Psychedelic Research in 2022 (PRO REPORT)

No matter what happens with stock prices or the economy, one thing is certain… Companies (and individuals) will never stop conducting the necessary research on psychedelic compounds.

This past year was no exception. One could even argue that 2022 proved to be the most progressive when it comes to progressing clinical trials and unveiling success stories that need to be heard.

The potential is clear and ready to be realized. How will psychedelic research further progress in 2023?

This has been an enormous year for psychedelic research. A handful of companies are progressing their drugs through clinical trials, which is a significant step towards bringing psychedelic treatment to the masses. Although some states, such as Oregon and Colorado, are legalizing psychedelic treatment, most states will not follow suit for quite some time. Gaining government approval for psychedelic drugs through clinical trials is the only way for the broader public to gain access. 

Clinical trials are not the only important research that is taking place. Studies are being done by universities and research institutions on everything from the neural effects of psychedelics to their effect on political views.

All research is crucial for the development of the psychedelic industry and the improvement of mental health treatment. There have been significant advancements in the treatment of mental health and central nervous system disorders this year. 

The research done in 2022 has proven that all of the main psychedelic compounds are safe for human consumption and beneficial to treating mental health conditions. This has played a crucial role in changing the false narrative that has turned people against psychedelics for decades.

Psychedelic research has three goals– overcome social stigmas, change regulations, and improve scientific understanding of the human mind and consciousness. With these goals in mind, it is safe to say that researchers were successful in 2022.

Clinical trials are offering the quickest route for people all over the world to gain access to psychedelic treatment. While many people are aware of the safety and efficacy of psychedelic treatment, governments don’t change laws without putting drugs through the bureaucratic ringer– and that is just what is happening. 

2022 was a year of firsts for psychedelic research. Dozens of clinical trials tested the efficacy of psychedelic compounds. Psychedelics have never been researched in this capacity. These studies are laying the groundwork for the future of mental health treatment. 

MDMA, psilocybin, and ketamine have taken the lead as the first psychedelics that will become widely available. These specific compounds have had the most clinical trials and moved the furthest along in the process. While it doesn’t mean that these compounds are ultimately superior to the other psychedelic compounds being developed and researched, trials have shown that they are effective in treating multiple indications.

The following is a comprehensive overview of the significant clinical trials that made progress during 2022.

This particular drug is in a unique position because in many countries it is not as highly scheduled as the rest of the compounds discussed in this report. Ketamine is used as a general anesthetic to sedate and manage pain in patients. It is currently being used off-label to treat depression, addiction, and other mental health disorders. Off-label prescriptions are not covered by insurance, so treatment is costly. FDA approval of ketamine to treat depression and anxiety could help increase access.

Clinics around the world are already offering ketamine treatment for multiple indications. Many biotech companies are developing ketamine analogs with various delivery methods to determine the most effective treatment methods.

Project Kestrel: Ketamine-assisted therapy for the treatment of alcohol use disorder – Awakn Life Sciences

The results from phase II a/b were released in January. Phase 3 will commence in 2023. This is the largest clinical trial of Ketamine-assisted therapy to date and the first phase 3 psychedelic trial to receive government funding.

Initiation of Clinical Study Investigating Neuroplasticity Biomarkers in Treatment-Resistant Depression Patients Undergoing Ketamine Treatment – Atai Life Sciences and Massachusetts General Hospital 

Perception Neuroscience, Completes Enrollment for Phase 2a Clinical Trial of PCN-101 (R-Ketamine) for Treatment-Resistant Depression – Atai Life Sciences Company

A Study of SLS-002 (Intranasal Racemic Ketamine) in Adults With Major Depressive Disorder at Imminent Risk of Suicide – Seelos Therapeutics Inc.

Phase 1/2 clinical Study of ketamine in the treatment of levodopa-induced dyskinesia in Parkinson’s disease – Pharmather

MAPS has been a leader in psychedelics since the beginning, and this year is no exception. The non-profit’s clinical trials continued to make history in 2022, and will likely do so again next year with its MDMA treatment for PTSD getting close to FDA approval.

MDMA will be the first psychedelic treatment to gain FDA approval. MDMA-assisted therapy has gotten attention for its treatment of PTSD. Given the large number of veterans that return from war with psychological issues, governments have no choice but to acknowledge any treatment that offers significant improvement in PTSD. 

