Micro-dosing as a Potential New Therapy for Various Psychiatric Disorders?

 

Source: Vanity Fair

In our culture today we tend to learn about new information via media whether that is movies, Instagram, or YouTube. Recently, one tv-show that has spurred some commotion is, Nine Perfect Strangers, which can be found on Hulu. In the beginning we are introduced to nine different people who have each gone through different perils throughout their life and have had a hard time overcoming them. Each of them decides to attend a retreat where they are promised healing and transformation. Towards the end of the show, it is uncovered that Masha the women who has been hosting this retreat has been micro dosing each of the guest. Each morning she was making a tea with a miniscule amount of psychedelics, which would help them deal with deeply rooted issues such as anxiety, depression, anger management issues and addiction. Interestingly, throughout the show we see the benefits of this micro dosing but also the drawbacks. If you are someone like me, you may be wondering whether this would work? Would this be a new treatment for patients in the future? No worries, these will all be questions that I will answer as I discuss more about micro-dosing in the upcoming paragraphs.

         There are pharmacological mechanisms of action for micro-dosing; however, it is possible that individual differences in metabolism, psychopathological diseases, personality, interpretation of signals may affect how micro-dosing outcomes manifest (Anderson et al., 2019). The receptor involved in micro-dosing is the serotonin 5HT-2A receptor. A variety of mutations of this receptor which may affect how the 5HT-2A agonists such as LSD and psilocybin are processed may be present in different individuals. This may be exemplified with an example of a healthy person in comparison to an individual who may be suffering with depression. In addition, the effect of these substances on 5HT-2A receptors has enhanced neural plasticity and neurogenesis along with neuroprotective effects, which are relevant to neurodegenerative diseases (Ona & Bouso, 2019). As we can see, micro-dosing will not have the same effect on everyone and there really isn’t a one dose fits all since there are genetic components involved in micro dosing that result in differential responses.

Source:  www.slashgear.com

So, you may be wondering if I begin micro-dosing what type of benefits could I possibly expect? Many personal accounts of micro-dosing have been uploaded on to YouTube and qualitative study was completed looking at some of these personal accounts. Anderson and Kjelleren (2019), classified their findings from these YouTube videos into four categories. The first category included enhanced state and heightened senses (more focus and energy, experiencing the present moment, improved mood and reductions in sadness, anger, and stress). The second category included insights and transformations (augmented self-reflection, thoughtful insights which led to deeper connections and changes in habits). The third category included improved abilities and optimal performance (increased creativity, enhanced productivity and effectiveness, and extraversion in social settings). In the final category was relief and cure for health conditions (benefits regarding depression, anxiety, and ADHD etc). These qualitative studies are informative, but survey studies are a little more helpful when potential benefits are emphasized. One survey study recruited 278 participants who had already been micro-dosing either with LSD or psilocybin. Anderson et al. (2019a) reported the major benefits of micro-dosing to be an improved mood (26.6%), improved focus (14.8%), creativity (12.9%). Some users even reported a reduction in caffeine (44.2%), alcohol (42.3%), cannabis (30.3%), and tobacco (21%). They also found that micro-dosing resulted in lower scores for dysfunctional attitudes and negative emotions, but higher scores for wisdom, creativity, and open mindedness (Anderson et al., 2019). It is easy to get caught up on all these positive results especially in an age when people want a quick fix to issues such as mental illness. I believe micro-dosing has very positive benefits, but it is important to consider the harmful effects as well before participating.

         There were some negative side effects reported by some of the participants from these previous studies. Anderson and Kjelleran (2019), mentioned how some users experienced increased anxiety, panic attacks, gastrointestinal cramps, restlessness, jitters, insomnia, decreased problem solving skills and cognitive function. In some instances, patients experienced a worsening of symptoms including mental health, over stimulations, or a bad trip when LSD was combined with cannabis. Honestly, the side effects continue from there and contradict the positive effects experienced in the paragraph above. To me, this emphasizes how little we still know about micro-dosing, and how studies are difficult to compare due to the difference in methods and variables which may or may not be confounding variables. I believe this may be a promising therapy for the future, but studies still need to be completed to have a firmer understanding of these positive and negative benefits.

