From documentary films like Fantastic Fungi to the online streaming show Nine Perfect Strangers, the topic of therapeutic psychedelics has taken center stage in the American conversation and zeitgeist – again. Author and journalist Michael Pollan tells Harvard Health, “For most of the 1950s and early 1960s, many in the psychiatric establishment regarded LSD and psilocybin as wonder drugs for treating anxiety, trauma, and addiction, among other ailments.” Pollan adds, “As these drugs came to be associated with bad trips and psychotic breaks, The federal government reclassified psilocybin as a Schedule I drug in the 1970s, and research on its therapeutic effects became non-existent.”
Today, a renaissance is taking place as mushrooms are now looked at as the “new superhero,” and the interest in psychedelics as a tool to help treat everything from headaches to depression is rapidly advancing. Join us as we journey into the world of psychedelics to reveal how these compounds affect the brain and the latest research on how psilocybin is treating mental health disorders. We also talk to experts from the front lines of the psilocybin boom and their thoughts on psilocybin microdosing therapy treatment, challenges, and new protocols.
The Genesis of Therapeutic Psilocybin
When discussing the origins of therapeutic psychedelics like psilocybin, it is vital to highlight that indigenous cultures have used mushrooms and other plants for sacramental and medicinal purposes for thousands of years. It’s just that the modern, scientific world finally caught on. In terms of the synthesis of psilocybin, Swiss chemist Albert Hofmann first isolated psilocybin in a lab in 1957. A year later, it was produced synthetically for the first time. For most of the 1950s and early 1960s, LSD (lysergic acid diethylamide) and psilocybin were researched and used to treat depression, PTSD, and addiction, among other mental health disorders and ailments. During this time of social upheaval, Timothy Leary and Richard Alpert, researchers at Harvard University, founded the Harvard Psilocybin Project. Their psychedelic use ranged from the Concord Prison Experiment, where inmates were given psilocybin to reduce recidivism, to “frequent” personal use. The project led the psychedelic movement and was quickly adopted into the 1960s counterculture. Regrettably, the stories of “bad trips” surrounded these new drugs – leading to national panic. In 1971, psilocybin was listed as a Schedule I drug in the U.S., making it illegal for all purposes.
The Psychedelic Movement Today
While psilocybin mushrooms have been decriminalized in three American cities, they are still illegal at the federal level and are categorized as a Schedule I controlled substance in the U.S. However, psilocybin has been studied extensively since the compound was granted Breakthrough Therapy designation for treating depression by the U.S. Food and Drug Administration. Through this fresh wave of research, magic mushrooms are starting to shed their old stigma. “In this new psychedelic age, the focus isn’t on ‘dropping out’ or rejecting mainstream culture; it’s about integrating intentional, measured, and responsible psychedelic use into our everyday lives,” according to psychedelic educational platform Third Wave. The organization adds, “Research is being conducted by many academic institutions and organizations, including MAPS, the Icahn Medical School Center for Psychedelic Psychotherapy and Trauma Research, and The Johns Hopkins Center for Psychedelic & Consciousness Research. Like the research in the 60s and 70s, studies are validating that psilocybin could have profound therapeutic effects.”
From healing post-traumatic headaches and anti-inflammatory use to treating mental health disorders and cognitive impairments, researchers have discovered that the therapeutic effects of psilocybin extend far beyond mystical experiences. These studies have effectively “broadened our understanding of the brain, the serotonin system, and the neurobiological basis of consciousness,” according to a recent literature review.
Psilocybin & the Brain: A “Reset” Button
According to Third Wave, psilocybin mushrooms (also known as “magic mushrooms” or “shrooms”) are fungi that contain the psychoactive compound psilocybin, capable of producing powerful hallucinations, changes in cognition and emotions, and other effects. Psychedelics such as LSD and psilocybin affect the brain’s serotonin system, primarily by binding to the serotonin 2A (5HT-2A) receptor. One study found, “An intake of psilocybin leads to significant 5-HT2AR (a subtype of the 5-HT2) occupancy in the human brain, and that both psilocin plasma levels and 5-HT2AR occupancy are closely associated with subjective intensity ratings, strongly supporting that stimulation of 5-HT2AR is a key determinant for the psychedelic experience.”
