# Going mediterranean

A bit of pharmacology now.

# [Depression and Mediterranean diet](https://readwise.io/reader/shared/01gq8h300d2xxfqnmzvayw4fgr/)

![Mediterranean Diet | Oldways](https://oldwayspt.org/sites/default/files/thumbnails/image/1-5pyramid_flyers20192.jpg align="center")

*Fuck that, too hard*

[First one (SMILES)](https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0791-y)

* 12 weeks, 67 participants, moderate-severe depression
    
* **32% of patients remitted** vs. 8% in the control group
    
* Number-to-treat ~4 compared to [SSRIs' ~7 and TCAs' 9](https://www.madinamerica.com/2021/05/numbers-needed-treat/#:~:text=According%20to%20a%20Cochrane%20review,7%2C%20and%209%20for%20tricyclics.)
    

[Another study](https://pubmed.ncbi.nlm.nih.gov/31596866/)

![](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6784975/bin/pone.0222768.g003.jpg align="left")

* 38 participants in each group completed the study
    
* Cohen's effect size of 0.75 compared to antidepressants' [improvement-model ES of 0.76](https://onlinelibrary.wiley.com/doi/10.1111/acps.13340)
    

[Third one](https://pubmed.ncbi.nlm.nih.gov/35441666/) (AMMEND)

![](https://cdn.psychopharmacologyinstitute.com/transcripts/%5B6103%5D%20Depression%20and%20Mediterranean%20Style%20Diet/image11.jpeg align="center")

* 72 participants completed, 12-week length
    
* 20-point Beck Depression Inventory drop vs. 6-point drop in the therapy group
    

## Conclusions

**Get yo ass to Italy and learn to eat Mediterranean**. Or just plan your diet accordingly.

# [Psilocybin microdosing](https://readwise.io/reader/shared/01gpjy8a16gm4yfx0qnnnp93kf/)

Oh, I've just laughed at that. Lemme just quote:

*"We recruited 34 individuals starting to microdose with psilocybin mushrooms (Psilocybe cubensis), one of the materials most frequently used for this purpose. Following a double-blind placebo-controlled experimental design, we investigated the acute and short-term effects of 0.5 g of dried mushrooms on* ***subjective experience, behavior, creativity (divergent and convergent thinking), perception, cognition, and brain activity.***

*The reported acute* ***effects were significantly more intense for the active dose*** *compared to the placebo, <mark>but only for participants who correctly identified their experimental condition.</mark>*

*These changes were accompanied by reduced EEG power in the theta band, together with preserved levels of Lempel-Ziv broadband signal complexity. For all other measurements there was <mark>no effect of microdosing except for few small changes towards cognitive impairment.</mark>"*

## Conclusions

* Dose hard if you do at all, preferably with a therapist ⇢ we **still don't know if microdosing has a big effect**, i.e. that the degree of neuroplasticity does it induce ([despite the trials](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830000/))
    
* Pair it with [behavioral changes, variety](https://www.verywellmind.com/what-is-brain-plasticity-2794886) and [activation](https://www.medicalnewstoday.com/articles/behavioral-activation#summary) along with healthy habits and eating
    
* Of course [comply with legal regulations in your country](https://www.bbc.com/russian/news-64410972#:~:text=%D0%9C%D0%BE%D1%81%D0%BA%D0%BE%D0%B2%D1%81%D0%BA%D0%B8%D0%B9%20%D1%81%D1%83%D0%B4%20%D0%BF%D1%80%D0%B8%D0%B3%D0%BE%D0%B2%D0%BE%D1%80%D0%B8%D0%BB%20%D0%95%D0%B2%D0%B3%D0%B5%D0%BD%D0%B8%D1%8E%20%D0%9C%D0%B0%D0%BA%D0%B0%D1%80%D0%B5%D0%BD%D0%BA%D0%BE,%D0%BC%D0%B0%D1%80%D0%B8%D1%85%D1%83%D0%B0%D0%BD%D1%8B%20%D0%B8%20%D0%BD%D0%B5%D1%81%D0%BA%D0%BE%D0%BB%D1%8C%D0%BA%D0%BE%20%D0%B1%D0%BE%D0%BB%D0%B5%D1%83%D1%82%D0%BE%D0%BB%D1%8F%D1%8E%D1%89%D0%B8%D1%85%20%D1%82%D0%B0%D0%B1%D0%BB%D0%B5%D1%82%D0%BE%D0%BA.), that goes without sayin'
    

# [Lithium's mechanism](https://readwise.io/reader/shared/01gr7jwz0c2jnhpsdvgkvpa7sq/)

![](https://cdn.psychopharmacologyinstitute.com/wpengine/uploads/Lithium-Mechanism-of-Action-21-1024x576.png align="center")

*OMG RLY*

* Lithium has **neuroprotective** and **neuroproliferative** effects (preservation of grey matter) in multiple brain regions. *Mechanism of it is still unknown (yet we can conclude it has something to do with other mechanisms, can't we).*
    
    ![](https://cdn.psychopharmacologyinstitute.com/wpengine/uploads/Lithium-Mechanism-of-Action-10-1024x576.png align="center")
    
