-Associated Degenerative Diseases. Oxid Med Cell Longev. 2019 Nov 11;2019:9613090. doi: 10.1155/2019/9613090. PMID: 31827713; PMCID: PMC6885225.
17C. Góth L, Eaton JW. Hereditary catalase deficiencies and increased risk of diabetes. Lancet. 2000 Nov 25;356(9244):1820-1. doi: 10.1016/S0140-6736(00)03238-4. PMID: 11117918.
18C. Habib LK, Lee MT, Yang J. Inhibitors of catalase-amyloid interactions protect cells from beta-amyloid-induced oxidative stress and toxicity. J Biol Chem. 2010 Dec 10;285(50):38933-43. doi: 10.1074/jbc.M110.132860. Epub 2010 Oct 5. PMID: 20923778; PMCID: PMC2998107.
19C. National Library of Medicine. CHRNA7 cholinergic receptor nicotinic alpha 7 subunit [ Homo sapiens (human) ]. Retrieved on May 3, 2024 from https://www.ncbi.nlm.nih.gov/gene/1139
20C. Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li JH, Wang H, Yang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJ. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature. 2003 Jan 23;421(6921):384-8. doi: 10.1038/nature01339. Epub 2002 Dec 22. PMID: 12508119.
21C. Bathina S, Das UN. Brain-derived neurotrophic factor and its clinical implications. Arch Med Sci. 2015 Dec 10;11(6):1164-78. doi: 10.5114/aoms.2015.56342. Epub 2015 Dec 11. PMID: 26788077; PMCID: PMC4697050.
22C. Koo JW, Russo SJ, Ferguson D, Nestler EJ, Duman RS. Nuclear factor-kappaB is a critical mediator of stress-impaired neurogenesis and depressive behavior. Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2669-74. doi: 10.1073/pnas.0910658107. Epub 2010 Jan 26. PMID: 20133768; PMCID: PMC2823860.
23C. Golan H, Levav T, Mendelsohn A, Huleihel M. Involvement of tumor necrosis factor alpha in hippocampal development and function. Cereb Cortex. 2004 Jan;14(1):97-105. doi: 10.1093/cercor/bhg108. PMID: 14654461.
24C. Aloe L, Rocco ML, Balzamino BO, Micera A. Nerve Growth Factor: A Focus on Neuroscience and Therapy. Curr Neuropharmacol. 2015;13(3):294-303. doi: 10.2174/1570159x13666150403231920. PMID: 26411962; PMCID: PMC4812798.
25C. Ji J, Maren S. Differential roles for hippocampal areas CA1 and CA3 in the contextual encoding and retrieval of extinguished fear. Learn Mem. 2008 Apr 3;15(4):244-51. doi: 10.1101/lm.794808. PMID: 18391185; PMCID: PMC2327266.
26C. Varsity Tutors. (n.d.). Biological and cognitive factors. Varsity Tutors. Retrieved 5/23/2024, from https://www.varsitytutors.com/ap_psychology-help/biological-and-cognitive-factors#:~:text=Context%2Ddependent%20memory%20is%20a,where%20you%20learned%20that%20information!
27C. Veerasammy S, Van Steenwinckel J, Le Charpentier T, Seo JH, Fleiss B, Gressens P, Levison SW. Perinatal IL-1β-induced inflammation suppresses Tbr2+ intermediate progenitor cell proliferation in the developing hippocampus accompanied by long-term behavioral deficits. Brain Behav Immun Health. 2020 Jul 17;7:100106. doi: 10.1016/j.bbih.2020.100106. PMID: 34589867; PMCID: PMC8474668.
28C. Marsland AL, Gianaros PJ, Abramowitch SM, Manuck SB, Hariri AR. Interleukin-6 covaries inversely with hippocampal grey matter volume in middle-aged adults. Biol Psychiatry. 2008 Sep 15;64(6):484-90. doi: 10.1016/j.biopsych.2008.04.016. Epub 2008 Jun 2. PMID: 18514163; PMCID: PMC2562462.
29C. Gruol DL. IL-6 regulation of synaptic function in the CNS. Neuropharmacology. 2015 Sep;96(Pt A):42-54. doi: 10.1016/j.neuropharm.2014.10.023. Epub 2014 Nov 22. PMID: 25445486; PMCID: PMC4446251.
30C. Gao C, Gill MB, Tronson NC, Guedea AL, Guzmán YF, Huh KH, Corcoran KA, Swanson GT, Radulovic J. Hippocampal NMDA receptor subunits differentially regulate fear memory formation and neuronal signal propagation. Hippocampus. 2010 Sep;20(9):1072-82. doi: 10.1002/hipo.20705. PMID: 19806658; PMCID: PMC2891656.
31C. Medina JH, Viola H. ERK1/2: A Key Cellular Component for the Formation, Retrieval, Reconsolidation and Persistence of Memory. Front Mol Neurosci. 2018 Oct 5;11:361. doi: 10.3389/fnmol.2018.00361. PMID: 30344477; PMCID: PMC6182090.
32C. Aida T, Ito Y, Takahashi YK, Tanaka K. Overstimulation of NMDA receptors impairs early brain development in vivo. PLoS One. 2012;7(5):e36853. doi: 10.1371/journal.pone.0036853. Epub 2012 May 11. PMID: 22606296; PMCID: PMC3350466.
33C. Blanke ML, VanDongen AMJ. Activation Mechanisms of the NMDA Receptor. In: Van Dongen AM, editor. Biology of the NMDA Receptor. Boca Raton (FL): CRC Press/Taylor & Francis; 2009. Chapter 13. Available from: https://www.ncbi.nlm.nih.gov/books/NBK5274/
34C. Moss DE. Is Combining an Anticholinergic with a Cholinesterase Inhibitor a Good Strategy for High-Level CNS Cholinesterase Inhibition? J Alzheimers Dis. 2019;71(4):1099-1103. doi: 10.3233/JAD-190626. PMID: 31476160; PMCID: PMC6839449.
35C. Ghossein N, Kang M, Lakhkar AD. Anticholinergic Medications. [Updated 2023 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK555893/
36C. GoodRx. (n.d.). Donepezil interactions. Retrieved 9/17/2024, from https://www.goodrx.com/donepezil/interactions
37C. Gust C, Pugliese N, Stern G. Suspected donepezil toxicity: A case report. Clin Case Rep. 2020 Sep 3;8(12):2818-2823. doi: 10.1002/ccr3.3245. PMID: 33363829; PMCID: PMC7752397.
38C. Adeyinka A, Kondamudi NP. Cholinergic Crisis. 2023 Aug 12. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 29494040.
39C. Vogel SM, Mican LM, Smith TL. Donepezil-induced QTc prolongation: A case report. Ment Health Clin. 2019 May 10;9(3):128-132. doi: 10.9740/mhc.2019.05.128. PMID: 31123660; PMCID: PMC6513057.
40C. Farzam K, Tivakaran VS. QT Prolonging Drugs. [Updated 2023 Jul 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534864/
41C. Kumar A, Gupta V, Sharma S. Donepezil. [Updated 2023 Aug 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513257/
42C. Ferreira-Vieira TH, Guimaraes IM, Silva FR, Ribeiro FM. Alzheimer’s disease: Targeting the Cholinergic System. Curr Neuropharmacol. 2016;14(1):101-15. doi:10.2174/1570159x13666150716165726. PMID: 26813123; PMCID: PMC4787279.
43C. Migirov A, Datta AR. Physiology, Anticholinergic Reaction. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK546589/
44C. Sheppard D, Epstein J, Holtzman MJ, Nadel JA, Boushey HA. Dose-dependent inhibition of cold air-induced bronchoconstriction by atropine. J Appl Physiol Respir Environ Exerc Physiol. 1982 Jul;53(1):169-74. doi: 10.1152/jappl.1982.53.1.169. PMID: 6749773.
45C. Masurkar PP, Chatterjee S, Sherer JT, Chen H, Johnson ML, Aparasu RR. Risk of overactive bladder associated with cholinesterase inhibitors in dementia. J Am Geriatr Soc. 2022 Mar;70(3):820-830. doi: 10.1111/jgs.17579. Epub 2021 Dec 2. PMID: 34854475.
46C. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 14896, beta-Pinene. Retrieved May 30, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/beta-Pinene.
47C. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 10290825, (+)-beta-Pinene. Retrieved May 30, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/10290825.
48C. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 440967, (-)-beta-Pinene. Retrieved May 30, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/nopinene.
