Psychedelics as a Therapeutic Intervention for Mental Health Disorders

This is Part One of a three-part series. Click to read Part Two and Part Three.

A 2013 meta-analysis looked at the prevalence of mental health disorders from 1980 - 2013 [1]. It was unusually large in scope, collecting data from 176 studies across both high-income and low-income countries. The results were staggering - 17.6% of adults had experienced a mental health disorder within the last 12 months, and 29.2% had experienced a mental health disorder in their lifetime.

Additionally, when we account for the social costs worldwide, mental health and substance use disorders are the leading cause of Years Lived with Disability (YLDs). They are the fifth largest factor in Disability Adjusted Life Years (DALYs), accounting for some 138.9 million DALYs, of which 40.7% are attributed to depressive disorders, 14.7% to anxiety disorders, and 20.5% to substance use disorders [6]. 

Currently, the standard treatments for common mental health disorders such as anxiety and depression include pharmacological interventions (SSRIs, SNRIs, tricyclic antidepressants, benzodiazepines, etc.), and talk therapy strategies such as cognitive behavioral therapy (CBT), dialectical behavioral therapy (DBT), and acceptance and commitment therapy (ACT).

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Common pharmacological interventions come with the risk of side effects such as headaches, GI distress, sexual dysfunction, weight gain, fatigue, and insomnia. Furthermore, studies indicate these medications are only effective in decreasing symptoms of anxiety and depression 25-45% of the time [2].

The side effect profile of standard pharmacological treatments for anxiety and depression and the variable efficacy leave vast numbers of people suffering and struggling to cope with the symptoms of common mental health disorders. Because of this, there is a push to find new treatment options that can offer more people relief from their symptoms, enhancing their quality of life and overall health and well-being. This need has led to renewed interest in the therapeutic potential of psychedelics as a treatment option for mental health disorders, and research on the use of psychedelics as a therapeutic intervention in the fields of medicine, psychology, and psychiatry has increased significantly over the last 5-10 years after being halted for decades [4].

To better understand the potential therapeutic value of psychedelics as an intervention for mental health disorders, this three-part series of articles will look at the current and historical state of psychedelic research in medicine. We will explore what we know (and do not know) about how psychedelics affect the brain and their therapeutic effects on symptoms of anxiety, depression, PTSD, and substance use disorders. 

The term psychedelics in health and medical research generally refers to serotonergic hallucinogens, which act as 5HT receptor agonists in the brain. Substances considered serotonergic hallucinogens include psilocybin, LSD (lysergic acid diethylamine), DMT (N,N-dimethyltryptamine), ayahuasca, and mescaline [3, 4, 5]. 

In recent years, health and medical research surrounding psychedelic compounds have been increasingly multidisciplinary, using various methodological approaches to gather evidence and data. These include rigorous double-blind and randomized controlled trials, neuroimaging using fMRI technologies, as well as self-reported surveys and questionnaires. 

The advances in medical technology and changes to the structural rigidity of health and medical research over the last 30 years have significantly expanded scientists’ possibilities to generate reliable and evidence-based data regarding the potential therapeutic value of psychedelics.

Unfortunately, the scientific and medical communities lost out on decades of potential data regarding psychedelics due to various social, cultural, and legislative factors. These factors resulted in restricted access to common psychedelic compounds, as well as the risk of legal consequences and possible criminal prosecution - factors that still exist as barriers to overcome in the pursuit of psychedelic research in medicine today.

Psychedelic research in medicine has spanned over half a century and first emerged with the discovery of LSD’s psychoactive effects by Albert Hoffman in 1943, with many notable scientific and cultural contributions to psychedelic knowledge occurring through to 1970 (see Table 1). However, despite having multiple positive results published in the fields of psychiatry and psychology in the 1950s and 1960s, research into the therapeutic potential of psychedelics was abruptly halted in 1970 with the signing of the Controlled Substances act by American president Richard Nixon, which classified LSD and psilocybin as Schedule 1 substances [3, 4].  

Substances classified as Schedule 1 are defined as having no medicinal value and a high potential for abuse - properties that are scientifically and factually inconsistent with that of LSD, psilocybin, and many other psychedelic compounds. Medical research on psilocybin and LSD has shown a significantly lower potential for abuse and dependency than many of the most harmful, highly addictive, and commonly abused substances we know of in society today, such as alcohol, cocaine, heroin, methamphetamines, and others. Research also indicates that psychedelic compounds such as LSD and psilocybin have anti-addictive properties and can be used as a treatment therapy for substance use disorders [3, 5]. 

The knowledge that psychedelic compounds had potential therapeutic value in treating mental health disorders such as anxiety and depression emerged in medical research before their classification as schedule 1 substances in 1970. Two recent meta-analyses looked at the retrospective findings of psychedelic research prior to their schedule 1 classification. They found that across 19 studies conducted between 1949 and 1973, 79% of patients showed clinically significant improvement in their symptoms post-treatment with psychedelics [4]. It is important to note that the experimental designs used in the first wave of psychedelic research in medicine lacked the standardization and control methods needed to form valid and reliable conclusions on their effects. However, despite the methodological constraints of early psychedelic research in medicine, the available results should have provided enough evidence of their potential medical value to inform legislators in 1970 that the classification of psilocybin and LSD as schedule 1 substances was scientifically inaccurate. 

