Depression reduction

From PsychonautWiki
Jump to navigation Jump to search

Depression reduction is the experience of minimizing the symptoms associated with depression and low mood states. It is distinct from effects such as cognitive euphoria, as it does not simply elevate the user's mood but instead results in a sense of stable emotional well-being.

Depression reduction most commonly occurs with adequate nutritional intake.[1][2][3][4][5] Severe depression is effectively reduced with conventional antidepressants; although in mild to moderate depression, SSRI's and tricyclic antidepressants appear (on average) to be either only minimally helpful or completely ineffective.[6] However, depression reduction can also occur under the influence of hormone replacement therapies[7][8] and modafinil.[9]


Euthymia (semantically the opposite of dysthymia) is a long-lasting and self-sustaining experience of stable emotional well-being.[10] This state is characterized by:

  • A lack disordered mood in patients with prior clinically diagnosed mood disorders; if sadness/anxiety/irritability are experienced they are short-lived and do not significantly impact everyday life.
  • Feeling cheerful, calm, active, and interested in things.
  • Possessing cognitive flexibility.
  • Sleep is refreshing or restorative.
  • A unifying outlook on life which guides actions and feelings to shape the future.
  • Being resistant to stress (resilience and anxiety or frustration tolerance).

This is unlikely to be an isolated effect component but rather the result of combining an appropriate environment with other coinciding effects such as rejuvenation, introspection, personal bias suppression, and spirituality intensification. It may also stem from the direct neurological changes that occur as a result of a substances’ pharmacological action.

Euthymia most commonly occurs at varying levels of efficacy under the influence of a range of different substances, primarily psychedelics in combination with psychotherapy,[11][12] or dissociatives.[13] However, it can also occur throughout the course of prescribed psychiatric medications and under the influence of certain entactogens.


Immediate relief

Scheduling activities is a behavioral treatment for depression that appears as effective as other psychological or pharmacological treatments.[14] There is a significant relationship between mood and the number of pleasant activities engaged in. Depressed individuals find fewer activities pleasant, engage in pleasant activities less frequently, and obtain less positive reinforcement.

Exercise is an evidence-based treatment for depression.[15][16][17][18][19] It also has the advantage of preventing the increased risk of drug-drug interactions. Moderate to heavy exercise of any type (including yoga) appears as effective, and do not significantly differ from, other pure forms of depression treatment such as psychotherapy or pharmacological treatment. Large changes in fitness do not appear necessary either.


Cognitive Behavioral Therapy is an effective treatment for adult depression.[20] There are no large differences in efficacy between major psychotherapies for mild to moderate depression.[21] There is also a large body of evidence supporting computerized care, and psychoeducational interventions.[22][23][24][25][26]

For patients with mild or moderate depression in natural settings, antidepressant relapse rate is high. Behavioral therapy may prevent relapses in the long-term.[27]

Psychedelic psychotherapy

A 2021 meta analysis examined 12 double-blind randomized controlled trials for classical psychedelics treating depressive symptoms.[11] A single-dose in combination with a psychotherapy treatment program created moderate to large reductions in negative mood symptoms. This reduction remained consistent at several intervals throughout the examined time-frame of 3 hours to 60 days; there were simply not enough randomized clinical trials to extend their timeframe. This effect was present in both healthy and disordered patients.

A 2020 meta analysis examined 9 placebo-controlled studies for psychedelic psychotherapy.[12] The studies had one to three doses in combination with a psychotherapy treatment program and results were measured several times over the course of 6 months. The authors' effect size indicated an 80% probability that a randomly selected patient receiving psychedelic psychotherapy outperforms a patient receiving placebo. Additionally, there were no incidents of severe adverse effects. The authors even compared their results to other meta analyses examining "gold standard" treatments for several mental health problems: psychedelic psychotherapy greatly outperformed.

Psychotherapy with 1-3 doses of a classical psychedelic greatly outperforms current pharmacological standards in regards to producing a depression reduction all while having minimal to no adverse effects. The benefits of only needing a single dose over the course of 6 months as opposed to a daily administration of a substance incurring larger side effects and not producing desired effects until the 2-4 week mark appear obvious.