49C. Salehi B, Upadhyay S, Erdogan Orhan I, Kumar Jugran A, L D Jayaweera S, A Dias D, Sharopov F, Taheri Y, Martins N, Baghalpour N, Cho WC, Sharifi-Rad J. Therapeutic Potential of α- and β-Pinene: A Miracle Gift of Nature. Biomolecules. 2019 Nov 14;9(11):738. doi: 10.3390/biom9110738. PMID: 31739596; PMCID: PMC6920849.
50C. Zhou JY, Tang FD, Mao GG, Bian RL. Effect of alpha-pinene on nuclear translocation of NF-kappa B in THP-1 cells. Acta Pharmacol Sin. 2004 Apr;25(4):480-4. PMID: 15066217.
51C. Alma MH, Nitz S, Kollmannsberger H, Digrak M, Efe FT, Yilmaz N. Chemical composition and antimicrobial activity of the essential oils from the gum of Turkish pistachio (Pistacia vera L.). J Agric Food Chem. 2004 Jun 16;52(12):3911-4. doi: 10.1021/jf040014e. PMID: 15186116.
52C. Miyazawa M, Yamafuji C. Inhibition of acetylcholinesterase activity by bicyclic monoterpenoids. J Agric Food Chem. 2005 Mar 9;53(5):1765-8. doi: 10.1021/jf040019b. PMID: 15740071.
53C. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 26049, 3-Carene. Retrieved November 20, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/3-Carene.
54C. Jeong JG, Kim YS, Min YK, Kim SH. Low concentration of 3-carene stimulates the differentiation of mouse osteoblastic MC3T3-E1 subclone 4 cells. Phytother Res. 2008 Jan;22(1):18-22. doi: 10.1002/ptr.2247. PMID: 17685387.
55C. Re L, Barocci S, Sonnino S, Mencarelli A, Vivani C, Paolucci G, Scarpantonio A, Rinaldi L, Mosca E. Linalool modifies the nicotinic receptor-ion channel kinetics at the mouse neuromuscular junction. Pharmacol Res. 2000 Aug;42(2):177-82. doi: 10.1006/phrs.2000.0671. PMID: 10887049.
56C. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 443158, Linalool, (-)-. Retrieved May 30, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/3R_-3_7-dimethylocta-1_6-dien-3-ol
58C. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 67179, Linalool, (+)-. Retrieved May 30, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/3S_-3_7-dimethylocta-1_6-dien-3-ol
59C. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 6549, Linalool, (+/-)-. Retrieved May 30, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Linalool
60C. Aelenei P, Rimbu CM, Guguianu E, Dimitriu G, Aprotosoaie AC, Brebu M, Horhogea CE, Miron A. Coriander essential oil and linalool - interactions with antibiotics against Gram-positive and Gram-negative bacteria. Lett Appl Microbiol. 2019 Feb;68(2):156-164. doi: 10.1111/lam.13100. Epub 2019 Jan 4. PMID: 30471142.
61C. Al-Khayri JM, Banadka A, Nandhini M, Nagella P, Al-Mssallem MQ, Alessa FM. Essential Oil from Coriandrum sativum: A review on Its Phytochemistry and Biological Activity. Molecules. 2023 Jan 10;28(2):696. doi: 10.3390/molecules28020696. PMID: 36677754; PMCID: PMC9864992.
62C. Li Y, Lv O, Zhou F, Li Q, Wu Z, Zheng Y. Linalool Inhibits LPS-Induced Inflammation in BV2 Microglia Cells by Activating Nrf2. Neurochem Res. 2015 Jul;40(7):1520-5. doi: 10.1007/s11064-015-1629-7. Epub 2015 Jun 4. PMID: 26040565.
63C. Del Prado-Audelo ML, Cortés H, Caballero-Florán IH, González-Torres M, Escutia-Guadarrama L, Bernal-Chávez SA, Giraldo-Gomez DM, Magaña JJ, Leyva-Gómez G. Therapeutic Applications of Terpenes on Inflammatory Diseases. Front Pharmacol. 2021 Aug 13;12:704197. doi: 10.3389/fphar.2021.704197. PMID: 34483907; PMCID: PMC8414653.
64C. Re L, Barocci S, Sonnino S, Mencarelli A, Vivani C, Paolucci G, Scarpantonio A, Rinaldi L, Mosca E. Linalool modifies the nicotinic receptor-ion channel kinetics at the mouse neuromuscular junction. Pharmacol Res. 2000 Aug;42(2):177-82. doi: 10.1006/phrs.2000.0671. PMID: 10887049.
65C. Kumar A, Gupta V, Sharma S. Donepezil. [Updated 2023 Aug 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513257/
66C. National Institute of Neurological Disorders and Stroke. Parkinson's Disease. Retreived 9/24/2024 from https://www.ninds.nih.gov/health-information/disorders/parkinsons-disease
67C. Dutra FL, Oliveira MM, Santos RS, Silva WS, Alviano DS, Vieira DP, Lopes AH. Effects of linalool and eugenol on the survival of Leishmania (L.) infantum chagasi within macrophages. Acta Trop. 2016 Dec;164:69-76. doi: 10.1016/j.actatropica.2016.08.026. Epub 2016 Aug 30. PMID: 27591136.
68C. Jansen C, Shimoda LMN, Kawakami JK, Ang L, Bacani AJ, Baker JD, Badowski C, Speck M, Stokes AJ, Small-Howard AL, Turner H. Myrcene and terpene regulation of TRPV1. Channels (Austin). 2019 Dec;13(1):344-366. doi: 10.1080/19336950.2019.1654347. PMID: 31446830; PMCID: PMC6768052.
69C. Rao VS, Menezes AM, Viana GS. Effect of myrcene on nociception in mice. J Pharm Pharmacol. 1990 Dec;42(12):877-8. doi: 10.1111/j.2042-7158.1990.tb07046.x. PMID: 1983154.
70C. Jordan BA, Gomes I, Rios C, Filipovska J, Devi LA. Functional interactions between mu opioid and alpha 2A-adrenergic receptors. Mol Pharmacol. 2003 Dec;64(6):1317-24. doi: 10.1124/mol.64.6.1317. PMID: 14645661.
71C. Eason MG, Jacinto MT, Liggett SB. Contribution of ligand structure to activation of alpha 2-adrenergic receptor subtype coupling to Gs. Mol Pharmacol. 1994 Apr;45(4):696-702. PMID: 7910371.
72C. Niemi G, Breivik H. Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose infusion of bupivacaine, fentanyl and adrenaline after major surgery. A randomised, double-blind, cross-over study with and without adrenaline. Acta Anaesthesiol Scand. 1998 Sep;42(8):897-909. doi: 10.1111/j.1399-6576.1998.tb05348.x. PMID: 9773133.
73C. De-Oliveira AC, Ribeiro-Pinto LF, Paumgartten JR. In vitro inhibition of CYP2B1 monooxygenase by beta-myrcene and other monoterpenoid compounds. Toxicol Lett. 1997 Jun 16;92(1):39-46. doi: 10.1016/s0378-4274(97)00034-9. PMID: 9242356.
74C. Lorenzetti BB, Souza GE, Sarti SJ, Santos Filho D, Ferreira SH. Myrcene mimics the peripheral analgesic activity of lemongrass tea. J Ethnopharmacol. 1991 Aug;34(1):43-8. doi: 10.1016/0378-8741(91)90187-i. PMID: 1753786.
75C. Samuelsson B, Morgenstern R, Jakobsson PJ. Membrane prostaglandin E synthase-1: a novel therapeutic target. Pharmacol Rev. 2007 Sep;59(3):207-24. doi: 10.1124/pr.59.3.1. PMID: 17878511.
76C. National Toxicology Program. NTP technical report on the toxicology and carcinogenesis studies of beta-myrcene (CAS No. 123-35-3) in F344/N rats and B6C3F1 mice (Gavage studies). Natl Toxicol Program Tech Rep Ser. 2010 Dec;(557):1-163. PMID: 21415873.
77C. do Vale TG, Furtado EC, Santos JG Jr, Viana GS. Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes from Lippia alba (Mill.) n.e. Brown. Phytomedicine. 2002 Dec;9(8):709-14. doi: 10.1078/094471102321621304. PMID: 12587690.
78C. da-Silva VA, de-Freitas JC, Mattos AP, Paiva-Gouvea W, Presgrave OA, Fingola FF, Menezes MA, Paumgartten FJ. Neurobehavioral study of the effect of beta-myrcene on rodents. Braz J Med Biol Res. 1991;24(8):827-31. PMID: 1797273.
