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Will we be treating depression with psychedelics?

Updated: Jun 8



Depression is the leading cause of disability worldwide, with up to 25% of women and 12% of men suffering from it in their lifetime1. It is a mental health disorder consisting of either a depressed mood or a loss of interest or pleasure. This can therefore lead to a loss of appetite, fatigue, concentration difficulties, guilt and suicide ideation2. It is thought to be due to low levels of chemicals in the brain called monoamines, such as serotonin. This is otherwise known as the “Monoamine Hypothesesis”3.


It is not unreasonable to predict that most people reading this article have, or knows someone who has, suffered from depression at least one point in their lives. Further there is currently no definitive treatment for depression. 30% of patients do not achieve full remissiona on traditional depression treatment4, compromising of antidepressants and CBT, so another therapy is needed.


This is where psychedelics could come in. One drug that has been recently explored in treatment of depression is psilocybin. Naturally found in “psilocybe” mushrooms, it has been historically used as a medicinal treatment for years. It has a similar structure to the drug serotonin5, hence psilocybin may be mimicking its effects. Further, psilocybin may increase the connectivity of the neurones in the brain, leading to the classic psychedelic state, or “high”. This, therefore, leads to increased openness of the patient3.


How does this relate to depression treatment? Patients with depression tend to be closed off to new perspectives, reducing the effectiveness of talking therapies. However, if the patient is given a single dose of psilocybin for example, the sense of openness the drug portrays alongside bpsychotherapy may help to provide a breakthrough, and therefore lead to remission in depressive symptoms. This effect has been seen in recent studies in patients who were deemed refractory. After one dose of psilocybin and associated psychotherapy, remission has been seen at one week after treatment in 58% of patients6. Further, there is evidence of psilocybin also being effective five weeks after one dose5 for refractory depression. Given the initial statistic of only 30% of all patients being treated on traditional therapies, these are incredible results.


There are definitely positives to using psychedelics as treatment. Of course, it is highly effective and may act as a new treatment that can really improve the quality of life of patients who otherwise had no other options. Further, it is likely that that infrequent doses are needed, which reduces the burden of daily medications as would be seen on antidepressants. Further, it actually has a low potential for abuse6.


However, there are also drawbacks. First of all, there can be side effects. There is host of short term and long-term side effects including psychosis (disordered thinking, paranoia, visual disturbances), flashbacks to certain drug experiences (formally known as hallucinogen persisting perception disorder, or HPPD) which seriously need to be considered. Psilocybin for example has not seen a case of HPPD yet, and different doses of LSD are safer than others7. Hence further research will need to be done to ensure a safe and effective dose and drug is selected.


Further, the studies I have mentioned are not long-term enough. Five weeks is not enough time to say for sure that psychedelics are a feasible treatment for depression which is a chronic and lifelong condition. They also tested small groups of people. 20 or so treatment-refractory depressive patients may not accurately represent how the whole group will respond to treatment, and hence the studies need to be done on a larger scale.


Lastly, even if side effects were bypassed, and the studies were stronger, there is still going to be a stigma around treatment with psychedelics8. Stigma is a big part of what has hindered greater amounts of research on this topic. Stigma may prevent patients and the general public from seeing it as a real potential treatment. Despite it being trialled as treatment in a controlled, safe and ethical environment by doctors and scientists alike, it is still an illicit drug that has been and is still being abused recreationally. Hence overcoming that in order to for psychedelics to be legitimised will be one of the biggest challenges of all.


So, the short answer? At the moment, I believe there is still a way to go before psychedelics are a part of regular treatment for depression. But there is a lot of potential, and it would be a shame to waste it.


Keywords:

aRemission: No longer symptomatic of that disease. E.g. patients diagnosed with depression who are no longer depressed.

bPsychotherapy: Any form of talking therapy.

cRefractory depression: these are patients who, after two different courses of antidepressants for a certain length of time still experience depressive symptoms.


References:

  1. Jinghui Wang, Xiaohang Wu, Weiyi Lai et al. Prevalence of depression and depressive symptoms among outpatients: a systematic review and meta-analysis. BMJ Open 2017;7:e017173. Available from: doi: 10.1136/bmjopen-2017-017173

  2. Tolentino JC, Schmidt SL. DSM-5 Criteria and Depression Severity: Implications for Clinical Practice. Front Psychiatry. 2018;9:450. Published 2018 Oct 2. doi:10.3389/fpsyt.2018.00450

  3. Emmanuel Jesulola, Ian J. Baguley. Understanding the pathophysiology of depression: From monoamines to the neurogenesis hypothesis model - are we there yet? Behavioural Brain Research. 2018. 341: 79-90. Available from: doi: https://doi.org/10.1016/j.bbr.2017.12.025

  4. Al-Harbi KS. Treatment-resistant depression: therapeutic trends, challenges, and future directions. Patient Prefer Adherence. 2012;6:369-88. doi: 10.2147/PPA.S29716. Epub 2012 May 1. PMID: 22654508; PMCID: PMC3363299.

  5. Carhart-Harris, R.L., Roseman, L., Bolstridge, M. et al. Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Sci Rep 7, 13187 (2017) doi:10.1038/s41598-017-13282-7

  6. Leor Roseman, Lysia Demetriou, Matthew B. Wall, David J. Nutt, Robin L. Carhart-Harris. Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression. Neuropharmacology. 2018. 142: 263-269. Available from: doi: https://doi.org/10.1016/j.neuropharm.2017.12.041

  7. Liechti, M. Modern Clinical Research on LSD. Neuropsychopharmacol 42, 2114–2127 (2017) doi:10.1038/npp.2017.86

  8. Psychedelics: Where we are now, why we got here, what we must do. Sean J. Belouin, and Jack E. Henningfield. Neuropharmacology. Volume 142, November 2018, Pages 7-19. https://doi.org/10.1016/j.neuropharm.2018.02.018


Article Written By Febisayo (Purpose Print Team)



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