These Previously Forbidden Drugs May Unlock a New Era of Psychiatric Medication
The Development of Psychedelics for Medical Therapeutic Use
Psychedelics: when most people hear this word, they think of stigmatized illegal substances and wild drug trips involving larger than life hallucinations. They think of terms such as “magic mushrooms” and large social gatherings. While this vision may portray the quintessential view of these drugs in the past, they have been discovered to hold great promise in the field of medicine moving forward. Psychedelics’ perception-altering capabilities may just be the solution to the antidepressant crisis we’ve been facing for decades.
Table of Contents
- The problem with SSRIs
- History of psychedelics’ medical applications
- What are psychedelics and which are most pertinent to the medical field?
- How do psychedelics work?
- What are the major concerns and unanswered questions about psychedelic drugs?
- What research is being done on psychedelics today?
- Key takeaways
The problem with SSRIs
Since their introduction in the 1980s, the primary class of drugs used to treat psychiatric conditions (depression, anxiety, OCD, etc.) have been Selective Serotonin Reuptake Inhibitors (SSRIs). These drugs work by increasing amounts of the neurotransmitter serotonin in the central nervous system. Serotonin’s job is to carry signals between neurons, so when SSRIs prevent the brain’s serotonin from being reabsorbed it must continue to carry more signals. This results in an efficiently functioning brain as well as a good mood. Popular SSRIs include Zoloft, Prozac, and Celexa.
From this description, SSRIs may sound very appealing. However, there have been an increasing number of patients who suffer from treatment resistant depression, meaning they are unaffected by SSRIs as well as other traditional types of antidepressant medication. It’s been estimated that up to 1/3 of adults with major depressive disorder (MDD) have this problem, often referred to as treatment resistant depression (TRD). Various other psychiatric conditions such as obsessive compulsive disorder (OCD) also have large populations resistant to treatment by SSRIs.
In response to these problems, many pharmaceutical research companies have attempted to create new alternatives to SSRIs, typically targeting other neurotransmitters such as GABA or dopamine as opposed to serotonin. However, these new treatments have many harmful side effects such as anxiety, suicidal thoughts, liver damage, nausea, headaches, constipation, vomiting, etc. Additionally, the novelty of these drugs and their manufacturing has the unintended consequence of making them incredibly expensive. For example, newly approved Brexanolone for treating postpartum depression currently costs up to $34,000 prior to assistance from an insurance provider.
These problems have made it evident to many members of the psychiatric community that a safer, effective, and more affordable new alternative to SSRIs is needed. However, the pharmaceutical industry is gradually shifting away from research and investment in the field of psychiatric medication. As a result, instead of trying to develop the new medications of the future, many prominent institutions have developed a renewed interest in a method of the past.
History of psychedelics’ medical applications
Psychedelics are a subtype of hallucinogenic drugs that alter a person’s perception and state of consciousness. Their usage dates all the way back to ancient Greece, where a plant with an effect very similar to modern day LSD was used for sacred ceremonies. However, such properties did not exist in synthesized drug form until the early 1900s. German pharmaceutical company Merck developed MDMA (also known as ecstasy or molly) in 1912, and swiss scientist Albert Hofmann synthesized lysergic acid diethylamide (LSD or acid) for the first time in 1938. Hofmann is also credited with the discovery of two other psychedelics including psilocybin (known more colloquially as “magic mushrooms”), which is one of the most common psychedelics in the present day.
Once psychedelics were synthesized into drug form, people quickly realized that they had great potential in the field of medicine. For a period in the 1950s, LSD specifically was a popular treatment for a variety of psychiatric conditions. However, over time psychedelics became more often used at raves or house parties, and ultimately became illegal in the US under the Controlled Substances Act of 1970. This law outlawed psychedelics based on their high potential for abuse which outweighed the appeal of their medical utility.
In 1971, former president Richard Nixon declared the war on drugs, which made it even more challenging for scientists to explore psychedelics regardless of their intentions. During this time, psychedelics were researched very little, and in the following decade SSRIs were a thrilling introduction to modern medicine. However, given the various problems with SSRIs and the state of the pharmaceutical industry in the 21st century, psychedelics have been recently revisited by a plethora of institutions.