79C. Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016 Mar;7(2):27-31. doi: 10.4103/0976-0105.177703. PMID: 27057123; PMCID: PMC4804402.
80C. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 5281515, Caryophyllene. Retrieved June 12, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Caryophyllene.
81C. Gertsch, J., Leonti, M., Raduner, S., Racz, I., Chen, J. Z., Xie, X. Q., Altmann, K. H., Karsak, M., & Zimmer, A. (2008). Beta-caryophyllene is a dietary cannabinoid. Proceedings of the National Academy of Sciences, 105(26), 9099–9104. https://doi.org/10.1073/pnas.0803601105
82C. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 20831623, (+)-beta-Caryophyllene. Retrieved June 12, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/be ta-Caryophyllene.
83C. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 5281522, Isocaryophyllene. Retrieved June 12, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Isocaryophyllene.
84C. Russo, Ethan. “Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects”. British Journal of Pharmacology. 29 December 2010
85C. Basile AC, Sertié JA, Freitas PC, Zanini AC. Anti-inflammatory activity of oleoresin from Brazilian Copaifera. J Ethnopharmacol. 1988 Jan;22(1):101-9. doi: 10.1016/0378-8741(88)90235-8. PMID: 3352280.
86C. Herrero-Jáuregui C, Casado MA, das Graças Bichara Zoghbi M, Célia Martins-da-Silva R. Chemical variability of Copaifera reticulata Ducke oleoresin. Chem Biodivers. 2011 Apr;8(4):674-85. doi: 10.1002/cbdv.201000258. PMID: 21480513.
87C. Legault J, Pichette A. Potentiating effect of beta-caryophyllene on anticancer activity of alpha-humulene, isocaryophyllene and paclitaxel.
88C. National Cancer institute. (n.d.) Paclitaxel. Retrieved 6/11/2024 from https://www.cancer.gov/about-cancer/treatment/drugs/paclitaxel
89C. Xi ZX, Peng XQ, Li X, Song R, Zhang HY, Liu QR, Yang HJ, Bi GH, Li J, Gardner EL. Brain cannabinoid CB₂ receptors modulate cocaine's actions in mice. Nat Neurosci. 2011 Jul 24;14(9):1160-6. doi: 10.1038/nn.2874. PMID: 21785434; PMCID: PMC3164946.
90C. Karsak M, Gaffal E, Date R, Wang-Eckhardt L, Rehnelt J, Petrosino S, Starowicz K, Steuder R, Schlicker E, Cravatt B, Mechoulam R, Buettner R, Werner S, Di Marzo V, Tüting T, Zimmer A. Attenuation of allergic contact dermatitis through the endocannabinoid system. Science. 2007 Jun 8;316(5830):1494-7. doi: 10.1126/science.1142265. PMID: 17556587.
91C. Li, L., Liu, X., Ge, W., Chen, C., Huang, Y., Jin, Z., Zhan, M., Duan, X., Liu, X., Kong, Y., Jiang, J., Li, X., Zeng, X., Li, F., Xu, S., Li, M., & Chen, H. (2022). CB2R deficiency exacerbates imiquimod-induced psoriasiform dermatitis and itch through the neuro-immune pathway. Pain Research Forum. Retrieved from https://www.iasp-pain.org/publications/pain-research-forum/papers-of-the-week/paper/190456-cb2r-deficiency-exacerbates-imiquimod-induced-psoriasiform-dermatitis-and-itch-through/
92C. Schlosburg JE, O'Neal ST, Conrad DH, Lichtman AH. CB1 receptors mediate rimonabant-induced pruritic responses in mice: investigation of locus of action. Psychopharmacology (Berl). 2011 Aug;216(3):323-31. doi: 10.1007/s00213-011-2224-5. Epub 2011 Feb 22. PMID: 21340468; PMCID: PMC3606913.
93C. Avila C, Massick S, Kaffenberger BH, Kwatra SG, Bechtel M. Cannabinoids for the treatment of chronic pruritus: A review. J Am Acad Dermatol. 2020 May;82(5):1205-1212. doi: 10.1016/j.jaad.2020.01.036. Epub 2020 Jan 25. PMID: 31987788.
94C. Campbell WE, Gammon DW, Smith P, Abrahams M, Purves TD. Composition and antimalarial activity in vitro of the essential oil of Tetradenia riparia. Planta Med. 1997 Jun;63(3):270-2. doi: 10.1055/s-2006-957672. PMID: 9225614.
95C. Rong Y, Liu F, Zhou H, Yu T, Qin Z, Cao Q, Liu L, Ma X, Qu L, Xu P, Liao X, Jiang Q, Zhang N, Xu X. Reprogramming of arachidonic acid metabolism using α-terpineol to alleviate asthma: insights from metabolomics. Food Funct. 2024 Apr 22;15(8):4292-4309. doi: 10.1039/d3fo04078j. PMID: 38526853.
96C. Jin JS, Chou JM, Tsai WC, Chen YC, Chen Y, Ong JR, Tsai YL. Effectively α-Terpineol Suppresses Glioblastoma Aggressive Behavior and Downregulates KDELC2 Expression. Phytomedicine. 2024 May;127:155471. doi: 10.1016/j.phymed.2024.155471. Epub 2024 Feb 23. PMID: 38452695.
97C. Bashir A, Mushtaq MN, Younis W, Anjum I. Fenchone, a monoterpene: Toxicity and diuretic profiling in rats. Front Pharmacol. 2023 Jan 26;14:1119360. doi: 10.3389/fphar.2023.1119360. PMID: 36778012; PMCID: PMC9909529.
98C. Belanger JT. Perillyl alcohol: applications in oncology. Altern Med Rev. 1998 Dec;3(6):448-57. PMID: 9855569.
99C. Tambe Y, Tsujiuchi H, Honda G, Ikeshiro Y, Tanaka S. Gastric cytoprotection of the non-steroidal anti-inflammatory sesquiterpene, beta-caryophyllene. Planta Med. 1996 Oct;62(5):469-70. doi: 10.1055/s-2006-957942. PMID: 9005452.
1D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 1742210, beta-CARYOPHYLLENE OXIDE. Retrieved June 20, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/ beta-CARYOPHYLLENE-OXIDE.
2D. Chavan MJ, Wakte PS, Shinde DB. Analgesic and anti-inflammatory activity of Caryophyllene oxide from Annona squamosa L. bark. Phytomedicine. 2010 Feb;17(2):149-51. doi: 10.1016/j.phymed.2009.05.016. Epub 2009 Jul 2. PMID: 19576741.
3D. Jun, N. J. , Mosaddik A., Moon J. Y., Jang K.‐C., Lee D.‐S., Ahn K. S., et al. 2011. Cytotoxic activity of β-caryophyllene oxide isolated from Jeju Guava (Psidium cattleianum Sabine) leaf. Rec. Nat. Prod. 5:242–246.
4D. Shahwar D, Ullah S, Khan MA, Ahmad N, Saeed A, Ullah S. Anticancer activity of Cinnamon tamala leaf constituents towards human ovarian cancer cells. Pak J Pharm Sci. 2015 May;28(3):969-72. PMID: 26004731.
5D. Yang D, Michel L, Chaumont JP, Millet-Clerc J. Use of caryophyllene oxide as an antifungal agent in an in vitro experimental model of onychomycosis. Mycopathologia. 1999 Nov;148(2):79-82. doi: 10.1023/a:1007178924408. PMID: 11189747.
6D. Dalavaye N, Nicholas M, Pillai M, Erridge S, Sodergren MH. The Clinical Translation of α-humulene - A Scoping Review. Planta Med. 2024 Aug;90(9):664-674. doi: 10.1055/a-2307-8183. Epub 2024 Apr 16. PMID: 38626911; PMCID: PMC11254484.
7D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 5281520, Humulene. Retrieved November 22, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Humulene.
8D. Chen H, Yuan J, Hao J, Wen Y, Lv Y, Chen L, Yang X. α-Humulene inhibits hepatocellular carcinoma cell proliferation and induces apoptosis through the inhibition of Akt signaling. Food Chem Toxicol. 2019 Dec;134:110830. doi: 10.1016/j.fct.2019.110830. Epub 2019 Sep 25. PMID: 31562948.