Ketamine and its isomers


Both ketamine and esketamine may increase bladder damage.

Ketamine possesses a strong abuse potential at typical antidepressive doses.[28][29] Ketamine has reported cases of severe bladder and liver injury. Esketamine, a newer nasal spray formulation of Ketamine, does not have any reported cases and is purported to have a better safety profile. However, in recent short-term clinical trials esketamine still more-than-doubled the amount of adverse bladder events when compared to placebo (6-10% vs 1-4%). Although 2/3 of esketamine incidents resolved themselves either without intervention or through a lowering of dosage, any physiological damage is acute and immediate: in typical dose regimens steady-state concentrations are not reached.

Ketamine offers a (dose-dependent) large immediate depression reduction for 30-50% of patients; its effect-sizes become moderate to small by day 7.[30][31][32] Weekly to biweekly dosing maintains a statistically significant depression reduction measured at Day 28 and repeated administration has resulted in cases of euthymia.[13][29] A family history of alcohol-use-disorder in a first-degree relative is associated with an improved antidepressive response, and a reduction of adverse mental effects such as dysphoria. Its antidepressant properties may also stem more generally from dissociatives' novelty and/or immersion intensifications.

Psychoactive substances

Compounds within our psychoactive substance index which may cause this effect include:


  1. Bender, Ansley; Hagan, Kelsey E.; Kingston, Neal (2017). "The association of folate and depression: A meta-analysis". Journal of Psychiatric Research. 95: 9–18. doi:10.1016/j.jpsychires.2017.07.019. ISSN 0022-3956. 
  2. Spedding, Simon (2014). "Vitamin D and Depression: A Systematic Review and Meta-Analysis Comparing Studies with and without Biological Flaws". Nutrients. 6 (4): 1501–1518. doi:10.3390/nu6041501. ISSN 2072-6643. 
  3. Sublette, M. Elizabeth; Ellis, Steven P.; Geant, Amy L.; Mann, J. John (2011). "Meta-Analysis of the Effects of Eicosapentaenoic Acid (EPA) in Clinical Trials in Depression". The Journal of Clinical Psychiatry. 72 (12): 1577–1584. doi:10.4088/JCP.10m06634. ISSN 0160-6689. 
  4. Huang, Ruixue; Wang, Ke; Hu, Jianan (2016). "Effect of Probiotics on Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials". Nutrients. 8 (8): 483. doi:10.3390/nu8080483. ISSN 2072-6643. 
  5. Ng, Qin Xiang; Koh, Shawn Shao Hong; Chan, Hwei Wuen; Ho, Collin Yih Xian (2017). "Clinical Use of Curcumin in Depression: A Meta-Analysis". Journal of the American Medical Directors Association. 18 (6): 503–508. doi:10.1016/j.jamda.2016.12.071. ISSN 1525-8610. 
  6. Fournier, Jay C.; DeRubeis, Robert J.; Hollon, Steven D.; Dimidjian, Sona; Amsterdam, Jay D.; Shelton, Richard C.; Fawcett, Jan (2010). "Antidepressant Drug Effects and Depression Severity". JAMA. 303 (1): 47. doi:10.1001/jama.2009.1943. ISSN 0098-7484. 
  7. Zarrouf, Fahd Aziz; Artz, Steven; Griffith, James; Sirbu, Cristian; Kommor, Martin (2009). "Testosterone and Depression". Journal of Psychiatric Practice. 15 (4): 289–305. doi:10.1097/01.pra.0000358315.88931.fc. ISSN 1538-1145. 
