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Cannabidiol Partially Blocks the Excessive Sleepiness in Hypocretindeficient Rats: Preliminary Data.
CNS Neurol Disord Drug Targets. 2019; 18(9):705-712.CN

Abstract

BACKGROUND

Excessive daytime sleepiness and cataplexy are among the symptoms of narcolepsy, a sleep disorder caused by the loss of hypocretin/orexin (HCRT/OX) neurons placed into the Hypothalamus (LH). Several treatments for managing narcolepsy include diverse drugs to induce alertness, such as antidepressants, amphetamine, or modafinil, etc. Recent evidence has shown that cannabidiol (CBD), a non-psychotropic derived from Cannabis sativa, shows positive therapeutic effects in neurodegenerative disorders, including Parkinson´s disease. Furthermore, CBD provokes alertness and enhances wake-related neurochemicals in laboratory animals. Thus, it is plausible to hypothesize that excessive somnolence observed in narcolepsy might be blocked by CBD.

OBJECTIVE

Here, we determined whether the systemic injection of CBD (5mg/kg, i.p.) would block the excessive sleepiness in a narcoleptic model.

METHODS

To test this idea, the neurotoxin hypocretin-2-saporin (HCRT2/SAP) was bilaterally injected into the LH of rats to eliminate HCRT leading to the establishment of narcoleptic-like behavior. Since excessive somnolence in HCRT2/SAP lesioned rats has been observed during the lights-off period, CBD was administered at the beginning of the dark phase.

RESULTS

Hourly analysis of sleep data showed that CBD blocked the sleepiness during the lights-off period across 7h post-injection in lesioned rats.

CONCLUSION

Taking together, these preliminary findings suggest that CBD might prevent sleepiness in narcolepsy.

Authors+Show Affiliations

Laboratorio de Neurociencias Moleculares e Integrativas, Escuela de Medicina, División Ciencias de la Salud, Universidad Anáhuac Mayab, Mérida, Yucatán, Mexico. Intercontinental Neuroscience Research Group, Merida, Yucatán, Mexico.Depto. de Neurociencia Cognitiva, División de Neurociencias, Instituto de Fisiología Celular. Universidad Nacional Autónoma de México, Ciudad de México, Mexico.Depto. de Neuropatología Molecular, División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.Laboratorio de Neurociencias Moleculares e Integrativas, Escuela de Medicina, División Ciencias de la Salud, Universidad Anáhuac Mayab, Mérida, Yucatán, Mexico. Intercontinental Neuroscience Research Group, Merida, Yucatán, Mexico.Institute for Drug Research, Medical Faculty, Hebrew University, Jerusalem, Israel.Depto. de Neuropatología Molecular, División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31642794

Citation

Murillo-Rodríguez, Eric, et al. "Cannabidiol Partially Blocks the Excessive Sleepiness in Hypocretindeficient Rats: Preliminary Data." CNS & Neurological Disorders Drug Targets, vol. 18, no. 9, 2019, pp. 705-712.
Murillo-Rodríguez E, Millán-Aldaco D, Palomero-Rivero M, et al. Cannabidiol Partially Blocks the Excessive Sleepiness in Hypocretindeficient Rats: Preliminary Data. CNS Neurol Disord Drug Targets. 2019;18(9):705-712.
Murillo-Rodríguez, E., Millán-Aldaco, D., Palomero-Rivero, M., Morales-Lara, D., Mechoulam, R., & Drucker-Colín, R. (2019). Cannabidiol Partially Blocks the Excessive Sleepiness in Hypocretindeficient Rats: Preliminary Data. CNS & Neurological Disorders Drug Targets, 18(9), 705-712. https://doi.org/10.2174/1871527318666191021143300
Murillo-Rodríguez E, et al. Cannabidiol Partially Blocks the Excessive Sleepiness in Hypocretindeficient Rats: Preliminary Data. CNS Neurol Disord Drug Targets. 2019;18(9):705-712. PubMed PMID: 31642794.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabidiol Partially Blocks the Excessive Sleepiness in Hypocretindeficient Rats: Preliminary Data. AU - Murillo-Rodríguez,Eric, AU - Millán-Aldaco,Diana, AU - Palomero-Rivero,Marcela, AU - Morales-Lara,Daniela, AU - Mechoulam,Raphael, AU - Drucker-Colín,René, PY - 2019/05/13/received PY - 2019/08/05/revised PY - 2019/09/13/accepted PY - 2019/10/24/pubmed PY - 2020/9/25/medline PY - 2019/10/24/entrez KW - Cannabidiol KW - hypocretin-deficient rats KW - lateral hypothalamus KW - narcolepsy KW - neurodegenerative disorder KW - rapid eye movement sleep. SP - 705 EP - 712 JF - CNS & neurological disorders drug targets JO - CNS Neurol Disord Drug Targets VL - 18 IS - 9 N2 - BACKGROUND: Excessive daytime sleepiness and cataplexy are among the symptoms of narcolepsy, a sleep disorder caused by the loss of hypocretin/orexin (HCRT/OX) neurons placed into the Hypothalamus (LH). Several treatments for managing narcolepsy include diverse drugs to induce alertness, such as antidepressants, amphetamine, or modafinil, etc. Recent evidence has shown that cannabidiol (CBD), a non-psychotropic derived from Cannabis sativa, shows positive therapeutic effects in neurodegenerative disorders, including Parkinson´s disease. Furthermore, CBD provokes alertness and enhances wake-related neurochemicals in laboratory animals. Thus, it is plausible to hypothesize that excessive somnolence observed in narcolepsy might be blocked by CBD. OBJECTIVE: Here, we determined whether the systemic injection of CBD (5mg/kg, i.p.) would block the excessive sleepiness in a narcoleptic model. METHODS: To test this idea, the neurotoxin hypocretin-2-saporin (HCRT2/SAP) was bilaterally injected into the LH of rats to eliminate HCRT leading to the establishment of narcoleptic-like behavior. Since excessive somnolence in HCRT2/SAP lesioned rats has been observed during the lights-off period, CBD was administered at the beginning of the dark phase. RESULTS: Hourly analysis of sleep data showed that CBD blocked the sleepiness during the lights-off period across 7h post-injection in lesioned rats. CONCLUSION: Taking together, these preliminary findings suggest that CBD might prevent sleepiness in narcolepsy. SN - 1996-3181 UR - https://www.unboundmedicine.com/medline/citation/31642794/Cannabidiol_Partially_Blocks_the_Excessive_Sleepiness_in_Hypocretindeficient_Rats:_Preliminary_Data_ DB - PRIME DP - Unbound Medicine ER -