Depression is a common mental disorder. Globally, more than 264 million people of all ages suffer from depression and is the leading cause of disability worldwide as well as a major contributor to the overall global burden of disease.

Can Psychedelic Therapy Help Beat Depression?

According to the World Health Organization, depression affects more than 264 million people globally. It is a leading cause of disability worldwide and, as too many people can attest, often plays a significant role in suicide.

Most psychedelics like psilocybin (also known as magic mushrooms), LSD, ketamine or MDMA are classified as Schedule I drugs by the United States Drug Enforcement Administration. This means they have no currently accepted medical use and a high potential for abuse.

You’d be forgiven for thinking that psychedelics couldn’t possibly do anything good for the millions of people suffering from depression. But in fact, many medical professionals and research believe the opposite is true.

New Treatments for Depression

Depression is different for everyone, so treating it needs to be different for everyone too.

For some, taking antidepressants daily has a hugely positive effect. For others, Cognitive Behavioral Therapy (CBT) helps them cope with the illness from day to day. But these treatments don’t work in all cases.  

Many people who suffer from Major Depressive Disorder, Recurrent Depressive Disorder, Bipolar Affective Disorder, and a host of other depression-related mental illnesses are resistant to all types of current treatment. Researchers are acutely aware of the need for new forms of therapy that could make a difference in these people’s lives.

That’s where psychedelic therapy comes in.

Psilocybin Breakthrough Therapy

In 2019 the United States Food And Drug Administration (FDA) designated psilocybin as a Breakthrough Therapy for Major Depressive Disorder. This is a huge milestone that will pave the way for more research into psychedelic therapy.

It can take over 10 years for a new drug to make it from the laboratory to a doctor’s prescription. There are extremely strict criteria to satisfy and stringent health and safety rules to follow. Just obtaining funding can take years, and then there are multiple development phases and clinical trials to undertake.

Breakthrough Therapy designation is only granted when clinical evidence shows that a drug may demonstrate substantial improvements over available therapy. It basically puts drugs on the fast track through this lengthy process.

Since the 1930s scientists have been aware of the great potential psychedelics could have for treating medical illnesses. Pioneering research was in progress up until the 1960s, when psychedelics finally made it out of the lab and into the hippie counterculture movement.

Recreational use, or more specifically misuse and abuse, became widespread and the scientific reputation of psychedelics plummeted. In 1970, they were banned outright by the Controlled Substances Act. Any research related to psychedelics, for any purpose, ground to a halt for decades.

So the fact that psilocybin is now a Breakthrough Therapy is a very big deal indeed. But why the major about-face, and why now?

Depression, Psychedelics and the Brain

The type of experience people have when under the influence of psychedelics is well documented. Seeing geometric shapes and colors, feeling emotions with extreme intensity, having a sense of spiritual awakening and viewing the world with new clarity are all common features of a ‘trip’.  

All of these elements are the result of how psychedelics effectively ‘rewire’ the brain. They disrupt the usual flow of signals between different parts of the brain, shutting down some networks and setting up others.

When psychedelics first enter your system, one of the first casualties of this rewiring is the Default Mode Network.

The Default Mode Network is a system of connected areas of the brain that kick into action when you’re not focusing on anything in particular. It’s active when you’re doing things like daydreaming, contemplating the past or future, or just ‘mulling things over’.

The results of several studies suggest that the Default Mode Network can be dysfunctional in those suffering from depression. It is overactive, or hyper-connected to other parts of the brain. This in part explains the persistent thoughts and unshakable negative moods that depressed people often experience.  

So when psychedelics like psilocybin, LSD, ketamine or MDMA kick in, they both quieten the Default Mode Network and provoke a new sense of clarity, peace and positivity. Negative thoughts are dulled or blocked entirely, and the resulting elevated mood and perception is much more conducive to psychological breakthroughs.

Psilocybin Therapy For Depression

This ‘brain rewiring’ that psychedelics cause can be volatile and even dangerous. For people who are prone to negative thoughts, as is common with depression, the experience of a psychedelic trip can be absolutely horrific. For those prone to mental illness or with a family history of it, psychedelics can provoke serious, lasting psychosis.

That’s why psychedelic therapy can only be successful when it’s done in a controlled, medically supervised manner as part of a larger treatment strategy.

