The Transformative Potential of Psychedelic Therapy

Depression is a debilitating mental health condition that affects millions worldwide. Its impact can be particularly severe for individuals with treatment-resistant depression (TRD), who endure persistent symptoms and limited relief despite the availability of various treatment options. Alarming statistics reveal the urgency of finding effective solutions: suicide claims the lives of approximately 40,000 Americans per year, which makes it the tenth leading cause of death in the U.S. (Marlan). The limited efficacy of existing treatments highlights the pressing need to address the complex nature of TRD. In recent years, an unconventional contender has emerged: psychedelics. While historically associated with counterculture and subject to societal stigmatization, these mind-altering substances are now capturing the attention of the medical community as a potential breakthrough in the treatment of TRD. By challenging preconceived notions, fostering informed discussions, and advocating for increased research and funding, we have the opportunity to rewrite the narrative surrounding TRD and provide a path towards healing and recovery for those in need.

Overview of Psychedelics

Before we begin a discussion about psychedelics, we must first formally define them. Psychedelics are a class of hallucinogenic drugs that have been used recreationally for decades as a way to alter perception, feeling, and consciousness. During the 1950s and 1960s, research done on psychedelics demonstrated their potential to treat depression and other medical conditions. Following their rise to popularity was the hippie counterculture movement, which promoted the recreational use of psychedelics as a way to expand consciousness. In 1970, President Nixon passed the Controlled Substances Act, which made psychedelics illegal in the United States. On top of that, they were federally classified as Schedule I controlled substances, a category reserved for drugs that have no accepted medical use and a high potential for abuse (Byock, 2018). Consequently, psychedelic research came to a screeching halt. Recent studies have re-examined their use in medicine and found decades later (yet again) that psychedelics have a remarkable potential to effectively provide relief for people who suffer from treatment-resistant depression and other chronic illnesses. Now, the goal for researchers and medical professionals is to determine which psychedelics have the ability to treat which mental illnesses.

There are many different types of psychedelics: classic and non-classic. Classic psychedelics alter serotonin receptors in the brain, which influence memory, learning, and happiness. The most popular classic psychedelic is lysergic acid diethylamide, more commonly known as LSD or acid. It is made by creating fungus on seeds of rye and is painted onto small pieces of paper that people can either place on their tongues or swallow (Campbell, 2001). Psilocybin is another classic psychedelic that occurs naturally in over 200 species of fungi and is typically referred to as “magic mushrooms” that are either eaten or taken as pills. Dimethyltryptamine, or DMT, is a classic psychedelic that is found naturally in many plants, but can also be made in a laboratory (Trott, 2019). The final classic psychedelic is mescaline, which is derived from the San Pedro Cactus plant, turned to powder, and put into capsules. Non-classic psychedelics consist of hallucinogens that do not interact with the same receptors. The most well-known of these is MDMA, or ecstasy, a synthetic party drug that acts as both a stimulant and a hallucinogen. Another popular non-classic psychedelic is ketamine, an anesthetic that is already being used by medical professionals to treat disorders such as depression, anxiety, and chronic pain.

Serotonin receptors are activated by the neurotransmitter serotonin, and play a major role in altering brain chemistry. Serotonin is a hormone that sends messages between brain cells, and influences various biological and neurochemical processes such as learning, memory, happiness, body temperature, mood, sleep, hunger, aggression, and sexual behavior. These serotonin receptors are found on the outside of the brain cell, but are mainly concentrated on the inside of the cell. Psilocybin, LSD, and other similar psychedelics have the unique ability to bind to inner receptors, which promotes the growth of new neural connections, as opposed to binding only to outer receptors, which do not form new connections (Fell, 2023). Forming new neural connections is important, as brain development builds on itself. The more connections we have, the faster and better our brain cells can communicate in complex ways. This allows our brains to be more neuroplastic, meaning we can easily alter our brain connections in order to learn new information and adapt to our environment.

The Effectiveness of Psychedelics in Treating TRD

Currently, the most basic treatment for patients with clinical depression is a selective serotonin reuptake inhibitor (SSRI) which is taken as a daily pill. Since low serotonin is associated with depression, SSRIs work by blocking (or inhibiting) serotonin’s reabsorption (or reuptake) after it is used to send a message to other cells. This allows the serotonin moving between cells to stay active in the body for longer so that more can be used by brain cells. SSRIs, however, fall short when it comes to their ability to access a brain cell’s inner serotonin receptors, making them less effective than psychedelics in treating depression. This was tested in a study done at John Hopkins School of Medicine, the leading and most productive research team in the United States conducting human research with psychedelics. The study found that after psilocybin treatment, patients reported substantial decreases in major depressive symptoms for up to a year (Mushrooms for depression? psilocybin is showing promising results, 2023). Standard antidepressants such as SSRIs must be taken for long periods of time, and typically take a few weeks before they even begin to relieve symptoms. Psilocybin, on the other hand, has the potential to relieve symptoms of depression almost immediately, with the effects lasting up to 12 months.

