Psychedelic Therapy: The State Of The Art In 2018

With the incredible amount of public attention being showered upon psychedelic research, and a growing acceptance in mainstream psychiatry, it is a good time to take a step-back and examine the current state of the clinical research as 2018 gets underway. 

Much has been made of the so-called “psychedelic renaissance,” which has emerged following a 30-year drought in psychedelics research and above-board therapeutic uses. Coupled with a surge in interest in plant medicines like ayahuasca and the recent popularization of micro-dosing psychedelics for both mental health and productivity, its safe to say that psychedelics have again penetrated mainstream consciousness. 

Its easy to get overly-excited about the current level of awareness and attention on this subject given how taboo it has been in professional and research settings. I remember encountering some of the the negative attitudes about psychedelic therapy when I worked in UCSF’s Psychiatry Department. They varied from “that’s a relic of the past” to “its reckless and dangerous.” Now, 10 years later, UCSF researchers are actually studying psilocybin. Its amazing how shifts in the cultural zeitgeist can radically change how a particular topic is viewed, and even how mainstream science looks at it. 

However, due to its controversial history and the now 50-year old “war on drugs,” evidence for psychedelic medicine needs to be substantial and impeccable. 

Promising But Preliminary

So where are we today in practical terms? What do we know and what can we prove in terms of psychedelics as therapies for mental health conditions? Based on the current clinical trials of psychedelics and humans with mental health diagnosis, one can really only say two things: its promising and its preliminary. 

As you can see in the table below every single study has shown significant benefits, and studies have been conducted on problems as varied as Obsessive Compulsive Disorder and Alcoholism. There have been exceedingly few serious adverse outcomes (ibogaine being the exception) and some really significant responses in the hardest to treat areas of mental health, such as treatment-resistant depression and chronic post-traumatic stress disorder (PTSD).

However, preliminary is the key word here. In most cases, these are small pilot studies with fewer than 20 participants receiving active treatment. And most of the studies were conducted too recently to demonstrate long-term benefits.

Clinical Trials on Psychedelics for Mental Health Conditions — As Of Q1 2018

Some Studies Further Along Than Others

However, there are some lines of inquiry that are further along than others. The Multidisciplinary Association of Psychedelic Studies’ (MAPS) herculean effort with MDMA-assisted psychotherapy for PTSD is finally reaching Phase III, with large-scale nationwide multi-site trials beginning this year. 

That is a significant accomplishment that is based on the back of 17 years of human trials and dedicated work by a crew of committed researchers and organizers, including study leads Michael and Annie Mithoefer and MAPS executive director Rick Doblin.

The results from the recently completed 107-participant Phase II trials show that MDMA-assisted psychotherapy is safe and can be a highly effective treatment for chronic and treatment-resistant PTSD. 68% of participants no longer had PTSD at their 12 month follow-up. Follow-up studies showed that these results persisted 4 years later. 

These results are truly incredible as PTSD is notoriously difficult to treat and there are very few current therapeutic treatments that work. Many people are stuck with debilitating PTSD symptoms their entire lives. 

The FDA even awarded the MAPS protocol for MDMA-assisted psychotherapy for PTSD the Breakthrough Therapy Designation in August of 2017, which is given when preliminary clinical evidence suggests that it may provide a “substantial improvement over existing therapies.” 

Psilocybin

The other line of research that has completed FDA-approved Phase II trials is the study of psilocybin as a treatment for cancer-related anxiety and depression conducted at Johns Hopkins and NYU. In both Phase II trials, one with 51 participants and the other with 29, subjects experiencing depression and anxiety related to diagnosis with a life-threatening form of cancer received psilocybin in conjunction with psychotherapy. The results for both studies were quite strong, showing rapid and substantial declines in subjective reports of anxiety and depression as well as improvements in mood and outlook on life and death. 

This is especially significant since there aren’t any good therapies addressing existential end-of-life-related distress, anxiety, and depression, conditions which are experienced by up to 40% of cancer patients. 

The incredible documentary, A New Understanding: The Science of Psilocybin, chronicles the personal stories of people with terminal illnesses experiencing profound healing through the use of psilocybin. 

Are These Treatments Safe? 

