A Brief History of Psychedelics
If it wasn’t for a strange bike ride 77 years ago, the role of psychedelics within the scientific community and its impact on our society may have been dwarfed. Psychedelics, derived from the Greek words psychē (soul) and dēloun (to make visible or to reveal) translating to “mind-manifesting”, have been around for thousands of years, and their impact on human development as well as the founding of religions or spiritual movements have been understated. Archeological findings of fossil evidence have linked humans with psychedelic substances going back as far as 10,000 years, and historical evidence has showcased cultural use over the past 5,000 years. Plants and fungi have been used to change the experience of consciousness for a very long time, especially in religious settings. Psychedelics' role in ceremonies, as well as its connections to the divine or spiritual experiences, have been hiding in plain sight. In 2008, Benny Shanon, an Israeli researcher from the Hebrew University, conducted research that found that when Moses received the ten commandments, he may have been high on psychedelics. There are two plants that are frequently mentioned in the old testament and the mix of the two could explain the experiences that Moses is said to have had. They contain the same molecules as the powerful Amazonian hallucinogenic brew ayahuasca that can still be found in the Sinai peninsula. Although no direct proof was tied to the research, the thought that the burning bush vision was caused by a hallucinogenic trip is certainly intriguing. Psychedelics’ presence is further shown across a wide variety of religions, with a legal decree (“Fatwa”) in 2017 by the Grand Ayatollah (the highest authority on Shi’ite Islam) allowing the use of certain psychedelic substances in a religious setting and the use of magic mushrooms by native Americans in ceremonies to this day. You might be wondering why this is the first time you learned about all of this. Historically, psychedelics had quite a bumpy trip. Throughout the 14th and 18th centuries, following the arrival of conquistadors in the Americas, the Roman Catholic Church was brutally suppressing old animistic pagan religions, and with that, drove the use of psychedelics in religious settings underground.
Up until the end of the 19th century, the potential of psychedelics was widely overlooked and forgotten. If it wasn’t for the breakthroughs and curiosity of academics and scientists such as Arthur Heffter, commonly viewed as the father of psychopharmacology for being the first to isolate and ingest pure mescaline in 1897, Anton Köllisch, who first synthesized MDMA while at Merck in 1912, and Richard H. F. Manske, who first synthesized DMT in 1931, many of the effects of psychedelic substances may have remained misunderstood. It was not until 1938 that Albert Hoffman, while working at Sandoz Laboratories on medicinal plants to isolate, purify, and synthesize their active compounds, synthesized LSD-25 (after the 25th attempt), leapfrogging psychedelics into a new chapter. Also known as lysergic acid diethylamide, synthesized from ergot, a rye fungus, LSD-25 was created in Hoffman’s search for a circulatory and respiratory stimulant as part of Sandoz (a pharmaceutical company). The results from testing on this synthesized molecule were not attracting special interest and therefore testing on LSD was discontinued and shelved. For over 5 years, LSD was collecting dust at Sandoz, until Hofmann, in fear of missing out on some of the molecule’s properties, decided to resynthesize it on April 16th, 1943. On that day, he accidentally absorbed 20 micrograms of LSD-25 through his fingertips which was followed by a remarkable experience, one he could only connect to the substance.
“I was forced to interrupt my work in the laboratory in the middle of the afternoon and proceed home, being affected by a remarkable restlessness, combined with a slight dizziness. At home I lay down and sank into a not unpleasant intoxicated-like condition, characterized by an extremely stimulated imagination. In a dreamlike state, with eyes closed (I found the daylight to be unpleasantly glaring), I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors. After some two hours this condition faded away.”
- Albert Hofmann, 16th of April 1943.
Shortly after this experience on the 19th of April, Hofmann, moved by what is now known to be the world’s first acid trip, was eager to explore the properties of LSD-25 and ingested 200 micrograms of LSD-25 diluted in 10cc of water. Although a small dose for many drugs, it was quite the opposite for LSD, given its high potency. What followed, was a wave of dizziness, feeling of anxiety, visual distortions, symptoms of paralysis, and a desire to laugh. In fear of losing his mind, Hofmann asked his assistant to escort him home. Given that it was wartime, no vehicles were allowed to drive around Switzerland during specific hours and Hofmann was forced to cycle home on his bike. The ride home, now commemorated every year on the 19th of April as bicycle day, is viewed as a landmark in the surge of psychedelics in the medical and scientific world as well as the creation of modern neuroscience.
