Alzheimer's Disease / Dementia and Cannabinoid Therapy

Those of you who know our background will know that Alzheimer’s Disease / Dementia is the health condition that inspired the creation of Cannacea. Our Tagrid’s 100 formula is named after our founders’ mother, Tagrid, who was diagnosed with early-onset Alzheimer’s Disease and Psychosis, and whose health and quality of life were revolutionized by this specialized full spectrum CBD-dominant hemp oil formula. Her life-changing response inspired the founding of Cannacea to share this clinical work and therapy with the World.

No less inspiring are the results of recent peer-reviewed clinical trials of full spectrum cannabinoid formulas for improving the quality of life of Dementia patients, covering prospective cohort studies and a randomized placebo-controlled trial (RCT).

Overview of Clinical Results

Analyzing four different peer-reviewed clinical trials that tested orally administered full spectrum cannabinoid formulations on subjects diagnosed with various forms of Dementia, the formulations ranged from CBD-dominant, to nearly equivalent CBD:THC ratio, through to THC-dominant:

• 25:1 CBD:THC ratio (2 trials with 1 follow-up) [1-3].
• 2:1 CBD:THC ratio [4].
• 1:44 CBD:THC ratio [5].

All four trials resulted in significant health improvements for the Dementia subjects using oral cannabinoid therapy, including reductions in the Behavioral and Psychological Symptoms of Dementia (BPSD) such as anxiety, agitation, aggression, psychosis and sleep disturbances, as directly quantified by statistically significant improvements in Neuropsychiatric Index Questionnaire (NPI-Q), Cohen-Mansfield Agitation Inventory (CMAI), and caregiver-reported quality of life [1-5]. One of the studies also applied the Mini-Mental State Examination (MMSE), where out of the 100% of subjects confirmed as having severe cognitive impairment (MMSE score <10) before cannabis treatment, 45% of the subjects improved to a reduced mild/moderate cognitive impairment (MMSE score 15-17) after cannabis treatment [5].

In Vitro and In Vivo Animal Structure/Function Studies

This is in addition to the breadth of data available from in vitro and in vivo animal experiments in Dementia models, which structurally showed how the application of CBD significantly reduced neuronal damage and deterioration by significantly reducing reactive gliosis and neuroinflammation while promoting neurogenesis [6]. Functionally, the application of CBD also reversed deficits in cognition and memory in both pharmacological and transgenic mouse models of Alzheimer’s Disease [6], while also improving brain glucose metabolism and memory in pharmacological rat models of Alzheimer’s Disease [7].

Computed Tomography (CT) scan of a human brain

Clinical Trial CBD Intake Ranges

In the CBD-dominant clinical trials reviewed, oral CBD showed significant efficacy from intakes as low as only 3 - 4 mg CBD taken 3x a day for total 10 mg CBD per day [2,3], all the way up to a mean of 175 mg CBD taken 3x a day for total 525 mg CBD per day [1].

Efficacy & Safety of CBD-dominant vs. THC-dominant Formulations

From CBD-dominant intakes to THC-dominant intakes, all four human clinical trials reported significant therapeutic effects, though CBD-dominant intakes may have lower adverse effect profiles than THC-dominant intakes, due to THC’s potential psychotropic, psychotomimetic, and anxiogenic effects [8].

The 2:1 CBD:THC ratio study administering a daily mean of 24 mg CBD with 12 mg THC reported no significant adverse effects due to pharmacological effects of the cannabinoids [4]. The THC-dominant study administering up to 20 mg THC per day also reported no adverse effects [5]. The low-intake CBD-dominant study did report some adverse effects [2], but those appear confounded by potential drug interactions as discussed below.

In the high-intake CBD-dominant study the five most statistically significant adverse effects, listed in decreasing order, were “decreased memory”, “hallucinations”, “sleepiness”, "dry mouth", and “confusion/disorientation” [1]. With a mean intake of 525 mg CBD per day split into 3 intakes of 175 mg CBD, such full spectrum formula with more typical 25:1 CBD:THC ratio provided a mean intake of 21 mg THC per day split into 3 intakes of 7 mg THC [1]. Of these five adverse effects, only sleepiness is normally reported with high intakes of CBD [9], indicating the other four adverse effects were more likely due to THC's common effects [8].