With the big exception of ibogaine, the studies show pretty clearly that, yes, administering psychedelic substances in a well-monitored psychotherapeutic context is safe. Hundreds of administrations of MDMA and psilocybin have been conducted in rigorously monitored studies in the last 10 years and there have been no reported serious adverse outcomes. Experiences of anxiety or increases in blood pressure that can come-up in the midst of the experience tend to be transitory. Participants also have trained experienced therapists sittings with them during their journeys. These are therapists who have worked closely with the participants and have established trust and a working relationship. 

The MDMA being used is also not your typical adulterated street Ecstasy. They use pharmaceutical-grade pure MDMA. These studies also rigorously screen-out people with histories of or at high risk for manic episodes or psychosis.

The model has been proven: MDMA and psilocybin in conjunction with psychotherapy can be administered safely and the current evidence suggests that they are very effective therapies. None the less, more study is needed.

How To Participate

There are two trials ongoing in the US that are currently recruiting new research participants and may be of wide interest. The first is Johns’ Hopkins study on the effects of psilocybin for major depressive disorder. It is a 24-participant study and is currently underway.  

The second is MAPS’ Phase III trial of MDMA-assisted psychotherapy. This is a multi-site study being conducted at locations across the US from New York to California. They are looking to recruit between 200 and 300 participants with severe PTSD. 

If you live in Europe, Helsinki University is about to start a 60-person study on psilocybin for major depressive disorder. The study is projected to start in September 2018 so they will likely begin recruiting shortly.

How To Support The Research

It is an exciting time for psychedelic research and soon may be an exciting time for legalized psychedelic-assisted psychotherapy. Rick Doblin at MAPS has talked extensively about MAPS’ vision for a network of legal MDMA clinics across the US where clients could receive MDMA-assisted psychotherapy in a safe therapeutic setting. That’s a vision worth supporting.

The first step is FDA approval for MDMA as a prescription medicine. He believes that this is possible by 2021. Conducting large-scale clinical trials without corporate funding is expensive. MAPS needs $25 Million to complete the Phase III trials and this is being funded 100% by donation, an unheard of phenomenon in pharmaceutical research. 

The best way to support psychedelic research and the legalization of psychedelic-assisted therapy is by making a donation to MAPS. 

Psychobiotics, The Future of Mental Health?

The gut microbiome has become one of the most exciting fields of medical inquiry of the last decade. Much of the research began as an effort to understand and address a variety of chronic stomach ailments that have come into popular focus over the last 25 years, conditions such as Crohn’s disease, gastroesophageal reflux disease (GERD), ulcerative colitis, and Irritable Bowel Syndrome (IBS). Psychotherapists and psychologists have long postulated a connection between psychological ailments, psychosocial stressors, and stomach disorders. For example, 61% of people with IBS also have a DSM-diagnosed anxiety disorder. The classic understanding posits that high stress levels and anxious tendencies can cause disturbances in the gastrointestinal tract, including high stomach acid levels and hyper-reactive bowels, that may lead to various GI disorders. 

And while that is true, recent findings regarding the impact of stomach bacteria on the mind and behavior have surprised the scientific community, challenged the classical paradigm, and opened up new lines of inquiry.

The Emergence of Psychobiotics

Professor Ted Dinan of University College Cork in Ireland, one of the pioneers in the field, introduced the term psychobiotics in 2012 to describe the specific bacteria that when consumed result in beneficial effects on mood, motivation, and cognition.  

A new book co-written by Professor Dinan just came out

To understand how infinitesimally small bacteria in the stomach can affect the subjective experience of depression or anxiety, we need to understand a bit about the stomach’s relationship with the brain, a relationship we still don’t fully understand, but that is the focus of increasing research globally.  

The Stomach Has A Brain

To begin with, it is important to note that the stomach has its own “brain:” the enteric nervous system. Often nicknamed “the second brain,” this mesh-like network of 500 million neurons lines our entire digestive tract from the esophagus to the anus. It is responsible for co-ordinating and managing all our digestive functions and it does so with input and feedback from the brain and central nervous system, via the vagus nerve.