“Kaleidoscopic, fantastic images surged in on me, alternating, variegated, opening and then closing themselves in circles and spirals, exploding in colored fountains, rearranging and hybridizing themselves in constant flux,” he wrote. “It was particularly remarkable how every acoustic perception, such as the sound of a door handle or a passing automobile, became transformed into optical perceptions. Every sound generated a vividly changing image, with its own consistent form and color.”
- LSD: My Problem Child by Albert Hoffman
From that day forward, Hofmann dedicated his life to LSD-25 and advocated its role in society. Soon after Hofmann’s experiences, Sandoz tried to promote LSD as Delysid, aimed at treating psychiatric disorders such as schizophrenia. As a result of Sandoz sending out samples all around the world to psychiatrists, academics, and scientists, LSD was briefly used as the standard treatment in conjunction with psychoanalysis. The initial results of this initiative led to remarkable findings wherein a 50% success rate was recognized when attempting to cure people of obsession, depression, alcoholism, and addiction as a whole. These results led to increased attention to LSD and other psychedelics, so much so that even the CIA and U.S. military was aiming to weaponize it in what is now known as Project MK-ULTRA. As quickly as it caught attention due to its scientific capabilities, it swiftly found its way out of the laboratory into wider use by writers, actors, well-known business people, and artists. The latter, in conjunction with the counterculture movement of the 60s (e.g. hippies, anti-war movement), made the drug a non grata for the States of New York and California, criminalizing its possession in 1966. This was followed by the Nixon administration’s prohibition of psychedelics in 1971 through the Controlled Substances Act and the 1971 United Nations Convention on Psychotropic Substances. Despite the low overall harm and toxicity of psychedelics, they were more heavily regulated by the U.N. than other more toxic and harmful drugs such as fentanyl, methamphetamine, and cocaine. Once again, psychedelics were forced underground and what followed was 30 years of lost potential, in what we call the psychedelics’ ice age, to research depression, addiction, and how the mind works.
Why Should We Care?
So, why should we care? Mental health, although largely unspoken and commonly stigmatized, has a far greater impact on our society than one might initially think. As a result, it has been one of the most neglected areas of public health. According to the World Health Organization, every 40 seconds a person commits suicide, with over 3 million people die every year from the harmful use of alcohol, and close to 1 billion people are living with a mental disorder. Cultural changes and technological advancements over the past decade have been said to be one of the key drivers behind increasing psychological distress in our society, and more specifically, amongst adolescents and young adults. This is reflected in the alarming rates of adolescents and young adults experiencing depressive symptoms in the last year increasing by 52% and 63%, respectively, while rates remained stable for adults aged 26 and older. In the United States alone, it is estimated that one in five U.S. adults live with some form of mental illness and almost 21 million Americans have at least one addiction. Beyond that, the cost of mental disorders in the United States has been estimated to reach $16 trillion by 2030, including lost productivity.
Some (Scary) Facts…
Close to 1 Billion people suffer from mental health conditions worldwide
Anxiety affects 284 million people in the world.
Depression affects 264 million people.
Alcohol use disorder affects 107 million people.
Drug use disorder affects 71 million people.
Bipolar disorder affects 46 million people.
Schizophrenia affects 20 million people.
Eating disorders affect 16 million people.
The problem is only amplified by externalities such as COVID-19 as well as the inadequate and inefficacious methods of the mental healthcare industry. Approximately one-third of patients will not respond to current antidepressant drugs. Those who do will usually require at least 2–4 weeks of treatment before they experience any beneficial effects, and adults who are on antidepressants are 2.5 times as likely to attempt suicide. Besides that, SSRI drugs - antidepressants that boost the level of serotonin in the brain - can take months to have any meaningful effects, and a first prescription is effective only about 30% of the time. Other antidepressants such as benzodiazepine are extremely addictive with up to 15% of its users becoming addicted. Both SSRIs and other commonly used antidepressants are known for high relapse rates or severe side effects which make people stop using them shortly after they start. Although it is clear that the status quo is alarming, it clearly benefits some. In 2017 alone, worldwide sales of antidepressant medication surpassed $14 billion.
The Renaissance of Psychedelics
2006 has been perceived as the year that marked the renaissance of psychedelics. With increasing media attention as well as renewed interest by scientific institutions, psychedelics have returned to the mainstream. One of the key players behind this revival is Roland Griffiths, a highly respected neuroscientist of John Hopkins University, now the Director of John Hopkins Center of Psychedelic and Consciousness Research. He made a mark for himself pioneering different experiments to determine addictiveness by understanding reinforcement, dependence, preferences, and withdrawal. One of his most renowned experiments is the self-administering of various drugs through a lever by rats or baboons. This led researchers to several groundbreaking publications such as food vs. cocaine? His research further led us to view caffeine less as a food and more as a drug, and enabled other researchers to measure and understand the addictiveness of different substances in experiments.
