Depression, Psilocybin & Anti-Depressants: Where Are We At With The Latest Research?

More than 80 percent of the public believes that depression is caused by a chemical imbalance (low serotonin) in the brain. Why? Where is the evidence? Let's explore.

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Researchers and scientists have long questioned the widespread use of antidepressants. Not only for lack of efficacy but for the harms associated with them.

They've also questioned the premise for these medications, primarily because the theory that depression is caused by a chemical imbalance in the brain is hotly contested.

For decades this theory has permeated the world of health and been accepted as truth despite very little evidence. As a result, antidepressant drugs have become a multibillion-dollar industry.

“And where there is a scientific vacuum, drug companies are happy to insert a marketing message and call it science. As a result, psychiatry has become a proving ground for outrageous manipulations of science in the service of profit.” 

Daniel J. Carlat, M.D., Associate Clinical Professor of Psychiatry at Tufts University School of Medicine

A systematic review was published last year in the journal Molecular Psychiatry. It looked at studies examining serotonin and depression involving tens of thousands of people. Scientists found that research that compared levels of serotonin and its breakdown products in the blood or brain fluids was no different between people diagnosed with depression and healthy people.

This comes despite the fact that up to 80% (as the review points out) of the public believe that depression is caused by low serotonin or a chemical imbalance in the brain.

Researchers also looked at studies where serotonin levels were artificially lowered in hundreds of people and concluded that lowering serotonin in this way did not produce depression in hundreds of healthy volunteers.

The idea that serotonin might be involved in depression was first proposed in the 1960s, and became known as the serotonin theory of depression. The public messaging started in the 1990s when the pharmaceutical industry was marketing its new range of antidepressant drugs, the Selective Serotonin Reuptake Inhibitors ( SSRIs) such as Prozac.

The study's lead author, Joanna Moncrieff, a professor of psychiatry at University College London and consultant psychiatrist at North East London NHS foundation trust explains,

"Many people take antidepressants because they have been led to believe their depression has a biochemical cause, but this new research suggests this belief is not grounded in evidence....It is high time to inform the public that this belief is not grounded in science.”

This is concerning given the fact that drugs like antidepressants change normal brain chemistry. They blunt both negative and positive emotions, and multiple studies have shown that they may only act through inducing hope (the placebo effect). Even if they can produce a more adequate hit of serotonin to the brain for a short period of time, there are more questions to be asked.

The researchers explain:

“Despite the fact that the serotonin theory of depression has been so influential, no comprehensive review has yet synthesized the relevant evidence.

Our comprehensive review of the major strands of research on serotonin shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity. Most studies found no evidence of reduced serotonin activity in people with depression compared to people without, and methods to reduce serotonin availability using tryptophan depletion do not consistently lower mood in volunteers.”

These concerns have been permeating medical literature for years.

A New England Journal of Medicine review on Major Depression from 2005 is one of multiple examples,

 "… numerous studies of norepinephrine and serotonin metabolites in plasma, urine, and cerebrospinal fluid as well as postmortem studies of the brains of patients with depression, have yet to identify the purported deficiency reliably."

People need this information in order to make properly informed decisions about whether to take antidepressants or seek alternative methods.

"Our view is that patients should not be told that depression is caused by low serotonin or by a chemical imbalance, and they should not be led to believe that antidepressants work by targeting these unproven abnormalities. We do not understand what antidepressants are doing to the brain exactly, and giving people this sort of misinformation prevents them from making an informed decision about whether to take antidepressants or not."

Moncrief

This research begs the question, why was the idea that serotonin is the cause or part of the cause of depression so widely endorsed in the scientific literature in the 1990s and 2000s?

The best explanation seems to be clever marketing. In 2012, the NEJM published 73 articles on original studies of new drugs, which represented drugs approved by the FDA since 2000. It was found that 82 percent of them had been funded by the pharmaceutical company selling the product, and 68 percent of them had authors who were employees of that company.

Finally, it was found that 50 percent had lead researchers who accepted money from a drug company.

A study published in the Journal of Clinical Epidemiology looked at 185 meta-analyses on antidepressant medication and found that one third of them were written by pharmaceutical industry employees. It also found that almost 80 percent of the studies had industry ties.