The Vagus Nerve

The vagus nerve is a very large bundle of nerves that runs from the brain stem to vital organs including the stomach. Scientists were astounded to discover that 90% of the nerve fibers in the vagus nerve are communicating signals from the gut to the brain in a bottom-up manner. 

That’s right, this major super-highway of nerve fibers is mainly delivering information, signals, and communication from our stomach to our brain. And much of that signaling is being generated by the gut bacteria through its constant dialogue with the second brain.

The vagus nerves terminates in the brain stem but has direct neural links to a variety of brain regions that are associated with processing and regulating mood, emotions, stress, and hunger. And it is these pathways that researchers think is fundamental to how the gastrointestinal microbiome can impact, and potentially cause, anxiety and depression. 

In fact, one novel therapy for treatment-resistant depression involves the ongoing electrical stimulation of the vagus nerve via a pacemaker-like implanted device.

The Gut Brain Axis

This bi-directional relationship between the brain and the GI system is called the “Gut-Brain Axis” and the star player in this relationship between the gut and the brain is our gastro-intestinal microbiome. This is the multi-billion strong community of microorganisms (bacteria, protozoa, and viruses) living in our gut that digest our food, synthesize important vitamins, and help mount immune responses to harmful pathogens we have consumed. The average human has between 3–6 pounds worth of these microorganisms in their GI tract and the evidence suggests that they evolved symbiotically with our body’s cells to provide vital functions that our cells can not. It's hard to underestimate the importance of these billions of bacteria living in our colon. Beyond their critical role in digestion they are intimately involved with our immune system, endocrine stress response system, and our central nervous system.

Making An Anxious Mouse Confident

One of the pioneering studies proving that stomach bacteria could affect behavioral responses was conducted in 2011 by Premysl Bersick at McMaster University. Bersick and his team experimented with fecal transplants (exactly what it sounds like) between mice that were genetically bred to be timid and anxious and mice genetically bred to be bold and exploratory.

Bersick showed that when the timid mice received fecal transplants from bold mice, they become less anxious and more exploratory. The reverse also held true: genetically bold mice were much more cautious and fearful after the introduction of stomach bacteria from anxious mice. Later research indicated that obese mice lost weight after receiving fecal transplants from thin mice, which has led to a novel new approach for treating obesity. 

Since then, dozens of studies on mice have been conducted pinpointing the effects of specific gut bacteria on mouse behavior and neurochemistry. Mice are used due to ease of experimental study and because the primary means of isolating the effects of one strain of bacteria is by using animals that have been bred, raised, and kept in a germ-free environment. Novel stomach bacteria are introduced one a time to see the effects on the mice’s behaviors and neurochemistry and the results have been truly incredible. 

The Tryptophan-Serotonin Connection

Tryptophan is an essential amino acid that we must get from food and a critical precursor for the synthesis of Serotonin. Tryptophan crosses the blood brain barrier and how much gets there is regulated by our gut microbiome. One animal study showed that the stomach microbe Bifidobacteria infantis was shown to significantly increase blood plasma tryptophan levels. The brain stores very little tryptophan and therefore needs fresh supplies daily to create Serotonin which is critical in mood regulation. It turns out that our gut bacteria have a powerful regulating effect on tryptophan levels and how much tryptophan reaches the brain.

The Role of GABA

A a 2011 study showed that genetically anxious mice fed broth with Lactobacillus rhamnosus were more exploratory and risk-taking and were less likely to give-up in a forced swim tests than the control mice. The mice fed L. rhamnosus also showed less cortisol secretion in response to stressors as well as an increase in the number of receptors for the neurotransmitter GABA. GABA is the principal inhibitory neurotransmitter and it tamps down neural activity throughout the central nervous system. It is also the target site for the anti-anxiety medication such as Xanax. When the vagus nerve of mice in this study were severed, the effect disappeared, making it clear that the the bacteria were acting through the vagus nerve to alter brain levels of GABA.

Specific strains of beneficial gut bacteria have also been shown to actually secrete GABA and recent unpublished research shows that consuming specific psychobiotics increases GABA levels in the brain, so we know that GABA is one of the neurotransmitters acted upon by the gut microbiome.

