Introduction

Research into the medical viability of psychedelics has come a long way since the dark ages of the 1970s prohibition. While all classical psychedelic drugs (psychedelics that act primarily on the serotonin system) are still Schedule I (the highest and most restrictive classification) under the Controlled Substances Act, many are once again being explored for their therapeutic benefits. 

Some psychedelic drugs, such as psilocybin and 3,4-Methyl​enedioxy​methamphetamine (MDMA), are undergoing Phase II and III clinical trials. In fact, there are some indications that MDMA may receive FDA approval for the treatment of post-traumatic stress disorder (PTSD) within the next year. This could not be more timely, as millions of Americans struggle with various mental health issues like depression, anxiety, and the aforementioned PTSD. Other psychedelics, like ayahuasca and DMT, are more and more in vogue. Thousands of Americans travel to South and Central America yearly to participate in ayahuasca ceremonies due to their purported spiritual and medicinal value. 

Several municipalities have recently decriminalized certain psychedelics. Colorado and Oregon took that a step further, and passed legislation that legalized the adult use of psilocybin (and other psychedelics) in therapeutic settings.

Recently, a comprehensive review of psychedelic research studies published from 1990 to 2015 evaluated the antidepressant, anti-anxiety, and anti-addiction effects of the compounds ayahuasca, psilocybin, and lysergic acid diethylamide (LSD), commonly referred to as acid.

This review was published in the journal Therapeutic Advances in Psychopharmacology by a team of researchers from the Department of Neuroscience and Behavior at the Brazil National Institute for Translational Medicine. It examined over 150 psychedelics studies and trials to determine if psychedelics were safe and effective — eventually narrowing the final list to six studies which met certain criteria.⁽¹⁾

Plant Medicine

Plant and fungus-derived hallucinogens like DMT and psilocybin (the active chemical found in magic mushrooms) have been used for many years as part of various rituals. 

Mental Disorders Are Very Common and Decrease Life Expectancy 

In 2019, roughly one in eight people, or about 970 million people worldwide, were living with a mental disorder. Depression and anxiety are the most common conditions. Due to the COVID-19 pandemic, their prevalence significantly increased. Isolation due to stay-at-home orders, fear of a potentially deadly virus, job losses, and financial difficulties are all factors that can lead to, or worsen, symptoms. Some estimates found a 26% increase in anxiety and a 28% increase in depression in just one year. According to the World Health Organization (WHO), individuals with severe mental health conditions have a shorter life expectancy, dying as much as 20 years earlier than healthy people.^(2, 3)

Depression affects roughly 280 million people, or 5% of the population worldwide, with women and older adults at higher risk according to the WHO. Depression can lead to suicide, and sadly, many people do not respond — or only partially respond — to antidepressant treatments. Additionally, over 260 million people have some type of anxiety disorder.⁽⁴⁾

Although various drugs and therapies are available for mental health disorders, many people don’t respond to standard therapy, and are therefore considered “treatment-resistant.”  This term refers to individuals who have participated in at least two treatments without improvement in their symptoms. Unfortunately, these cases are very high. Some estimates show treatment resistance affects 20–60% of individuals with psychiatric disorders.⁽⁵⁾

Could DMT, Psilocybin, and LSD Help Individuals with Anxiety, Depression, and Substance Use Disorder?

In the last three decades, ayahuasca rituals have travelled from South America to the United States, Europe, Asia, and Africa. Researchers have also become interested in learning more about the potential benefits of ayahuasca and other compounds with hallucinogenic qualities, like psilocybin and LSD, for various mental health issues. Research studies often combine these hallucinogenic compounds with non-drug therapies, such as psychological counseling. 

According to scientists, these three substances work in similar ways. They activate the receptors of certain neurotransmitters, such as serotonin and glutamate, which play important roles in mood, sleep, immune system function, appetite, digestion, breathing, and other crucuial physiological processes.

Animal and experimental studies of ayahuasca consumers indicate that this brew may have antidepressant, anti-addictive, and anti-anxiety effects. These findings are very promising for individuals struggling with mental health conditions, particularly those resistant to treatment. Studies evaluating short- and long-term users also suggest that ayahuasca is relatively safe.  

Research studies evaluating psilocybin and LSD conducted in the 1950s and 1960s found that these substances had potential uses in the treatment of obsessive-compulsive disorder (OCD), substance use disorders, and as an add-on therapy for terminally ill individuals. The research was interrupted in the following decades and resumed in the 1990s. Newer research based on animal and human studies also found some evidence that psilocybin and LSD may have anti-anxiety, antidepressant, and anti-addiction qualities. Also, these substances seem reasonably safe when administered in medical settings, under medical supervision. This has potentially significant implications, as current medications for depression and anxiety disorders have limited efficacy, and many people impacted by these conditions continue to experience significant symptoms.

In total, the results from the 2016 systematic review of scientific studies suggest that psychedelic drugs like ayahuasca, psilocybin, and LSD may have the potential to manage depression, anxiety, and substance use disorders. 

Hallucinogenic Drugs Study Methodology

Brazilian researchers evaluated clinical trials published over 25 years, from 1990 to 2015, looking for studies published in peer-reviewed journals. Only studies that included participants diagnosed with anxiety, depression, or substance use disorder — according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) — were considered. Additionally, researchers looked at all clinical trials that assessed the effects of ayahuasca, psilocybin, or LSD for anxiety and depressive or substance dependence symptoms. Out of 151 studies available, only six of them met the criteria set up by the researchers, and in accordance with the Systematic Reviews and Meta-Analyses guidelines (PRISMA). 