In 2012, GSK paid a $3 billion fine for bribing doctors and illegally promoting drugs for off-label uses. GSK withheld clinical trial results that showed its antidepressant, Paxil, not only doesn’t work for adolescents and children but more alarmingly that it can increase the likelihood of suicidal thoughts in this group.

A study published in the British Medical Journal by researchers at the Nordic Cochrane Center in Copenhagen showed that pharmaceutical companies were not disclosing all information regarding the results of their drug trials.

Researchers looked at documents from 70 different double-blind, placebo-controlled trials of SSRI meds and serotonin and norepinephrine reuptake inhibitors (SNRI) and found that the full extent of serious harm in clinical study reports went unreported.

"[This study] confirms that the full degree of harm of antidepressants is not reported. They are not reported in the published literature, we know that – and it appears that they are not properly reported in clinical study reports that go to the regulators and from the basis of decisions about licensing."

Moncrieff

I don’t write this to offer medical advice, but to raise awareness about whether or not these medications are meant for everyone, or whether alternative methods of relieving depression are worth exploring.

The evidence supporting anti-depressants appears more anecdotal than “scientific.”

It’s a very difficult and complex issue that science may never really be able to pinpoint, and depression in one person may have a different root cause compared to depression in another person.

There are millions, even billions, of chemical reactions that make up the dynamic system that is responsible for your mood, perceptions, and how you experience life.

“The medical profession is being bought by the pharmaceutical industry, not only in terms of the practice of medicine, but also in terms of teaching and research. The academic institutions of this country are allowing themselves to be the paid agents of the pharmaceutical industry. I think it’s disgraceful.”  

Arnold Seymour Relman (1923-2014), Harvard Professor of Medicine and Former Editor-in-Chief of the New England Medical Journal

Psilocybin

There is now a plethora of research suggesting psilocybin may have therapeutic effects for depression. A chemical found inside fungi known as “magic mushrooms,” psilocybin is a completely natural substance that has been used by various cultures for thousands of years for both ceremonial and medicinal purposes.

Academic research and study on this subject has spanned nearly 70 years, despite the fact that there was a 30-year hiatus during the “war on drugs.” This made these substances very hard to access for academic purposes. As a result, we went through multiple decades where no clinical research was done on these compounds.

It wasn’t until 1997 that the first post-drug-war Psilocybin study was conducted by a team of researchers at the University of Zurich.

The team of researchers led by Dr. Franz Vollenweider explored whether brain function under the influence of psilocybin was consistent with the brain function of chronic schizophrenia patients, finding that these brain states were significantly contrasted. They also found that psilocybin increased cerebral glucose metabolism (brain activity) in many areas, and had dampening effects on the Default Mode Network. 

Studies and early-phase clinical trials already concluded at John Hopkins University, The Multidisciplinary Association for Psychedelic Studies (MAPS), The Beckley Foundation, Yale, Stanford, Berkeley, New York University, and more have shown Psychedelics to be both safe and efficient in treating a host of psychological conditions. Some of these conditions include depression, addiction, anxiety, OCD, PTSD, and eating disorders.

As a result of all of this research, governing bodies are beginning to follow suit. The Federal Drug Administration (FDA) has designated psilocybin a breakthrough therapy for Major Depressive Disorder (MDD), and Health Canada has granted several licenses to private and public companies in order to study psilocybin and other psychedelics.

Over a dozen accredited institutions, a few of which include Harvard, Stanford, Yale, The Usona Institute, The Heffter Institute, Johns Hopkins University, and the University of Toronto are in the process of clinical trials/studies to determine the potential of psilocybin as a therapeutic aid.

For example, in one small 2020 study conducted by researchers from Johns Hopkins University looking at adults with major depressive disorder, half of all patients who were given 2 doses of psilocybin achieved complete remission from their symptoms for at least one month.

But, as with other medications, the patients did end up resorting back to depression. This is where the conversation needs to go beyond symptom management and into true core healing. Symptom management is great in the short term to help people, but a greater societal focus on healing at the root is important. But that is another discussion.