  8. Walther, A., Breidenstein, J., Miller, R. (1 January 2019). "Association of Testosterone Treatment With Alleviation of Depressive Symptoms in Men: A Systematic Review and Meta-analysis". JAMA Psychiatry. 76 (1): 31. doi:10.1001/jamapsychiatry.2018.2734. ISSN 2168-622X. Retrieved 29 May 2022. 
  9. Rock, P. L.; Roiser, J. P.; Riedel, W. J.; Blackwell, A. D. (2013). "Cognitive impairment in depression: a systematic review and meta-analysis". Psychological Medicine. 44 (10): 2029–2040. doi:10.1017/S0033291713002535. ISSN 0033-2917. 
  10. Fava, Giovanni A.; Bech, Per (2015). "The Concept of Euthymia". Psychotherapy and Psychosomatics. 85 (1): 1–5. doi:10.1159/000441244. ISSN 0033-3190. 
  11. 11.0 11.1 Galvão-Coelho, Nicole L.; Marx, Wolfgang; Gonzalez, Maria; Sinclair, Justin; de Manincor, Michael; Perkins, Daniel; Sarris, Jerome (2021). "Classic serotonergic psychedelics for mood and depressive symptoms: a meta-analysis of mood disorder patients and healthy participants". Psychopharmacology. 238 (2): 341–354. doi:10.1007/s00213-020-05719-1. ISSN 0033-3158. 
  12. 12.0 12.1 Luoma, Jason B.; Chwyl, Christina; Bathje, Geoff J.; Davis, Alan K.; Lancelotta, Rafael (2020). "A Meta-Analysis of Placebo-Controlled Trials of Psychedelic-Assisted Therapy". Journal of Psychoactive Drugs. 52 (4): 289–299. doi:10.1080/02791072.2020.1769878. ISSN 0279-1072. 
  13. 13.0 13.1 Ryan, Wesley C.; Marta, Cole J.; Koek, Ralph J. (2014). "Ketamine and Depression: A Review". International Journal of Transpersonal Studies. 33 (2): 40–74. doi:10.24972/ijts.2014.33.2.40. ISSN 1321-0122. 
  14. Cuijpers, Pim; van Straten, Annemieke; Warmerdam, Lisanne (2007). "Behavioral activation treatments of depression: A meta-analysis". Clinical Psychology Review. 27 (3): 318–326. doi:10.1016/j.cpr.2006.11.001. ISSN 0272-7358. 
  15. Craft, Lynette L.; Landers, Daniel M. (1998). "The Effect of Exercise on Clinical Depression and Depression Resulting from Mental Illness: A Meta-Analysis". Journal of Sport and Exercise Psychology. 20 (4): 339–357. doi:10.1123/jsep.20.4.339. ISSN 0895-2779. 
  16. Kvam, Siri; Kleppe, Catrine Lykkedrang; Nordhus, Inger Hilde; Hovland, Anders (2016). "Exercise as a treatment for depression: A meta-analysis". Journal of Affective Disorders. 202: 67–86. doi:10.1016/j.jad.2016.03.063. ISSN 0165-0327. 
  17. Schuch, Felipe B.; Vancampfort, Davy; Richards, Justin; Rosenbaum, Simon; Ward, Philip B.; Stubbs, Brendon (2016). "Exercise as a treatment for depression: A meta-analysis adjusting for publication bias". Journal of Psychiatric Research. 77: 42–51. doi:10.1016/j.jpsychires.2016.02.023. ISSN 0022-3956. 
  18. Cramer, Holger; Lauche, Romy; Langhorst, Jost; Dobos, Gustav (2013). "YOGA FOR DEPRESSION: A SYSTEMATIC REVIEW AND META-ANALYSIS". Depression and Anxiety. 30 (11): 1068–1083. doi:10.1002/da.22166. ISSN 1091-4269. 
  19. Josefsson, T.; Lindwall, M.; Archer, T. (2014). "Physical exercise intervention in depressive disorders: Meta-analysis and systematic review". Scandinavian Journal of Medicine & Science in Sports. 24 (2): 259–272. doi:10.1111/sms.12050. ISSN 0905-7188. 
  20. Cuijpers, P., Berking, M., Andersson, G., Quigley, L., Kleiboer, A., & Dobson, K. S. (2013). A meta-analysis of cognitive-behavioural therapy for adult depression, alone and in comparison with other treatments. The Canadian Journal of Psychiatry, 58(7), 376-385. (15) |