As a result of his personal interest in the dimensions of consciousness and his acquaintance with academic outsiders such as Bob Jesse and Rick Doblin, Griffiths was seeking to explore the potential of psychedelics. After roughly 40 years, Griffiths ignited the revival of academic research in the field by publishing the landmark paper: “Psilocybin Can Occasion Mystical Type Experiences Having Substantial and Sustained Personal Meaning and Spiritual Significance” alongside Richards, McCann, and Jesse in the Journal of Psychopharmacology. Being the first rigorously designed, double-blind, placebo-controlled clinical study to examine the psychological effects of a psychedelic, its significance cannot be understated. The study, involving 36 patients who were chronically or terminally ill and spiritually inclined, researched the impact of Psilocybin to relieve the stress associated with severe chronic diseases such as cancer. Although only a single dose was administered to the 36 patients, 64% of the patients still considered the experience to have valuable after-effects, with an increase in their sense of well-being or life satisfaction at the time a follow-up study was conducted 14 months later. The research further flipped the narrative on psychedelics, given that the research was peer-reviewed and widely applauded by world-renowned drug researchers and drug abuse officials. As a result, Griffiths was able to reinforce the distinction between classic psychedelics such as psilocybin, LSD, DMT, and mescaline, and the more common drugs of abuse with their demonstrated toxicity and potential for addiction. From there, research on psychedelic compounds by academic institutions grew significantly, aiming to rehabilitate other banned substances for therapeutic applications.
The revival of psychedelics has gone hand-in-hand with the understanding that existing therapies for mental health illnesses are limited. While the current set of drugs and therapies are only recognized to work well for a subset of the population, psychedelics represent a paradigm shift in the treatment of mental health, having robust and long-lasting anti-depressant effects without the negative effects associated with SSRIs. As described by William A. Richards, one of the researchers who successfully treated patients with hallucinogens in the 1960s and early 1970s, psychedelics act as a therapeutic accelerant, a skeleton key that unlocks an interior door to places we don’t generally have access to. What does this all mean? Let’s take a look at what recent research has unraveled and the science behind psychedelics.
The Science
With the newly regained interest in studying the effects of psychedelics, many substances have been introduced to the laboratory and more importantly to clinical trials. Even though there are many new compounds making headway, we will focus on the compounds leading the way: psilocybin, MDMA, LSD, ketamine, and ibogaine. Most of the studies follow a classic model for psychedelic therapy in which the participants lie on a couch and wear eyeshades while listening to music, having a sober participant monitor the activities and experiences to make sure everything is okay. Researchers do not talk to or guide subjects during the trip, but before each session, they prepare people for what they might experience and guide them through how they should approach it; this is vital to the effectiveness of the treatment. The purity of the compound, the setting, and the environment are also crucial factors to a successful outcome. Before we dive in, you can find an overview of different substances in the realm of psychedelics and what conditions they may treat below.
Psilocybin
Psilocybin, a psychoactive compound found in what is commonly known as 'magic mushrooms', has shown extraordinary results in clinical settings with little to no side-effects. Among the top 10 most used drugs that have caused harm to others and self, it is ranked as #10 while alcohol is #1. “When administered after careful preparation and in a therapeutic context, psilocybin can lead to deep reflection about one’s life and spark motivation to change,” says Matthew Johnson, Ph.D.
Inflection Points:
FDA designates psilocybin as a breakthrough therapy.
An American company is awarded a patent for synthetic psilocybin for treatment-resistant depression.
John Hopkins launched the Center for Psychedelic & Consciousness Research in 2020, leading the way on psilocybin research.
DC votes to decriminalize hallucinogenic mushrooms.
Clinical Results:
In 2014, a study by John Hopkins University showed an 80% success rate in terminating nicotine addiction 6 months after a single treatment and a 67% success rate at the 12-month mark. Today’s most effective treatment has a 35% success rate at the 6-month mark.
In the same study, 85% of subjects rate it as one of their top 5 most meaningful and spiritually significant experiences of their life.
In 2019, a small study conducted at the University of Alabama at Birmingham showed a 100% success rate in terminating crack addiction. 30% of the patients in the test group have not touched crack since and 70% had one or two relapses before fully giving up crack.