9D. Bungau SG, Vesa CM, Bustea C, Purza AL, Tit DM, Brisc MC, Radu AF. Antioxidant and Hypoglycemic Potential of Essential Oils in Diabetes Mellitus and Its Complications. Int J Mol Sci. 2023 Nov 19;24(22):16501. doi: 10.3390/ijms242216501. PMID: 38003691; PMCID: PMC10671358.
10D. Rogerio AP, Andrade EL, Leite DF, Figueiredo CP, Calixto JB. Preventive and therapeutic anti-inflammatory properties of the sesquiterpene alpha-humulene in experimental airways allergic inflammation. Br J Pharmacol. 2009 Oct;158(4):1074-87. doi: 10.1111/j.1476-5381.2009.00177.x. Epub 2009 May 8. PMID: 19438512; PMCID: PMC2785529.
11D. Dos Santos Negreiros P, da Costa DS, da Silva VG, de Carvalho Lima IB, Nunes DB, de Melo Sousa FB, de Souza Lopes Araújo T, Medeiros JVR, Dos Santos RF, de Cássia Meneses Oliveira R. Antidiarrheal activity of α-terpineol in mice. Biomed Pharmacother. 2019 Feb;110:631-640. doi: 10.1016/j.biopha.2018.11.131. Epub 2018 Dec 9. PMID: 30540974.
12D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 17100, Alpha-Terpineol. Retrieved June 12, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Alpha-Terpineol.
13D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 443162, (-)-alpha-Terpineol. Retrieved June 13, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/2-_1S_-4-methylcyclohex-3-en-1-yl_propan-2-ol.
14D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 11230, 4-Terpineol, (+/-)-. Retrieved June 12, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/4-Terpineol.
15D. Cao W, Li Y, Zeng Z, Lei S. Terpinen-4-ol Induces Ferroptosis of Glioma Cells via Downregulating JUN Proto-Oncogene. Molecules. 2023 Jun 8;28(12):4643. doi: 10.3390/molecules28124643. PMID: 37375197; PMCID: PMC10301057.
16D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 11467, gamma-Terpineol. Retrieved June 12, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/gamma-Terpineol.
17D. Wu ZL, Yin ZQ, Du YH, Feng RZ, Ye KC, Wei Q, Hu Y, He L, Liao L, Wang Y. γ-terpineol inhibits cell growth and induces apoptosis in human liver cancer BEL-7402 cells in vitro. Int J Clin Exp Pathol. 2014 Sep 15;7(10):6524-33. PMID: 25400730; PMCID: PMC4230123.
18D. Jin JS, Chou JM, Tsai WC, Chen YC, Chen Y, Ong JR, Tsai YL. Effectively α-Terpineol Suppresses Glioblastoma Aggressive Behavior and Downregulates KDELC2 Expression. Phytomedicine. 2024 May;127:155471. doi: 10.1016/j.phymed.2024.155471. Epub 2024 Feb 23. PMID: 38452695.
19D. Rong Y, Liu F, Zhou H, Yu T, Qin Z, Cao Q, Liu L, Ma X, Qu L, Xu P, Liao X, Jiang Q, Zhang N, Xu X. Reprogramming of arachidonic acid metabolism using α-terpineol to alleviate asthma: insights from metabolomics. Food Funct. 2024 Apr 22;15(8):4292-4309. doi: 10.1039/d3fo04078j. PMID: 38526853.
20D. Bicas JL, Neri-Numa IA, Ruiz AL, De Carvalho JE, Pastore GM. Evaluation of the antioxidant and antiproliferative potential of bioflavors. Food Chem Toxicol. 2011 Jul;49(7):1610-5. doi: 10.1016/j.fct.2011.04.012. Epub 2011 Apr 19. PMID: 21540069.
21D. Choi YJ, Sim WC, Choi HK, Lee SH, Lee BH. α-Terpineol induces fatty liver in mice mediated by the AMP-activated kinase and sterol response element binding protein pathway. Food Chem Toxicol. 2013 May;55:129-36. doi: 10.1016/j.fct.2012.12.025. Epub 2012 Dec 28. PMID: 23274539.
22D. Kamiya H, Haraguchi A, Mitarai H, Yuda A, Wada H, Shuxin W, Ziqing R, Weihao S, Wada N. In vitro evaluation of the antimicrobial properties of terpinen-4-ol on apical periodontitis-associated bacteria. J Infect Chemother. 2024 Apr;30(4):306-314. doi: 10.1016/j.jiac.2023.10.021. Epub 2023 Nov 3. PMID: 37922985.
23D. Yu H, Guo P, Xie X, Wang Y, Chen G. Ferroptosis, a new form of cell death, and its relationships with tumourous diseases. J Cell Mol Med. 2017 Apr;21(4):648-657. doi: 10.1111/jcmm.13008. Epub 2016 Nov 10. PMID: 27860262; PMCID: PMC5345622.
24D. Arafat K, Al-Azawi AM, Sulaiman S, Attoub S. Exploring the Anticancer Potential of Origanum majorana Essential Oil Monoterpenes Alone and in Combination against Non-Small Cell Lung Cancer. Nutrients. 2023 Dec 4;15(23):5010. doi: 10.3390/nu15235010. PMID: 38068868; PMCID: PMC10708317.
25D. Shapira S, Pleban S, Kazanov D, Tirosh P, Arber N. Terpinen-4-ol: A Novel and Promising Therapeutic Agent for Human Gastrointestinal Cancers. PLoS One. 2016 Jun 8;11(6):e0156540. doi: 10.1371/journal.pone.0156540. PMID: 27275783; PMCID: PMC4898785.
26D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 5281553, beta-OCIMENE, (3E)-. Retrieved June 13, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/beta-OCIMENE_-_3E.
27D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 5320250, beta-Ocimene, (3Z)-. Retrieved June 13, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/beta-Ocimene_-_3Z.
28D. National Center for Advancing Translational Sciences. (n.d.). Pilocarpus microphyllus leaf. Global Substance Registration System. Retrieved June 16, 2024, from https://gsrs.ncats.nih.gov/ginas/app/beta/substances/TY68V0X4KL
29D. Kim MJ, Yang KW, Kim SS, Park SM, Park KJ, Kim KS, Choi YH, Cho KK, Hyun CG. Chemical composition and anti-inflammation activity of essential oils from Citrus unshiu flower. Nat Prod Commun. 2014 May;9(5):727-30. PMID: 25026734.
30D. Oboh G, Ademosun AO, Odubanjo OV, Akinbola IA. Antioxidative properties and inhibition of key enzymes relevant to type-2 diabetes and hypertension by essential oils from black pepper. Adv Pharmacol Sci. 2013;2013:926047. doi: 10.1155/2013/926047. Epub 2013 Nov 21. PMID: 24348547; PMCID: PMC3856121.
31D. Mahdavifard S, Nakhjavani M. 1,8 cineole protects type 2 diabetic rats against diabetic nephropathy via inducing the activity of glyoxalase-I and lowering the level of transforming growth factor-1β. J Diabetes Metab Disord. 2022 Mar 9;21(1):567-572. doi: 10.1007/s40200-022-01014-2. PMID: 35673442; PMCID: PMC9167362.
32D. Cascone P, Iodice L, Maffei ME, Bossi S, Arimura G, Guerrieri E. Tobacco overexpressing β-ocimene induces direct and indirect responses against aphids in receiver tomato plants. J Plant Physiol. 2015 Jan 15;173:28-32. doi: 10.1016/j.jplph.2014.08.011. Epub 2014 Sep 2. PMID: 25462075.
33D. Takaishi M, Fujita F, Uchida K, Yamamoto S, Sawada Shimizu M, Hatai Uotsu C, Shimizu M, Tominaga M. 1,8-cineole, a TRPM8 agonist, is a novel natural antagonist of human TRPA1. Mol Pain. 2012 Nov 29;8:86. doi: 10.1186/1744-8069-8-86. PMID: 23192000; PMCID: PMC3567430.
34D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 2758, Eucalyptol. Retrieved June 14, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Eucalyptol.
35D. Mahdavifard S, Nakhjavani M. 1,8 cineole protects type 2 diabetic rats against diabetic nephropathy via inducing the activity of glyoxalase-I and lowering the level of transforming growth factor-1β. J Diabetes Metab Disord. 2022 Mar 9;21(1):567-572. doi: 10.1007/s40200-022-01014-2. PMID: 35673442; PMCID: PMC9167362.
