Cannabinoids and terpenes for dementia
Dementia is an incredibly difficult-to-manage condition that affects a large portionof the elderly population. And, to date, there is no treatment that effectively managesits symptoms or prevents its progression. Dementia is considered an umbrella term that encompasses all types of cognitive decline worse than one would expect from normal aging. Many patients with dementia will develop Alzheimer’s disease (AD), a severe condition whose symptomsincludes behavioral and psychiatric changes, as well as difficulties with mental processes such as memory.
Since cannabis is associated with memory impairment, the last thing you would expect is for cannabis to be used as a therapeutic for AD – but, surprisingly, there is considerable evidence indicating that it may indeed be beneficial. While much of these data ispreclinical, there does seem to be a physiological link between cannabinoid function and Alzheimer’s pathology.
For many years, researchers have tried to explainthe link between β-amyloid plaques (protein clumps in the brain) andAD symptoms. [1]While the plaquesprovide a biomarker against which to measure the effects of different therapies, there has been little success in developing compounds that both reduce this protein and alleviate symptoms. However, an in vitro pharmacological study found that low concentrations of tetrahydrocannabinol (THC) wereable toreducethe levels of a β-amyloid precursor in a
dose-dependent manner, suggesting a novel method of targeting this protein. [2]
Cannabinoids also may be beneficial through a different pathway. Currently approved therapies for ADtarget a neurotransmitter (brain chemical) called acetylcholine (ACh) that plays an important role in memory and attention. THC was found to inhibit the degradation of ACh, thereby preventing its β-amyloid accumulation. [3]. Additionally, a preclinical study found that a low dose of THC improved cognitive impairments in a mouse model of AD. [4]
While this preliminary evidence suggests that cannabinoids may indeed be beneficial in reversing ADpathology and symptoms, titrating the right dose of THC to prevent psychoactive effects in a population that already experiences psychiatric symptoms is a major challenge.
Bypassing this issue, research has also indicated that terpenes may also be promising as well.β-Caryophyllene prevented cognitive decline and reduced β-amyloid levels in the brains of mouse models. [5] Additionally, another cannabis terpene – linalool – reversed spatial memory deficits as well as anxiety in another ADmouse model. [6] This and second preclinical study also demonstrated linalool reducing β-amyloid levels, further strengthening the linkage correlating these two factors. [7]
While the majority of evidence that supports of role for cannabinoids and terpenes in the pathophysiology of AD is based on preclinical research, studies in patients have indicated that cannabis be may effective in treating the behavioral aspects of AD. [8] In fact, a team of researchers at King’s College London recently announced a Phase 2 trial evaluating the effect of Sativex, a cannabis-based oral spray, on agitation and aggression in patients with dementia in general.
The data currently available seems to indicate that there is a physiological pathway by which cannabinoids could influence dementia.
[Image]References
- Kametani, F., Hasegawa, M., “Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer’s Disease”, Front Neurosci, 2018, Volume 12, pg. 1-11.
(impact factor: 3.877; cited by: 29)
2. Caoa, C., Lic, Y., Liu, H., et al., “The Potential Therapeutic Effects of THC on Alzheimer’s Disease”, J Alzheimers Dis, 2014;42(3):973-84.(impact factor: 3.920 cited by: 38)
3.Eubanks, L.M., Rogers, C.J. Beuscher, A.E., “A Molecular Link Between the Active Component of Marijuana and Alzheimer’s Disease Pathology”,Mol Pharm, 2006, Volume 3, pg. 773–777. (impact factor: 4.556; cited by: 184)
4. Bilkei-Gorzo, A., Albayram, O., Draffehn, A., et al., “A Chronic Low Dose of Δ9-tetrahydrocannabinol (THC) Restores Cognitive Function in Old Mice”, Nat Med, 2017, Volume 23, pg. 782-787. (impact factor: 32.621; cited by: 45)
5. Cheng, Y., Dong, Z., Liu, S.,“β-Caryophyllene Ameliorates the Alzheimer-Like Phenotype in APP/PS1 Mice through CB2 Receptor Activation and the PPARγ Pathway”, Pharmacology, 2014, Volume 94, pg. 1-12.(impact factor: 2.9896; cited by: 47) - Sabogal-Guáqueta, A.M., Osorio, E., Cardona-Gómez, G.P.,“Linalool Reverses Neuropathological and Behavioral Impairments in Old Triple Transgenic Alzheimer’s Mice”, Neuropharmacology, 2016, Volume 102, pg. 111-120. (impact factor: 4.249; cited by: 40)
7. Xu, P., Wang, K., Lu, C., et al., “Protective Effects of Linalool Against Amyloid Beta-induced Cognitive Deficits and Damages in Mice”,Life Sci, 2017,Volume 174, pg. 21-27. (impact factor: 2.702; cited by: 18)
8. Aso, E., Ferrer, I., “Cannabinoids for Treatment of Alzheimer’s Disease: Moving Toward the Clinic”, Front Pharmacol, 2014,Volume 5, pg. 1-11.(impact factor: 3.831; cited by: 100)