The factual inconsistencies in scientific reasoning for categorizing LSD and psilocybin as Schedule 1 substances have created significant skepticism and controversy regarding the intention behind the scheduling decision. It is widely understood that psychedelics were classified as Schedule 1 substances in 1970, not because of their potential for harm, but because of their role in counter-cultural movements of the time and the desire of various institutions and special interest groups to exert moral authority over the population [4, 5]. However, the classification of psychedelic compounds as Schedule 1 substances resulted in a widespread misunderstanding of their properties and effects, a rise in social stigma and criminal persecution around the use of these compounds, as well as a 25-year lapse in medical research on the potential therapeutic value of psychedelics.

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Fortunately, beginning in the early 1990s, health and medical researchers worldwide have driven a renewed interest in understanding the potential benefits of psychedelics as a therapeutic intervention for mental health disorders.

The current wave of psychedelic research in medicine has focused on generating valid and reliable evidence to inform our understanding of psychedelics from a neuroscience and brain function perspective, a clinical therapeutic perspective, and a patient experience perspective.

This comprehensive and multidisciplinary approach to psychedelic research in medicine provides scientists and medical researchers an opportunity to further understand the brain function of patients dealing with mental health disorders and develop new and more effective treatments to ease the pain and suffering associated with depression, anxiety, PTSD, substance use disorders, and other mental health diagnoses.

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A critical pillar that differentiates current psychedelic research in medicine from research conducted before 1970 is the adherence to scientific rigor focused on strict experimental designs, methodologies, control conditions, and the critical appraisal of data and results [4, 7]. Nevertheless, the potential role of psychedelics in medical research specifically in the fields of psychology, psychiatry and neuroscience is significant, with one of the pioneers of psychedelic research in medicine - Dr. Stanislav Grof - comparing the value of psychedelics as a tool in psychology and psychiatry with that of the value of the microscope in biology and the telescope in astronomy [7].

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Current research on the action and effects of psychedelic compounds on brain function is driven by advancements in brain imaging technologies such as functional Magnetic Resonance Imaging (fMRI). These neuroimaging technologies allow researchers to observe the functional changes occurring within the brain during a psychedelic experience by measuring and mapping changes in blood flow within anatomical regions of the brain. Medical knowledge of the specific functions and specializations within different brain regions, combined with measurable changes in blood flow and neural activity, provides researchers with essential data needed to further assess and understand the physiological mechanisms and psychopharmacological effects of psychedelic compounds within the brain.

In addition to the objective and quantifiable data that psychedelic fMRI studies provide, research subjects can communicate the subjective effects of a psychedelic experience in real-time. This concurrent approach to gathering data allows researchers to identify potential associations and causal relationships between the qualitative patient experience and the quantitative empirical data. Another benefit of psychedelic research using fMRI and neuroimaging technologies is that they allow researchers to capture, map, and measure brain function at multiple time points. This provides researchers the opportunity to compare and contrast psychedelic effects on brain functionality over time, generating important data on functional brain changes pre-intervention and at multiple time points post-intervention. 

A significant area of current psychedelic research in medicine is that which looks at the value and safety of psychedelic compounds as a clinical therapeutic for mental health disorders. This research focuses on generating empirical evidence regarding the measurable and quantifiable effects of psychedelic compounds on symptoms of mental health disorders and developing data on the variability of therapeutic effects based on dosing and experimental conditions. These studies use control (non-intervention) groups, experimental (intervention) groups, and often comparison (other intervention/standard treatment) groups. This is the kind of rigorous, structured research required for institutional approval of psychedelics as a therapeutic medical intervention and providing significant evidentiary value needed to change legislative controls on the access to and use of psychedelic compounds in society.

In recent years, the most active research in this area has focused on the antidepressive, anxiolytic (anti-anxiety), and antiaddictive effects of classic serotonergic psychedelic compounds. This research attempts to measure these properties and compare the efficacy of psychedelic compounds as a therapeutic intervention for mental health disorders, with the standard of care and first-line treatments currently available and widely used today (SSRIs, CBT, etc.) [3, 5, 8]. This type of research uses controlled dosing and standardized mental health assessment tools to measure the effects of psychedelics as a therapeutic intervention reliably. However, many of these studies combine the use of psychedelic compounds with psychotherapy, which can lead to some limitations in reliably identifying the effect of psychedelic compounds separately from the effect of psychotherapy.

In addition to the quantitative research being done, it is also important to consider meaningful qualitative data regarding the subjective feelings and individual experiences of people who have used psychedelic compounds. This is true as a mental health intervention, a tool for exploring altered states of consciousness and/or enhancing a person’s lived experience.

Despite the restrictive classification and illegality of psychedelic compounds, these substances play a role in many cultural movements and continue to be accessed and used by individuals throughout society today. Thus, generating additional understanding of the broad spectrum of psychedelic experiences, how individuals use and make sense of these experiences, and the role of psychedelics in improving one’s quality of life adds significant value to our foundational knowledge of psychedelics. 

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Neuroimaging, brain function studies, clinical trials, and qualitative research all generate crucial data needed to help inform and guide policymakers, legislators, physicians, and other medical practitioners in making evidence-based decisions regarding the use of psychedelic compounds as a therapeutic intervention for mental health disorders.

Additionally, individuals interested in trying psychedelics to relieve their mental health symptoms must have access to reliable information to safely use and integrate psychedelics into their mental health toolkit. Therefore, in part two of this series, we will take a closer look at the action of psychedelic compounds on the brain, how psychedelics affect the functional processes within different brain regions, and what that means in terms of the potential therapeutic benefits of psychedelics.

Click to read Part Two and Part Three.

Lunaa is one of our community bloggers here at Chemical Collective. If you’re interested in joining our blogging team and getting paid to write about subjects you’re passionate about, please reach out to Matt via email at [email protected]

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