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While there are now more clinical trials than ever before on the therapeutic applications of psychedelics, the medicinal use of such substances is not new. Indigenous cultures worldwide have used plants, roots, vines, and fungi that produce altered states of consciousness in healing rituals for thousands of years.
The contemporary study of psychedelics began in the 1940s after lysergic acid diethylamide (LSD) was synthesized in 1938 by Swiss chemist Albert Hofmann.1 Initially synthesized in an attempt to create ergot byproducts that could be used to treat postpartum hemorrhage, by the late 1940s LSD had become a substance of interest to psychotherapists.2
The therapeutic use and study of LSD continued throughout the 1950s and into the 1960s, where it was also found to be successful in the treatment of alcoholism. Researchers also discovered that when combined with other appropriate therapies LSD was effective in reducing anxiety, depression, and physical pain in patients with advanced cancer.3
Although early scientific psychedelic research showed therapeutic promise, further research nearly ceased with the 1970 Controlled Substances Act. Substances such as LSD, psilocybin, N,N-Dimethyltryptamine (DMT), and mescaline were classified in a Schedule I category. In this new classification, psychedelics became as restricted as heroin. To this day, they are legally deemed more dangerous than cocaine, methamphetamine, fentanyl, methadone, and oxycodone.
While large-scale studies came to a halt, these new regulations did not stop some from continuing to study psychedelics. Through the efforts of scientists and supporters, underground research continued and the tide began to change. The early 2000s saw the third wave of psychedelic research, and now there are more published studies of their medicinal potential.
Today these studies are conducted in research facilities such as the Johns Hopkins Center for Psychedelic and Consciousness Research, which has $17 million in funding to study psilocybin. Massachusetts General Hospital recently created the Center for the Neuroscience of Psychedelics in an effort to understand the effects and therapeutic potential of psychedelics. The Multidisciplinary Association for Psychedelic Studies (MAPS) in California was founded in 1986 and continues to be a leader in psychedelic research.
The most widely studied psychedelic substance to date is 3,4-Methylenedioxymethamphetamine (MDMA). In the late 1970s and early 1980s, a group of psychiatrists began taking a closer look at MDMA’s ability to support wellbeing. One early study showed that MDMA helped to increase communication and “enhanced insight, empathy, and peaceful feelings.”4
MDMA was then widely studied for the treatment of post-traumatic stress disorder (PTSD). In 2017, the U.S. Food and Drug Administration (FDA) granted breakthrough therapy designation for MDMA-assisted therapy in the treatment of PTSD.5 The decision was based on results from six Phase 2 MDMA clinical trials, with the FDA maintaining that MDMA “may demonstrate substantial improvement over existing therapies.”6
Recently published Phase 3 MDMA clinical trials state that MDMA-assisted therapy “represents a potential breakthrough treatment that merits expedited clinical evaluation,” especially in individuals with severe PTSD.7 Before MDMA can be approved for medical use, the FDA requires one more positive Phase 3 clinical trial.
Psilocybin, the active compound in “magic mushrooms,” is another psychedelic substance that has gained attention because of its potential for the treatment of depression, anxiety, addiction, and more. Increased interest in psilocybin began in 2012 when a front-page story in The New York Times revealed that terminally-ill cancer patients who received large doses of psilocybin in a large-scale study felt less distress about dying.8
In 2020, researchers at Johns Hopkins discovered that just two doses of psilocybin combined with psychotherapy yielded fast and significant declines in symptoms of depression.9 Half of the participants showed complete remission at a four-week follow up, with most showing overall improvement.
A 2019 Johns Hopkins clinical trial found that fifteen participants who took psilocybin experienced an 80% smoking cessation success rate over six months.10 This is compared to patients who took varenicline, generally considered to be the most effective pharmaceutical smoking cessation aid, with an estimated 35% success rate.
Microdosing psilocybin has also become an area of scientific interest. Microdosing is taking approximately one-tenth of the dose that would normally elicit psychoactive effects. While published research on microdosing is limited, emerging claims are that it can help ease depression, reduce anxiety, increase creativity, and enhance energy levels.
Scientific interest in microdosing mushrooms is based on almost a decade of this anecdotal evidence. The first microdosing study was conducted in the Netherlands, with results published in 2018.11 Researchers found that although there were no changes in overall thinking, reasoning, and problem solving, there were substantial changes in both convergent and divergent thinking, which are considered to be pillars of the creative process.
When it comes to psilocybin, some U.S. states are taking note of the research. In 2019, Denver became the first U.S. city to decriminalize psilocybin-containing mushrooms. Several cities have followed suit, including Oakland, Santa Cruz, Cambridge, Somerville, and Washington D.C. In 2020, Oregon legalized psilocybin-assisted treatment programs in controlled settings. In addition, a system was created within the state of Oregon to produce and distribute psilocybin throughout the state.