One researcher investigating the potential of psychedelic therapy for depression is David Nutt, Edmond J Safra Professor of Neuropsychopharmacology at Imperial College London. After years of trying, Nutt obtained funding and permission to conduct a study on patients with treatment-resistant depression. Both CBT and up to 20 different antidepressant medications had failed to produce effective results for these people.

Nutt and his team first administered a very low dose of psilocybin, the psychedelic compound found in magic mushrooms, to participants. This dose was deliberately low and intended to ensure there were no ‘paradoxical reactions’ (aka bad trips).

Following the initial tester dose, patients received a larger 25mg dose of psilocybin. At all times, there were two therapists with each participant to supervise and guide them through the entire experience. Each patient also spent time before the session preparing for the potential effects, positive or negative, with these therapists.

Therapy continued afterwards, with every participant attending an ‘integration session’ the following day to unpack and make sense of the experience.

Nutt found that from this integration session or very soon afterwards, many participants’ moods had significantly improved. The majority of them reported feeling benefits for several weeks or months afterwards. Even six months later, some participants were still noting a positive impact after a single dose of psilocybin.

MDMA Therapy for Depression

MDMA has been the subject of psychedelic therapy studies for several years already, and is another psychedelic that has won Breakthrough Therapy designation by the FDA. The Multidisciplinary Association For Psychedelic Studies (MAPS) has been working with the FDA to agree on Phase 3 protocol designs after a rigorous Special Protocol Assessment (SPA) process following this designation.

So far, the main focus for MDMA therapy is on treating Post Traumatic Stress Disorder (PTSD). Several studies are currently in phase 3 trials and expected to be completed in 2021. Phase 2 trials are also ongoing in Europe. If all goes well, it’s possible that the FDA could approve MDMA-assisted psychotherapy as a prescription treatment for PTSD as early as 2022.

It’s not uncommon for people with PTSD to also experience other mental health problems, particularly depression and anxiety. So MDMA psychedelic therapy can not only reduce some of the worst symptoms of PTSD, but potentially help alleviate the significant knock-on effects on a person’s overall mental health too.

One example of MDMA therapy reducing the symptoms and effects of depression dates all the way back to 2012. A study by researchers at the University of South Australia and the University of Adelaide investigated ‘Antidepressant‐like effects of ecstasy in subjects with a predisposition to depression’.

When drug-free, the group of 20 people in the treatment group had greater mood disturbance and depressive symptoms than the 20 people in the control group. During social gathering, the treatment group who consumed MDMA reported a significant decrease in depressive symptoms.

This is just one study of many that have shown similar results, so it looks like MDMA therapy for mental health conditions like PTSD, depression and anxiety will continue to thrive.

What about other Psychedelic Therapy?

Esketamine, a more potent form of ketamine, is one of the few psychedelics that has won FDA approval to treat patients with treatment-resistant depression. Patients receive a dose of esketamine via a nasal spray, a much faster route to get the necessary signals to the necessary parts of the brain.

Adam Kaplin, Assistant Professor of Psychiatry and Behavioral Sciences at Johns Hopkins, was one of the researchers involved in a multi-site international trial on intranasal esketamine. According to Kaplin’s results, across all sites participating in the trial the response rate was between 53% and 69% during the first month of treatment.

LSD is another psychedelic currently being used in clinical trials. In Switzerland, University Hospital Basel is currently conducting a trial of LSD therapy on 60 people suffering from Major Depressive Disorder.

One group of patients in the study will receive two doses of 100 micrograms of LSD, while another group will receive lower doses of 25 micrograms. Following the doses researchers will assess changes in patients’ symptoms, personalities, moods and cognitive responses to certain stimuli. The study began in January 2020 and results are expected in 2023.

Although the future of psychedelic therapy looks brighter than ever, there are still limitations. Only a small few psychedelics have won Breakthrough Therapy designation so far, and in all cases, it was no easy feat to achieve. Most studies are still very much in preliminary stages and any kind of approval or designation is still a long way off.

Furthermore, in the current medical landscape psychedelic therapy is still viewed as non-mainstream. It’s something to attempt only after current treatments have already failed.

For many people suffering from depression, antidepressant medication or CBT (or a combination of the two) is likely to have at least some benefit. While there’s no doubt that this will improve their quality of life, it also means that psychedelic therapy - and the further progress it could encourage - will no longer be accessible to them.

But with larger trials, more Breakthrough Therapy designations, and more public awareness, more peoples’ lives can hopefully change for the better with the help of psychedelic therapy.

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