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Therapeutic Effects of Psychedelics

Even though some psychedelics have been in use for millennia,1 only recently have they become recognized as potential medicines by regulatory bodies. Moreover, they are currently being studied in numerous randomized controlled clinical trials. Using psychedelics can result in some short-term and long-term effects, which can be positive or negative. On this page, we look into the studies which have observed therapeutic effects of psychedelics in several indications.


Lysergic acid diethylamide (LSD) in depressive patients was first studied in 1952.2 Since then, a number of studies on psychedelics and depression have suggested positive outcomes. In 2015, a small open-label study showed that a single dose of ayahuasca can help in relieving depression.3 In 2021, a study by Davis and colleagues suggested that psilocybin is efficacious in treating major depressive disorder (MDD). Even before the studies have confirmed positive outcomes in treating depression with psychedelics, scientists had reasonable grounds to assume their efficacy. For example, several studies showed that there was a higher expression of 5-HT2A cortical brain receptors {call-out, text: Receptors are created (expressed) from instructions in the DNA of the cell\, and they can be increased (upregulated) when the signal is weak\, or decreased (downregulated) when it is strong (source).} in depressed and suicidal patients,4 while the binding of 5-HT2A receptor in hippocampus was decreased.5 Regarding the effects of psychedelics on the brain, it has been observed that they activate 5-HT2A receptors and increase levels of cortical glutamate {call-out, text: The major excitatory neurotransmitter in the nervous system.6}.7 A 2010 study by Vollenweider and Kometer found that classic psychedelics can indirectly activate glutamate networks and possibly improve brain neuroplasticity through stimulation of some glutamate receptors. This consequently increases the level of Brain Derived Neurotrophic Factor (BDNF) {call-out, text: A key molecule involved in plastic changes in the brain related to learning and memory.8},9 which are atypically low in depressed patients, but normalized with the help of antidepressant treatments.10 Thanks to the studies like these, The FDA granted psilocybin breakthrough therapy designations {call-out, text: Breakthrough Therapy designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s) (source).} for depression in 2018.11

End of life anxiety and depression

In 1964, Kast and Collins observed that LSD had an analgesic effect similar to opiates, and that it was present even after LSD’s acute psychologic effects.12 The following study by Kast found that patients who received LSD had psychologic adjustment improvement, better responsiveness to their families and surroundings, and enhanced ability to enjoy everyday life.13 Grob et al. (2011) recently used a crossover design and administered 0.2 mg/kg psilocybin versus niacin placebo to 12 patients with advanced-stage cancer with a diagnosis of anxiety related to their cancer. Grob et al. (2011) reported nonsignificant trends for benefits of psilocybin compared with placebo on measures of depression and anxiety. Compared with pretreatment baseline, however, the patients’ Spielberger State-Trait Anxiety Inventory (STAI) trait anxiety subscale scores revealed a significant reduction in anxiety at 1 and 3 months after treatment. Similarly, the patients’ Beck Depression Inventory (BDI) scores showed an improvement of mood that reached significance at 6 months compared with baseline.14 Griffiths (2016) concluded that a single moderate to high dose of psilocybin, if given under supportive conditions to carefully screened and prepared participants, produced substantial and enduring decreases in anxiety and depression in patients with a life-threatening cancer diagnosis.15 Gasser et al. (2014) employed LSD-assisted therapy in 12 patients with anxiety related to a diagnosis of life-threatening diseases. Patients received either 200 mg LSD (free base) or a 20 mg “active placebo” dose of LSD with an open-label crossover to 200 mg LSD after unblinding. There were no serious adverse effects associated with the treatment. Positive trends found using the STAI were sustained for 12 months after treatment.16 In a subsequent study, Gasser et al. (2015) followed up the same participants 12 months later to examine long-term effects on anxiety and explore subjective experiences and lasting psychologic effects. Nine of the original subjects participated. Gasser et al. (2015) found that the STAI state and trait scores did not increase after the end of the study. Seven of nine participants reported a sustained reduction in anxiety. None of the participants reported lasting negative effects. The authors concluded that LSD-assisted psychotherapy in patients with life threatening illness demonstrated safety and positive stable treatment outcomes at long-term follow-up.17