Hallucinogens Study Results

Based on this review of research studies, scientists consistently found that ayahuasca, psilocybin, and LSD have anti-anxiety, antidepressant, and anti-addiction effects (particularly for tobacco and alcohol dependence). These drugs may also help doctors to understand mental health conditions and develop other drugs and therapies. 

• In one study, ayahuasca use produced a significant decrease (up to 82%) in depressive scores according to three depression scales used by the researchers. It was also well tolerated. 
• In another study, participants diagnosed with obsessive-compulsive disorder (OCD) received various doses of psilocybin. Researchers found improvement in symptoms, with a reduction of Yale–Brown Obsessive Compulsive Scale (YBOCS) scores. The reduction ranged from 23% to 100% in all participants.
• Psilocybin was beneficial in managing tobacco dependence in a small study involving 18 participants. 80% (12 out of 15) abstained at the 6-month follow-up. Cravings and temptation to smoke were significantly decreased, and no important side effects were reported during psilocybin use. 
• Psilocybin may also help with alcohol dependence, based on a study conducted on 10 participants diagnosed with alcohol use disorder. They received two doses of psilocybin and 12 sessions of psychological therapy. The consumption of alcohol significantly decreased after the psilocybin doses were administered. Improvements were maintained at the 36-week follow-up. 
• LSD was used in a double-blind, randomized, active placebo-controlled study (meaning a study where participants are randomly assigned to either a placebo or the test drug and neither the participants nor the researchers have knowledge of which they are taking). The study evaluated LSD’s potential benefits in 12 individuals diagnosed with anxiety associated with cancer and other serious, life-threatening conditions. This research study included psychotherapy sessions and two LSD-assisted psychotherapy sessions. At the two-month follow-up, the score that measures anxiety — the State-Trait Anxiety Inventory (STAI) — significantly decreased, suggesting an improvement in anxiety symptoms. Furthermore, the improvement in STAI scores was maintained for 12 months, and no significant adverse reactions were reported. 

While the results were positive, researchers of this systematic review noted some limitations. There were only six studies, and these studies had a small number of participants. Three of these research papers were not placebo-controlled studies. Double-blind, placebo-controlled trials are considered the gold standard for clinical studies because they have better design and the best chance to determine whether a drug is effective.

Potential Impact of the Hallucinogenic Drugs Studies

Overall, the research is optimistic, suggesting that hallucinogens such as psilocybin, LSD, and ayahuasca may potentially treat depression, anxiety, and substance use disorders, even in cases where standard treatment failed. While larger, well-designed studies are needed to confirm the preliminary findings of this systematic review, the results are still very exciting. If scientists and medical researchers can prove psychedelics’ safety and efficacy, their discoveries could potentially lead to a cascade of legal changes. This, in turn, would likely lead to easier access to these powerful compounds for further research.

However, the potential does not end there. Other research suggests that psychedelic drugs hold significant promise as tools for self-growth and well-being. A growing body of evidence suggests that small doses of psychedelics (aka microdosing) could increase productivity and creativity, while decreasing anxiety and possibly even rates of depression. Support for research, such as the report featured here, is a vital part of raising awareness and shifting public perception about psychedelics.^(6, 7, 8)

Sources

Sources

1. dos Santos, R. G., Osório, F. L., Crippa, J. A. S., Riba, J., Zuardi, A. W., & Hallak, J. E. C. (2016). Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years. Therapeutic Advances in Psychopharmacology, 6(3), 193–213. https://doi.org/10.1177/2045125316638008

2. Gates, P. J., Sabioni, P., Copeland, J., Le Foll, B., & Gowing, L. (2016). Psychosocial interventions for cannabis use disorder. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.cd005336.pub4

3. World Health Organization: Mental Health Disorders https://www.who.int/news-room/fact-sheets/detail/mental-disorders

4. World Health Organization (WHO): Depression https://www.who.int/news-room/fact-sheets/detail/depression

5. Howes, O. D., Thase, M. E., & Pillinger, T. (2021). Treatment resistance in psychiatry: state of the art and new directions. Molecular Psychiatry. 27, 58-72. https://doi.org/10.1038/s41380-021-01200-3

6. Mans, K., Kettner, H., Erritzoe, D., Haijen, E. C., Kaelen, M., & L., R. (2021). Sustained, Multifaceted Improvements in Mental Well-Being Following Psychedelic Experiences in a Prospective Opportunity Sample. Frontiers in Psychiatry, 12. https://doi.org/10.3389/fpsyt.2021.647909

7. Joel Bornemann (2020) The Viability of Microdosing Psychedelics as a Strategy to Enhance Cognition and Well-being – An Early Review, Journal of Psychoactive Drugs, 52:4, 300-308, DOI: 10.1080/02791072.2020.1761573

8. Rootman, J.M., Kryskow, P., Harvey, K. et al. Adults who microdose psychedelics report health related motivations and lower levels of anxiety and depression compared to non-microdosers. Sci Rep 11, 22479 (2021). https://doi.org/10.1038/s41598-021-01811-4