A study conducted by Johns Hopkins University in 2016 showed great results in patients with depression. 80% of patients with life-threatening cancer showed significant decreases in depression and anxiety at the 6-month mark following a high-dose, psilocybin treatment.
In a feasibility trial conducted in 2016 by The Lancet Psychiatry, a group of subjects with treatment-resistant depression showed markedly reduced symptoms 1 week and 3 months after two high dose psilocybin treatments, given 7 days apart.
Challenges & Toxicity:
Psilocybin appears to be one of the safest “recreational” drugs and is not addictive. It sends the fewest people to the emergency room of any drug on the market, and in a clinical setting, there have been no reports of any serious adverse effects.
There have been reports associating it with deaths. However, a majority of these reports involve the mixing of drugs, impure substance, underlying medical issues, alcohol involvement, and other external factors that make it difficult to point to psilocybin as the causation.
Experiences deemed as “bad trips” can be associated with fear, anxiety, panic, and depersonalization. Even though unpleasant, studies show people still value the experience as meaningful.
LSD
From 1950 to 1970, LSD was used in the treatment of anxiety, depression, psychosomatic diseases, and addiction. In 1968, LSD was made illegal and the last FDA approved study of LSD in patients ended in 1980. It has taken decades for a resurgence of interest in LSD research and its potential in mitigating the mental health crisis, but now we are once again exploring the many benefits associated with administering the compound in a clinical setting.
Inflection Points:
After a long history of stigmatization, LSD is once again being researched for use in treatment.
LSD is being trialed for everything from Alzheimer’s disease to alcoholism.
New York University is conducting the first clinical trial on the effects of LSD in combination with MDMA.
Clinical Results:
A study published in 2020 conducted by the Beckley Foundation and Maastricht University showed that microdosing LSD increased pain tolerance by 20%. Subjects also reported a decrease in the subjective experience of painfulness and unpleasantness. These results are groundbreaking and comparable to those observed after the administration of opioids, such as oxycodone and morphine to healthy volunteers.
In 2016, Human Brain Mapping published a study showing that LSD acutely induced global increases in brain entropy which is associated with greater openness.
A study conducted by the University of Basel in 2016 showed that a 200 μg dose of LSD produced greater feelings of closeness to others, happiness, openness, and trust.
In 2014, a study showed that in patients with anxiety associated with a life-threatening disease, anxiety was reduced for 2 months after two doses of LSD.
Challenges & Toxicity:
In a review of the harmful effects of the top 10 most used drugs, LSD sits at the #9 spot where alcohol is #1. LSD is not addictive, and humans have the ability to build up a tolerance, much like how we build up a tolerance toward caffeine. However, LSD is unpredictable, and just like any other psychedelic experience, the setting is crucial to a good outcome.
LSD is still in the early stages of clinical trials. There is much that is not yet known and research on the compound has been hampered due to its stigma.
Ketamine
Ketamine started out as an anesthesia medicine in the 1960s on the battlefields of Vietnam. Low doses can relieve pain and also reduce the number of addictive painkillers needed later on. By accident, it was later discovered that ketamine possessed an antidepressant activity that acted within hours rather than weeks. “Recent data suggest that ketamine, given intravenously, might be the most important breakthrough in antidepressant treatment in decades,” says Thomas Insel, MD.
Inflection Points:
In 2000, ketamine was discovered to have rapid, robust, and sustained antidepressant effects.
In 2019, the FDA and European Commission approved an (S)-ketamine nasal-spray for treatment-resistant depression
Clinical Results:
Research funded by the National Institute of Mental Health showed that patients with major depressive disorder who were resistant to other treatments showed significant improvement in symptoms within 110 minutes of treatment. 35% maintained a significant response for at least 1 week.
In subsequent years, results from a number of placebo-controlled studies have revealed that ketamine is largely effective and long-acting in the treatment of bipolar disorder, treatment-resistant major depressive disorder, and produces antisuicidal and anti-anhedonic effects in mood disorders.
In some studies on Ketamine where the subjects get ketamine through an IV or a nasal mist about once a week in a clinic setting have shown that up to 85% got better.
Challenges & Toxicity:
When misused, it can impair sight and sound, lead to out-of-body experiences and hallucinations, and impact the ability of speech and movement. Tragically, this has led ketamine to be used as a date-rape drug.
Ketamine is significantly faster acting than other agents, but it also comes with more side effects, abuse potential, and certain toxicities.