Over a dozen clinical trials are being funded and run by major companies and research institutions. MDMA-assisted therapy for the treatment of PTSD is furthest along. The compound is also progressing through clinical trials for addiction, eating disorders, and anxiety.

MAPS has a strong lead in MDMA clinical trials. On November 17, 2022, they announced to completion of their second phase 3 trial for the treatment of PTSD with MDMA-assisted therapy. This was the first study of an entheogenic compound to make it to phase three clinical trials. With the completion of the study, MAPS will move to gain FDA approval in 2023. 

The results from the first phase 3 trials, published in May of 2021, saw improvement in 88% of participants. That makes it significantly more effective than other available treatments for PTSD.

A Multi-Site Phase 3 Study of MDMA-Assisted Therapy for PTSD (MAPP2) – MAPS

A Placebo-Controlled, Randomized, Blinded, Dose Finding Phase 2 Pilot Safety Study of MDMA-Assisted Therapy for Social Anxiety in Autistic Adults (MAA-1) – MAPS

An Open-Label, Multi-Site Phase 2 Study of the Safety and Feasibility of MDMA-Assisted Therapy for Eating Disorders – MAPS

Compass Pathways made a name for itself with the completion of the largest psilocybin study to date, which finished at the end of 2021. They recently announced the pivotal program design for the phase III trial– the first phase III trial for psilocybin.

While the phase IIb results weren’t what some were hoping for, they did show improvement in the patient’s depressive symptoms. If the results from phase 3 are positive,  COMP360 (Compass’s formulation of psilocybin) may gain FDA approval sometime in 2024/2025.

COMP360 is likely to be the first psilocybin treatment to hit the market through the FDA channels. The results of these clinical trials will have major implications in all areas of the industry. They will give concrete data to lawmakers, influence the psychedelic stock index, and affect how other companies move forward with their drug development plans. 

MDMA treatment for PTSD has been designated a breakthrough therapy by the FDA– making it a promising indication to go after. MDMA has certainly taken the lead in effective compounds to treat PTSD, but psilocybin and other compounds are also being researched for this indication. 

PTSD has helped psychedelics gain bipartisan support. In the US, in particular, conservatives have historically been strongly opposed to psychedelics. However, helping veterans has remained at the top of their agenda. Since many veterans struggle with PTSD– a mental health condition for which there are few viable treatment options – Republicans have recently started to support psychedelic reform. 

The first indication that psychedelics will gain FDA approval is PTSD– likely coming in the next two years. With the success of the MAPS trials, more companies will continue to research compounds and best practices in treating PTSD with psychedelic-assisted therapy. 

A Multi-Site Phase 3 Study of MDMA-Assisted Therapy for PTSD (MAPP2)– MAPS

Approval granted for the first North American take-home multi-dose psilocybin clinical trial evaluating the safety and efficacy of APEX-52 (psilocybin) in treating depression in Veterans with Post Traumatic Stress Disorder (“PTSD”).– Apex Labs

There was a big shake-up in depression treatment this year. It has long been believed that depression is caused by a chemical imbalance in the brain, however, a systematic review (published in July) brings into question the studies that support that claim. The data suggesting that depression is caused by a chemical imbalance is not as definitive as once thought. The review sent scientists back to the drawing board to discover what causes depression.

Between 2015 and 2018, the CDC reported that 13.2% of Americans had used anti-depressants, which may not be as effective as previously believed because they rely on chemical imbalance theory. There is evidence that anti-depressants have little benefit compared to a placebo. The pandemic caused a 21% increase in antidepressants, anxiety, and sleeping pills. New and improved treatments for depression are desperately needed.

Psilocybin treatment for depression will be next up to the plate– following MDMA for PTSD. It gained ‘breakthrough’ status from the FDA in 2021, and clinical trials for depression continue to move forward with positive results. 

DMT and 5-MeO-DMT have gained traction along with psilocybin and ketamine for the treatment of depression. The two main sub-categories of depression that clinical trials are focusing on is treatment-resistant depression (TRD) and major depressive disorder (MDD).