Which psychedelics are most pertinent to the medical field?
While it’s certainly plausible that other psychedelics hold promise in treating medical conditions (particularly psychiatric disorders), research so far has largely focused on LSD, psilocybin, and MDMA. These drugs are all serotonin agonists. Serotonin agonists are a class of drug which activate serotonin receptors, in this case a type called 5-HT receptors which are critical in treating conditions rooted in depression or anxiety. Additionally, whether directly or indirectly, each of these drugs also increases levels of dopamine. Dopamine is a neuromodulator associated with the brain’s reward system, and can induce feelings of happiness and satisfaction.
Within the umbrella of psychiatric conditions, each of the aforementioned psychedelics has been explored for treating a different set of conditions. MDMA has largely been investigated as a treatment for PTSD, social anxiety, and anxiety in terminally ill patients. Psilocybin has been mostly researched in cases of OCD, addiction, and treatment-resistant unipolar depression. Finally, LSD is being researched as treatment for generalized anxiety and unipolar depression.
How do psychedelics work?
At a scientific level, there are still many questions as to how psychedelics work in the brain and what makes them so effective in treating psychiatric conditions. What we do know is that psychedelics change the rate at which various subsets of neurons fire in the brain. Since the increases in serotonin induced by the drugs discussed above occur across brain regions, there is no one function which psychedelics affect but instead a combination of many, making it more challenging to pinpoint the exact process the brain undergoes when exposed to psychedelics.
While there are many theories about why psychedelics have exactly the effect they do, one of the more popular theories is the Thalamic Filter Model. The word thalamic is derived from brain regions called the thalamus and hypothalamus. These two regions are involved in how our brain filters and interprets information, then distributes it to other regions.
When a person is on psychedelics, the Thalamic Filter Model suggests that their thalamus is impaired from filtering external information to the same degree that it typically does. This can result in a sensory overload, where many more thoughts and observations make it past this filter. The abundance of additional thoughts infiltrating the brain induce dreamlike hallucinations and enable people on psychedelics to gain a completely new perspective of themselves and the world around them. This new perspective alongside the increase in serotonin that can induce happier feelings enable many people to revisit upsetting or traumatic experiences and unearth incredible new insights.
While the Thalamic Filter Model is one of the more popular models explaining the brain’s response to psychedelics and is somewhat supported by modern research, there are certainly other theories about how psychedelics work in the brain. These include that psychedelics induce alterations in the brain’s reward system, functionally alter the 5-HT receptors, or directly trigger an increase in neuroplasticity (the brain’s ability to change and grow). However, these all remain simply theories to explain one of the major questions up in the air regarding psychedelic drugs.
What are the major unanswered questions about psychedelic drugs?
As stated above, the number one question scientists continue to work towards figuring out is how exactly psychedelics work in the brain. Despite the fact that the use of psychedelics in medically approved quantities has been proven not to be detrimental to human health, many inquiring minds still hope to discover the truth about how these drugs work. Such a discovery would not only mark a major milestone in the scientific community but also help therapists as they work to determine how to optimize psychedelic-assisted therapy sessions.
This leads into the next question, because not knowing the mechanisms of action which psychedelic drugs utilize has acted as a roadblock in scientifically determining the best way to conduct psychedelic assisted therapy. The therapy component of psychedelic medical treatments is critical in order to help patients as much as possible and take advantage of their new perspectives on the world to develop a lasting shift in mindset, so answering this question would enable therapists to make psychedelic treatments even more effective for patients with psychiatric conditions.
Additionally, scientists are still exploring the proper dosages of psychedelic. The dose needs to be enough to experience the shift needed for effective psychedelic therapy, but not so much that it could trigger conditions caused by alterations in brain chemistry such as hallucinogen persisting perception disorder (where patients randomly experience sensations from a prior drug trip, this condition is most commonly associated with LSD), serotonin syndrome, or drug-induced psychosis.
One final concern which scientists hope to gain more insight on is how to predict a patient’s reaction or rate of success in response to a given treatment. This will likely be attempted through the use of a machine learning model which will require large amounts of research to train and perfect. However, creating such a model is a goal which researchers across the field of medicine continue to strive for. Institutions such as the University of Toronto have groups working on a machine learning model capable of predicting drug response for cancer treatments, and once this standard has been met it will become far easier to replicate in the case of other medical treatments.
