Summary: Depression is on the rise. Major depression needs medical care, as it considerably increases the risk of self-harm. Although many medications help treat the condition, they work very slowly, generally taking weeks to start working. This is quite unlike psychedelic substances that alter mental state almost instantly. It appears that many of these illicit drugs can even help treat depression, especially psychedelic substances like magic mushroom, Ecstasy, or MDMA. However, the problem with these drugs is that they cause a prolonged trip or euphoria. Researchers think that for managing depression, the much shorter and controlled trip may work. Thus, they need to develop drugs that act only for about a couple of hours. Additionally, some researchers believe that these drugs may work even without causing euphoria or trip. Thus, some are trying to develop psychedelic analogs that would help treat depression but not cause euphoria or addiction. These agents may also help treat PTSD effectively, providing alternative approaches that could benefit those in opioid addiction treatment as well.
The psychedelic effect is experienced by consuming a prodrug called psilocybin, a substance found in many mushrooms. However, it is incredibly high in mushrooms of the genus Psilocybe, and these mushrooms are also called magic mushrooms.
However, psilocybin is relatively common and is present in more than 200 mushrooms varieties. When consumed, it changes to psilocin, causing a mild-altering effect, or euphoria. Many people report having a wonderful spiritual experience by ingesting psilocybin; they call it “a trip.” Thus, little doubt that it may help get rid of depression and PTSD.
Depression and PTSD are significant mental health problems in the US and globally. What is worrisome is their rising prevalence. Though severe cases of depression are treated well with some existing drugs, but there are some issues like low efficacy and a relatively long time needed to experience benefits. In addition, some of these drugs take weeks before the mental state of patients improves.
At present, psychedelic substances are illegal to use, and even possession of psychedelic mushrooms is unlawful in most nations. However, their use is allowed for medicinal reasons or in clinical studies.
Unlike anti-depressants, psilocybin works almost immediately. However, one of the significant hurdles in using commonly available psychedelic drugs like LSD is that they have a prolonged duration of action, with the so-called trip lasting as much as 12 hours. Researchers think that such a long duration of action or trip is unnecessary and even poses a health threat. Thus, there is a need to develop psychedelic drugs with a shorter period of action1.
Of course, there are some substances with quite a short duration of action and excellent safety profile like 5-MeO-DMT, and its action lasts only about 15-minutes. But researchers think that such a duration is too short. So what they are aiming for is something in between. They believe that the sweet spot is about two hours.
The idea of using such substances to manage depression or PTSD is not new. People have used tranquilizers like ketamine to manage depression for a long time, though not legally. However, in 2019, US FDA approved ketamine-based nasal spray for faster depression management. It is safe, acts fast, and is also suitable for resistant depression. So, why not consider psilocybin, which is even more potent2.
There is some sound science behind the use of psilocybin for managing depression. Studies show that it acts on 5-HT-2A receptors in the brain, boosting neuroplasticity. Thus, it promotes faster rewiring of the brain, causing rapid and prolonged benefits in depression.
Researchers think that one does not need such a prolonged action as that caused by LSD. Just a couple of hours of trip is enough to cause massive neural changes. However, they expect any such therapy to be done strictly under medical supervision requiring pre and post-psychotherapy.
On the other hand, some researchers believe that this mild altering action of psilocybin is not needed at all. They think that it would work without such an effect or a trip. Thus, some manufacturers are trying to develop drugs that do not cause euphoria or trip and yet help relieve depression. Such a medication would not lead to substance abuse and have a much safer safety profile.
There is a real chance that we may see such a drug approved in the coming years. Thus, Defense Advanced Research Projects Agency (DARPA) has even given a research grant of $26.9 million for research into the subject3. DARPA wants to see the development of a quick and powerful drug for treating psychiatric conditions but a drug that does not cause hallucinogenic ride.
Recently, even a study has been published showing that Ecstasy or MDMA may help manage PTSD. The so-called MDMA-assisted therapy was twice more effective as a placebo for relieving PTSD symptoms. Furthermore, it was effective for 67% of participants. These results are definitely encouraging, showing that psychedelic drugs could prove as a quick fix for many psychiatric disorders4.
References
- Yakowicz W. The Future Of Psychedelic Medicine Might Skip The Trip. Forbes. Accessed February 12, 2022. https://www.forbes.com/sites/willyakowicz/2021/06/23/the-future-of-psychedelic-medicine-might-skip-the-trip-rick-doblin-bryan-roth-mindmed-darpa-maps/
- Yakowicz W. Why Ketamine-Assisted Therapy Has Gone Mainstream. Forbes. Accessed February 12, 2022. https://www.forbes.com/sites/willyakowicz/2021/10/18/why-ketamine-assisted-therapy-has-gone-mainstream/
- Roth Leads $26.9 Million Project to Create Better Psychiatric Medications. Newsroom. Published June 15, 2020. Accessed February 12, 2022. https://news.unchealthcare.org/2020/06/roth-leads-26-9-million-project-to-create-better-psychiatric-medications/
- Mitchell JM, Bogenschutz M, Lilienstein A, et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021;27(6):1025-1033. doi:10.1038/s41591-021-01336-3