36D. Bellumori M, Innocenti M, Congiu F, Cencetti G, Raio A, Menicucci F, Mulinacci N, Michelozzi M. Within-Plant Variation in Rosmarinus officinalis L. Terpenes and Phenols and Their Antimicrobial Activity against the Rosemary Phytopathogens Alternaria alternata and Pseudomonas viridiflava. Molecules. 2021 Jun 5;26(11):3425. doi: 10.3390/molecules26113425. PMID: 34198771; PMCID: PMC8201224.
37D. Juergens UR. Anti-inflammatory properties of the monoterpene 1.8-cineole: current evidence for co-medication in inflammatory airway diseases. Drug Res (Stuttg). 2014 Dec;64(12):638-46. doi: 10.1055/s-0034-1372609. Epub 2014 May 15. PMID: 24831245.
38D. Seol GH, Kim KY. Eucalyptol and Its Role in Chronic Diseases. Adv Exp Med Biol. 2016;929:389-398. doi: 10.1007/978-3-319-41342-6_18. PMID: 27771935.
39D. National Institute of Diabetes and Digestive and Kidney Diseases. (n.d.). Low Blood Glucose (Hypoglycemia). National Institutes of Health. Retrieved June 14, 2024, from https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/low-blood-glucose-hypoglycemia
40D. Riyazi A, Hensel A, Bauer K, Geissler N, Schaaf S, Verspohl EJ. The effect of the volatile oil from ginger rhizomes (Zingiber officinale), its fractions and isolated compounds on the 5-HT3 receptor complex and the serotoninergic system of the rat ileum. Planta Med. 2007 Apr;73(4):355-62. doi: 10.1055/s-2007-967171. PMID: 17511060.
41D. National Cancer Institute. 5-HT3 receptor antagonist. Retrieved 11/24/2024 from https://www.cancer.gov/publications/dictionaries/cancer-terms/def/5-ht3-receptor-antagonist
42D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 442482, alpha-PHELLANDRENE, (-)-. Retrieved June 16, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/5R_-2-methyl-5-propan-2-ylcyclohexa-1_3-diene.
43D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 443160, (+)-alpha-Phellandrene. Retrieved June 16, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/5S_-2-methyl-5-propan-2-ylcyclohexa-1_3-diene.
44D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 7460, alpha-PHELLANDRENE. Retrieved June 16, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/alpha-PHELLANDRENE.
45D. Benjumea D, Abdala S, Hernandez-Luis F, Pérez-Paz P, Martin-Herrera D. Diuretic activity of Artemisia thuscula, an endemic Canary species. J Ethnopharmacol. 2005 Aug 22;100(1-2):205-9. doi: 10.1016/j.jep.2005.03.005. PMID: 16054534.
46D. Lin JJ, Hsu SC, Lu KW, Ma YS, Wu CC, Lu HF, Chen JC, Lin JG, Wu PP, Chung JG. Alpha-phellandrene-induced apoptosis in mice leukemia WEHI-3 cells in vitro. Environ Toxicol. 2016 Nov;31(11):1640-1651. doi: 10.1002/tox.22168. Epub 2015 Jul 15. PMID: 26174008.
47D. Bhattacharya, R., Sharma, P., Bose, D. et al. Synergistic potential of α-Phellandrene combined with conventional antifungal agents and its mechanism against antibiotic resistant Candida albicans. CABI Agric Biosci 5, 17 (2024). https://doi.org/10.1186/s43170-024-00218-1
48D. Hsieh SL, Li YC, Chang WC, Chung JG, Hsieh LC, Wu CC. Induction of necrosis in human liver tumor cells by α-phellandrene. Nutr Cancer. 2014;66(6):970-9. doi: 10.1080/01635581.2014.936946. Epub 2014 Jul 31. PMID: 25077527.
49D. Hsieh LC, Hsieh SL, Chen CT, Chung JG, Wang JJ, Wu CC. Induction of α-phellandrene on autophagy in human liver tumor cells. Am J Chin Med. 2015;43(1):121-36. doi: 10.1142/S0192415X15500081. Epub 2015 Feb 4. PMID: 25649747.
50D. Siqueira HDS, Neto BS, Sousa DP, Gomes BS, da Silva FV, Cunha FVM, Wanderley CWS, Pinheiro G, Cândido AGF, Wong DVT, Ribeiro RA, Lima-Júnior RCP, Oliveira FA. α-Phellandrene, a cyclic monoterpene, attenuates inflammatory response through neutrophil migration inhibition and mast cell degranulation. Life Sci. 2016 Sep 1;160:27-33. doi: 10.1016/j.lfs.2016.07.008. Epub 2016 Jul 20. PMID: 27449945.
51D. Susanto AC, Hartajanie L, Wu CC. α‑Phellandrene enhances the apoptosis of HT‑29 cells induced by 5‑fluorouracil by modulating the mitochondria‑dependent pathway. Oncol Rep. 2024 Apr;51(4):61. doi: 10.3892/or.2024.8720. Epub 2024 Mar 8. PMID: 38456489; PMCID: PMC10940876.
52D. Andrei C, Zanfirescu A, Nițulescu GM, Olaru OT, Negreș S. Natural Active Ingredients and TRPV1 Modulation: Focus on Key Chemical Moieties Involved in Ligand-Target Interaction. Plants (Basel). 2023 Jan 11;12(2):339. doi: 10.3390/plants12020339. PMID: 36679051; PMCID: PMC9860573.
53D. Melo LT, Duailibe MA, Pessoa LM, da Costa FN, Vieira-Neto AE, de Vasconcellos Abdon AP, Campos AR. (-)-α-Bisabolol reduces orofacial nociceptive behavior in rodents. Naunyn Schmiedebergs Arch Pharmacol. 2017 Feb;390(2):187-195. doi: 10.1007/s00210-016-1319-2. Epub 2016 Nov 29. PMID: 27900410.
54D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 442343, Levomenol. Retrieved June 17, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Levomenol.
55D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 1549992, Bisabolol. Retrieved June 17, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Bisabolol.
56D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 10586, alpha-Bisabolol. Retrieved June 17, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/alpha-Bisabolol.
57D. Eddin LB, Jha NK, Goyal SN, Agrawal YO, Subramanya SB, Bastaki SMA, Ojha S. Health Benefits, Pharmacological Effects, Molecular Mechanisms, and Therapeutic Potential of α-Bisabolol. Nutrients. 2022 Mar 25;14(7):1370. doi: 10.3390/nu14071370. PMID: 35405982; PMCID: PMC9002489.
58D. Solovăstru LG, Stîncanu A, De Ascentii A, Capparé G, Mattana P, Vâţă D. Randomized, controlled study of innovative spray formulation containing ozonated oil and α-bisabolol in the topical treatment of chronic venous leg ulcers. Adv Skin Wound Care. 2015 Sep;28(9):406-9. doi: 10.1097/01.ASW.0000470155.29821.ed. PMID: 26280699.
59D. Licari A, Ruffinazzi G, DE Filippo M, Castagnoli R, Marseglia A, Agostinis F, Puviani M, Milani M, Marseglia GL. A starch, glycyrretinic, zinc oxide and bisabolol based cream in the treatment of chronic mild-to-moderate atopic dermatitis in children: a three-center, assessor blinded trial. Minerva Pediatr. 2017 Dec;69(6):470-475. doi: 10.23736/S0026-4946.17.05015-0. PMID: 29181960.
60D. Arenberger P, Arenbergerová M, Drozenová H, Hladíková M, Holcová S. Effect of topical heparin and levomenol on atopic dermatitis: a randomized four-arm, placebo-controlled, double-blind clinical study. J Eur Acad Dermatol Venereol. 2011 Jun;25(6):688-94. doi: 10.1111/j.1468-3083.2010.03950.x. Epub 2011 Jan 9. PMID: 21214633.
61D. Crocco EI, Veasey JV, Boin MF, Lellis RF, Alves RO. A novel cream formulation containing nicotinamide 4%, arbutin 3%, bisabolol 1%, and retinaldehyde 0.05% for treatment of epidermal melasma. Cutis. 2015 Nov;96(5):337-42. PMID: 26682557.
62D. Javed H, Meeran MFN, Azimullah S, Bader Eddin L, Dwivedi VD, Jha NK, Ojha S. α-Bisabolol, a Dietary Bioactive Phytochemical Attenuates Dopaminergic Neurodegeneration through Modulation of Oxidative Stress, Neuroinflammation and Apoptosis in Rotenone-Induced Rat Model of Parkinson's disease. Biomolecules. 2020 Oct 8;10(10):1421. doi: 10.3390/biom10101421. PMID: 33049992; PMCID: PMC7599960.