Such clinical evidence of potential THC adverse effects from high intakes of full spectrum CBD-dominant formulations, especially for more sensitive geriatric and dementia populations, supports the need for offering lower relative THC levels as formulated into Cannacea Tagrid’s 100 with its tailored 70:1 CBD:THC ratio minimum.

Importance of Monitoring and Correcting for Potential Drug Interactions

In the low-intake CBD-dominant trial reviewed, clear adverse effects and subsequent participation withdrawals were also seen in some subjects [2]. By analyzing each subject’s complete pharmacological protocol disclosed in the study, these adverse effects may have been from the pharmaceutical drug cocktails some subjects were simultaneously taking [2,9,10]. Phytocannabinoids often inhibit various CYP450 enzymes that metabolize many drugs, thereby increasing drug plasma levels, which amplifies those drugs' intended and adverse effects [9,10].

Cannacea provides health professionals with extensive drug and supplement interaction resources in our Clinical Supplement Monograph (Section 6), and our Drug/Supplement Interactions List (also linked in our Clinical Monograph), which resources - intended solely for health professionals - are made available through the Cannacea Practitioner Site.

Conclusion

We hope this summary of peer-reviewed clinical science inspires hope and natural solutions to improve the health and life quality of those diagnosed with Alzheimer’s Disease and Dementia. Such clinical evidence also supports the tried and tested approach of starting with a low phytocannabinoid intake and building up slowly to the lowest-possible intake that provides sufficient therapeutic benefit, which personalized intake respects each person’s unique condition, Endocannabinoid System tone, and sensitivities. Such a progressively increased, tailored approach also supports the need to carefully monitor and correct for any potential effects of interactions between the cannabinoids and pharmaceutical drugs also taken. The clinical data further emphasizes the importance of selecting full spectrum formulas with an appropriate level of relative THC to maximize THC’s therapeutic effects while minimizing its adverse effects.

We are here to empower the public and the medical community, so please feel free to reach out to us or comment below!

Disclaimer: These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.

References

1. Hermush, V et al. (2022). Effects of rich cannabidiol oil on behavioral disturbances in patients with dementia: A placebo controlled randomized clinical trial. Frontiers in Medicine 9: 951889.
2. Papadopoulou, L et al. (2022). Neuropsychiatric Symptoms in Dementia. The Added Value of Cannabinoids. Are they a Safe and Effective Choice? Case Series with Cannabidiol 3%. Annals of Case Reports 7: 799.
3. Alexandri, F et al. (2023). The Effect of Cannabidiol 3% on Neuropsychiatric Symptoms in Dementia – Six-Month Follow-Up. Clinical Gerontologist (May 8): 1-8.
4. Pautex, S et al. (2022). Cannabinoids for behavioral symptoms in severe dementia: Safety and feasibility in a long-term pilot observational study in nineteen patients. Frontiers in Aging Neuroscience 14: 957665.
5. Palmieri, B, Vadala, M (2023). Oral THC:CBD cannabis extract in main symptoms of Alzheimer disease: agitation and weight loss. La Clinica Terapeutica 174(1): 53-60.
6. Watt, G, Karl, T (2017). In vivo Evidence for Therapeutic Properties of Cannabidiol (CBD) for Alzheimer’s Disease. Frontiers in Pharmacology 8: 20.
7. de Paula Faria, D et al. (2022). Cannabidiol Treatment Improves Glucose Metabolism and Memory in Streptozotocin-Induced Alzheimer’s Disease Rat Model: A Proof-of-Concept Study. International Journal of Molecular Sciences 23(3): 1076.
8. Filipiuc, LE et al. (2021). Major Phytocannabinoids and Their Related Compounds: Should We Only Search for Drugs That Act on Cannabinoid Receptors? Pharmaceutics 13: 1823.
9. Huestis, MA et al. (2019). Cannabidiol Adverse Effects and Toxicity. Current Neuropharmacology 17(10): 974-989.
10. Kocis, PT, Vrana, KE (2020). Delta-9-Tetrahydrocannabinol and Cannabidiol DrugDrug Interactions. Medical Cannabis and Cannabinoids 3: 61-73.