An Endogenous AntiDepressant

In the process of breaking down indigestible nutrients such as fiber, our gut flora produce short chain fatty acids that have various metabolic effects. One of these, butyrate, has been documented in several studies to have antidepressant properties. Butyrate has the ability to cross the blood brain barrier and effect central nervous system neurochemistry, including raising levels of Serotonin in the brain. And it is a key product of our intestinal microbiome because it is also used as food by the cells lining the colon.

Mediating Our Stress Hormones

Several strains of Bifidobacterium and Lactobacillus bacteria have been shown to decrease cortisol and norepinephrine levels and result in reduced anxious behaviors in animal studies and reduced self-reported anxiety in human studies. The research suggests that benefecial stomach bacteria can temper the Hypothalmus-Pituitary-Adrenal Axis that is the primary mechanism of the fight-or-flight stress response system.

Stress hormones also inhibit the immune system, which is why chronic stress creates susceptibility to infection and illness leading to chronic low-grade inflammation. This is a marker commonly seen with depressed patients.

Human Trials

While there are is a ton of experimental research on mice and a growing base of exploratory studies on humans, there is a substantial gap between the animal research findings and the clinical data on humans. We just haven’t seen the kind of rigorous randomized double-blind placebo-controlled clinical studies evaluating the effects of psychobiotics on human subjects with mental health diagnosis.

To date, there has been one study of this kind, conducted in Iran in 2016 and it indeed found significant decreases in depressive symptoms versus the control group for subjects with Major Depressive Disorder that were administered Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium bifidum for 8 weeks.

Furthermore, three recent meta-studies that examined all of the human research in the field up to now all came to the same conclusion: probiotics can lead to reductions in symptoms of depression and anxiety, improve mood and reduce stress response in humans with or without depressive or anxiety disorders.

Which Psychobiotics?

While we are still in the early stages in our understanding of psychobiotics, there are a few strains of bacteria that have demonstrated beneficial effects on mood and anxiety in both animal studies and preliminary human studies. And the good news is many of these are found in yogurt and other fermented foods. These include:

Bifidobacteria Species: B. longum, B. bifidum, B. breve, B. infantis, B. bulgaricus

Lactobacillus Species: L. helveticus, L. rhamnosus, L. plantarum, L. reuteri, L. casei, L. bulgaricus, and L. acidophilus

But before you go out and start shopping for the latest in psychobiotic supplements, keep in mind that:

• Psychobiotics need to be ingested alive and in enough quantity to survive the tortuous voyage to your lower intestines and colon. We’re talking 10–100 billion Colony Forming Units (CFUs) required.
• Psychobiotics have synergistic effects when consumed together. Therefore, it is better to consume a cocktail of known psychobiotics together versus individually.

Combinations of probiotics shown to work well together

• These bacteria take time to build-up colonies in your GI tract. This means that, similar to antidepressants, you need to consume them for a few weeks before knowing if they will have a psychological benefit. The average administration period used in human studies is around 4 weeks.
• Also similar to antidepressants, you need to keep taking them as many can’t naturally survive long-term in the gut. In various studies the beneficial effects of probiotic supplementation stopped within days once the consumption of them ceased.

The Importance of Nutrition and Prebiotics

There is actually a whole lot more you can do for your gut health than consuming psychobiotics and without these other steps, it's questionable whether psychobiotics can deliver on their potential in the first place. The message from the research is that the health and balance of your intestinal microbiome are hugely important and psychobiotics are just one tool of many. 

Frankly, dietary and lifestyle changes will have a bigger impact than psychobiotics at this pont. Here are a few guidelines that many of the researchers in the field follow themselves:

• Eat Yogurt — This is the original probiotic. Make sure it has live bacteria added after pasteurization. Most “live” yogurt contains psychobiotics bacterial strains.
• Eat a variety of fermented foods such as kimchi, sauerkraut and kefir. These also naturally contain many of the psychobiotics listed above.
• Try to avoid antibiotics unless absolutely necessary. They kill off huge amounts of healthy gut bacteria.
• Eat a great diversity of high fiber plant-based foods (eg fruits and veggies). Different bacteria eat different types of fibers so just taking a fiber supplement will not increase the diversity of your gut biome, which is the key to gut health.
• Limit processed foods as much as possible. They get absorbed swiftly in the upper GI tract and stomach and starve the lower GI tract and intestines, where most of the gut microbiome resides. High-fat/low-fiber diets are known to reduce intestinal microbial diversity
• Consider the Mediterranean diet which in addition to supporting a healthy gut biome is shown to be antidepressant in nature

