Mental Health Crisis
Mental health is as important as physical health. Unfortunately, our society is experiencing an epidemic of anxiety, ADHD, addiction, and depression. Estimates put people suffering from mental illness at 20.78% of Americans, with 4.84% of adults reporting serious thoughts about suicide.
Depending on who you ask, different people will blame this on different causes, usually depending on their political leaning; it can be social media and smartphones, “wokeness,” our socio-political system, discrimination, poor healthcare system, poverty, the Covid pandemic, and lockdowns, etc.
In any case, this is a serious societal problem that needs to be addressed. And while solving the many root causes of the issues would be ideal, it is also clear that there is no silver bullet. So, if new scientific insights about our brains can help, we could design better therapies to address these issues.
Reconsidering Psilocybin
Psilocybin is the active compound in so-called “magic mushrooms.” These have long been used as psychedelics for recreational purposes, as well as various ancient rituals in traditional cultures all over the world.
This extensive “amateur” use has been associated with various positive mental health effects, from healing PTSD or depression to religious-like revelations or overall improvements in the user’s state of mind.
They are also associated with drug use in general. So, in the context of the “war on drugs” and a devastating opioid & overdose crisis killing more than 100,000 Americans per year, it has long been a stigmatized field of research. It was often outright illegal to pursue, or at least looked at with suspicion or skepticism, and received little funding.
In recent years, this has changed, along with regulations, resulting in psilocybin research being authorized again in what has been called a “Psychedelic Renaissance in Clinical Research,” with 54% of the top-cited 100 scientific publications produced in the past decade (2010-2020).
People are realizing that these are powerful compounds. They are worth studying and they’re not just drugs of abuse, which is how they were treated in the past.”
Dr. Jason Wallach – Assistant Professor of Pharmaceutical Sciences
In addition, psychedelics have also been associated with negative experiences, so tight medical supervision is required for any investigation on the topic.
An Almost Blank Scientific Field
Because most research on this topic is old or underfunded, very little fundamental research has been done on what exactly psilocybin does to the brain.
This is changing with a recent article in the prestigious scientific publication Nature, titled “Psilocybin desynchronizes the human brain,” published by researchers and doctors (33 authors) at the Washington University School of Medicine, Beth Israel Deaconess Medical Center, Advocate Christ Health Care, Florida State University, University of Pennsylvania, University of Minnesota, and the University of California.
The researchers analyzed the drug’s effect in a clinical study where the brain was scanned with MRI before taking the drug, during its effect, and up to 3 weeks after, with some participants coming back six months later.
Rebooting The Brain?
The intake of psilocybin was shown to change how the different parts of the brain interconnect. Normally, the “default mode network” sees some areas of the brain become simultaneously active when the brain is not working on anything in particular.
When taking psilocybin, this activity is desynchronized. It is likely the cause of the psychedelic effect, with parts of the brain suddenly not interacting with each other in the usual, synchronized way.
The effect persisted while the drug was active, and then the network reestablished itself. However, slight differences from pre-psilocybin scans persisted for weeks.
Source: Washington University School of Medicine
Among these long-term effects was a persistent decrease in the hippocamp functional activity, a region associated with clinical depression.
It is also known that psychedelics stimulate the production of synapses in the hippocampus and cortex, which have been linked to antidepressant-like effects in animal models.
Real-Time Monitoring Of Psychedelic Effects
A key effect of the desynchronization was to make all the participants’ brains look similar, which matched the subjective perception of a disappearance of the self during the “trip”.
The research also demonstrated that the intensity of the drug’s perceived effects, such as transcendence, connectedness, and awe, was directly correlated to the magnitude of the changes affecting the functional networks.
Lastly, the study also found that when patients were asked to complete a simple auditory-visual matching task significantly decreased the magnitude of psilocybin-associated network disruption and desynchronization. This can be used to reduce too intense or distressing thoughts or emotions induced by the drug.
Source: Nature
Toward Precise Clinical Trials
The last indication of a scientifically measurable tracking of the intensity of the drug’s effect on one person is key for further progress. Until now, most studies have relied on subjective measurements, which are inherently less reliable and harder to collect when the patients are “tripping.”
“In psychiatry, we often don’t know who should get a particular medicine and how much or how often. As a result, we end up prescribing one medicine after another, tinkering with the dosage, until we find something that works. By using this approach in clinical trials, we can identify the factors that determine who benefits and who doesn’t, and make better use of the medicines we have.”
