User:Etienne Robillard/Notebook/THC

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Synopsis

  • Delta9-tetrahydrocannabinol (THC) is the main psychoactive constituent of the Cannabis sativa L (Marijuana) plant.
  • Others marijuana-derived cannabinoids includes Cannabichromene (CBC), Cannabidiol (CBD), Cannabinol (CBN), Cannabigerol (CBG), and Tetrahydrocannabivarin (THCV).
  • Marijuana-derived cannabinoids are known as phytocannabinoids.
  • THCA is the biosynthetic precursor of THC.

Antidepressant properties of THC

  • THC stimulate anandamide biosynthesis by binding to the CB1 receptor, thus producing a antidepressant and neuroprotective effect. [1]

Neuroprotective properties of THC

Alzheimer

  • THC may inhibit acetylcholinesterase-induced intraneuronal amyloid beta aggregation in Alzheimer's disease. [2]
  • THC may prevent intracellular amyloid beta proteotoxicity and inflammatory response. [3]

Antipsychotic-induced dopamine supersensitivity

  • THC is effective glutamatergic agent for reversing drug-induced neuronal excitotoxicity. [4]

Cognitive aging

  • THC may reverse the cognitive aging process in the brain. (Reference needed)

Glaucoma

  • THC may reduce intraocular pressure (IOP) in retinal ganglion cells (RGCs) through intracellular CB1 receptor activation.
    • A potential treatment for glaucoma to prevent optic nerve damage.

Tardive diskinesia

Traumatic brain injury

Posttraumatic stress disorder

  • THC may reduce chronic nightmares frequency and alter dreaming activity?

Sleep regulation

  • THC may affect REM-sleep rebound. [5]
  • THC may reduce REM-sleep and increase slow wave sleep (SWS).

Effects of THC on neurogenesis, synaptogenesis and BDNF signaling

  • Hippocampal CB1 receptors regulate stress-induced neuroinflammation in the hippocampus. [6]
  • THC enhance adult hippocampal neurogenesis and BDNF signaling through intracellular CB1 receptor activation. [7][8]
  • Intracellular CB1 activation promote neuronal cell proliferation, differentiation, maturation, and neurite growth. [9]

Neuropsychology of THC tolerance

  • CB1 receptor sensitization can be restored by taking breaks of oral THC administration. (Reference needed)
  • Alcohol increase THC levels in blood. (Reference needed)
  • THC tolerance is genetic and regulated by the AKT1 gene.

Notes

  • THC may increase serotonergic tone. [10]
  • Possible cross-talk between dopaminergic vitamin D, delta9-THC, and endogenous cannabinoids (anandamide) ?

Experimental

  • Endogenous retrograde trafficking may promote hippocampal development (neurogenesis) and synaptogenesis.
  • Arachidonic acid/DHA levels affect neural stem/progenitor cells (NSPCs) proliferation in the hippocampus. (Reference needed)
  • THC may enhance corticostriatal functional connectivity though increased c-Fos expression. [11]
  • Long-term THC administration may depletes melatonin synthesis.

References

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866040/ [Website2]
    Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L.
  2. https://www.ncbi.nlm.nih.gov/pubmed/17140265 [Eubanks-2006]
    A molecular link between the active component of marijuana and Alzheimer's disease pathology.
  3. http://www.nature.com/articles/npjamd201612 [Website4]
    Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids.
  4. https://www.ncbi.nlm.nih.gov/pubmed/19969019 [Pope-2010]
    Endocannabinoid signaling in neurotoxicity and neuroprotection.
  5. https://www.ncbi.nlm.nih.gov/pubmed/12895525 [Murillo-2003]
    Potential role of the cannabinoid receptor CB1 in rapid eye movement sleep rebound.
  6. https://www.ncbi.nlm.nih.gov/pubmed/21150911 [Zoppi-2011]
    Regulatory role of cannabinoid receptor 1 in stress-induced excitotoxicity and neuroinflammation.
  7. https://www.ncbi.nlm.nih.gov/pubmed/16224541 [Jiang-2005]
    Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects.
  8. https://www.ncbi.nlm.nih.gov/pubmed/17828287 [Campbell-2007]
    Alzheimer's disease; taking the edge off with cannabinoids?
  9. https://www.ncbi.nlm.nih.gov/pubmed/23704915 [Xapelli-2013]
    Activation of type 1 cannabinoid receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures.
  10. https://www.ncbi.nlm.nih.gov/pubmed/22045940 [Nutt-2011]
    Low serotonergic tone and elevated risk for substance misuse.
  11. https://www.ncbi.nlm.nih.gov/pubmed/26377899 [Todd-2016]
    Neural correlates of interactions between cannabidiol and Δ(9) -tetrahydrocannabinol in mice: implications for medical cannabis.
  12. https://www.ncbi.nlm.nih.gov/pubmed/21460829 [Xiong-2011]
    Cannabinoid potentiation of glycine receptors contributes to cannabis-induced analgesia.
  13. https://www.ncbi.nlm.nih.gov/pubmed/28481360 [Gorzo-2017]
    A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice.
  14. https://www.ncbi.nlm.nih.gov/pubmed/25264643 [Nguyen-2014]
    Effect of marijuana use on outcomes in traumatic brain injury.

See also