* Chronic administration of **lithium** ⇢ ⬇️ functionality of **GPCR** subunits ⇢ ⬇️ **dopaminergic neurotransmission is inhibited**
    
    ![](https://cdn.psychopharmacologyinstitute.com/wpengine/uploads/Lithium-Mechanism-of-Action-12-1024x576.png align="center")
    
* Chronic administration ⇢ **lithium induces ⬇️ NMDA downregulation.** *Lithium acutely stimulates the NMDA receptor, increasing glutamate availability in the postsynaptic neuron.*
    
    ![](https://cdn.psychopharmacologyinstitute.com/wpengine/uploads/Lithium-Mechanism-of-Action-14-1024x576.png align="center")
    
* **Lithium** ⇢ ⬆️ **GABA levels in cerebrospinal fluid**. At the **presynaptic** level, lithium increases ⬆️ GABA release. At the postsynaptic level it **upregulates ⬆️ GABA-B** receptors.
    
    ![](https://cdn.psychopharmacologyinstitute.com/wpengine/uploads/Lithium-Mechanism-of-Action-17-1024x576.png align="center")
    
* **Lithium** ⬇️ **IMPase** and **IPPase** when they are in excess ⇢ ⬇️ myoinositol synthesis. *However, the* [*myoinositol depletion hypothesis*](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751514/#:~:text=Inositol%20depletion%20hypothesis%20%E2%80%93%20valproic%20acid,of%20structurally%20disparate%20antibipolar%20drugs.) *hasn't been yet proven.*
    
    ![](https://cdn.psychopharmacologyinstitute.com/wpengine/uploads/Lithium-Mechanism-of-Action-18-1024x576.png align="center")
    
* **Lithium ⬇️ PKC** and its downstream target **MARCKS** ⇢ linked to antimanic effects.
    
    ![](https://cdn.psychopharmacologyinstitute.com/wpengine/uploads/Lithium-Mechanism-of-Action-19-1024x576.png align="center")
    
* **Lithium ⬇️ GSK-3**. GSK-3 stands for Glycogen Synthase Kinase 3. *This enzyme is involved in gene transcription and synaptic plasticity and activated under conditions of chronic stress such as mania.*
    
    ![](https://cdn.psychopharmacologyinstitute.com/wpengine/uploads/Lithium-Mechanism-of-Action-20-1024x576.png align="center")
    
* **Lithium ⬆️ CREB transcription factor**, a downstream target of adenylyl cyclase ⇢ ⬆️ **production of BDNF and Bcl-2**, neuroprotective factors.
    

## Conclusions

Just some information as [lithium can potentially cause](https://doi.org/10.1016/S0140-6736%2811%2961516-X) hypothyroidism (⇢ weight gain) and kidney damage. Some quotes:

*"A daily* ***adult lithium intake of 1 mg/day*** *has been proposed. However, treatment* ***dosages of lithium orotate range from 200 µg to 25 mg****. In my practice, I typically start my patients at 5 mg per day, and then see how they’re feeling after 1 week."*

*"It is my opinion that lithium supplementation will have added benefit when* ***combined with high-dose omega-3 fish oil (eg, 3-6 g/d), as well as B-vitamin complex, including folinic acid, methylcobalamin, and niacin****. Supplementing a complex of B vitamins offers greater value for brain function as compared to supplementing single B vitamins."*

# [Infections and Alzheimer's risks](https://readwise.io/reader/shared/01gqyh27s583j3vr5x0rxxj0tg/)

![Infectious Burden and Alzheimer Disease: Is There a Link?](https://cdn.sanity.io/images/0vv8moc6/psychtimes/fd34f41f00d10b94f5aca09b2963cdb02ddf09a7-1031x905.jpg?fit=crop&auto=format align="center")

In short: chronic inflammation caused by certain infections (either [herpes](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234998/), [borrelia](https://lymediseaseassociation.org/lyme-tbd/research-articles/peer-reviewed-articles/borrelia-burgdorferi-in-the-alzheimers-brain/#:~:text=burgdorferi%20can%20be%20found%20in,pathology%2C%20and%20chronic%20neurodegenerative%20diseases.) etc.) can certainly increase AD risks long-term, especially in predisposed populations. **Keep safe, and use antivirals** if needed:

*"Interestingly, according to recent registry-based studies, the risk of developing dementia with both symptomatic HSV and herpes zoster infection appears to be* ***reduced after antiviral treatment (hazard ratio \[HR\] 0.09, 0.55, and 0.76, respectively)****.*[*<sup>15</sup>*](https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/trc2.12119#trc212119-bib-0015)*<sup>, </sup>* [*<sup>18</sup>*](https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/trc2.12119#trc212119-bib-0018)*<sup>, </sup>* [*<sup>22</sup>*](https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/trc2.12119#trc212119-bib-0022) *The protective effect of antiviral drugs showed a* ***dose-response relationship in which a longer duration of treatment (&gt;30 days) appeared to have a greater preventive impact*** *on dementia incidence compared to a shorter regime.*[*<sup>22</sup>*](https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/trc2.12119#trc212119-bib-0022)*<sup>"</sup>*