Traditional psychedelics have shown great potential for treating issues like depression, anxiety, PTSD, and addiction. Psilocybin and MDMA will likely be available for patients in the next couple of years with other psychedelic compounds like LSD and DMT following suit. Even if these compounds can significantly help those who have access to them, there are constraints on these traditional psychedelic compounds that make it hard to roll out widespread treatment options. A growing number of biotechnology companies are working on new compounds to help overcome the limitations of the currently known psychedelic compounds– these are called psychedelic analogues.
In pharmacology, an Analogue is defined as: “A therapeutic agent with structural or chemical similarity to, or which mimics the effects of, another agent, but which differs chemically.” An analogue is a drug compound that is based on another but is not molecularly identical and has varied effects on the human body. Analogues may be created to solve a variety of problems. They could be synthesized to overcome safety concerns and reduce the number of resources needed for people to access psychedelic medicines.
An analogue can be developed to address a variety of different issues. They may change the duration of a psychoactive experience by reducing the half-life of a compound, attempting to control adverse effects, or playing to the strengths of a drug while removing less desirable effects.
To grasp the importance of developing psychedelic analogues, you first need to understand the benefits and limitations of the current psychedelic compounds and treatment model available.
Psychedelic Treatment Model
Development of the modern psychedelic treatment model began back in the 50s when research into psychedelic compounds first started. Many of the concepts and principles that were used 70 years ago are still integral to psychedelic treatment today. There are even similarities in the clinical setting to ancient psychedelic rituals that were around long before the west discovered entheogens.
Though clinical psychedelic treatment has largely separated itself from the practices of traditional psychedelic ceremonies, there remain some similarities. The idea of “set and setting,” which plays a large role in clinical psychedelic-assisted therapy, has been used for hundreds, if not thousands of years. Many traditional cultures have strict parameters on the structure of psychedelic ceremonies. For example, the Shipibo tribe in the Amazon Jungle only performs Ayahuasca ceremonies at night in the pitch dark with a highly experienced Shaman. The Peruvian Q’ero people perform San Pedro ceremonies hiking out in the mountains from sunrise to sunset with no food or water. Both types of ceremonies use songs and prayers designed to help people find physical, mental, and spiritual healing. There are specific practices to help people heal that the leader of the ceremony is versed in.
It wasn’t until the 1960s that psychedelics were taken in casual settings such as a Haight street apartment or a grateful dead concert. The structure of current psychedelic treatments available varies greatly. This is largely because regulations (or lack thereof) surrounding psychedelic treatment have caused the decentralization of practitioners. Despite an array of rather scattered styles between psychedelic practitioners, most clinics and traditional treatment centers do follow a structure based on a few ground principles.
In addition to attention to set and setting, there are three district stages that you will find in most psychedelic treatment programs: preparation, psychedelic experience, and integration. All components are equally important in reaping the benefits of treatment. They all also pose limitations to the exponential growth of psychedelics.
The first step of psychedelic treatment is preparation. During this stage, the patient speaks with the practitioner to establish eligibility for treatment and prepare the patient for the psychedelic experience. The therapist or facilitator will often (and always should) collect information to ensure the patient’s safety. These tests can range from simply a simple questionnaire to an extensive health screening.
Most psychedelics do not have any known adverse physical effects, so they do not require extensive testing. Psilocybin, mescaline, and LSD have no known lethal dose, so they are very safe and do not require as much pre-screening. Ketamine, MDMA, and Ibogaine can have adverse effects, though unlikely if facilitated by a qualified medical professional. Ibogaine is the one psychedelic that is known to cause heart arrhythmias which can result in death, so comprehensive prescreening to ensure that patients are physically qualified to take the substance is crucial in maintaining safety. Beond Ibogaine Treatment center is a perfect example of a responsible ibogaine clinic– they require a full health screening to qualify and then run additional tests once the patient arrives.