Gut Ecosystem Management

The general ethos for cultivating a healthy gut microbiome is to think of it as a rainforest or other complex ecosystem. The more diverse the ecosystem, the more resilient it is when exposed to pathogens. Furthermore, the more diverse your gut biome is the less likelihood of one microorganism wielding excessive influence resulting in unhealthy microbial imbalances. The best way to increase the diversity of your stomach microbiome is to eat a variety of different kinds of fiber-rich and naturally probiotic foods. Diversity of diet truly is the key to stomach health and potentially to mental and emotional health as well. 

Can Ayahuasca Really Cure Depression?

There has been a lot of attention on the Amazonian plant medicine Ayahuasca over the last few years, especially for its therapeutic potential. But, frankly, there has also been a lot of hype. Statements such as “its 10 years of therapy in 1 night” get bandied about regularly. And the psychedelic press makes big proclamations like “A Single Session Of Ayahuasca Defeats Depression” when new research is released. Meanwhile, the mainstream press relishes in the ayahuasca tragedy stories or overly sensational stories about the visions or the purging. In the end it creates a cloud of misinformation and confusion about what ayahuasca is and what it can do. The truth is that while rigorous clinical trials scientifically studying the effects on humans is scant, there is a lot of evidence, anecdotally, clinically, and neurochemically, in favor of ayahuasca as an anti-depressive agent.

Working with Ayahuasca: Anecdotal Observations

Based on my own professional experience working in Peru full-time as an ayahuasca retreat facilitator, guide, and apprentice shaman for the past 2 years I can unequivocally say that I know that ayahuasca *can* cure depression. During that time, I’ve worked with and met countless people who specifically sought-out ayahuasca to treat their depression. Part of the reason is journalist Kyra Sylak's 2006 National Geographic article on her experience attending an ayahuasca retreat in the Peruvian Amazon. In it, she chronicled her dramatic recovery from depression and PTSD. That article was one of the most viewed National Geographic articles of all time and led to a lot of publicity around ayahuasca as a miracle cure for depression. Many people suffering from life-long and treatment-resistant depression came down to Peru in search of that miracle.

What I saw was that ayahuasca can indeed cure depression in some people, but it is not a panacea for everything or everyone. I worked with several guests who reported complete remission of their depression, not to mention major changes in their outlook on life and the healing of life-long traumas and emotional wounds. I also met several people who had attended their first ayahuasca retreat many years ago and reported that it literally saved their life. They were back now to work on different things or because they really enjoyed the experience. One guest told me that she was literally about to commit suicide several years ago when someone gave her the National Geographic article and it gave her enough hope to try one last remedy. These kinds of stories are not uncommon.

But there are also people who after 1 terrifying ceremony, decide that this is not for them and leave in a hurry. And there are also people who feel and look great when they finish their retreat only to return 6 months or a year later reporting a significant backslide. Most often this is due to them returning to the same depressogenic environment and not being able to make the structural life changes needed. Sometimes this is because these changes seemed too painful, daunting or traumatic to undertake (eg getting out of a relationship, quitting a job, moving, setting limits with family members, etc.) and over time the effects of, say, living in a toxic relationship, took their toll. For others, ayahuasca will clear the depression cloud that has been hanging over them but they’re going to need to do their part in terms of lifestyle changes when they get home to really liberate themselves permanently from depression. The people who, from what I’ve seen, get the most out of their ayahuasca experience do just this, using it as a springboard to make some major life changes (quitting drinking/smoking, begin meditating, improve nutrition, career changes, etc.)

But perhaps most importantly, I’ve seen ayahuasca help heal the root issues at the core of people’s depressions. Things like childhood trauma, old negative beliefs and patterns of thinking, and pervasive feelings of alienation and meaninglessness. And these are things that can take a long time to heal in traditional psychotherapy. This to me is more impressive because we are talking about more than just depression, but about changing the fundamental way people relate to themselves and their world. This is where the power in ayahuasca medicine lies and, in my opinion, the relief from depression is simply a reflection of the profound transformation occurring underneath.