Researchers are continuing to investigate ketamine’s underlying mechanism of action so they can progress with identifying and developing new agents that work similarly but offer fewer side effects, as well as prolonged therapeutic effects.
MDMA
MDMA, commonly known as ecstasy or molly, has shown incredible promise in treating PTSD and has been designated a breakthrough therapy by the FDA. Again, it is important to note that pure MDMA is not the same as molly or ecstasy. In clinical settings, administering MDMA in proper dosage and frequency is considered safe for humans. Unlike many of the current treatment methods for PTSD, MDMA has to be administered only a few times for it to have a lasting effect.
Inflection Points:
MDMA has received breakthrough therapy designation from the FDA in treating PTSD and psychological damage caused by sexual assault, war, violent crime, and other traumas.
MDMA therapy for PTSD is now entering the final Phase 3 stage of drug development, with a target set for licensing by the FDA and EMA in 2021.
Clinical Results:
In 2010, 20 patients with treatment-resistant PTSD received either inactive placebo or two or three sessions of MDMA. At the 12-month follow-up, 83% of the experimental group no longer met the criteria for PTSD, compared with just 25% of the patients in the placebo group.
In 2018, a study funded by MAPS showed similar results. Active doses (75 mg and 125 mg) of MDMA with adjunctive psychotherapy in a controlled setting were effective and well-tolerated in reducing PTSD symptoms in veterans and first responders.
Traditional depression medicines can take up to 6 weeks to provide relief. In a study on MDMA in 2012, people with a predisposition to depression showed a significant reduction in depressive symptoms instantaneously with long-lasting effects.
Challenges & Toxicity:
There is no evidence of neurotoxicity with MDMA when used in isolation and no evidence of lasting neurocognitive impairments. However, impurities in the drug can cause problems.
Over 1,600 doses of clinical MDMA have been administered in research settings in recent years, with only one report of a drug-related self-limiting serious adverse event and no deaths.
There is some evidence that MDMA might have an addictive component to it.
Ibogaine
Ibogaine is a naturally occurring psychoactive alkaloid that can be found in the West African bush iboga. It is a mild stimulant in small doses, but with larger ones, it can induce a profound psychedelic state. Ibogaine has been shown to reduce withdrawal symptoms from opiates and temporarily eliminate substance-related cravings.
Inflection Points:
In 1901, Dybowsky and Landrin isolated ibogaine for the first time.
18-Methoxycoronaridine (18-MC) is a derivative of ibogaine and was first synthesized in a laboratory in 1996.
The publicly listed neuro-pharmaceutical company MindMed has successfully obtained a patent for 18MC.
In April 2020, MindMed began dosing the first patients in an additional Phase 1 human safety trial of 18-MC for opioid withdrawal and opioid use disorder.
Clinical Results:
Ibogaine has shown the potential to decrease patients’ misuse of stimulants, opiates, and alcohol, and to reduce symptoms of withdrawal (from opiates) after the administration of a single dose.
In a study with 30 opioid-dependent subjects, at a 1-month posttreatment follow-up, 15 subjects (50%) reported no opioid use during the previous 30 days. In the same study, SOWS (scale of withdrawal symptoms) scores were cut in half posttreatment relative to pretreatment.
Challenges & Toxicity:
Ibogaine therapy can cost between US$5,000 and US$8,000 per course of treatment when paid for privately.
It is still very early in the study of ibogaine, and further research and investment will be required to validate early findings.
Mapping out the Industry
Market Sizing
On par with increasing academic interest, new startups fluxed into the psychedelic medicine market at a high pace over the past 5 years. In the first half of 2020 alone, over $150M was invested into the 6 leading psychedelic startups across the world. As most of the companies operating in the market are still in startup mode, the gaps are many and large. Although still in its infancy, the global psychedelics market is estimated to grow to over $7Bn by 2027 from an estimated $2Bn in 2020. This figure is quite conservative considering the societal cost of psychedelic-treatable illnesses in addition to the value of lost research over the past 4 decades. To put this in perspective, an estimation of how psychedelic medicine can relieve the economic burden of psychedelic-treatable illnesses can be found below.