Psychedelics aren’t widely regulated yet, so there is no standard for patient screening. Treatment programs, such as Field Trip Health or MindBloom’s Ketamine-assisted therapy have a more formal screening process. However, retreat centers in Peru, Mexico, and Costa Rica will often have a simple questionnaire asking participants their reasoning for seeking psychedelic treatment and the names of medications that they are on. Some medications, such as SSRI’s can have adverse effects when taken with psychedelics. Many people who seek treatments are on anti-depressants and it can be difficult to come off of them. This poses one roadblock in treating depression with psychedelics.
Most psychedelic-assisted therapy programs have preparation sessions so that the therapist can get to know the needs of the patients and answer any questions. But again, this varies greatly among the available programs since many of them operate outside of strict regulations.
Early studies show that the patient’s mindset going into psychedelic treatment will have a huge impact on the outcome. So, spending time with a guide or community to set intentions and plan for the experience is just as important as the experience itself. Many treatment centers will do this virtually before the psychedelic session or retreat. This takes up time from a qualified guide. So, while it is incredibly important to the process, this step does drive up the cost of treatment.
Once the patients have been screened and psychologically prepared, they continue into the psychedelic treatment. Traditionally, these sessions are called “ceremonies” and are done in a group. It has been done this way in many cultures around the globe for thousands of years. In Peru, they perform healing ceremonies using Ayahuasca and San Pedro. Magic Mushrooms were traditionally taken in this setting in Mexico as well. These types of ceremonies are usually led by the community’s healer called a shaman and encourage healing through the support of a community.
There are many retreats available in Mexico, Peru, Costa Rica, and Jamaica that embody this traditional structure. There are benefits to doing psychedelics in a group environment. A study done by Imperial College London found that those who participated in group psychedelic therapy, such as retreats and traditional ceremonies, reported increased feelings of social connectedness. Support from a community is an important part of healing from mental health disorders and addiction. This makes group environments very beneficial, however, it is not without its risks.
Psychedelics can sometimes have unpredictable psychological effects on people, and if those leading group sessions are not properly qualified issues can arise. During an Ayahuasca ceremony in Iquitos, Peru in 2015, one participant attacked another with a knife and after a struggle between the two, the perpetrator was stabbed and killed. This is an extreme and incredibly rare instance, but it does show the importance of having qualified practitioners leading psychedelic ceremonies.
The man leading the ceremony still works with Ayahuasca, but he is known in the area as an ayahuascero who practices “witchcraft.” That is a very loaded work that you may be quick to dismiss, however, I urge you to put it into context. What that means is that he used his place of authority to take advantage of people in a vulnerable state. Think of it less as a supernatural being conjuring up spells and more like a therapist who emotionally abuses their patient. This is a very real concern that regulatory structures aim to prevent. Psychotherapists are ruled by a code of conduct which is even more important when working with mind-altering substances.
When someone takes psychedelics, they are in a particularly vulnerable state and are susceptible to manipulation. The psychedelic experience, especially with medicines such as ayahuasca and ibogaine, can also in rare cases cause visions or mental states that cause someone (in extreme cases) to put themselves or others in harm’s way. Without the presence of a practitioner who is qualified to manage adverse effects, there is a potential for danger.
Documentation of these cases can also be found in the San Francisco psychedelic movement in the 60s and 70s. Dozens of people were ending up in the hospital after taking LSD and having mental breakdowns. It should be noted that many of these people were taking the drug irresponsibly and often in amounts greater than what is needed to have a medicinal experience.
Both traditional practices and the developing clinical model aim to avoid these risks by having patients in a safe environment with a qualified facilitator. This makes it hard to democratize psychedelics, as Timothy Leary proposed. It should be noted that many people have tried psychedelics on their own and had perfectly safe and transformational experiences. However, having someone qualified to help with the experience can increase the benefits, and the clinical model understands this.