Another study done by scientists at UC San Francisco and Imperial College London found that psilocybin can free patients from rigid thought patterns that make it difficult for them to adopt new insight and perspectives. The study consisted of 60 participants with TRD who were either given psilocybin or a placebo antidepressant (an SSRI called escitalopram). In addition, both groups also went through the same psychotherapy sessions. Brain scans done before and after treatment revealed that patients who received the psilocybin treatment showed less depressive symptoms. These improvements were correlated with visible physical changes in the brain such as increased communication in areas that had not been previously well connected, and less connections in brain areas that are associated with depression. The scientists describe it as “flattening the brain’s landscape” (Kurtzman, 2022). People with depression can be viewed as having dips and concavities in their brain’s landscape that make it difficult for them to experience fluidity in their thought patterns. For the participants who took the antidepressant, no physical changes were seen in the brain scans, indicating that psilocybin functions differently in the brain compared to SSRIs. Overall, psychedelics have proven to be a more effective and durable treatment for depression as opposed to traditional antidepressants.

Addressing Concerns and Misconceptions

Though there have been many successful clinical trials of psychedelics treating various illnesses, there is still a lot to be done before psychedelics can be approved for medical use. The main issue is that, despite all available evidence, the United States government decided in 1970 that psychedelics are extremely dangerous, highly addictive, and must be regulated and criminalized at the highest level. This, however, is objectively false. Psychedelics are exceptionally safe and non-addictive. Due to the Controlled Substances Act, the development of psychedelics as medicine is now facing several challenges, as many people are hesitant to use them and support research. There are some potential risks and side effects, of course, as there are with any medication. Nausea and vomiting are not unusual, and the temporary disruption of visual and spatial orientation can induce anxiety. This is why every patient who is treated with psychedelics goes through a careful and extensive screening process to make sure they are fit to take hallucinogens, and every treatment is monitored and guided by at least two psychiatrists. With adequate counseling and preparation from trained professionals, the psychedelic experience can give people a heightened sense of clarity, confidence, and a profound sense of connection to others, while also renewing one’s hope and sense of purpose in life.

As for developing an addiction, the risk is very low. Theoretically, any drug that interacts with your brain’s reward system could lead to addiction or dependency. This reward system is the neurotransmitter dopamine, which allows you to feel pleasure, satisfaction, and motivation (Nichols, 2016). Classic psychedelics, as previously mentioned, do not act through dopamine, but rather serotonin. Drugs that act through dopamine are opioids, synthetic Schedule II drugs that are (legally) prescribed as a pain reliever, and are also responsible for more than 80,000 deaths in 2021 alone (U.S. Department of Health and Human Services, 2023). Despite being used in medicine since the 1860s, opioids are highly addictive substances that carry a significant risk of overdose. Many people who are prescribed opioids for pain begin to develop a physical and psychological dependence, making it challenging for individuals to stop using them without experiencing withdrawal symptoms. In contrast, psychedelics have a fundamentally different mechanism of action. They are not addictive and have a remarkably low potential of lethal overdose because they are interacting with different brain hormones.

An addiction study using animals as subjects found that animals do not self administer hallucinogens as they do with sugar and stimulants. This indicates that these substances work differently in the brain, and further supports that psychedelics do not lead to an addiction (Fantegrossi et al., 2008). Additionally, lifetime use of psychedelics does not appear to cause brain damage later in life. In a study involving 130,000 participants, with 13 percent reporting psychedelic use, researchers discovered no correlation between lifetime psychedelic use and an increased risk of mental health conditions. In fact, in many instances, psychedelic use was associated with lower levels of mental health issues among patients (Krebs & Johansen). This finding challenges common misconceptions and highlights the potential benefits of psychedelics.

Ethical Considerations

It is important to note that while there may be some risks involved when taking psychedelics, there are certainly also risks of not taking psychedelics. Approximately 280 million people in the world have depression, and 30% of those diagnosed with depression are treatment-resistant (World Health Organization, 2023). TRD describes depression that remains unresponsive to at least two different antidepressant treatments. For patients with TRD, psychotherapy and current drug treatments are often insufficient. Without proper treatment, these people have to endure severe psychological and often even physical suffering every single day. A sense of unending worthlessness and grief compels many of these people to eventually end their lives. Over the past two decades, suicide rates have risen over 24% among middle aged adults, and for people aged 15 to 24, suicide is the second-leading cause of death in the U.S. (Byock, 2018). Patients with TRD are not left with many options, and their suffering contributes to thousands of deaths each year. It is important that we are able to provide access to innovative treatments for individuals with TRD who have lost their meaning and value in life.

There is a need to balance the risks and benefits of psychedelics, and it is clear that the potential benefits of psychedelic therapy unquestionably outweigh the risks, especially considering the severity and chronic nature of TRD. The dangers of taking psychedelics are minimal, especially when done in a controlled setting with trained professionals. Skepticism in using psychedelics as medicine is warranted, in fact it is essential, as this is what drives science forward. The real danger is cynicism. Unscientific bias and straight up science denial is far more harmful, and prevents people from getting the treatment they desperately need. The prohibition of psychedelics was motivated by reasons of money, power, and control. We must not let politics, fear, and incorrect assumptions about psychedelics discourage further research so that we can provide life-saving treatment to people who have been deprived of hope and a sense of purpose.