Phase I clinical study of BPL-003, a synthetic intranasal formulation of 5-Methoxy-N, N-Dimethyltryptamine (5-MeO-DMT)– Beckley Psytech

Phase II trial on BMND01 candidate, a novel liquid inhaled formulation of N, N-Dimethyltryptamine (“DMT”) for Treatment-Resistant Depression (“TRD”)– Biomind Labs

The largest trial was done with DMT. Testing the safety of a 10-minute trip.

Phase III Trial testing COMP360 for Treatment-Resistant Depression is to Commence at end of 2022.– Compass Pathways

Phase IIa clinical trial of an intravenous formulation of N, N-dimethyltryptamine candidate, SPL026, with psychotherapy for the treatment of Major Depressive Disorder.– Small Pharma

Phase 1/2a clinical trial of CYB003, a proprietary deuterated psilocybin analog that is being developed for the treatment of the major depressive disorder (“MDD”).– Cybin

Phase IIa trial of intrevaneous DMT for major depressive disorder completed. –Small Pharma

Anxiety is another indication that has gained traction as one that would benefit from psychedelic treatment. In 2020, 30.2 million Americans used benzodiazepines– a highly addictive anti-anxiety medication. One million of those were under the age of 17. 

This drug numbs emotion to help people feel better, but it doesn’t solve the root problem that is causing anxiety. This causes mental dependence along with high-physical dependence to the drug. 

Scientists are looking at psychedelic treatment as a solution that helps patients face and overcome the fear that is causing them anxiety. Ketamine is already being used in clinics to treat anxiety, and clinical trials testing other psychedelic compounds are underway. 

Psychedelics for the treatment of anxiety disorders will not make it to market until after drugs are available for PTSD, depression, and addiction because those clinical trials are further along. 

Studies are looking at psychedelic treatment for generalized anxiety disorder, as well as anxiety as a result of other indications such as a terminal illness, job trauma, and autism.

Phase II psilocybin clinical trial. This trial is aimed at studying the potential relief of COVID-19-associated mental health concerns in frontline healthcare providers – ATMA Journey Centers Inc.

Phase 2b dose-optimization trial of MM-120, a pharmaceutically optimized form of lysergic acid diethylamide (LSD), for the treatment of Generalized Anxiety Disorder (GAD). – MindMed

World-first psilocybin clinical trial in the treatment of Generalised Anxiety Disorder. – Monash University

Drug and alcohol treatment was a $42 billion industry in 2020, with projections to grow 20% by 2025. Unfortunately, the current addiction treatment systems available offer embarrassingly low success rates in helping people overcome addiction. 

Alcohol use disorder was one of the first indications to be rigorously studied when psychedelic research first began in the mid-20th century. Because of past research proving its efficacy and the strong market potential, addiction has been one of the most commonly studied indications for psychedelic treatment. 

There are studies testing all psychedelic compounds for the treatment of various addictions, including, but not limited to, alcohol use disorder, opioid dependence, smoking cessation, and cocaine addiction. 

Addiction has not been at the forefront of psychedelic clinical trials like depression and PTSD have been, perhaps because there is an incredible amount of money to be made from patients relapsing and returning to rehab centers repeatedly. Insurance companies and governments, on the other hand, would save millions if a new and more effective addiction treatment became available.

Over 20 million Americans are addicted to alcohol and/or other drugs. Only 1 in 10 will receive help, largely due to the cost of treatment. Psychedelic-assisted therapy costs less than a 30-day rehab program, making it much more accessible to the people who need it. 

Governments and insurance companies are incentivized to approve psychedelics for treatment because addiction costs billions of dollars every year due to medical issues and lost productivity. 

Here are some of the top addiction-focused clinical trials that happened this year. 

Phase I clinical study of BPL-003, a synthetic intranasal formulation of 5-Methoxy-N, N-Dimethyltryptamine (5-MeO-DMT) – Beckley Psytech

Phase 2 clinical trial investigating psilocybin for the treatment of alcohol use disorder (AUD). – Clairvoyant

Phase I/II clinical study (the “Study”) to evaluate the safety and feasibility of psilocybin in adults with methamphetamine. – Revive Therapeutics

treatment for cocaine addiction using MEAI, a novel psychedelic molecule of Clearmind Medicine Inc. –SciSpark Ltd.