Beyond that, the dissolution of the taboo surrounding mental health has led to an astounding growth in demand for antidepressants. As a result of the ongoing COVID-19 pandemic, the global antidepressant market is expected to grow from $14.3Bn in 2019 to about $28.6Bn by the end of the year, leaving most manufacturers struggling to meet the market demand. The surge in demand for solutions has made leeway for alternative medicine and therapy to meet the demand. Given the exciting research and results thereof, the entry of psychedelics into the market may be more timely than ever. Moreover, the short and long-term effects of just a few doses and the low toxicity and addictiveness of psychedelic medicine will prove to be a massive disruption to the $15Bn market of traditional treatments. With capital rapidly flowing into the psychedelics market, low barriers to entry, clinical trials increasing at a fast pace, the psychedelics market is at a turning point posed for immense growth.
Frontrunners
Let’s have a closer look at some of the major players that have been driving the momentum of the psychedelics market.
Compass Pathways
Founding Date: June 2016
HQ: London, United Kingdom
Founders: Ekaterina Malievskaia, George Goldsmith, Lars Christian Wilde
Funding Raised: $116.2M
Notable Investors: Peter Thiel, Galaxy Investment Partners, Moore Capital Management
Stage: IPO (18 September 2020)
Substances: Psilocybin
Compass Pathways was founded in London in 2016 to study the approach of psilocybin-assisted therapies to treat mental illnesses. Since then, they have synthesized a derivative of psilocybin which is known as COMP360, and have studied its effectiveness for treatment-resistant depression. COMP360 received a Breakthrough Therapy designation in 2018 by the FDA, leapfrogging its clinical development and time to market. Compass Pathways is now in Phase 2b clinical trials wherein the efficacy of COMP360 is tested. If everything goes well, COMP360 psilocybin therapy could be approved and launched around 2023-2024 in the U.S. and Europe.
Breakthroughs:
December 2019: Compass Pathways and King’s College released promising results of placebo-controlled clinical trials wherein COMP360 was administered to healthy individuals. The study highlighted the feasibility of COMP360 in a controlled setting with therapist support.
January 2020: Compass Pathways granted a patent covering the use of COMPASS’s synthesized investigational psilocybin formulation, COMP360, in a psilocybin therapy protocol for patients with treatment-resistant depression.
September 2020: Compass Pathways becomes the first psychedelics firm to list on a major U.S. Stock Exchange: the NASDAQ.
November 2020: Compass Pathways joins the Psychiatry Consortium to accelerate drug discovery in mental health care. This will enable them to tap into the vast network of leading medical research charities and pharmaceutical companies, aiming to identify and validate novel drug targets to address the unmet needs of people with mental health conditions.
CB Therapeutics
Founding Date: May 2015
HQ: San Diego, United States
Founders: Jacob Vogan, Sher Ali Butt
Funding Raised: $7.6M
Notable Investors: Y Combinator, LYVC, Fort Ventures, Pioneer Fund, EvoNexus, Kingsley Advani
Stage: Series A
Substances: DMT, LSD, Psilocybin, MDMA, and other substances
CB Therapeutics is a leading biotech startup that has been able to use yeast, bacteria, and cell-free expression systems in the production of high-value molecules and therapeutic compounds. After 4 years of research and development, Sher and Jacob caught on to the therapeutic potential of psychedelic compounds and cannabinoids for the treatment of depression, PTSD, anxiety, addiction, and other mental health conditions. CB Therapeutics taps into this potential by producing these compounds more rapidly, utilizing fewer resources at greater yields and with higher purity than other players in the market. Over the past 2 years, they have achieved
several breakthroughs in the biosynthesis of a variety of compounds and are building a platform to repeat this process at scale. To date, CB Therapeutics has developed a large and fully licensed commercial batch facility, including research labs and a production facility.
Breakthroughs:
December 2019: CB Therapeutics successfully biosynthesized Psilocybin typically found in plants and fungi and has filed a patent for the production process. These analog compounds are very similar to their natural counterparts and may prove to be more effective, targeted, and safer for therapeutic purposes.
April 2020: CB Therapeutics is awarded a patent for its Bioinformatics platform for the creation and annotation of libraries of biosynthetic pathway genes from next-generation sequencing data. The software allows them to process raw biological data and search for new enzymes in an unlimited number of data sets simultaneously.
April 2020: CB Therapeutics enters into a collaboration agreement with Cleveland Clinic for the manufacture of Psilocybin, DMT, and MDMA therapeutic compounds for clinical trials to treat depression, addiction, and PTSD.
June 2020: CB Therapeutics successfully biosynthesized DMT in yeast and has filed a patent for the production process. The analysis of raw analytical DMT samples has shown the biosynthetic process to be significantly more efficient, of higher purity, and less expensive than existing chemical and biosynthetic techniques, extraction from plants, or other production methods.
