After decades of inactivity, scientific research on psychedelic drugs is resuming and gaining popularity. From Michael Pollan’s best-selling book, “How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence,” which was made into a Netflix docu-series, to being featured on “Last Week Tonight with John Oliver,” an alternative medicine renaissance seeking to push the boundaries of psychiatry, pharmacology, and brain science has renewed public interest in psychedelic drugs like LSD and “magic mushrooms.”

Words like “magic mushrooms,” “LSD,” and “psychedelic,” (meaning “mind manifesting”) have commonly been associated with hippies, flower power, and the beatnik poets of the 1960s and 70s as well as acid flashbacks and psychotic breaks.

The counterculture movement of the 60s and 70s was a phenomenon of societal disruption, youthful expressions of freedom, and rebellion against authority. In response, the U.S. federal government, particularly the Nixon administration, felt a need to maintain law and order and limited access to psychedelic drugs.

In 1970, President Richard Nixon declared a global “War on Drugs” by signing the Controlled Substances Act into law. This deemed substances with a “high potential for abuse” and “no currently accepted medical use” Schedule 1. Drugs such as psilocybin, MDMA, marijuana, mescaline (peyote), bath salts, quaaludes, GHB, and heroin, are examples. The U.S. government pressured allies the world around to follow suit. The funding and presence of drug control agencies grew rapidly, penalties for law breakers increased, and the era of mass incarceration was born.

Caught in the crossfire of the “culture wars” and legal battles over psychedelic drugs, were serious (and sometimes well-intentioned but not so serious) research efforts going on in legitimate institutions around the world looking into these mysterious substances that seemed to have incredible mind-altering power.

While it is estimated that more than 1000 scientific articles regarding various hallucinogens (another term for psychedelics) were published from 1950-1975, that all came to a grinding halt. Recently scientists have begun the painstaking process of unearthing the psychedelic research of the past and rediscovering the therapeutic benefits psychedelic drugs may offer patients.

One of the first organizations to receive approval for federal funding of research into the potential medical uses of psychedelics in the United States is the Johns Hopkins Center for Psychedelic and Consciousness Research (CPCR), founded in 2000. Their stated mission is “to advance the scientific understanding of psychedelics and their potential for treating mental health disorders, enhancing well-being, and expanding our understanding of consciousness.” One area of interest and promise is “magic mushrooms,” known in the scientific community as psilocybin.

Psilocybin (metabolized in the body as psilocin) is the compound found in certain kinds of mushrooms, many of which belong to the genus psilocybe, which has a mind-altering effect. The effects are usually described as highly variable but generally euphoric with changes in mental and visual perception. This description does little to convey the powerful intensity of experience these innocuous little brown mushrooms can bring about. Researchers are investigating a whole host of potential applications of psilocybin including treating anxiety, depression, obsessive compulsive disorder, addiction, eating disorders, and more, and using their findings to learn more about the brain and consciousness in the process.

Current research is largely built off the astonishing findings from the CPCR’s very first publication that found that psilocybin can produce enduring positive effects in “healthy normals,” a term used to describe people in relatively good health of mind and body. The 2006 landmark study published in the NIH Journal of Psychopharmacology found that a single dose of psilocybin can occasion “mystical-type experiences” which had “substantial and sustained personal meaning and spiritual significance.”

Participants ranked the psilocybin experiences as among the most meaningful in their lives, comparable to “the birth of a first child or death of a parent.” Two thirds regarded the experiences as one of the “top five most spiritually significant experiences,” and one third called it the single most spiritually significant experience of their life. Follow up data from more than a year later shows lasting improvements in “personal well-being, life satisfaction, and positive behavior change.”

Much of the mechanistic neurobiology and related brain function is still a mystery needing explanation. Psilocybin, along with a few other notable classic psychedelics like lysergic acid dythalimide-25 (LSD) and dimethyltryptamine (DMT) are understood to interact with areas of the brain built for neurotransmitters. These three compounds, known as tryptamines, have chemical structures that bear a striking resemblance to serotonin, and act on the same 5-HT2A receptors in the brain. Serotonin is an important neurotransmitter known to relate to mood, learning, feelings of reward, memory, and other changes in the brain.

Researchers at CPCR and elsewhere are finding that participants who had the most complete mystical experience had the most positive therapeutic effects. This suggests the important mechanisms at play may not really be a pharmacological matter of molecules interacting with receptors. Instead, understood through an experiential lens, it is the profundity of the mystical experience that these compounds can occasion which leads to lasting psychological change.

It is with these realizations in mind that have led some media outlets to describe this style of work as “applied mysticism” or “modern shamanism.” Participants, once they’ve taken their synthetic psilocybin in pill form from a ceremonial looking chalice, are usually in relaxing environments with low lighting. They lie on a couch with eye shades and headphones listening to soothing music. Sitters carefully observe the participant and offer gentle reassurance and encouragement.

Sitters (also known as guides) refer to the long established “flight instructions” designed from first wave psychedelic research. They offer mantras such as “trust the trajectory,” or “trust, let go, be open.” Guides are taught to inform participants they will not be left alone and that “if you feel like you are dying, melting, dissolving, or exploding – go ahead.” Participants are told they may experience “death or transcendence of your ego or everyday self,” but to trust it is always followed by “rebirth to normative space and time,” and that “the safest way to return to normal is to entrust yourself unconditionally to the emerging experience.”