The new model for psychedelic treatment integrates the experience with talk therapy. This model is new, so the details are still being hammered out. Most psychedelic therapists understand the importance of set and setting, so great care is being taken to develop environments where patients feel safe and comfortable.
This style of treatment is often done in a private room inside a clinic furnished with a bed for the patients to lie down in during the psychedelic experience. These spaces may have a very sterile, medical atmosphere, but most make an effort to create a more homey feel by adding pictures and soft decore.
In the clinical setting, there are generally one or two therapists who sit with the patient throughout the experience. Depending on the compound being taken, sessions can take up to twelve hours making it a time-consuming and exhausting endeavor for both the patient and therapist. Analogues that shorten the half-life of compounds such as psilocybin and MDMA
Once the psychedelic experience is completed, the integration begins. This is when everything that was learned from the medicine is processed and integrated into the participant’s life.
Not all programs include integration even though it is an important part of the process. This is where traditional talk therapy and other psychotherapy methods are beneficial. But again, the time and financial requirements are limiting factors.
Now that you’ve got a solid understanding of the psychedelic-assisted therapy treatment model, let’s take a look at what problems analogues can solve to make psychedelics available to the people who need them.
WHAT PROBLEMS DO PSYCHEDELIC ANALOGUES SOLVE?
One of the big problems that analogues aim to solve is the scalability of psychedelic treatment. People have found powerful healing through psychedelic compounds like magic mushrooms. LSD, Ayahuasca, and more. Unfortunately, access to these psychedelic treatments is limited to those who have the time and resources available to seek them out.
These treatments are expensive and often require people to travel outside of the country for a week or more. In the next few years, some of these treatments will be available in the United States, parts of Europe, and Canada. They will still be expensive because they take a large number of resources to make them available.
Psychedelic treatments can take up to twelve hours for a single session. Therapists would only be able to treat a small number of patients every month. Paying for this amount of time with a qualified therapist is expensive, especially if insurance companies do not cover any of the cost.
Because of the constraints on time and money, only a small percentage of people who could benefit from psychedelic-assisted therapy would have access to it. This is where psychedelic analogues enter the picture. A growing number of biotech companies are working to create psychedelic-inspired drugs that overcome some of the obstacles that traditional psychedelic compounds pose.
Josh Bartch, CEO of psychedelic biotech company Mydecine, said: “For these treatment modalities to be adopted and accepted by the general medical community, there must be a drug product that can be administered at existing clinics and hospitals in less time, and that will be reimbursed by insurance providers. We believe shortening the half-life of MDMA is an important, necessary step to making this possible.” Josh makes an important point about the limitations of the current psychedelic compounds available. Having psychedelic treatments available to traditional therapists would make it possible for a smooth process in which patients could receive in the care of a therapist that they trust.
Manipulating the half-life of psychedelic compounds such as MDMA, psilocybin, and LSD has been the focus of several biotech companies. Shortening the duration of the psychedelic experience would increase the number of patients that would be able to receive it and reduce the cost of treatment by shortening the duration that therapist supervision would be required.
Another problem that psychedelic analogues have the potential to solve is safety. That is not to say that the current psychedelic compounds available are dangerous substances. Compared to most available drugs that treat depression, anxiety, addiction, and PTSD, psychedelics are an alternative with almost no known adverse effects.
Other than the heart risks associated with the use of ibogaine, there are no known adverse physical effects of taking psychedelics. However, when taken in the wrong setting, psychedelics can be harmful.
Psychedelics, especially psilocybin, LSD, DMT, and Ibogaine put people into an altered state of mind that can make them vulnerable. Psychedelics can cause mental distress through troubling visions or forcing people to confront difficult emotions. This is commonly known as a “bad trip.”
The term “bad trip” alludes to a state in which the psychedelic experience is not beneficial, however, that is not true. These challenging experiences can be vastly beneficial, especially if someone is working through a traumatic event that is continuing to cause them distress, as happens with PTSD. Psychedelic compounds force people to confront these difficult events, which can be incredibly painful and stressful. If a person goes through this without proper support that is where danger can arise.