September 2020: CB Therapeutics achieves a major breakthrough, having been able to refine its in-house downstream processing, allowing for a 99.6% pure CBC, which is a rare cannabinoid molecule. By doing so, CB proved that it is able to drive down the cost of purification in parallel with increasing the purity to over 99%. The process is patent-pending.
ATAI Life Sciences
Founding Date: 2018
HQ: Munich, Germany
Founders: Christian Angermayer, Florian Brand, Lars Christian Wilde
Funding Raised: $200.1M
Stage: Series C
Notable Investors: Thiel Capital, Apeiron Investments, What if Ventures, Future Ventures, Galaxy Capital Partners, Catalio Capital
Stage: Series C
Substances: Psilocybin, MDMA, DMT, Arketamine, Ibogaine, and other substances
ATAI, based out of Berlin and with offices worldwide, is a biotech startup founded in 2018 with the purpose of addressing the growing unmet needs of mental health patients. It is dedicated to acquiring, incubating, and efficiently developing innovative therapeutics to treat mental health disorders. By combining funding, technology, scientific and regulatory expertise, and best practices with a focus on psychedelic therapies, ATAI has made a mark for itself, accelerating the development of new medicines across its entities. They have done this by decentralizing the drug development across 10 companies that they have acquired, such as DemeRx, Compass Pathways, and Neuronasal, working across a variety of compounds and technologies, ranging from psilocybin, MDMA to Introspect. The success of this approach is reflected in the recent Series C investment from prominent investors such as Peter Thiel, Steve Jurvetson, and Mike Novogratz, which to date has been the largest private raise for a psychedelics startup. They are anticipating an IPO in mid-2021.
Breakthroughs:
September 2019: ATAI partners with GABA Therapeutics to develop a novel “GABA modulator” for the treatment of mood disorders.
January 2020: ATAI announces a joint venture with DemeRx to develop Ibogaine for Opioid use disorder.
July 2020: ATAI acquires Kures to develop novel therapeutics for opioid abuse.
February 2020: ATAI launches a joint venture with Cyclica to build a drug development platform for mental health disorders.
August 2020: ATAI partners with IntelGenx to develop pharmaceutical-grade polymeric film technologies for the delivery of psychedelic medicines
November 2020: ATAI partners with Neuronasal Inc. to develop a new treatment for mild traumatic brain injury (mTBI) and also receives IND (investigational new drug) clearance to continue into Phase I trials of mTBI therapeutic.
November 2020: ATAI launches Introspect, a digital therapeutics tool leveraging emerging technologies to counter mental disorders.
November 2020: ATAI launches EmpathBio to treat PTSD with a novel MDMA product.
November 2020: Largest private funding round to date in a psychedelics startup (as of 01.12.2020) with $125M in backing from prominent investors such as Thiel Capital, Galaxy Digital Partners, and Future Ventures.
Field Trip Health
Founding Date: 2019
HQ: Toronto, Canada
Founders: Mujeeb Jafferi, Ryan Yermus, Joseph del Moral, Ronan Levy, Hannan Fleiman
Funding Raised: $20M
Notable Investors: What If Ventures, Subversive Capital, Bolt, etc.
Stage: IPO (CSE)
Substances: Ketamine, Psilocybin, FT-105, with more to come...
Founded in 2019 by cannabis entrepreneurs and based out of Toronto, Field Trip addresses mental health disorders by establishing treatment clinics offering psychedelic-assisted therapy across the United States, Canada, and the Netherlands. In addition, it aims to conduct its own drug development and drug manufacturing based on a wide range of psychedelic compounds such as psilocybin, for which it has partnered with the University of the West Indies in Jamaica, and its proprietary novel psychedelic molecule FT-105 with which it aims to launch clinical trials at the end of 2021. For now, Field Trip operates three psychotherapy clinics in Toronto, Los Angeles, Chicago, and New York through which it offers ketamine-assisted therapy sessions to treat anxiety and depression as it is the only legal psychedelic approved by the FDA. Eventually, they aim to move beyond ketamine and scale up to over 75 treatment clinics as certain compounds gain FDA approval or become legal such as the legalization of psilocybin in the state of Oregon.
Breakthroughs:
March 2020: Field Trip opens the first-of-its-kind psychedelic-enhanced psychotherapy clinic in Toronto, Canada.
April 2020: Field Trip spins-out its drug discovery arm “Field Trip Discovery”.
July 2020: Field Trip launches Basecamp, a therapeutic program for combat veterans, first responders, and healthcare workers.