What Does The Research Show?

While there are mountains of anecdotal evidence, there have only been two serious clinical studies that have been conducted examining the effects of ayahuasca on depression. In both studies depressed subjects were recruited, provided ayahuasca in a controlled setting, and followed-up with afterwards.

The first was a a small study conducted in Brazil in 2016 that examined the effects of ayahuasca on people with recurrent Major Depressive Disorder. In the study, subjects were given a one-time administration of ayahuasca in a hospital setting while seated quietly in a dimly-lit room. The study showed that the average depression score for subjects dropped from 19.2 on the HAM-D scale, a standard depression measurement questionnaire, to 7.5 at 21 days of follow-up. That is the equivalent of going from a moderate depression to full remission, so these results are pretty dramatic. However, this study only had 17 subjects and was neither blind nor placebo-controlled. It also followed subjects for only 21 days so who knows how they were doing 6 months or 1 year later. It was a promising preliminary study but definitely not the final word on ayahuasca and depression.

The same Brazilian team of researchers followed up a year later with a more thorough double-blind placebo controlled study of 29 subjects with treatment-resistant depression (14 in the ayahuasca and 15 in the control). This study is a big deal because it is the first double-blind placebo controlled study conducted on ayahuasca. They also showed that average HAM-D scores of the subjects administered a single dose of ayahuasca dropped from 21.8 to below 10. At the 1-week follow-up, 36% of the ayahuasca-drinking subjects were in full remission while only 8% of the control group was in remission. Again, very promising. However, clinically speaking these groups are too small to draw any definitive conclusions from. Furthermore, due to high drop-out rates, the team wasn’t able to continue the study beyond 1 week. That is a serious limitation as treatment-resistant depression is a long-term condition.

But these 2 clinical studies confirm the results of previous exploratory studies that administered ayahuasca to small groups of clinically depressant research participants. They also showed similar 50-60% declines in HAM-D scores up to 28 days later.

For comparison, the average drop in HAM-D scores in clinical trials for all FDA-approved SSRI-based anti-depressants was approximately 40%. And these were achieved with trials that explicitly excluded the very difficult treatment-resistant clients which where the focus of the ayahuasca studies. So the ayahuasca results, while preliminary are definitely promising, especially since this was after only a one-time administration of ayahuasca while current pharmaceutical treatments require weeks to build up in the body and then must be taken daily on an ongoing basis.

The Hoasca Project

Other researchers have taken the approach of studying the psychological health of long-term ayahuasca drinkers. The most famous of these non-clinical studies on ayahuasca, is the Hoasca Project, also conducted in Brazil, which administered psychological, biochemical, and physiological tests to long-term members of the Uniao do Vegetal Church in Manaus, who drink ayahuasca regularly in a religious context as a sacrament. These subjects had been drinking ayahuasca for many years, in some cases hundreds of times. Researchers compared the results of their psychological and biological tests with the results from a control group of age- and gender-matched subjects from the community. Now this was also a small study with only 30 total subjects, 15 of which were in the control. But the results revealed that most members of the UDV group had battled with alcoholism, addiction and depression prior to their participation in the ayahuasca church but none of the members currently met the criteria for a psychiatric or substance abuse diagnosis. The UDV members had experienced remission in all their psychiatric conditions, including depression, over the course of their participation with the ayahuasca church. This compares with the control group where 2 members had active psychiatric diagnosis. Other similar retrospective studies have showed essentially the same thing: long-term drinkers of ayahuasca appear to be psychologically healthier than their age/gender-matched community counter-parts and have significantly lower levels of addiction and psychiatric conditions.

Perhaps the most intriguing finding of the Hoasca Project was that the long-term ayahuasca drinkers showed significant increases in serotonin (5HT) transporters levels. Serotonin transporters are intimately related to the regulation of serotonin levels in the brain and are the target site for SSRI-based anti-depressants, so this finding showed one potential pathway by which ayahuasca can treat depression.