A note on open-label studies

On this page, we reference various open-label studies, even though they are less reliable than double-blind placebo controlled studies. Open-label studies cannot be used as evidence for effectiveness due to unintended bias, but they can lead to interesting hypotheses and show which knowledge gaps should be addressed in the future.References:
  1. Begola, M. J.; Schillerstrom, J. E. (2019). Hallucinogens and Their Therapeutic Use: A Literature Review. Journal of psychiatric practice, 25(5), 334–346.
  2. Savage C. (1952). Lysergic acid diethylamide; a clinical-psychological study. The American Journal of Psychiatry, 108(12), 896–900.
  3. Osório, F.; Sanches, R. F.; Macedo, L. R.; Santos, R. G.; Maia-de-Oliveira, J. P.; Wichert-Ana, L.; Araujo, D. B.; Riba, J.; Crippa, J. A.; Hallak, J. E. (2015). Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report. Revista Brasileira de Psiquiatria, 37(1), 13–20.
  4. Mendelson, S. D. (2000). The current status of the platelet 5-HT(2A) receptor in depression. Journal of Affective Disorders, 57(1-3), 13–24.
  5. Mintun, M. A.; Sheline, Y. I.; Moerlein, S. M.; Vlassenko, A. G.; Huang, Y.; Snyder, A. Z. (2004). Decreased hippocampal 5-HT2A receptor binding in major depressive disorder: in vivo measurement with [18F]altanserin positron emission tomography. Biological Psychiatry, 55(3), 217–224.
  6. Institute of Medicine (US) Forum on Neuroscience and Nervous System Disorders. .; . 2, . Available from: (2011). Overview of the Glutamatergic System. Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System: Workshop Summary. Washington (DC): National Academies Press (US).
  7. Aghajanian, G. K; Marek, G. J. (1997). Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells. Neuropharmacology, 36(4-5), 589-99.
  8. Miranda, M.; Morici, J. F.; Zanoni, M. B.; Bekinschtein, P. (2019). Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain. Front. Cell. Neurosci., 13, 363.
  9. Vollenweider, F. X.; Kometer, M. (2010). The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. Nature reviews. Neuroscience, 11(),(9), 642–651.
  10. Sen, S., Duman, R.; Sanacora, G. (2008). Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biological Psychiatry, 64(6), 527–532.
  11. U. S. Food and Drug Administration (2018). Breakthrough Therapy.
  12. Kast, E. C.; Collins, V. J. (1964). Study of lysergic acid diethylamide as an analgesic agent. Anesthesia and Analgesia, 43, 285–291.
  13. Kast, E. (1966). LSD and the dying patient. Chic Med Sch Q, 26(2), 80-7.
  14. Grob, C. S.; Danforth, A. L.; Chopra, G. S.; Hagerty, M.; McKay, C. R.; Halberstadt, A. L.; Greer, G. R. (2011). Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Archives of General Psychiatry, 68(1), 71–78.
  15. Griffiths, R. R.; Johnson, M. W.; Carducci, M. A.; Umbricht, A.; Richards, W. A.; Richards, B. D.; Cosimano, M. P.; Klinedinst, M. A. (2016). Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of Psychopharmacology, 30(12), 1181-1197.
  16. Gasser, P.; Holstein, D.; Michel, Y.; Doblin, R.; Yazar-Klosinski, B.; Passie, T.; Brenneisen, R. (2014). Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. The Journal of Nervous and Mental Disease, 202(7), 513–520.
  17. Gasser, P.; Kirchner, K.; Passie, T. (2015). LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: a qualitative study of acute and sustained subjective effects. Journal of Psychopharmacology (Oxford, England), 29(1), 57–68.