October 2020: Field Trip gets publicly listed and commences trading on the CSE.
November 2020: Field Trip expands to the Netherlands, aiming to provide psychedelic-assisted therapy with legal truffles containing psilocybin at a Field Trip Health Center in Amsterdam.
November 2020: Field Trip prepares its expansion into the Oregon market, following the legalization of psilocybin in the state.
The Future of Psychedelic Medicine
Although psychedelics have come a long way, from acting as a medium to communicate with higher beings to being outlawed for several decades, it is currently at the tipping point towards widespread recognition and mainstream adoption as modern medicine. This is reflected in the rapid dissolution of stigmas and the dedication to furthering research in the field, displayed by major academic institutions and non-profit research organizations such as Berkeley, Yale, John Hopkins, MAPS, and Imperial College among many others. These institutions are leading the way to a world in which we think very differently about mental health. Promising findings early on have accelerated the number of studies conducted, and regulations are bound to catch up soon as research grows more robust. These developments and the increasing awareness of the ineffectiveness of existing mental health treatments have acted as an inflection point for the psychedelic industry as a whole, and the COVID-19 pandemic has only accelerated awareness around the issue. With traditional pharma companies struggling to keep up with the skyrocketing demand for antidepressants, psychedelic medicine has been pushed forward as an evident alternative. Investors have taken note, which is reflected in the largest private funding round raised by any psychedelics startup, ATAI Life Sciences, and the widely publicized IPOs such as the one of Compass Pathways’s. Whilst startups and many academic institutions have paved the way forward, formidable challenges still lie ahead as regulators are slow to adapt and certain academic institutions continue to resist and stigmatize the potential of psychedelics while traditional pharma remains at the sideline.
For psychedelic medicine to fully shift into the mainstream, it will be essential for regulators to pay attention to best practices from countries such as the United States, the Netherlands, Brasil, and Jamaica, which have been prime movers in the decriminalization and or legalization of psychedelic substances for recreational or medical use. In both Europe and the United States, regulators have been making leeway, easing up restrictions on the use of MDMA to treat PTSD, and psilocybin to treat depression. As in most of the aforementioned countries, a close collaboration between the public and private industry is crucial in finding a middle-ground for restrictions and to assure stronger education of psychedelic medicine’s potential. Although a lot of progress is being made, several constraints still impede psychedelic research as a result of the 1971 United Nations Convention on Psychotropic Substances. The convention placed psychedelics in its most regulated bucket, Schedule 1, placing it above far more toxic and harmful drugs such as fentanyl, methamphetamine, and cocaine. As such, we foresee a regulatory shift in the upcoming 2 to 3 years wherein psychedelic compounds will be regulated in a similar fashion to SSRIs and recreational drugs, such as alcohol and cannabis. Since psychedelics can still be of harm to some people, we are of the opinion that certain psychedelics compounds should only be available in controlled environments with licensed therapists. This will rid us of the public perception that psychedelics are associated with hippies, misfits, and place psychedelics in the realm of accepted therapeutics. This regulatory shift is already in motion with the recent legalization of psilocybin mushrooms in Oregon. However, with challenges in regulation and public misbelief come many opportunities in finding the right approaches to psychedelic-assisted therapy, educational tools, and novel distribution channels for this massively untapped market.
For now, psychedelic-assisted therapies are niche and fairly expensive. The main reason for this is the absence of insurance players willing to reimburse psychedelic-based medicine or psychedelic-assisted therapies. We foresee this gap to be a pending catalyst for global adoption and one of the greatest short-term opportunities for the psychedelic market. Besides that, R&D-heavy companies that are able to rapidly expand their IP portfolio, through unique production technologies or an aggressive acquisition approach, will place themselves at the forefront of this market. Alongside companies that are building the endpoint distribution (e.g. psychedelic-assisted therapy centers), they will build the currently-yet-to-exist infrastructure and supply chains that will enable the global uptake of psychedelics in modern medicine. Furthermore, educational tools, apps, and marketplaces connecting people with the proper psychedelic treatments and centers will shift the public belief and drive adoption. Although pharma has stayed on the sideline, we foresee that in 2021 they may enter the psychedelic space as a result of the overwhelmingly positive research results, the surge in demand for alternative mental health treatments amidst the pandemic, and the negative spotlight on SSRIs. We are truly excited for 2021 as we see psychedelics moving into the mainstream and continuing its momentum through several promising clinical trials and further research.
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The future belongs to the curious,
Neal and Lukas