         In my view this is an exciting field, in which more research needs to be completed before more of the public jumps on the micro-dosing bandwagon. As we have seen from other therapies such as cannabidiol (CBD), that micro-dosing will not be an end all therapy where it will fix each issue that you have but will be helpful in mitigating issues you may be experiencing. This therapy is gaining momentum in the medical community, but research is still being completed before it will be offered as a legal therapy. We have a lot to look forward to as the scientific community continues to discover more about micro-dosing.

 By Ashely Wahlman, A Master’s of Medical Science Student at the University of Kentucky College of Medicine

 Sources:

Anderson, T., Petranker, R., Christopher, A., Rosenbaum, D., Weissman, C., Dinh-Williams, L. A., Hui, K., & Hapke, E. (2019). Psychedelic microdosing benefits and challenges: an empirical codebook. Harm reduction journal, 16(1), 43. https://doi.org/10.1186/s12954-019-0308-4

Anderson, M., and Kjellgren,A. (2019). Twenty Percent better with 20 micrograms?A qualitative study of psychedelic microdosing self-rapports and discussion on YouTube.Harm reduction Journal,16(1).

Ona,G., and Bouso, J.C.(2020).Psychedlic drugs as a long-needed innovation in psychiatry. Qeios, https://doi.org/10.32388/T3EM5E.2

 

Sleep and No-Sickness? The Preventative Impact of Melatonin on Covid-19 Patients

 

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Being the hardworking students that we are, we tend to allow our sleep schedules to fall out of “circadian-rhythm” (haha get it?). We tend to give into the marketing of pretty Starbucks coffee drinks to keep us awake and the idea of studying for hours prioritizing good grades over getting a good night’s sleep. This contributes to the 50 to 70 million Americans who suffer from sleep disorders or sleep deprivation and more than 60 million Americans who take sleep medications every year. It is estimated that Americans spend more than $41 billion on sleep aids and remedies (Penn Medicine). But sleeping issues have been around since our earliest existence, so what did we do before?

 

When we think of sleep remedies, we can look back as early as early Egyptian and ancient Roman times. One of the most well-known ancient remedies is chamomile. Not only was it great for sleeping issues but has many other positive effects including its ability to act as a cold remedy (Wise Ape, 2021). Today we often use it as a common nighttime staple to help us sleep and relax. However, for some people it does not work, or they need something stronger to aid their sleep. This is where the understanding and pharmacological production of melatonin became a game changer to the sleep-deprived people of the world and now possibly Covid-19 patients? First, let’s understand where melatonin comes from.

 

Melatonin is a natural hormone that is produced by our pineal gland. It is a derivative of tryptophan, an important amino acid necessary for maintaining of many of bodily functions. It was first isolated by Aaron B Lerner in 1958 of Yale University School of Medicine when he was conducting vitiligo research on frogs. He isolated a hormone melatonin thinking it would lighten the skin of frogs, only it didn’t. Instead, he found that it was responsible for maintaining cycles of wakefulness and rest. With respect to its target, melatonin binds to two type of G-protein receptors, MT1 and MT2, in the suprachiasmatic nucleus, a tiny region of the hypothalamus in the brain. High levels of melatonin can induce sleep. When our sleep schedule is normal, darkness prompts our pineal gland to secrete melatonin. The lack of melatonin production during the day will elicit wakefulness. This is why if your sleep schedule is off because you are doing things like staring at your phone until 2am, you are exposing yourself to blue light which will not let you produce melatonin. Now you are a walking zombie at your 8am class because you got no sleep. However, as important as melatonin is to sleep, it has been found to have other amazing benefits, including helping in learning and memory, fertility and reproduction, and most-recently immune activity (Srinivasan et al., 2005). This finding has been used to explore its benefits to Covid-19 patients.