Psilocybin also decreases the metabolic activity of parts of the thalamus. Researchers hypothesize this underlies the sensory alterations associated with hallucinogens. As the thalamic filtering of information decreases, the infamous ‘doors of perception’ open wider. Dr. Jerrold Rosenbaum, the director of the Center for the Neuroscience of Psychedelics at Massachusetts General Hospital, tells Harvard Health, “Psychedelics induce the brain to change transiently in ways that appear to allow a reset to take place and permit alterations in previously stuck ways of feeling and thinking about things.” Rosenbaum reveals several ways in which psychedelics can accomplish these changes in the brain:
- New connections are briefly made in neural networks while the resting state of the brain (the “default mode network”) loses connectivity — then it restores itself. This action is how stuck patterns of thinking shift.
- New connections between neurons are formed, also known as neuroplasticity. Psychedelics like psilocybin have been found to increase BDNF production and neurogenesis.
- Psychedelics allow patients to enter a transient state where they can better process memories, feelings, and past trauma.
In terms of the “reset effect” of psilocybin, a recent study in the Proceedings of the National Academy of Sciences took a deep dive into how this process works in the brain. Scientists created a human brain model on psilocybin (based on brain images taken from participants), which showed that the brain creates a feedback loop of neuron activity and neurotransmitter release. This reaction allows the brain to tap into inaccessible states, including the “destabilization” of individual brain networks and creating a more global network across the brain. Morten Kringlebach, the study’s first author, tells Inverse, “Using this model will be crucial for truly understanding how psilocybin can rebalance neuropsychiatric disorders such as treatment-resistant depression and addiction.”
Psilocybin for Treatment-Resistant Depression: The Latest Research
Though psilocybin use is being studied for different mental health disorders, the latest research coming out of academic institutions is centering around the use of the compound for treatment-resistant depression. Case in point, Yale researchers uncovered that a single dose of psilocybin could cause structural changes in the brain – counteracting symptoms of depression. A recent study in J.A.M.A. Psychiatry also concluded that a randomized clinical trial found that psilocybin-assisted therapy was effective in producing significant, rapid, and sustained antidepressant effects in patients with major depressive disorder. Another 2021 study in the New England Journal of Medicine revealed that patients with moderate to severe major depressive disorder who received two doses of psilocybin did just as well, if not better, at six weeks than patients who received daily dosages of antidepressant medication.
These research studies are producing robust evidence for the use of psilocybin-assisted therapy. Still, there are many unanswered questions in this space. As psychedelics are prohibited in most states, “The growing popularity of their therapeutic potential is leading many people to use psychedelics on their own rather than waiting for legal, medical access,” states a BMC review. The report adds, “Many therapists are providing support for clients using psychedelics. However, incorporating psychedelics into traditional psychotherapy poses some risk given their prohibited status, and many therapists are unsure of how they might practice in this area.” With so many barriers, what does the future look like for psilocybin-assisted therapy?
The Third Wave
Tune in to the social audio app Clubhouse and the Psychedelic New Hour, and anyone can find out about what’s new in therapeutic psychedelics. You’ll hear about how researchers, therapists, non-profit organizations, and even silicon valley investors are finding ways to promote, fund, research, and educate about the psychedelic medicine movement. Listeners will also hear the results of personal experiments with psychedelics. From enhancing social ability to increasing focus and attention – the benefits of taking sub-threshold doses are wide-ranging. However, with powerful psychedelics comes great responsibility. “Despite their burgeoning promise in the field of research and psychiatry, psychedelic drugs are not yet considered to be mainstream medicine, and their use is still largely condoned only in experimental or monitored settings,” states Peter Grinspoon, MD in Harvard Health. Still, to meet the growing public demands about safe, structured, and responsible psychedelic use, organizations like Third Wave and its founder Paul F. Austin are working to share trusted, research-based content that helps individuals during their journey.
The organization’s name refers to the different waves of the psychedelic movement. Their website states, “The first wave of psychedelics saw indigenous communities around the globe using plant medicines for thousands of years. The second wave began with the invention of LSD that led to research into the uses of psychedelics, then suddenly ended when the U.S. government made all psychedelics illegal. The Third Wave is about integrating intentional, measured, and responsible psychedelic use into our everyday lives.” When asked about one of the biggest hurdles during this psychedelic wave, Paul Austin tells Endominance, “The biggest challenge in the legalizing of psilocybin mushrooms is education. There is an utter lack of education around these substances. And a lot of that is because of the war on drugs and the stigma put onto non-normative drugs, including cannabis. So with the legalization of cannabis, all of a sudden, we’re now saying, ‘Well, how are we objectively measuring drugs, and why might psychedelics be beneficial?'” Austin goes on to add, “Now it’s time to close the gap. It’s not a lack of research. We have thousands of papers from the fifties. It’s a lack of knowledge. In particular, the benefits around psychedelics, how they lead to neurogenesis and help treat depression, and how they’ve been used for millennia. So that’s why at Third Wave, we focus so much on education and teaching. Because in closing that gap, it helps to ensure that people learn how to use psychedelics responsibly and intentionally, ideally beginning at a microdose level.”