  21. Cuijpers, Pim; van Straten, Annemieke; Andersson, Gerhard; van Oppen, Patricia (2008). "Psychotherapy for depression in adults: A meta-analysis of comparative outcome studies". Journal of Consulting and Clinical Psychology. 76 (6): 909–922. doi:10.1037/a0013075. ISSN 1939-2117. 
  22. Cuijpers, P. (1997). "Bibliotherapy in unipolar depression: A meta-analysis". Journal of Behavior Therapy and Experimental Psychiatry. 28 (2): 139–147. doi:10.1016/S0005-7916(97)00005-0. ISSN 0005-7916. 
  23. Donker, T., Griffiths, K. M., Cuijpers, P., & Christensen, H. (2009). Psychoeducation for depression, anxiety and psychological distress: a meta-analysis. BMC medicine, 7(1), 1-9. (18) |
  24. Richards, Derek; Richardson, Thomas (2012). "Computer-based psychological treatments for depression: A systematic review and meta-analysis". Clinical Psychology Review. 32 (4): 329–342. doi:10.1016/j.cpr.2012.02.004. ISSN 0272-7358. 
  25. Spek, Viola; Cuijpers, Pim; Nyklícek, Ivan; Riper, Heleen; Keyzer, Jules; Pop, Victor (2006). "Internet-based cognitive behaviour therapy for symptoms of depression and anxiety: a meta-analysis". Psychological Medicine. 37 (03): 319. doi:10.1017/S0033291706008944. ISSN 0033-2917. 
  26. Andersson, Gerhard; Cuijpers, Pim (2009). "Internet-Based and Other Computerized Psychological Treatments for Adult Depression: A Meta-Analysis". Cognitive Behaviour Therapy. 38 (4): 196–205. doi:10.1080/16506070903318960. ISSN 1650-6073. 
  27. Gloaguen, V., Cottraux, J., Cucherat, M., & Blackburn, I. M. (1998). A meta-analysis of the effects of cognitive therapy in depressed patients. Journal of affective disorders, 49(1), 59-72. (22) |
  28. Kokane, Saurabh S.; Armant, Ross J.; Bolaños-Guzmán, Carlos A.; Perrotti, Linda I. (2020). "Overlap in the neural circuitry and molecular mechanisms underlying ketamine abuse and its use as an antidepressant". Behavioural Brain Research. 384: 112548. doi:10.1016/j.bbr.2020.112548. ISSN 0166-4328. 
  29. 29.0 29.1 Bozymski, Kevin M.; Crouse, Ericka L.; Titus-Lay, Erika N.; Ott, Carol A.; Nofziger, Jill L.; Kirkwood, Cynthia K. (2019). "Esketamine: A Novel Option for Treatment-Resistant Depression". Annals of Pharmacotherapy. 54 (6): 567–576. doi:10.1177/1060028019892644. ISSN 1060-0280. 
  30. Xu, Ying; Hackett, Maree; Carter, Gregory; Loo, Colleen; Gálvez, Verònica; Glozier, Nick; Glue, Paul; Lapidus, Kyle; McGirr, Alexander; Somogyi, Andrew A.; Mitchell, Philip B.; Rodgers, Anthony (2016). "Effects of Low-Dose and Very Low-Dose Ketamine among Patients with Major Depression: a Systematic Review and Meta-Analysis". International Journal of Neuropsychopharmacology. 19 (4): pyv124. doi:10.1093/ijnp/pyv124. ISSN 1461-1457. 
  31. Lee, Ellen E.; Della Selva, Megan P.; Liu, Anson; Himelhoch, Seth (2015). "Ketamine as a novel treatment for major depressive disorder and bipolar depression: a systematic review and quantitative meta-analysis". General Hospital Psychiatry. 37 (2): 178–184. doi:10.1016/j.genhosppsych.2015.01.003. ISSN 0163-8343. 
  32. Pennybaker, Steven J.; Niciu, Mark J.; Luckenbaugh, David A.; Zarate, Carlos A. (2017). "Symptomatology and predictors of antidepressant efficacy in extended responders to a single ketamine infusion". Journal of Affective Disorders. 208: 560–566. doi:10.1016/j.jad.2016.10.026. ISSN 0165-0327.