June 19, 2023

The Past and Future of Psychedelics

The Past and Future of Psychedelics

Depression, anxiety, and other mental health issues affect billions of people worldwide, and current treatments often come with significant drawbacks, including addiction, side effects, and limited efficacy. On the other hand, psychedelic-assisted therapy is on the rise, with never before seen positive effects even after a single treatment. But these therapies are extremely expensive, limited, and illegal in most of the world while they send patients down a hallucinogenic rabbit hole that most people are rightfully afraid of. But if a non-hallucinogenic compound could be extracted or synthesized with all the therapeutic benefits of psychedelics, it would revolutionize the field of psychiatry and tap into a $50 billion market ripe for disruption.

The Johns Hopkins Experiments

In 2010, sixty-three years old New Yorker Dinah Bazer was diagnosed with mixed-cell ovarian cancer. Usually, more than half of women in her situation don't survive past five years after their diagnosis, but Dinah was fortunate to catch her tumor early. After undergoing six rounds of chemotherapy and two years of follow-up appointments, the cancer was in remission. But Dinah was still plagued by existential dread that the disease could return at any moment.

In 2012, Dinah expressed her worries to a nurse during a check-up, and she was recommended to participate in a study conducted by the psychiatric team of Johns Hopkins University. The study aimed to determine if psilocybin, the active ingredient in magic mushrooms, could relieve depression and anxiety in cancer patients. The findings of this randomized, double-blind, placebo-controlled trial were released in the respected Journal of Psychopharmacology in November 2016. They showed that 87% of the 29 volunteers reported reduced or eliminated the fear of death, with increased life satisfaction and mental well-being even months after just a single treatment. The results were described as "unprecedented in the field of psychiatry”, and according to famous mycologist Paul Stamets, even people inside the FDA declared that "they’ve never seen anything with such a strong safety profile that gives so much benefit for such a low cost over such a long time.”

The Eleusinian Mysteries

The unexpected results of the John Hopkins study not only provided insight into the future of psychiatry but also solved a 3000-year-old mystery.

The ancient Greeks are well known for their contributions in various fields such as philosophy, science, art, politics, theater, and architecture, but there was something else they created that, up until now, was shrouded in history. Before Jerusalem and Mecca, there was a small town near Athens called Eleusis that was considered the religious and spiritual capital of the ancient world. Each year the high priests of Greece gathered there to hold a secret ritual that was so secretive that initiates were sworn to silence, and the exact details of what took place were never revealed to the public. But according to the few accounts we do have, this was a place where the best and brightest of Athens and Rome went to drink a mysterious potion named “Kykeon” to have a mind-blowing visionary experience that would eliminate their fear of death. The description of the ritual aligns perfectly with the experiences reported in the John Hopkins trial and in the over 3000 psilocybin trials since. And when archeochemists examined cups that may have been used in Eleusis, they found trace remains of ergot, which is the mushroom LSD was synthesized from in the 20th century.

The so-called Eleusinian Mysteries ran for almost two millennia, from 1600 BC to 391 AD, when Roman Emperor Theodosius I declared Christianity to be the official religion of the Roman Empire and banned all other religions and practices. According to one account, the Greeks even begged to keep the Mysteries going, saying that “Eleusis is what holds the entire human race together. Without it, human existence will be unbearable."

The Mental Health Crisis

There’s no doubt that today we’re experiencing an unprecedented mental health crisis worldwide, and for many people around the globe, existence seems unbearable. According to the World Health Organization, one in four people around the globe will experience some form of mental or neurological disorder at some point in their life. In the US alone, there are an estimated 1.4 million suicide attempts annually which makes it the 10th leading cause of death, with suicide rates increasing by over 30% since 1999. And while psychotherapy has made many advances over the past decades to tackle these issues, psychopharmacology is frustratingly lagging behind.

Currently, the gold standard to treat depression and anxiety are the infamous antidepressants, otherwise known as selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs). In general, these substances work by changing the levels of certain chemicals in the brain, such as serotonin, dopamine, and norepinephrine. While 14% of the US population uses these drugs on a regular basis, we don’t even fully understand the mechanism of how they work. And there are a lot of problems with them.

  • They take weeks before they start to have an effect.
  • 30% of patients show no improvement.
  • They have horrendous side effects like nausea, drowsiness, vertigo, and sexual dysfunction.
  • A proper treatment regimen is six months at a minimum.
  • A small percentage of people who want to quit the drugs experience "antidepressant discontinuation syndrome,” which includes depression, anxiety, irritability, insomnia, suicidal thoughts, and flu-like symptoms.

Even leading medical experts are now warning that using SSRIs or MAOIs for long periods of time could be addictive and can cause permanent damage to the patients’ bodies and mental well-being. But for people with mental health issues, there are not a lot of other options when it comes to pharmaceutical treatment.

The War on Drugs

Psychedelics like Magic Mushrooms (Psilocybin) or LSD (Ergot) are associated with harmful drug culture, loss of control, and visual hallucinations. At first glance, nobody would question why they have been banned from our societies. But beneath the surface, their neurobiological effects are actually quite similar to what antidepressants aim to replicate.

Psychedelic substances act on the 5-HT2A receptor in the brain to increase the release of serotonin, which then produces its characteristic changes in perception, mood, and cognition.

On the other hand, SSRIs work by blocking the reuptake of serotonin, increasing the concentration of serotonin in the synaptic cleft, and enhancing the activity of serotonin in the brain.

Even to the average person, the mechanism of the antidepressants should sound much more invasive and unnatural than what mushrooms do by simply boosting the way the mind works. And if we consider that Psilocybin and LSD are non-addictive and, unlike SSRIs, even one treatment can fundamentally change a patient's mental health for the better, suddenly we feel the urge to reexamine our pre-existing notions and ask the important questions; why did we sideline natural remedies that helped humanity for millenniums?