63D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 5356544, (+)-Nerolidol. Retrieved November 25, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/d-Nerolidol.
64D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 5320128, cis-Nerolidol. Retrieved November 25, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/cis-Nerolidol.
65D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 5284507, trans-Nerolidol. Retrieved November 25, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/trans-Nerolidol.
66D. Cazella LN, Glamoclija J, Soković M, Gonçalves JE, Linde GA, Colauto NB, Gazim ZC. Antimicrobial Activity of Essential Oil of Baccharis dracunculifolia DC (Asteraceae) Aerial Parts at Flowering Period. Front Plant Sci. 2019 Jan 29;10:27. doi: 10.3389/fpls.2019.00027. PMID: 30761171; PMCID: PMC6361755.
67D. Glumac M, Čikeš Čulić V, Marinović-Terzić I, Radan M. Mechanism of cis-Nerolidol-Induced Bladder Carcinoma Cell Death. Cancers (Basel). 2023 Feb 3;15(3):981. doi: 10.3390/cancers15030981. PMID: 36765938; PMCID: PMC9913136.
68D. Inoue Y, Shiraishi A, Hada T, Hirose K, Hamashima H, Shimada J. The antibacterial effects of terpene alcohols on Staphylococcus aureus and their mode of action. FEMS Microbiol Lett. 2004 Aug 15;237(2):325-31. doi: 10.1016/j.femsle.2004.06.049. PMID: 15321680.
69D. Curvelo JAR, Marques AM, Barreto ALS, Romanos MTV, Portela MB, Kaplan MAC, Soares RMA. A novel nerolidol-rich essential oil from Piper claussenianum modulates Candida albicans biofilm. J Med Microbiol. 2014 May;63(Pt 5):697-702. doi: 10.1099/jmm.0.063834-0. Epub 2014 Feb 12. PMID: 24523158.
70D. Chan WK, Tan LT, Chan KG, Lee LH, Goh BH. Nerolidol: A Sesquiterpene Alcohol with Multi-Faceted Pharmacological and Biological Activities. Molecules. 2016 Apr 28;21(5):529. doi: 10.3390/molecules21050529. PMID: 27136520; PMCID: PMC6272852.
71D. Chow EWL, Pang LM, Wang Y. From Jekyll to Hyde: The Yeast-Hyphal Transition of Candida albicans. Pathogens. 2021 Jul 7;10(7):859. doi: 10.3390/pathogens10070859. PMID: 34358008; PMCID: PMC8308684.
72D. Klopell FC, Lemos M, Sousa JP, Comunello E, Maistro EL, Bastos JK, de Andrade SF. Nerolidol, an antiulcer constituent from the essential oil of Baccharis dracunculifolia DC (Asteraceae). Z Naturforsch C J Biosci. 2007 Jul-Aug;62(7-8):537-42. doi: 10.1515/znc-2007-7-812. PMID: 17913068.
73D. Vinholes J, Gonçalves P, Martel F, Coimbra MA, Rocha SM. Assessment of the antioxidant and antiproliferative effects of sesquiterpenic compounds in in vitro Caco-2 cell models. Food Chem. 2014 Aug 1;156:204-11. doi: 10.1016/j.foodchem.2014.01.106. Epub 2014 Feb 7. PMID: 24629959.
74D. Lipinski B. Hydroxyl radical and its scavengers in health and disease. Oxid Med Cell Longev. 2011;2011:809696. doi: 10.1155/2011/809696. Epub 2011 Jul 17. PMID: 21904647; PMCID: PMC3166784.
75D. Iqbal D, Khan MS, Waiz M, Rehman MT, Alaidarous M, Jamal A, Alothaim AS, AlAjmi MF, Alshehri BM, Banawas S, Alsaweed M, Madkhali Y, Algarni A, Alsagaby SA, Alturaiki W. Exploring the Binding Pattern of Geraniol with Acetylcholinesterase through In Silico Docking, Molecular Dynamics Simulation, and In Vitro Enzyme Inhibition Kinetics Studies. Cells. 2021 Dec 14;10(12):3533. doi: 10.3390/cells10123533. PMID: 34944045; PMCID: PMC8700130.
76D. Liu Y, Zhou S, Huang X, Rehman HM. Mechanistic insight of the potential of geraniol against Alzheimer's disease. Eur J Med Res. 2022 Jun 14;27(1):93. doi: 10.1186/s40001-022-00699-8. PMID: 35701806; PMCID: PMC9199166.
77D. Katsukawa M, Nakata R, Koeji S, Hori K, Takahashi S, Inoue H. Citronellol and geraniol, components of rose oil, activate peroxisome proliferator-activated receptor α and γ and suppress cyclooxygenase-2 expression. Biosci Biotechnol Biochem. 2011;75(5):1010-2. doi: 10.1271/bbb.110039. Epub 2011 May 20. PMID: 21597168.
78D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 643820, Nerol. Retrieved June 19, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Nerol.
79D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 637566, Geraniol. Retrieved November 26, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Geraniol.
80D. Crespo R, Rodenak-Kladniew BE, Castro MA, Soberón MV, Lavarías SML. Induction of oxidative stress as a possible mechanism by which geraniol affects the proliferation of human A549 and HepG2 tumor cells. Chem Biol Interact. 2020 Apr 1;320:109029. doi: 10.1016/j.cbi.2020.109029. Epub 2020 Feb 28. PMID: 32119866.
81D. Zhang YF, Huang Y, Ni YH, Xu ZM. Systematic elucidation of the mechanism of geraniol via network pharmacology. Drug Des Devel Ther. 2019 Apr 4;13:1069-1075. doi: 10.2147/DDDT.S189088. PMID: 31040644; PMCID: PMC6455000.
82D. Carnesecchi S, Schneider Y, Ceraline J, Duranton B, Gosse F, Seiler N, Raul F. Geraniol, a component of plant essential oils, inhibits growth and polyamine biosynthesis in human colon cancer cells. J Pharmacol Exp Ther. 2001 Jul;298(1):197-200. PMID: 11408542.
83D. Liu Y, Zhou S, Huang X, Rehman HM. Mechanistic insight of the potential of geraniol against Alzheimer's disease. Eur J Med Res. 2022 Jun 14;27(1):93. doi: 10.1186/s40001-022-00699-8. PMID: 35701806; PMCID: PMC9199166.
84D. Deng XY, Xue JS, Li HY, Ma ZQ, Fu Q, Qu R, Ma SP. Geraniol produces antidepressant-like effects in a chronic unpredictable mild stress mice model. Physiol Behav. 2015 Dec 1;152(Pt A):264-71. doi: 10.1016/j.physbeh.2015.10.008. Epub 2015 Oct 8. PMID: 26454213.
85D. Islam MT, Quispe C, Islam MA, Ali ES, Saha S, Asha UH, Mondal M, Razis AFA, Sunusi U, Kamal RM, Kumar M, Sharifi-Rad J. Effects of nerol on paracetamol-induced liver damage in Wistar albino rats. Biomed Pharmacother. 2021 Aug;140:111732. doi: 10.1016/j.biopha.2021.111732. Epub 2021 Jun 12. PMID: 34130201.
86D. Kim CM, Ko YJ, Lee SB, Jang SJ. Adjuvant antimicrobial activity and resensitization efficacy of geraniol in combination with antibiotics on Acinetobacter baumannii clinical isolates. PLoS One. 2022 Jul 21;17(7):e0271516. doi: 10.1371/journal.pone.0271516. PMID: 35862390; PMCID: PMC9302793.
87D. Friedman M, Henika PR, Mandrell RE. Bactericidal activities of plant essential oils and some of their isolated constituents against Campylobacter jejuni, Escherichia coli, Listeria monocytogenes, and Salmonella enterica. J Food Prot. 2002 Oct;65(10):1545-60. doi: 10.4315/0362-028x-65.10.1545. PMID: 12380738.
88D. Rekha KR, Selvakumar GP, Sethupathy S, Santha K, Sivakamasundari RI. Geraniol ameliorates the motor behavior and neurotrophic factors inadequacy in MPTP-induced mice model of Parkinson's disease. J Mol Neurosci. 2013 Nov;51(3):851-62. doi: 10.1007/s12031-013-0074-9. Epub 2013 Aug 13. PMID: 23943375; PMCID: PMC3824202.