Reducing Stigma

The first step to reduce stigma surrounding psychedelics is to change the public’s perception of these substances, and to separate them from their historical association with counterculture and negative social stigma. They are not to be seen as drugs, but rather as medicines. An article published in Science warns readers that by narrowly defining a drug class by only one of its effects, we risk overlooking the full spectrum of uses and potential benefits that these substances have to offer. The term “psychedelics” simply fails to encompass the diverse range of applications for these substances. Patients may be hesitant to use them purely because of their name. The article suggests alternate terms such as “psychoplastogens” or “neuroplastogens” to reduce prejudice and better depict the full scope of their uses in medicine (Schindler & D'Souza, 2022). Reclassifying psychedelics as medications that have the incredible ability to produce rapid and sustained effects on brain structure and function can help paint a more accurate picture of their capabilities to the public.

The second step is to decriminalize psychedelics. The decriminalization of psychedelics would reduce criminal penalties of use and possession, and can also lessen the negative stigma surrounding the substances. The Schedule I status of psychedelics prevents scientists from conducting legitimate medical research on them. However, in 2017, the FDA granted breakthrough status to both MDMA and psilocybin as treatments, which recognizes a substance’s therapeutic potential and places it on a fast track to approval (Ducharme, 2023). The road to FDA approval typically consists of three phases of clinical trials to ensure the safety and efficacy of the medicine. In 2022, psilocybin entered its third phase, the final phase before receiving approval by the FDA for medicinal use. Once psychedelics receive FDA approval, they will be legally permitted for use in a controlled therapeutic setting, which we may see as soon as 2024.

Ways to Support Research and Funding

Even if you are not actively involved in the ongoing research of psychedelics, you can still take action. In the state of California, there are several representatives you can contact to advocate for policy changes regarding the use of psychedelics in medicine. California is divided into multiple congressional districts, each with its own representative in the U.S. House of Representatives. To identify your specific representative, you can visit the official U.S. House of Representatives website and enter your zip code. When contacting these representatives, it is important to clearly express your support for policy changes, and share relevant information such as scientific studies, anecdotal evidence, and the potential benefits of psychedelic-assisted therapies. Explain why you believe these changes are important, emphasizing the potential positive impact on mental health treatment, patient well-being, and the broader community. You can reach out to them through email, phone calls, or by attending town hall meetings and other public events where you may have the opportunity to express your views directly. Remember to be respectful, concise, and specific in your communication.

It is also important to educate yourself on the latest scientific research, clinical trials, and policy developments surrounding psychedelics. There are several reputable organizations and research institutions that focus on psychedelic research and policy reform. These organizations work to raise awareness, educate the public, and advocate for changes in policies related to psychedelics. The Multidisciplinary Association for Psychedelic Studies (MAPS) is a leading organization in the field of psychedelic research. Since creating the non-profit in 1986, founder Rick Doblin has dedicated the last 37 years to psychedelic research in order to change the public’s perception about their uses through research and education (Emerson, Ponté, Jerome, & Doblin, 2014). They conduct clinical trials, sponsor research projects, and work towards the legalization and regulation of psychedelic substances. In addition, they also host events, fundraisers, and educational programs to support the organization’s mission.

The National Institutes of Health (NIH) has also started to contribute to psychedelic research in recent years. While there were restrictions on psychedelic research in the past, the NIH has recognized the potential therapeutic value of these substances and, for the first time in more than 50 years, has began to fund studies in this field. In 2021, the NIH offered a 4 million dollar grant to John Hopkins Medicine to conduct research on psychedelics ​​(Johns Hopkins Medicine receives first federal grant for psychedelic treatment research in 50 Years, 2021). This grant allowed the leading psychedelic research team to thoroughly investigate the therapeutic effects of psilocybin. You can support John Hopkins Center for Psychedelic & Consciousness Research by making donations directly through their website. By supporting reputable research organizations, students can contribute to advancing our understanding of psychedelics and their potential therapeutic applications.

Conclusion

Given the available research and evidence, psychedelics deserve serious consideration as a legitimate treatment for depression. TRD presents significant challenges, and psychedelics offer promising results. Various clinical trials have shown the efficacy of psychedelics such as psilocybin and LSD in alleviating symptoms and promoting lasting improvements. While risks and potential side effects exist, careful screening and guided therapy under supervision of trained professionals mitigate these risks. Ethical considerations urge us to prioritize access to innovative treatments for individuals with TRD who endure immense suffering and face limited options. Balancing the risks and benefits of psychedelics, it is evident that the potential benefits far outweigh the risks. Further research and funding are essential to unlock the full potential of psychedelics as a treatment option for TRD. Supporting scientific studies, engaging with policymakers, and staying informed can help drive progress. By embracing a more accepting approach to these remarkable substances, we can reshape the 1960s-era narrative of psychedelics, offer hope, and revolutionize mental health care.

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