Yale researchers showed (2021) that a single dose of psilocybin given to mice prompted an immediate and long-lasting increase in connections between neurons, similar neuronal connections that are lost in depression.

“We not only saw a 10% increase in the number of neuronal connections, but also they were on average about 10% larger, so the connections were stronger as well,” said Yale’s Alex Kwan, associate professor of psychiatry and of neuroscience and senior author of the paper.

A randomized double-blind trial study published in 2016 by Dr. Roland Griffiths (and colleagues), a former professor of neuroscience, psychiatry, behavioural science, and director of the Center for Psychedelic and Consciousness Research at Johns Hopkins University found long term and sustained decreases in their depressive symptoms. In this case, doses were given in 5 week intervals.

“At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction.”

Below is an excellent discussion with Dr. Griffiths and Dr. Rhonda Patrick that was had a few years ago before his recent passing. I am just starting my exploration into this subject, and have found that Griffiths's work is an excellent place to start. This conversation goes more in depth with regard to the studies he has conducted on depression and the use of psychedelic therapies.

What’s great about the video as well is that Ronald dives into the potential harms and dangers of psychedelics. These risks are often overlooked by the general population and are important to take note of in the same way we do with anti-depressant drugs.

The Takeaway

When it comes to issues such as depression, nutritional, holistic and mindful interventions never really see the light of day and are often not discussed or recommended by your everyday psychiatrist.

In today’s day and age, self-education is a must, and that goes for doctors as well. When it comes to solutions to these issues, one may consider options outside of the pharmaceutical industry and dive into other resources to seek out interventions that may not be motivated by profit.

This is why awareness is key. As more people become aware of this type of information they begin to seek out alternatives and make new choices.

It would be helpful if more effort and funding were applied to study other interventions that may not provide profit for the pharmaceutical industry. Perhaps this also shows the limitation in basing public well being on a capitalistic economy. Perhaps it’s simply a measure of our societal worldview.

Depression may not be a problem with brain structure, chemical flow and neurotransmitters. Instead, the mood of depression we experience comes from other factors that in turn may lead to changes in biology, brain structure, chemical flows etc. Mainstream medicine does not identify this issue, because the issue is not biological and is instead rooted in human experience, trauma, how one perceives the world and so much more.

Beyond major traumatic events, if we experience too much chronic stress, early childhood adversities, poor diet and nutrition, underlying health conditions, or a poor or toxic environment, we can end up with nervous system dysregulation.

Modern life throws a lot at us. It's important to understand the effects of chronic stress and how it can change the brain and body, as well as shape our consciousness, health and overall well-being.

Our collective human experience doesn’t seem natural. Many people have to spend the majority of their time doing something they are not passionate about simply to put food in their mouths and pay the bills. This type of experience and life does not seem natural to human beings, just like a zoo or an aquarium doesn’t seem natural to an animal.

Despite all of this emerging information, many health experts still emphasize the success and efficacy of antidepressant drugs.

Are These Substances Real Solutions?

I think it’s quite clear that psychedelic substances, and even anti-depressant drugs can help and assist people. My personal opinion is psilocybin may be of greater assistance than anti-depressant drugs when used in controlled settings.

That being said, other work needs to be done to achieve wellness. These substances may be a great tool, but perhaps only as a bandaid or a symptom management technique. I am not sure they address the core problems that cause depression, and severe depression in many individuals.

Many experts in the field who recommend these substances also stress the importance of mindfulness techniques like breath work, meditation, journaling and more.

This is something science is just starting to grasp as well, as shown by research coming out of UCLA's Mindfulness Awareness Research Center. According to them:

“Having an attitude of gratitude changes the molecular structure of the brain, keeps gray matter functioning, and makes us healthier and happier. When you feel happiness, the central nervous system is affected. You are more peaceful, less reactive and less resistant. Now that's a really cool way of taking care of your well-being.”

There are many studies showing that people who count their blessings tend to be far happier and experience less depression. This would be one of many practices one could use to literally change their brain, either with the assistance of substances or not.

At the end of the day, the main point is that there are other options out there for people that go beyond anti-depressant drugs. And it’s a shame these options aren’t emphasized and pushed by practitioners in the same manner pharmaceutical drugs are.