Ayahuasca: A complex brew

Ayahuasca is not one individual plant but a combination of plants cooked together to create a drinkable brew. The two primary ingredients are the vine ayahuasca (Banisterias Caapi) and the leaves of the chacruna plant (Psychotria Viridis), although ayahuasqueros will often include many other medicinal plants in their cook or use analogs in lieu of chacruna. Each of these two primary ingredients has their own antidepressant compounds. For example, the ayahuasca vine contains a variety of psychoactive alkaloids known as beta-harmalines that are inhibitors of the Monoamine Oxidase (MAO) enzyme. MAO inhibitors were the first anti-depressants ever developed and the Harmine in ayahuasca is a powerful one. Studies of rats administered with Harmine show a variety of anti-depressant and anti-anxiety like effects and increases in BDNF, which is a protein that supports the growth and function of neurons. 

The chacruna plant contains significant quantities of Dimethyltryptamine (DMT), which is the compound responsible for the visual and visionary experience associated with ayahuasca. DMT strongly affects a variety of Serotonin receptors in the brain as they are very close cousins. One of the serotonin receptors that DMT activates is known as 5HT-2A. This is an important receptor for a lot of psychedelics/entheogens and is considered by some to be a primary neurochemical pathway for psychedelic/visionary experiences. And studies show that harmine also binds to the 5HT-2A receptor, so ayahuasca may be delivering a double dose of serotonin activation at the 2A receptor. 

Recent studies show that some of the very medications psychiatrists prescribe to supplement traditional anti-depressants when they aren’t effective are major 5HT-2A receptor agonists. So we know that targeting 5HT-2A receptors can have anti-depressant properties, especially for those with intractable treatment-resistant depression.  

Powerful anti-depressant compounds, but what else?

At a minimum, ayahuasca contains two very powerful psychoactive compound that have anti-depressant effects. But how can they lessen depression in one session while traditional anti-depressant medications targeting the same neurochemistry take weeks? This is still a mystery. But even the reductionist scientific understanding of ayahuasca shows that there may be more going on than serotonin receptor activation. For example, there is neuro-imaging evidence showing that ayahuasca causes marked reductions in activity and disruptions in connectivity in a network in the brain that is known to be over-active in people with depression.

My personal opinion is that the scientific understanding barely scratches the surface. A ceremonial ayahuasca experience includes a variety of ingredients (the individual, the setting, the peers and community, the shaman/facilitator, the specific constituents of the brew, the beliefs and understandings of how it works by the user, the spiritual nature of the experience for many, the physical purging that is a big part of the experience, etc.) and almost none of them have been examined scientifically. For example, only relatively recently have researchers discovered that psychedelic-caused mystical experiences can themselves have beneficial effects on mood, outlook, and personality.

Frankly, the scientific method does not lend itself well to examining such subjective experiences but that doesn’t mean that we can’t learn from the fruits of of that framework. However, it does mean that in many ways the scientific understanding is way behind the traditional Amazonian knowledge and wisdom that has been accumulated over hundreds of years and passed down from teacher to student. These traditions don’t have a western scientific theory for how Ayahuasca works, but they have tremendous practical knowledge and wisdom on how to wield ayahuasca effectively for maximum benefit.

The Power of Exercise for Mental Clarity and Emotional Stability

Most people look at exercise as a something you do solely for your body. Specifically, many people look at exercising as simply a calorie destruction mechanism to be engaged in so that that they don’t get fat. Much of our current attitude around exercise comes from 1980s fitness concepts such as the the carlorie-in/calorie-out complex. Doing something to avoid something else is usually a very poor motivator for humans. As a result exercise often falls into the basket of “things I should do” that while enthusiastically embraced right around New Years, eventually ends up being discarded by the time spring cleaning rolls around.

But vigorous exercise isn’t just about your body. Its one of the most emotionally beneficial and mentally constructive activities we can engage in. It generates mental clarity, creative thinking, flow states, and releases a powerful cocktail of painkillers, mood regulators, and stimulants. These are endogenous versions of all the drugs that people turn to recreationally or for numbing, coping, and self-soothing. Biochemically its like smoking a joint, snorting cocaine, shooting heroine and popping some Prosac all at the same time. The difference is that neurochemicals are brilliantly generated by your body in just the right balanced amount to give you all the benefits without the compulsive dopamine-reward-system hijacking associated with addictions or the crash afterwards. No wonder it is such an effective intervention for substance abuse and addictions.