The uncomfortable spaces that psychedelics put people in can be very beneficial. MDMA-assisted therapy for PTSD is thought to be so beneficial because it allows patients to open up emotionally about painful experiences that they may have been suppressing. By talking through the experience with a therapist (and the help of the compound) they can process it emotionally and reframe their thoughts around it so that they can move forward from the trauma.
Psychedelic-assisted therapy has shown great efficacy rates, however, not many people have access to this type of treatment. Sessions are a huge time and financial commitment that many people simply cannot afford. Of course, there is the option to get psychedelics from the underground market and take them without any support or guidance. Many people have had incredibly healing experiences this way, but there are instances when people have negative experiences because they do not have support to help guide them through the difficult process.
Researchers could potentially identify what in these compounds help people with mental health issues and create medicines that do the same thing without the unpredictable psychoactive effects. At this point, it is theoretical. We know that psychedelics are effective, but it is not entirely understood why.
Research suggests that psychedelics help create new neurological connections in the brain. Scientists could potentially isolate this effect and create drugs that effectively help rewire the brain to overcome mental illness.
Another safety issue that psychedelic analogs could potentially overcome is the risk of heart issues that ibogaine poses. Ibogaine is a psychedelic that has shown promise in helping to treat a variety of issues, but most notably is its ability to help opioid addicts detox in as little as 24 hours.
Ibogaine is a compound derived from the West-African Iboga shrub. It is perhaps the strongest psychedelic known to man and is one of the few psychedelics that can have adverse physical effects. It has been known to cause heart arrhythmias that can result in death. Risk can be avoided with proper medical staff on duty, but the cost of that is high. Creating a drug with the same benefits as Ibogaine without the risks would reduce the number of resources needed for treatment which would mean more people could be treated within the same framework.
Some psychedelic biotech companies, such as Gigamesh pharmaceutical, are working to create a compound that has the healing effects of ibogaine without the risk of heart issues. Ibogaine resets the body’s natural opioid system, making it the most effective treatment option for opioid addiction. If scientists could isolate what helps the body detox from opioids, they could potentially make a drug that effectively helps people overcome opioid addiction.
The Future of Psychedelic Analogues
The idea of psychedelic analogues gives hope to a large population struggling with anxiety, depression, addiction, and PTSD. They are showing promise, but it should be noted that the concept is still largely in the idea phase.
None of these compounds have fully made it through trials to gain FDA approval. A small number of them are in the early stages of clinical trials, but most psychedelic analogues that will be available in the future are still in the early development stages.
During an interview with psychedelicinvest.com, Mydecine’s CEO said that the psychedelic analogues that will have the biggest impact on the treatment of mental health have likely not even been synthesized yet. This is a brand new concept and the full reach of these compounds may not be known until a decade from now.
For now, investors and psychedelic enthusiasts alike must accept a high level of uncertainty surrounding psychedelic analogues. What is driving this new industry forward is hope. Many have hope that these new treatments will offer solutions to mental health problems that no other has been able to previously offer. There is hope that one of these new compounds will be the medicine to replace addictive drugs with a long list of side effects like SSRIs and benzodiazepines.
For investors, there is hope that at the end of the difficult path that is to bring a new drug to market there will be a huge pot of gold. The process of bringing a new medicine to market is long, especially when using compounds that are schedule 1, as most psychedelics are. Investors have been pouring hundreds of millions of dollars into companies like Mydecine ($MYCO), Compass Pathways ($CMPS), Atai Life Sciences ($ATAI), and MindMed ($MNMD)– to name a few.
Throughout the coming years, we will see vast development in this field, some outcomes will be expected and some will be beyond what even the experts are projecting. There is a lot of uncertainty, but it will without a doubt be exciting to watch.