89D. Tian J, Lu Z, Wang Y, Zhang M, Wang X, Tang X, Peng X, Zeng H. Nerol triggers mitochondrial dysfunction and disruption via elevation of Ca2+ and ROS in Candida albicans. Int J Biochem Cell Biol. 2017 Apr;85:114-122. doi: 10.1016/j.biocel.2017.02.006. Epub 2017 Feb 14. PMID: 28213053.
90D. Cui L, Zhang B, Zou S, Liu J, Wang P, Li H, Zhang Z. Fenchone Ameliorates Constipation-Predominant Irritable Bowel Syndrome via Modulation of SCF/c-Kit Pathway and Gut Microbiota. J Microbiol Biotechnol. 2024 Feb 28;34(2):367-378. doi: 10.4014/jmb.2308.08011. Epub 2023 Oct 28. PMID: 38073315; PMCID: PMC10940742.
91D. Takaishi M, Uchida K, Fujita F, Tominaga M. Inhibitory effects of monoterpenes on human TRPA1 and the structural basis of their activity. J Physiol Sci. 2014 Jan;64(1):47-57. doi: 10.1007/s12576-013-0289-0. PMID: 24122170; PMCID: PMC3889502.
92D. Nawaz S, Irfan HM, Alamgeer, Arshad L, Jahan S. Attenuation of CFA-induced chronic inflammation by a bicyclic monoterpene fenchone targeting inducible nitric oxide, prostaglandins, C-reactive protein and urea. Inflammopharmacology. 2023 Oct;31(5):2479-2491. doi: 10.1007/s10787-023-01333-7. Epub 2023 Sep 9. PMID: 37689616.
93D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 14525, Fenchone. Retrieved June 21, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Fenchone.
94D. Bashir A, Mushtaq MN, Younis W, Anjum I. Fenchone, a monoterpene: Toxicity and diuretic profiling in rats. Front Pharmacol. 2023 Jan 26;14:1119360. doi: 10.3389/fphar.2023.1119360. PMID: 36778012; PMCID: PMC9909529.
95D. Vogt-Eisele AK, Weber K, Sherkheli MA, Vielhaber G, Panten J, Gisselmann G, Hatt H. Monoterpenoid agonists of TRPV3. Br J Pharmacol. 2007 Jun;151(4):530-40. doi: 10.1038/sj.bjp.0707245. Epub 2007 Apr 10. PMID: 17420775; PMCID: PMC2013969.
96D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 440966, (-)-Camphene. Retrieved June 21, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/440966.
97D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 92221, (+)-Camphene. Retrieved June 21, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/92221.
98D. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 6616, Camphene. Retrieved June 21, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Camphene.
99D. Stamatiou R, Anagnostopoulou M, Ioannidou-Kabouri K, Rapti C, Lazou A. Camphene as a Protective Agent in Myocardial Ischemia/Reperfusion Injury. Antioxidants (Basel). 2024 Mar 28;13(4):405. doi: 10.3390/antiox13040405. PMID: 38671853; PMCID: PMC11047447.
1E. Yang L, Liu H, Xia D, Wang S. Antioxidant Properties of Camphene-Based Thiosemicarbazones: Experimental and Theoretical Evaluation. Molecules. 2020 Mar 6;25(5):1192. doi: 10.3390/molecules25051192. PMID: 32155763; PMCID: PMC7179440.
2E. Spiteller G. Peroxyl radicals are essential reagents in the oxidation steps of the Maillard reaction leading to generation of advanced glycation end products. Ann N Y Acad Sci. 2008 Apr;1126:128-33. doi: 10.1196/annals.1433.031. PMID: 18448806.
3E. MDPI. (n.d.). Cedrol exhibits antinociceptive effects via TRPA1 and TRPV1 modulation. Molecules, 29(4), 815. Retrieved 11/25/2024 from https://www.mdpi.com/1420-3049/29/4/815
4E. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 65575, Cedrol. Retrieved June 21, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Cedrol.
5E. Wisconsin Horticulture - Division of Extension. Malabar spinach, Basella alba. Retrieved 6/21/2024 from https://hort.extension.wisc.edu/articles/malabar-spinach-basella-alba/
6E. Xu C, Jin SQ, Jin C, Dai ZH, Wu YH, He GL, Ma HW, Xu CY, Fang WL. Cedrol, a Ginger-derived sesquiterpineol, suppresses estrogen-deficient osteoporosis by intervening NFATc1 and reactive oxygen species. Int Immunopharmacol. 2023 Apr;117:109893. doi: 10.1016/j.intimp.2023.109893. Epub 2023 Feb 27. PMID: 36842234.
7E. Zhang YM, Shen J, Zhao JM, Guan J, Wei XR, Miao DY, Li W, Xie YC, Zhao YQ. Cedrol from Ginger Ameliorates Rheumatoid Arthritis via Reducing Inflammation and Selectively Inhibiting JAK3 Phosphorylation. J Agric Food Chem. 2021 May 12;69(18):5332-5343. doi: 10.1021/acs.jafc.1c00284. Epub 2021 Apr 28. Erratum in: J Agric Food Chem. 2021 Jul 21;69(28):8063. doi: 10.1021/acs.jafc.1c03690. PMID: 33908779.
8E. Zhang Y, Liu Y, Peng F, Wei X, Hao H, Li W, Zhao Y. Cedrol from ginger alleviates rheumatoid arthritis through dynamic regulation of intestinal microenvironment. Food Funct. 2022 Nov 14;13(22):11825-11839. doi: 10.1039/d2fo01983c. PMID: 36314362.
9E. Zhao Y, Li M, Guo J, Fang J, Geng R, Wang Y, Liu T, Kang SG, Huang K, Tong T. Cedrol, a Major Component of Cedarwood Oil, Ameliorates High-Fat Diet-Induced Obesity in Mice. Mol Nutr Food Res. 2023 Jul;67(14):e2200665. doi: 10.1002/mnfr.202200665. Epub 2023 May 23. PMID: 37143286.
10E. Yun HJ, Jeoung DJ, Jin S, Park JH, Lee EW, Lee HT, Choi YH, Kim BW, Kwon HJ. Induction of Cell Cycle Arrest, Apoptosis, and Reducing the Expression of MCM Proteins in Human Lung Carcinoma A549 Cells by Cedrol, Isolated from Juniperus chinensis. J Microbiol Biotechnol. 2022 Jul 28;32(7):918-926. doi: 10.4014/jmb.2205.05012. Epub 2022 Jul 1. PMID: 35880481; PMCID: PMC9628924.
11E. Zhang Z, Li M, Tan Q, Chen J, Sun J, Li J, Sun L, Chen N, Song Q, Zhao X, Li H, Zhang X. A moderate anticoccidial effect of cedrol on Eimeria tenella in broiler chickens. Parasitol Int. 2023 Dec;97:102779. doi: 10.1016/j.parint.2023.102779. Epub 2023 Jul 13. PMID: 37451395.
12E. Zhang Y, Wang JW, Qu FZ, Zhang YM, Su GY, Zhao YQ. Hair growth promotion effect of cedrol cream and its dermatopharmacokinetics. RSC Adv. 2018 Dec 18;8(73):42170-42178. doi: 10.1039/c8ra08667b. PMID: 35558774; PMCID: PMC9092075.
13E. Zhou Y, Jia L, Zhang G, Chen G, Zhou D, Shi X, Fu Q, Li N. Cedrol-loaded dissolvable microneedles based on flexible backing for promoting hair growth. Expert Opin Drug Deliv. 2023 Jul-Dec;20(9):1267-1276. doi: 10.1080/17425247.2023.2244413. Epub 2023 Aug 8. PMID: 37553988.
14E. Forouzanfar F, Pourbagher-Shahri AM, Ghazavi H. Evaluation of Antiarthritic and Antinociceptive Effects of Cedrol in a Rat Model of Arthritis. Oxid Med Cell Longev. 2022 Apr 25;2022:4943965. doi: 10.1155/2022/4943965. PMID: 35509836; PMCID: PMC9060983.
15E. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 10364, Carvacrol. Retrieved November 26, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Carvacrol.
16E. Mączka W, Twardawska M, Grabarczyk M, Wińska K. Carvacrol-A Natural Phenolic Compound with Antimicrobial Properties. Antibiotics (Basel). 2023 Apr 27;12(5):824. doi: 10.3390/antibiotics12050824. PMID: 37237727; PMCID: PMC10215463.