Well… because of those dreaded hippies.

The 1970s saw a drastic shift in drug policy in the United States. As counterculture movements gained strength in the late 60s, the Nixon administration panicked. They blamed drugs use for rising crime rates, social unrest, and a decline in moral values. In response to these concerns, President Nixon declared a "war on drugs" and passed the Controlled Substances Act of 1970, which classified drugs into different schedules based on their perceived risk to public health.

Psychedelics, which have been used for thousands of years in various cultures for their therapeutic benefits, were caught up in this crackdown and deemed illegal too. Suddenly, earth medicines like magic mushrooms, cannabis, peyote, and ayahuasca (DMT) were Schedule I drugs in the company of such destructive and harmful substances as crack, speed, meth, and cocaine. They suddenly became part of a class of drugs considered to "have a high potential for abuse and no accepted medical use”. And for the next 50 years, it wasn’t just illegal to manufacture, distribute or possess them, but even to research and study them. Therefore their potential benefits in psychiatry have been overlooked for decades, causing insurmountable damage to millions of people who could’ve received alternative, organic, and historically well-known treatments.

The CBD Revolution

Now, billions of dollars and millions of lives later, the war on drugs is finally cooling down. In the past ten years, the doors for research and legalization slowly started to open up. And it all started with cannabis.

We’ve known for a long time that cannabis has a number of therapeutic benefits, including pain relief, anti-inflammatory effects, and the ability to reduce symptoms of anxiety and depression. It also has antipsychotic and neuroprotective effects, making it a promising treatment for conditions such as schizophrenia and epilepsy too. But while there are many progressive states in the US that managed to gain partial legalization, the cannabis market is still constrained globally and on the federal level too. But turns out people don’t even want to get high that much. They want the medical benefits.

With the passing of the 2018 Farm Bill, CBD (the non-psychoactive compound of the cannabis plant) became widely available as a standalone product. Without the mind-altering highs but with all the therapeutic benefits, the CBD compound rapidly became a global sensation, with a market that’s on track to reach 20 billion USD by 2024. With no undesired psychotropic effects, CBD was not just easier to get legalized, but it appealed to all sorts of demographics that would otherwise never touch cannabis. And with its own unique therapeutical properties, CBD was destined to succeed. But it was also the key to finally reevaluate our pre-existing notions of some of these substances.

Psychedelic Medicines

Unlike cannabis, true psychedelics can not be consumed recreationally. It’s not a walk in the park. (Well, technically, it can be, but the trees would breathe, and the grass would sing… ) While legalization for psilocybin could only be a few years away in the US, these substances are a few of the most potent hallucinogens known to man, and there’s a reason to be cautious with them. But they clearly offer us an amazing opportunity to create new and innovative treatments for mental health disorders.

  • The effects are proven. From Ancient Greece to the Johns Hopkins trials, to thousands of clinical studies and millions of psychonauts, these substances, beyond doubt, have been demonstrated to be the most powerful tools to keep our minds healthy and blissful.
  • These substances check every box. They boost serotonin, dopamine, and norepinephrine without being addictive. They are highly effective even after a single dose. And most importantly, they induce neuroplasticity which is the brain’s ability to change and reorganize itself in response to environmental stimulation or injury. With enhanced neuroplasticity, the brain is able to create new connections between neurons supercharging the healing process from traumas.
  • The demand for novel mental health treatments is robust. Based on a recent estimate, in the US and the EU alone, 1 billion people are struggling with mental health issues on a daily basis. 162 million people fight with substance abuse, 264 million with anxiety disorder, 300 million with PTSD, and 322 million with depression. It’s a potentially 50 billion USD market ready for the picking.

But the problem is that we never had anything like psychedelics in healthcare before. There’s not even a regulatory framework we could work with. Their legalization will be a slow and painstaking process and very much limited to a few states in the US and perhaps a few countries in the EU. They will remain illegal in most of the world and out of reach for most people in need. And even if that wasn’t the case, most people would never want to experience life-changing visual hallucinations for hours on end.

So just like in the case of CBD, people want the medical benefits without the high. And that would be something that regulators could work with too.

Psychedelic Drugs Without The Psychedelia

Like cannabis, that has a psychoactive and non-psychoactive compound, psychedelic plants and fungi can be broken down into smaller bits too. And the next great pharmaceutical opportunity belongs to those who extract or synthesize the CBD-like compound in psychedelics that carry therapeutic benefits without the unwanted hallucinogenic effect.

  • In January 2023, a team of scientists from China reportedly designed a new drug that they say acts in a similar fashion to LSD and psilocybin but without leading to hallucinations. In trials on mice, the drug produced antidepressive effects without psychedelic ones.
  • As one of the most promising startups in the field of non-hallucinogenic psychoplastogens, Delix Therapeutics recently identified DLX-1, a non-hallucinogenic psychedelic analog with neuroplasticity-promoting and antidepressant properties.
  • Researchers at the University of California created a non-hallucinogenic version of the psychedelic drug ibogaine, with the potential for treating addiction, depression, and other psychiatric disorders.

Overall, the hunt to create the non-hallucinogenic modern version of the Greeks’ famous “Kykeon” is about to heat up, with more than a billion people waiting to get back their ancient healers that were said to make human existence blissful.

Peter V

Not living up to my potential since 1990.As a functional dysfunctional who got max points on the ADHD diagnostic test, I’m dedicated to help people on their mental health journey and to provide them information on how to support their brains to unlock their full potential.

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