Another increasingly popular psychedelic compound is ayahuasca, a traditional medicine used by indigenous peoples of the Amazon basin. Ayahuasca is a beverage made from the plants Banisteriopsis caapi and Psychotria viridis, which respectively contain β-carbolines and DMT. Traditional Amazonian healers refer to ayahuasca as the “master healer” for its profound effects on body and mind. Experiences with ayahuasca have been associated with improvement in depression and anxiety, and a growing body of evidence supports the ritualistic use of ayahuasca for its “important therapeutic potential.”12
One alternative to traditional addiction treatment is a psychoactive African root bark known as iboga. It has been used for centuries by people of the Bwiti religion in rites of passage and as a healing agent for compulsive behavior. Ibogaine, the active alkaloid found in the bitter iboga root, is used in some countries to help individuals overcome addiction, especially to opiates. In a powerful psychedelic experience that can last upwards of twelve hours, it is said that iboga releases subconscious trauma, making it easier to understand one’s addiction. It is also said to “reset” brain receptors back to their pre-addicted state, offering a “clean slate.”13
The most powerful psychedelic substance is said to be found in secretions from the Bufo alvarius toad, more commonly known as the Sonoran desert toad. The active ingredient in this secretion is 5-Methoxy-N, N-dimethyltryptamine (5-MeO-DMT), and its use is not as common or widely studied as other psychedelic substances. There are a handful of studies, however, that suggest its therapeutic potential. A single inhalation from dried toad secretion containing 5-MeO-DMT is said to be connected to sustained life satisfaction, mindfulness, and a decline in symptoms of anxiety, depression, and stress at baseline, within 24 hours, and at four weeks after use.14 There is also research showing that a single dose of 5-Meo-DMT promotes neurogenesis.15
“The potential significance of LSD and other psychedelics for psychiatry and psychology,” suggests Dr. Stanislav Grof, a psychiatrist with over sixty years of research experience in non-ordinary states of consciousness and who is one of the founders of transpersonal psychology, “is comparable to the value the microscope has for biology or the telescope has for astronomy.”16 When looking at the vast therapeutic potential found in an array of naturally-occurring and synthetic psychedelic substances, what Grof suggests is not far off. The future of medicine must take an interdisciplinary approach and include all advances that offer promising therapeutic potential.
- Dyck, Erika (2015). LSD: a new treatment emerging from the past. PubMed https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592308/
- Busch, A. K. (1950). L.S.D. 25 as an aid in psychotherapy; preliminary report of a new drug. PubMed. https://pubmed.ncbi.nlm.nih.gov/14793387/
- Peter, G. (2010). Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases. The Journal of Nervous and Mental Disease. https://journals.lww.com/jonmd/Fulltext/2014/07000/Safety_and_Efficacy_of_Lysergic_Acid.1.aspx
- Hermle, L. (1993). Psychological effects of MDE in normal subjects. Are entactogens a new class of psychoactive agents? PubMed. https://pubmed.ncbi.nlm.nih.gov/8471129
- Feduccia et al. (2019) Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline. Frontiers in Psychology https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751381/
- Mithoefer, M. C. et al. (2019). MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized control trials. Psychopharmacology. https://doi.org/10.1007/s00213-019-05249-5
- Mitchell, J. M. (2021). Putting the MD back into MDMA. Nature Medicine. https://www.nature.com/articles/s41591-021-01336-3
- Slater, Lauren. How Psychedelic Drugs Can Help Patients Face Death. (2012). The New York Times. https://www.nytimes.com/2012/04/22/magazine/how-psychedelic-drugs-can-help-patients-face-death.html
- Psychedelic Treatment with Psilocybin Relieves Major Depression, Study Shows. (2020). Johns Hopkins Medicine Newsroom. https://www.hopkinsmedicine.org/news/newsroom/news-releases/psychedelic-treatment-with-psilocybin-relieves-major-depression-study-shows
- “Magic Mushrooms” Help Longtime Smokers Quit. (2014). https://www.hopkinsmedicine.org/news/stories/mushrooms_quit_smoking.html
- Prochazkova, L. et al. (2018). Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting. Psychopharmacology. https://link.springer.com/article/10.1007/s00213-018-5049-7
- Sarris, Jerome. et al. (2021). Ayahuasca use and reported effects on depression and anxiety symptoms: An international cross-sectional study of 11,912 consumers. ScienceDirect. https://www.sciencedirect.com/science/article/pii/S2666915321000251
- Wasko, M. J. (2018). DARK Classics in Chemical Neuroscience: Ibogaine. PubMed. https://pubmed.ncbi.nlm.nih.gov/30216039/
- Uthaug, M.V. et al. (2019) A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms. Psychopharmacology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695371/
- Lima de Cruz, Moulin, Petiz, Leao (2018). A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131656/
- Grof, S. (2009). LSD: Doorway to the Numinous The Groundbreaking Psychedelic Research into Realms of the Human Unconscious. Park Street Press.
JENNIFER M. KEEHN was introduced to Eastern Philosophy at the age of eleven, and has been on a lifelong spiritual quest. Passionate about inspiring others to live their best lives, she offers holistic opportunities for healing and self-transformation at her oceanfront yoga and wellness studio in Baja California, Mexico.