Dr. Ginger E. Nicol – associate professor of psychiatry
Not only could this be applied to the drug’s clinical use, but it could also help produce much cleaner data from clinical studies, for example, by finding what predisposes some patients to react stronger or weaker to psilocybin, like genes, diet, age, sex, etc.
The study was performed on healthy, non-depressed individuals. The same investigation will need to be done with people with poor mental health to verify if the desynchronization phenomenon works the same way for them. And if it correlates to the previously reported positive reduction of depression symptoms by usage of psychedelics.
Investing In Psychedelics & Mental Health
Psychedelics is very much a nascent industry due to its complex legal framework. It is nevertheless already a $603M market, expected to grow to $1.18B by 2034.
You can invest in psychedelics-related companies through many brokers, and you can find on this website our recommendations for the best brokers in the USA, Canada, Australia, the UK, as well as many other countries.
If you are not interested in picking specific psychedelics and mental health companies, you can also look into ETFs like AdvisorShares Psychedelics ETF (PSIL) to capitalize on the growth of the psychedelics & mental health sector as a whole.
Psychedelic & Mental Health Companies
1. Compass Pathways
Compass Pathways’ main focus is developing psilocybin therapy for treatment-resistant depression. It is also investigating solutions for post-traumatic stress disorder and anorexia nervosa.
It realized 2 of the largest psilocybin studies ever completed and has one program already in phase 3 of clinical trials.
Source: Compass
Overall, the company has discovered that the treatment is efficient for a group of patients (sustained responders, in blue) while not really having a positive impact on another (non-responders, in green).
Source: Compass
Companies like Compass that focus on psilocybin are likely to benefit from the growing corpus of research on the topic, as well as the general acceptance that a brain “reset” like described in this article could be a key factor in finding a solution for treatment-resistant depression, PTSD, and other mental health issues.
This is especially true if brain scans could give insight into why some people end up in the non-responder category, and if such a profile can be predicted before starting the treatment.
2. Mind Medicine (MindMed)
MindMed is developing psychedelic drugs in order to treat anxiety, autism, ADHD, addiction, and depression.
The company’s R&D pipeline is most advanced in anxiety, a problem affecting 21% of the US population and even a higher rate for younger generations.
Source: Compass
The core idea behind the company’s science is that psychedelics can improve brain plasticity. Most mental illnesses are due to “negative plasticity”:
Negative plasticity occurs when the brain creates associations between disparate experiences and the brain’s fight-or-flight-reactions, which include body experiences such as rapid heartbeat and sweating, along with mental experiences like fear and panic that commonly accompany anxiety
By triggering plasticity, psychedelics could allow for the formation of new associations that are positive instead.
MM-120 works by increasing the connectivity between brain regions, creating temporary effects of mood alteration and durable effects of neurogenesis and anxiety reduction.
Source: Compass
So far, MM-120 phase 2 of the clinical trial has shown good results, with an improved remission rate at week 4 of treatment versus placebo.
Its MM-120 & MM-402 (a variant of MDMA) drugs are IP-protected and novel molecules, providing some protection for the company against competitors copying its innovations up to 2043.
3. ATAI Life Sciences
ATAI Life Sciences is a biopharmaceutical company investigating various compounds, including psilocybin, to develop novel therapies for mental health issues. This includes depression, schizophrenia, opioid addiction, and anxiety.
The company pipeline is a mix of more advanced products from strategic investments in Compass Pathways and Beckley PsyTech, and its own proprietary research programs.
Source: Atai
On depression, the company’s portfolio is composed of psilocin, psilocybin, DMT, and 5-MeO-DMT.
A key focus of the company is to concentrate on medicine that can work in only 2 hours, for it to be managed as an in-clinic treatment. This follows the paradigm established by Spravato®, a drug made from Esketamine, used in cases of depression (commercialized by Johnson & Johnson).
This way, the treatment can reach more people, be less costly, and overall have a higher chance of being adopted by patients and medical professionals.
4. Cybin Inc.
Cybin is a biotech company working on psilocybin and novel psychedelic molecules. Its most advanced programs are in depression, with others in alcohol disorder and anxiety.
Source: Cybin
So far, phase 2 of clinical trials for depression has shown a significant effect against depression of its product CYB003 (a psilocybin analog after a single dose against placebo. A second dose can increase the effect, with incrementally higher remission rates.
It is also a much stronger effect than existing approved therapies, with a strong durable effect at 4 months after 2 doses.
Source: Cybin
The company seems well positioned to reach FDA clearing in the next few years, at least as far as such prediction can be made, thanks to these strong preliminary results.