Microdosing: Benefits and Limitations
Alongside the psychedelic renaissance is a popular protocol known as microdosing. Microdosing is the act of integrating sub-perceptual doses of psychedelics, such as psilocybin mushrooms, into an individual’s weekly routine. A microdose is typically 5-10 percent of a standard dose of a psychoactive substance. Third Wave states, “The story of microdosing began with James Fadiman, Ph.D., and his book, The Psychedelic Explorer’s Guide: Safe, Therapeutic, and Sacred Journeys, which explores microdosing as a subculture of psychedelic use. In 2015, Fadiman gave a podcast interview with entrepreneur, “bio-hacker,” and author Tim Ferriss, which introduced microdosing to his fans and attracted mainstream journalists’ attention.”
As far as the act of microdosing, the trickiest and controversial part is estimating how much psilocybin is in a particular mushroom. Different species and strains of mushrooms have varying quantities of psilocybin. For example, Psilocybe cubensis, the classic magic mushroom, a typical microdose is 0.1 to 0.3 grams, although that amount may be smaller for people with clinical issues. Though Third Wave offers in-depth guides and education on microdosing, the organization highlights the legalities, challenges, and unknowns associated with the protocol.
The Future of Psilocybin-Assisted Therapy & Integration Practices
Psilocybin therapy and integrative practices are on the cusp of a colossal shift. In November 2020, Oregon became the first state to legalize the therapeutic use of magic mushrooms (Ballot Measure 109). Currently, the state is in a two-year development period in which a state advisory board is ironing out the rules and regulations for psilocybin therapy, according to Oregon news station KGW8. During this time, members of the Oregon Psilocybin Advisory Board will now be working with a psychedelic research center at Harvard Law School directed by Mason Marks. Together, they will be producing a comprehensive report on the psychedelic’s science, history, and culture as regulators prepare to license facilities to administer it. Marks told Marijuana Moment, “To the extent that the report can help inform their decision making, it should be made available for that purpose. Hopefully, it can provide a bit of a roadmap for fruitful collaboration between states and the federal government.” States like California and Colorado are following similar paths to legalizing psychedelic therapy.
Integrating the Experience
spoke with Stephanie Podasca, licensed mental health counselor and owner of Whole Sky Therapy, to better understand psilocybin-assisted therapy. Podasca’s practice incorporates psychedelic integration therapy, which offers safe preparation, education, and meaningful integration of a client’s psychedelic journey or microdosing protocol. When asked how a session can help patients who are microdosing, Podasca offers, “Sessions that occur before, during, and after someone’s microdosing protocol can serve the client in a number of beneficial ways. Firstly, it’s helpful to track if the microdosing is having a positive, negative, or neutral impact on the client’s original goals. Secondly, working with a therapist or coach can help someone connect more deeply to any emotional, mental, or physical changes they notice and feel.”
She goes on to add, “In my personal experience, I notice that clients begin to feel a bit more open to talking about difficult emotions or experiences. They seem to be more willing to try new things in sessions such as mindfulness practices, expressive arts, or somatic-focused therapy. This openness brings about greater self-awareness and curiosity for one’s experience. To some degree, it has helped them break through the fog of anxiety and depression that keeps holding them back from feeling more connected to their life and relationships.” Podasca ends with, “Lastly, these sessions bring attention to the wholeness of someone’s life experience using a holistic model that includes body, mind, spirit, community, and creativity. Like taking other psychotropic medications for mental health issues, it’s crucial that microdosing doesn’t happen in isolation. It takes the whole system of the person to work together for them to create and see the changes they need.”
A Call for More Research
According to Psychedelic Support, “With limited research, questions around safety are important for microdosers to consider. Classical psychedelics like psilocybin and LSD have low toxicity and few serious adverse events. When significant adverse events do occur, they arise because of poor adherence to guidelines around set, setting, and dosing. Pre-existing mental health conditions, such as psychosis-related disorders, can also be a risk factor for negative effects.” The need for blinded and controlled trials in this area is crucial. “Survey data and anecdotal reports are leading to new avenues of drug development research. Through these reports, questions around the safety of repeated use or psychological dependence will be addressed,” states Psychedelic Support.
Disclaimer: The information provided on the site is for educational purposes only and does not substitute for professional medical advice. Consult a medical professional or healthcare provider if you are seeking medical advice, diagnoses, or treatment for any medical condition or disorder.