Phase 2b smoking cessation clinical trial for MYCO-001 (psilocybin) – Mydecine & Johns Hopkins University

behavioral addiction study investigating ketamine as a treatment for Gambling Disorder. – Awakn Life Sciences

Phase II Ibogaine for Opioid dependence – Iceers

Some companies are moving past the common indications, such as PTSD, depression, and addiction. This area of research is so new that scientists don’t know how far the utilization of psychedelic therapy will go. 

Studies, mostly in the preclinical and phase I stages, are being done to test the psychedelic treatment on behavioral disorders, eating disorders, autism, and more. These studies will begin turning up more definitive results late next year and into 2024.

Phase 1 DMT Human Dosing Study in Healthy Individuals For Stroke Regeneration – Algernon Pharmaceuticals

double-blind randomized controlled phase II clinical trial investigating the efficacy of COMP360 psilocybin in people with anorexia nervosa. – Compass Pathways

Phase II trial treating Binge Eating Disorder (“BED”) with psilocybin in conjunction with psychotherapy. – Tryp Therapeutics

A Double-Blind, Randomized, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single, Ascending, Subcutaneous Doses of FT-104 HCl In Healthy Volunteers. – Field Trip Health (shortened half-life psilocybin)

phase one clinical trial testing the physiological and psychological effects of orally administered psilocybin and psilocin, and sublingually administered psilocin in healthy adults. – Filament Health (first naturally derived psilocybin and first psilocin)

Biotech companies aren’t the only ones researching psychedelic compounds. There are dozens of research institutions studying the effects of psychedelics on a variety of indications, and also how these compounds generally affect the human brain and body. It should be noted that clinical trials do happen through research institutions such as universities and non-profits. However, the depth of research that they are able to do spans beyond that.

Some of the major researchers have been: Johns Hopkins University, Beckley Institute, and University Hospital Basel– to name a few. The research being done through these channels is a bit different because it is not confined to what will ultimately produce the most returns for investors. 

Some researchers focus more on what psychedelic experiences can tell us about the human mind. Others are looking at medicines such as ayahuasca– something that has a low potential for a clinical setting but may still have substantial benefits.

Clinical trials are limited by several factors. All for-profit companies are bound to investor returns. Even non-profits, such as MAPS, must consider which treatments will gain approval the quickest based on political and social factors. That can, unfortunately, cause promising compounds and treatments to be under-pursued. 

Research institutions are bridging this gap and progressing psychedelic science through studies that for-profit companies simply cannot do– especially given the current state of the economy and the huge amount of capital that these studies require. 

Clinical trials are meant to test the safety and efficacy of treatment for a specific indication. Research institutions perform a broader range of research to make new discoveries on all aspects of psychedelics, which expands overall knowledge about these mysterious compounds. There is still much that is unknown about the effects that they have on the human mind and body, and scientists all over the world are seeking answers. 

These studies support the biotech companies that are working to bring new drugs to market by advancing psychedelic sciences. The following is a small sample of the vast amount of research that has been done over the past year. The list aims to highlight the various areas of psychedelic medicine and psychology that are being studied.

The serotonin theory of depression: a systematic umbrella review of the evidence – Multiple contributors

Psilocybin Treatment for Major Depression is Effective for Up to a Year for Most Patients. – Johns Hopkins

Study on the potential therapeutic effects of psilocybin on autistic adults. – Kings College London & was funded by Compass Pathways

Observational study on the benefits of ayahuasca for individuals who have experienced trauma. –Unlimited Sciences

Changes in music-evoked emotion and ventral striatal functional connectivity after psilocybin therapy for depression –Imperial College London

Effect of lysergic acid diethylamide (LSD) on reinforcement learning in humans – University of Cambridge

The Alexander Shulgin Research Institute was created to carry on the legacy of Alexander “Sasha” Shulgin– a chemist and pharmacologist who perhaps did more psychedelic research than anyone in history. For 50 years he synthesized psychoactive compounds and tested them on himself, his wife, and a small group of their friends. He is known as “the godfather of ecstasy” because he is credited with popularising MDMA.

Shasha died in 2014, and his wife Anne passed earlier this year. Their contributions to the psychedelic movement were immeasurable, and the institute’s mission is to carry on the work that Sasha did during his life. He created hundreds of psychoactive drugs that the research institute plans to research further. 

The institute raised over 7 million dollars in 2021. In June, a collaboration with CaaMTech was announced to continue research on his catalog of novel compounds.