Conventional researchers like to see nice clean explanations of cause and effect, not airy notions of personal meaning and spiritual significance. Scientists have been seeking to understand what psychological elements are at play during one of these so-called mystical experiences by performing a “interpretative phenomenological analysis.” Published in the Journal of Humanistic Psychology in 2017, researchers reviewed transcripts from psilocybin assisted therapy sessions and concluded nearly all sessions included certain central themes.

Relational embeddedness was described as having insights or transformative realizations regarding significant personal relationships. One participant fondly reimagined his daughters as “beings of radiant light.” Emotional range includes positive emotions of great breadth and depth beyond what they were able to experience in their daily lives, as well as difficult emotions like temporary feelings of despair, fear, or sadness. One participant was quoted as saying they felt like they “experienced all of the emotions I know how to experience.”

Many participants made claims regarding the importance of “experiential understanding,” regarding certain “wisdom lessons” like the nature of space-time, the interconnectedness of all things, and the role of love in the universe. Other common themes included meaningful visual phenomena, music as a conveyor of experience, and revised life priorities.

Roland Griffiths is a longtime Johns Hopkins researcher and one of the principal investigators and program director at CPCR. As a respected psychopharmacologist, he studies the effects various substances have on people’s minds and behavior. His numerous publications on caffeine and addiction in the past have led to the addition of caffeine withdrawal syndrome to the American Psychiatric Associations (APA) mental disorders comprehensive manual, the DSM-5.

Griffiths reflects on that 2006 psychedelics study: “For me the data from those first sessions were, I don’t want to use the word mind blowing, but it was unprecedented the kinds of things we were seeing there, in terms of the deep meaning and lasting spiritual significance of these effects. I’ve given lots of drugs to lots of people, and what you get are drug experiences. What’s unique about psychedelics is the meaning that comes out of the experience.”

Armed with the knowledge that beneficial mystical experiences can be induced reliably and safely in the lab, researchers turned their attention towards patients in clinical settings to discover novel therapeutics.

In 2016, researchers at NYU and Johns Hopkins conducted two placebo controlled randomized trials and published them as a pair in the Journal of Psychopharmacology. These studies found that a single dose of psilocybin produced “rapid and sustained” clinically significant reductions of anxiety and depression in patients with life threatening cancer diagnoses in 60-80 percent of participants. Six months later, as many as 80 percent or more reported a moderate or greater increase in well-being and life satisfaction.

No other psychiatric intervention has ever demonstrated this degree of success to date. By comparison, a current common depression medication, like SSRIs, when first introduced were approved with approximately one third of the effect seen in these trials. The work was endorsed by numerous leaders in the field of psychiatry, including two past presidents of the APA who described the work as showing “much potential for new scientific insights and clinical application.”

Jeffrey Guss, psychiatrist and co-author on the “interpretative phenomenological analysis” paper describes what he interprets as the “egolytic,” or “mind loosening” effects of psilocybin. Under the spell of the mushrooms, patients may allow themselves to “let go of rigid patterns of thought, allowing us to perceive new meanings with less fear.” While the sample size was relatively small, 80 participants total between the two, these 2016 studies represent the largest and most rigorous of their kind to date. Researchers hope to build from these trials to establish a basis for new standards of palliative care.

Mood disorders are common among cancer patients and treating them is hypothesized to improve outcomes, not just help patients experience a more peaceful death. Anxious and depressed patients are less likely to adhere to treatment, have increased rates of disability, pain, feelings of hopelessness, rates of suicide, desire for a hastened death, and decreased quality of life, social function, and survival rates.

Research is now expanding these findings into experimenting on treatment possibilities for other incurable or psychologically distressing diseases like Alzheimer’s, Lyme disease, and Fibromyalgia. In 2020, researchers at CPCR expanded their work to those diagnosed with major depressive disorder. The World Health Organization estimates 5 percent of people suffer from depression, some 280 million globally. The study published in JAMA Psychiatry found that one month after psilocybin-assisted psychotherapy more than 70 percent demonstrated clinically significant improvements and more than half were deemed in remission.

Researchers at Imperial College in London conducted a few psilocybin studies inspired by the CPCR’s work which found improvement in all participants who had treatment-resistant depression after one week and more than half still showed benefit after three months. The first study was published in Lancet Psychiatry in 2016. Both of these small studies showed “marked and rapid” benefits with no adverse responses, leading the drug research regulatory bodies in Europe to approve much larger studies.

One notable observation from the follow up data from Imperial College studies is that over time symptoms returned in nearly half of participants. This suggests the potential need for repeated doses and investigations into long-term effectiveness. Despite this sober reminder that these substances are not a one and done panacea, researchers are still optimistic that carefully controlled and ethically practiced psychedelic treatments could revolutionize mental health care.

While still only scratching the surface, the resurgence in psychedelic research is showing intense promise. Researchers caution their scientific peers and journalistic coverage of the experiments to keep a level head. These compounds are not wonder drugs, and we have a lot left to learn.