 

SARS-CoV-2 can cause severe inflammatory responses and oxidative stress; two biological events alleviated by melatonin. One way melatonin can act is by reducing oxidative stress through its ability to increase an antioxidant known as glutathione. Glutathione is an important antioxidant that combats damage within cells, such as free radicals. With respect to COVID-19, a common symptom resulting from viral infection is oxidative stress caused by an increase in free radicals. Thus, melatonin can increase glutathione levels and reduce conditions of oxidative stress in COVID-19 patients. In addition, melatonin has anti-inflammatory abilities which arise from its affinity to G-protein-coupled receptors which control the secondary signaling pathways that impact the immune response. With respect to COVID-19, the infecting SARS-CoV-2 virus binds with high affinity to angiotensin-converting enzyme 2 (ACE2) receptors on the epithelial lining of the lungs. This binding triggers a proinflammatory response. However, calmodulin, an important messenger protein in the G-protein-coupled secondary pathway, controls the amount of ACE2 receptors on the plasma membrane. Melatonin can inhibit the coupling of ACE2 receptors and SAR-COV2 during viral particle fusion through its inhibition of calmodulin as it is regulated by the secondary messenger pathway (Cross et al., 2021). But if you don’t believe me, just look at how complex melatonin’s target pathway is (Cecon et al., 2017).

Fig. 1. Melatonin receptor pathway. Graph from E Cecon et al., Melatonin receptors: molecular pharmacology and signaling in the context of system bias. British Journal of Pharmacology. (5 July 2017).

Complex, I know! There are so many other ways melatonin has proven to be a great drug for other disease use other than just sleep. But from those short explanations on how melatonin can work, you get the idea. This is an incredible new form of exploration that can truly help so many people fighting COVID-19. As incredible as these findings do sound, we are still exploring the full accuracy and positive effectiveness of this drug on COVID-19 patients. More importantly, it is imperative to stay on top of new research and findings as we are constantly at risk of COVID-19 as the world begins opening up again. So now we ask the big question, do we bring this idea further to light that COVID-19 is a potential drug market for COVID-19? Researchers have already explored melatonin’s benefits in viral disease similar to COVID-19 so why not to treat COVID-19 patients? One problem is that we could be risking another “Ivermectin” fiasco, with multiple people storming our local CVS and buying all of the over-the counter melatonin thinking it can completely fight COVID-19 (only this being a much safer and beneficial option if you are a struggling college student who never sleeps). What do you think?

By Sarah Mandviwala, A Master's of Medical Science Student at the University of Kentucky

 

Works Cited

Ape, T. W. (2018, April 17). The history of chamomile tea. Wise Ape. Retrieved October 12, 2021, from https://www.wiseapetea.com/blogs/knowledge/the-history-of-chamomile-tea.

Cecon, E., Oishi, A., & Jockers, R. (2017, August 17). BPS Publications. British Pharmacological Society | Journals. Retrieved October 12, 2021, from https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bph.13950#:~:text=Melatonin%20receptor%20signalling%20pathways.,and%20increase%20in%20intracellular%20Ca2%2B.

Cross, K. M., Landis, D. M., Sehgal, L., & Payne, J. D. (2021, August). Melatonin for the early treatment of covid-19: A narrative review of current evidence and possible efficacy. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. Retrieved October 12, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190272/#bib38.

Melatonin and zolpidem: Do sleeping aids actually work? Penn Medicine. (n.d.). Retrieved October 12, 2021, from https://www.pennmedicine.org/updates/blogs/health-and-wellness/2018/july/sleeping-aids.

Srinivasan, V., Maestroni, G. J. M., Cardinali, D. P., Esquifino, A. I., Perumal, S. R. P., & Miller, S. C. (2005, November 29). Melatonin, Immune Function and aging. Immunity & ageing : I & A. Retrieved October 12, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1325257/.