Improved mood, stress, and cognitive function

More important, it is a powerful mood stabilizer. That’s right, exercise combats depression and anxiety and stabilizes mood. In fact many studies show that it is at least as effective as prescription anti-depressants. And there is a ton of research that support this. It’s the same with stress reduction. Studies show that regular exercise reduces the effects of acute and chronic stress. And the benefits are seen after a single bout of exercise. Its not like anti-depressants where it takes weeks to build up in your system to have an effect. These benefits accrue instantly. Anything that combats addiction, stress, and depression is something that the whole country should be paying attention to since all 3 are at record levels. Finally, there is evidence showing that cognitive and executive function is improved immediately following vigorous exercise. Who doesn’t want quicker, clearer and more creative thinking and improved decision making before they start their work day? And regular exercise prevents cognitive decline over-time. Its even being used as an intervention to treat age-related cognitive decline and dementia.

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Approximately 30 minutes with a heart-rate approaching 60–80% of maximum heart-rate has been shown to be the ideal range

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Best of all, exercise doesn’t cost anything, doesn’t require special gear, and can be done anywhere. The incredible amount of research done on exercise has even helped us to dial in the ideal amount needed for wellbeing and mood support. Approximately 30 minutes with a heart-rate approaching 60–80% of maximum heart-rate has been shown to be the ideal range. But personally, I think you can ditch the heart-rate monitor and test it out for yourself. There is an intensity level and duration at which your mind starts to feel clear, your mood lifts, and you feel excited about, well, everything. Colors look brighter, trees look more interesting and you just feel good. That is the sweet spot. It doesn’t mean you’re going to feel that way every single time but that is roughly the intensity-druation zone you are looking for. You can go beyond that, but its not necessary unless you have some physical goals (cardiovascular training, weight loss, etc.) that you are going for.

Make It Green If You Can

One thing you can do to improve the mood and stress-reduction benefits of your exercise routine is to do it in some kind of green or natural environment. I know not everyone has access to this, especially in a city, but running in a park, forest, mountain, or any green environment has been shown to improve the mood effects of exercise. Now the studies have been small but they are supported by the ample evidence base on the mood and stress benefits (not to mention, immune system, heart rage, and blood pressure benefits) of spending time in nature. Japan has been the leader in researching and promoting what is known there as Shinrin-Yoku or “forest bathing.” Its even integrated into their medical system. But fret not if you can’t find a nice forest to go run in. Even cycling in front of a computer screen video of a forest showed better mood results than watching an entertainment video.

Making The Time

So make the time in the morning. Why morning? First, you are much more likely to get it done if you do it first thing in the morning, before the day’s commitments, stresses, workloads and procrastination take over. Your will to exercise isn’t yet taxed by the demands of the day. Second, why wouldn’t you want these benefits to accrue all day long? When you exercise in the morning, all the cognitive, stress, and mood benefits carry forward throughout your whole day (to different extents)*.

Its pretty easy to squeeze in a 20 minute jog first thing when you wake-up if you lay your running clothes out the night before. Try it. If you haven’t exercised in a while, make it a walk around the block the first day. Then work you way up to a 20 minute walk and then switch to a light jog. Keep working your way up until you’ve reached your sweet spot. And it doesn’t have to be running, which is notoriously high-impact and probably not great to do every single day. Get a jump-rope and do some jump roping. Go for a bike ride or a swim if you have the time and the facilities. Do push-ups, crunches, and burpees at home for 15 minutes. Follow a video-based at-home exercise routine. There are so many ways to move your body and raise your heart-rate for 20–30 minutes. And you can alternate them for variety and to balance your body’s movements.

But do something. Your mind, your heart, and your body will thank you. And trust me, your future you will thank you down the road as well. Keep this up in your life and you may find that it is the best investment you ever made.

(*) NYU Center for Neural Science even assembled this handy little chart showing the cognitive, emotional, and physiological benefits of exercise at various intensity levels/durations as well as which physiological systems benefit and for how long.

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