What research is being done on psychedelics today?
Many psychiatrists and pharmacologists are hopeful for the future of psychedelics as treatment for psychiatric conditions, particularly for patients who have treatment-resistant symptoms. Because of the evident potential of psychedelics’ medical applications, prominent universities such as Yale, Johns Hopkins, Stanford, Northwestern, UCLA, and many others throughout the world have dedicated labs or educational programs to the study of psychedelics for psychiatric conditions.
One recent study which portrays the evident potential of this field was a successful first round study at NYU Langone which significantly reduced and even cured many alcohol addictions through the use of synthetic psilocybin and psychedelic assisted therapy sessions. The study was a double blind randomized trial where participants received two doses of psilocybin over the course of 12 weeks with an optional third dose. For many patients, the psychedelic treatment induced symbolic hallucinations and new shifts in perspective (i.e. one patient reported seeing an alcohol bottle disintegrating into sand in the middle of the desert) which enabled them to look at their alcohol addictions from a new, more candid perspective.
As a result of the treatment, 83% of patients from the experimental group saw a decline in heavy drinking and 48% became fully abstinent. Study participant John Costas has even credited the treatment he underwent during the study with saving his life. This study serves to demonstrate the major potential of psychedelics for curing various psychedelic disorders in new ways, and shows hope particularly for patients struggling with alcoholism or other life-impairing addictions.
Given the stigma that has surrounded psychedelic drugs for decades and the reputation they have in society, many people remain skeptical about the use of psychedelics to treat medical conditions. One common fear is that they will cause addiction or death by overdose; however, it is important to note that psychedelics are actually one of the safest known classes of drugs used for the central nervous system. The drugs discussed for these applications (i.e. psilocybin, LSD) are not addictive and there have not been any overdose deaths as a result of ingesting the standard doses discussed for medical practices.
Despite such skeptics, for those focused on the facts it is easy to see the major potential psychedelic treatments hold and the immense impact they could have on the millions stuck suffering from psychiatric conditions. Only time will tell, but from today’s standpoint it seems that psychedelic drugs have the potential to unlock a new era of treating treatment resistant psychiatric conditions and change the field of psychiatry for good.
Key takeaways
- Selective Serotonin Reuptake Inhibitors (SSRIs) are currently the main class of psychiatric medication. Many patients are resistant to these medications and the new alternatives have many negative side effects, presenting the need for a new solution.
- Psychedelics are a class of hallucinogenic drug that were used to treat depression many years ago, but after being banned by the US government in the 1970 lost their popularity. Recently, they gave regained the interest of many scientists for applications in psychiatry.
- LSD, MDMA, and psilocybin (magic mushrooms) are the psychedelics currently being most researched for medical applications. They are all serotonin agonists, meaning they increase the amount of serotonin in the brain.
- There are many theories about how psychedelics work, but one of the most popular is the Thalamic Filter Model which suggests that psychedelics decrease the ability of a brain region called the thalamus to filter external information, leading to major shifts in perception of oneself and their surroundings.
- When used in a medical context, synthetic concentrations of the psychedelic are given to a patient in small doses. They then often experience hallucinations, and undergo therapy while under the influence as the drug often enables patients to experience major epiphanies or shifts in their mindset.
- There are still many unanswered questions about psychedelics, but many universities have created labs or even designated departments specifically for researching the applications of psychedelics to treat psychiatric conditions.
- Psychedelics may be able to change the world of treatment for conditions such as unipolar depression, anxiety, OCD, PTSD, alcoholism or other addictions, and severe social anxiety among others which are life impairing for millions of people.
Thank you so much for reading my article, I hope you enjoyed it! My name is Raina Bornstein and I’m 16 years old. I’m passionate about branches of neuroscience and biotechnology, especially when they connect to treating neurological conditions. I’d love to connect on LinkedIn or Twitter, or you can reach out to me at rainabornstein@gmail.com to talk or collaborate. I can’t wait to hear from you!
