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Psychedelic drugs are hallucinogenic substances ranging from manufactured chemical combinations to naturally occurring chemicals in certain plants. Most psychedelics are federally controlled, with some having fewer restrictions under certain state-level legislations. Researchers continue to study the clinical applications and safety of psychedelics such as MDMA (3,4-methylenedioxymethamphetamine), psilocybin, and ketamine.

Legality & Use

MDMA and psilocybin are Schedule I drugs under the federal Controlled Substances Act, meaning these substances have a high potential for abuse, no currently accepted medical use in treatment in the United States, and a lack of accepted safety for use under medical supervision.^1,2 However, in 2017, the Food and Drug Administration gave MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) a “Breakthrough Therapy” designation due to evidence suggesting that it may be helpful in this circumstance.^3,4 Recently, the state of Oregon passed legislation to legalize psilocybin and implement the first regulatory framework for psilocybin services in the US.⁵

Ketamine is another psychedelic that is federally controlled; however, it is a Schedule III drug, meaning that it has less potential for abuse than substances in Schedules I or II, its abuse may lead to moderate or low physical dependence or high psychological dependence, and it has accepted medical use for treatment in the US.^1,2 Ketamine is a dissociative anesthetic given as a surgical anesthesia to humans and animals. Most recently, ketamine has emerged as a promising intervention for depression.

Applications for Mental Health

While the psychedelic drugs MDMA, ketamine, and psilocybin (the active chemical in psychedelic mushrooms) may be more commonly associated with their hallucinogenic properties for recreational purposes, they have also been studied for mental health applications.

• MDMA-assisted psychotherapy has been used for patients experiencing PTSD with positive results.⁷
• Preliminary study results indicate psilocybin’s effectiveness in reducing depressive symptoms.⁸
• Pharmacological preparations of ketamine have been prescribed and administered at in-office or other supervised settings for psychiatric treatments with beneficial results.^9,10

References

1. Drug Enforcement Administration. Controlled substances: alphabetical order. Published April 12, 2022. Accessed April 18, 2022. https://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha.pdf
2. Drug Enforcement Administration. Controlled substance schedules. Accessed April 19, 2022. https://www.deadiversion.usdoj.gov/schedules/#define
3. National Institute on Drug Abuse. MDMA (Ecstasy/Molly) drug facts. Published June 2020. Accessed April 19, 2022. https://nida.nih.gov/publications/drugfacts/mdma-ecstasymolly
4. Feduccia AA, Jerome L, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R. Breakthrough for trauma treatment: safety and efficacy of MDMA-assisted psychotherapy compared to Paroxetine and Sertraline. Front Psychiatry. 2019;10:650. doi:10.3389/fpsyt.2019.00650
5. Oregon Health Authority. Oregon psilocybin services. Accessed April 19, 2022. https://www.oregon.gov/oha/PH/PREVENTIONWELLNESS/Pages/Oregon-Psilocybin-Services.aspx
6. Jelen LA, Stone JM. Ketamine for depression. Int Rev Psychiatry. 2021;33(3):207-228. doi:10.1080/09540261.2020.1854194
7. Smith KW, Sicignano DJ, Hernandez AV, White CM. MDMA-assisted psychotherapy for treatment of posttraumatic stress disorder: a systematic review with meta-analysis. J Clin Pharmacol. 2022;62(4):463-471. doi:10.1002/jcph.1995
8. Li NX, Hu YR, Chen WN, Zhang B. Dose effect of psilocybin on primary and secondary depression: a preliminary systematic review and meta-analysis. J Affect Disord. 2022;296:26-34. doi:10.1016/j.jad.2021.09.041
9. An D, Wei C, Wang J, Wu A. Intranasal ketamine for depression in adults: a systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials. Front Psychol. 2021;12:648691. doi:10.3389/fpsyg.2021.648691
10.  Cavenaghi VB, da Costa LP, Lacerda ALT, Hirata ES, Miguel EC, Fraguas R. Subcutaneous ketamine in depression: a systematic review. Front Psychiatry. 2021;12:513068. doi:10.3389/fpsyt.2021.513068