17E. Lozon Y, Sultan A, Lansdell SJ, Prytkova T, Sadek B, Yang KH, Howarth FC, Millar NS, Oz M. Inhibition of human α7 nicotinic acetylcholine receptors by cyclic monoterpene carveol. Eur J Pharmacol. 2016 Apr 5;776:44-51. doi: 10.1016/j.ejphar.2016.02.004. Epub 2016 Feb 2. PMID: 26849939.
18E. Yousef EH, Abo El-Magd NF, El Gayar AM. Carvacrol enhances anti-tumor activity and mitigates cardiotoxicity of sorafenib in thioacetamide-induced hepatocellular carcinoma model through inhibiting TRPM7. Life Sci. 2023 Jul 1;324:121735. doi: 10.1016/j.lfs.2023.121735. Epub 2023 May 2. PMID: 37142088.
19E. Melo FH, Moura BA, de Sousa DP, de Vasconcelos SM, Macedo DS, Fonteles MM, Viana GS, de Sousa FC. Antidepressant-like effect of carvacrol (5-Isopropyl-2-methylphenol) in mice: involvement of dopaminergic system. Fundam Clin Pharmacol. 2011 Jun;25(3):362-7. doi: 10.1111/j.1472-8206.2010.00850.x. PMID: 20608992.
20E. Sharifi-Rad M, Varoni EM, Iriti M, Martorell M, Setzer WN, Del Mar Contreras M, Salehi B, Soltani-Nejad A, Rajabi S, Tajbakhsh M, Sharifi-Rad J. Carvacrol and human health: A comprehensive review. Phytother Res. 2018 Sep;32(9):1675-1687. doi: 10.1002/ptr.6103. Epub 2018 May 9. PMID: 29744941.
21E. Singh J, Luqman S, Meena A. Carvacrol as a Prospective Regulator of Cancer Targets/Signalling Pathways. Curr Mol Pharmacol. 2023 Mar 27;16(5):542-558. doi: 10.2174/1874467215666220705142954. PMID: 35792130.
22E. Fan K, Li X, Cao Y, Qi H, Li L, Zhang Q, Sun H. Carvacrol inhibits proliferation and induces apoptosis in human colon cancer cells. Anticancer Drugs. 2015 Sep;26(8):813-23. doi: 10.1097/CAD.0000000000000263. PMID: 26214321.
23E. Priestley CM, Williamson EM, Wafford KA, Sattelle DB. Thymol, a constituent of thyme essential oil, is a positive allosteric modulator of human GABA(A) receptors and a homo-oligomeric GABA receptor from Drosophila melanogaster. Br J Pharmacol. 2003 Dec;140(8):1363-72. doi: 10.1038/sj.bjp.0705542. Epub 2003 Nov 17. PMID: 14623762; PMCID: PMC1574153.
24E. Begrow F, Engelbertz J, Feistel B, Lehnfeld R, Bauer K, Verspohl EJ. Impact of thymol in thyme extracts on their antispasmodic action and ciliary clearance. Planta Med. 2010 Mar;76(4):311-8. doi: 10.1055/s-0029-1186179. Epub 2009 Oct 6. PMID: 19809973.
25E. Meeran, M. F. N., Javed, H., Al Taee, H., Azimullah, S., & Ojha, S. K. (2017). Pharmacological properties and molecular mechanisms of thymol: Prospects for its therapeutic potential and pharmaceutical development. Frontiers in Pharmacology, 8, Article 380. https://doi.org/10.3389/fphar.2017.00380
26E. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 6989, Thymol. Retrieved November 28, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Thymol.
27E. Toschi, A., Tugnoli, B., Rossi, B. et al. Thymol modulates the endocannabinoid system and gut chemosensing of weaning pigs. BMC Vet Res 16, 289 (2020). https://doi.org/10.1186/s12917-020-02516-y
28E. Di Marzo V, Izzo AA. Endocannabinoid overactivity and intestinal inflammation. Gut. 2006 Oct;55(10):1373-6. doi: 10.1136/gut.2005.090472. PMID: 16966693; PMCID: PMC1856409.
29E. Abosamak NER, Shahin MH. Beta2 Receptor Agonists and Antagonists. [Updated 2023 Jul 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559069/
30E. Olsen RW. GABAA receptor: Positive and negative allosteric modulators. Neuropharmacology. 2018 Jul 1;136(Pt A):10-22. doi: 10.1016/j.neuropharm.2018.01.036. Epub 2018 Jan 31. PMID: 29407219; PMCID: PMC6027637.
31E. Triggle DJ. L-type calcium channels. Curr Pharm Des. 2006;12(4):443-57. doi: 10.2174/138161206775474503. PMID: 16472138.
32E. Striessnig J, Ortner NJ, Pinggera A. Pharmacology of L-type Calcium Channels: Novel Drugs for Old Targets? Curr Mol Pharmacol. 2015;8(2):110-22. doi: 10.2174/1874467208666150507105845. PMID: 25966690; PMCID: PMC5384371.
33E. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 10887971, Sabinene. Retrieved June 21, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/Sabinene.
34E. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 11051711, (-)-Sabinene. Retrieved June 21, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/11051711.
35E. Ryu Y, Lee D, Jung SH, Lee KJ, Jin H, Kim SJ, Lee HM, Kim B, Won KJ. Sabinene Prevents Skeletal Muscle Atrophy by Inhibiting the MAPK-MuRF-1 Pathway in Rats. Int J Mol Sci. 2019 Oct 8;20(19):4955. doi: 10.3390/ijms20194955. PMID: 31597276; PMCID: PMC6801606.
36E. Valente J, Zuzarte M, Gonçalves MJ, Lopes MC, Cavaleiro C, Salgueiro L, Cruz MT. Antifungal, antioxidant and anti-inflammatory activities of Oenanthe crocata L. essential oil. Food Chem Toxicol. 2013 Dec;62:349-54. doi: 10.1016/j.fct.2013.08.083. Epub 2013 Sep 5. PMID: 24012643.
37E. Hung NH, Quan PM, Satyal P, Dai DN, Hoa VV, Huy NG, Giang LD, Ha NT, Huong LT, Hien VT, Setzer WN. Acetylcholinesterase Inhibitory Activities of Essential Oils from Vietnamese Traditional Medicinal Plants. Molecules. 2022 Oct 20;27(20):7092. doi: 10.3390/molecules27207092. PMID: 36296686; PMCID: PMC9610647.
38E. Leafly. (n.d.). Ocimene: Effects, benefits, and where to find it. Retrieved 12/7/2024, from https://www.leafly.com
39E. Papke RL, Horenstein NA. Therapeutic Targeting of α7 Nicotinic Acetylcholine Receptors. Pharmacol Rev. 2021 Jul;73(3):1118-1149. doi: 10.1124/pharmrev.120.000097. PMID: 34301823; PMCID: PMC8318519.
40E. Pohanka M. Alpha7 nicotinic acetylcholine receptor is a target in pharmacology and toxicology. Int J Mol Sci. 2012;13(2):2219-2238. doi: 10.3390/ijms13022219. Epub 2012 Feb 17. PMID: 22408449; PMCID: PMC3292018.
41E. Theriot J, Wermuth HR, Ashurst JV. Antiemetics, Selective 5-HT3 Antagonists. [Updated 2024 Apr 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513318/
42E. Komorowska-Müller JA, Schmöle AC. CB2 Receptor in Microglia: The Guardian of Self-Control. Int J Mol Sci. 2020 Dec 22;22(1):19. doi: 10.3390/ijms22010019. PMID: 33375006; PMCID: PMC7792761.
43E. Foong AL, Grindrod KA, Patel T, Kellar J. Demystifying serotonin syndrome (or serotonin toxicity). Can Fam Physician. 2018 Oct;64(10):720-727. PMID: 30315014; PMCID: PMC6184959.
44E. Tagen M, Klumpers LE. Review of delta-8-tetrahydrocannabinol (Δ8 -THC): Comparative pharmacology with Δ9 -THC. Br J Pharmacol. 2022 Aug;179(15):3915-3933. doi: 10.1111/bph.15865. Epub 2022 Jun 1. Erratum in: Br J Pharmacol. 2023 Jan;180(1):130. doi: 10.1111/bph.15990. PMID: 35523678.
45E. Weston-Green K, Clunas H, Jimenez Naranjo C. A Review of the Potential Use of Pinene and Linalool as Terpene-Based Medicines for Brain Health: Discovering Novel Therapeutics in the Flavours and Fragrances of Cannabis. Front Psychiatry. 2021 Aug 26;12:583211. doi: 10.3389/fpsyt.2021.583211. PMID: 34512404; PMCID: PMC8426550.