Psychedelic startups are betting on synthetic versions of psilocybin "magic" mushrooms as the future
The trend of using "magic" mushrooms, which contain the psychedelic compound psilocybin, is on the rise in North America, evidenced by the emergence of mushroom dispensaries and the legalization of psychedelic therapy in several states.
Despite this modern fascination, the use of these fungi dates back thousands, if not millions, of years, with ancient humans likely turning to them for their potential to enhance creativity, and spiritual connection, and to combat mental health issues such as depression and anxiety.
Recognizing psilocybin's therapeutic potential, the U.S. Food and Drug Administration (FDA) has granted it "Breakthrough Therapy" status twice, accelerating its path through the drug approval process. Although it's projected to receive FDA approval by 2026, its current legal status at the federal level remains illegal.
Future psilocybin therapies might not involve natural mushrooms but could rely on synthetically produced psilocybin.
This raises questions about the differences between the natural and synthetic forms, especially as some believe that the natural mushrooms' complex chemical makeup might offer a more profound experience, known as the "entourage effect." This concept suggests that the combination of compounds in magic mushrooms works together to produce a more significant effect than psilocybin alone.
Despite the challenges posed by federal laws, some companies are investing heavily in researching the entourage effect, believing that natural mushrooms might offer a unique therapeutic potential. Over 180 species of psilocybin-producing mushrooms exist, each developed not for human use but possibly as a defense mechanism against pests. The similarity between psilocybin and the neurotransmitter serotonin is what allows these mushrooms to affect human brains.
Interest in the entourage effect extends beyond psilocybin, with research into other psychedelics like ayahuasca showing potential benefits from a combination of compounds. However, the pursuit of these natural compound formulations raises concerns about the motives behind pharmaceutical companies' interests, with some fearing that profit rather than patient benefit drives the research.
As the debate between natural and synthetic psychedelics continues, what remains clear is the ancient and ongoing human interest in these substances for their mind-altering and potentially therapeutic effects. The future might see a blend of natural and synthetic approaches to psychedelic therapy, as researchers work to uncover the full potential of these complex compounds.
A recent study discovered that a single dose of synthetic psilocybin, the active compound in magic mushrooms known for its mind-altering effects, showed promising results in alleviating depression among individuals with treatment-resistant depression.
Conducted as a randomized, double-blind clinical trial, the study compared the effects of different doses of a synthetic psilocybin named COMP360. The trial, regarded as the largest of its kind, administered doses of 25 milligrams, 10 milligrams, and 1 milligram in the presence of trained therapists.
Published in The New England Journal of Medicine, the study revealed significant and rapid improvements in depression symptoms among participants who received the 25-milligram dose of COMP360. Dr. Guy Goodwin, a coauthor of the study and a professor emeritus of psychiatry at the University of Oxford, emphasized the immediate and sustained response observed with this dosage.
The synthetic compound COMP360, distinct from naturally occurring psilocybin extracted from mushrooms, is chemically synthesized to produce a crystalline form. Dr. Matthew Johnson, a professor specializing in psychedelics and consciousness at Johns Hopkins Medicine, noted the clinical significance of the dose-response relationship observed in the study.
However, despite the promising results, experts underscored the need for further research to address certain concerns before the drug could be considered for widespread clinical use. Dr. Anthony Cleare, a professor of psychopharmacology and affective disorders at King's College London, highlighted the necessity of investigating potential side effects and strategies to prevent relapse after treatment.
The study involved 233 participants with treatment-resistant depression across multiple sites in North America and Europe.
Participants were required to discontinue antidepressant medications prior to the trial to ensure the efficacy of psychedelic treatment, as antidepressants saturate the brain's serotonin receptors, hindering the action of psychedelics.
Psychological support was provided throughout the psychedelic sessions, which lasted several hours, and additional therapy sessions were conducted in the following weeks. While significant improvements were observed in depression symptoms immediately after treatment, the effects diminished over a 12-week period.
Despite the observed benefits, safety concerns were raised regarding adverse effects such as headaches, nausea, and fatigue, which were reported by a majority of participants. Additionally, a small number of individuals experienced suicidal thoughts or self-injury during the follow-up period, emphasizing the importance of careful monitoring and risk assessment in future trials.
While the psilocybin study results are promising, uncertainties remain regarding the effectiveness of COMP360 compared to existing treatments for depression. Further research is needed to address these uncertainties and determine the potential of psychedelic therapy as a viable treatment option for various forms of depression.
A recent study published in the New England Journal of Medicine suggests that psilocybin, the active compound found in magic mushrooms, could offer promising prospects in the treatment of depression.
Researchers conducted a randomized trial involving adults suffering from treatment-resistant depression, wherein a one-time dose of synthetic psilocybin was administered. Dr. Steve Levine, senior vice president at Compass Pathways, explained that patients in the study had previously tried various medications without success.
Psilocybin participants were divided into groups receiving different doses of psilocybin—25 mg, 10 mg, or 1 mg (as the control group). Alongside the doses, patients received psychological support, and the administration took place in the presence of therapists. Three weeks post-dose, depression levels were evaluated using the Montgomery–Åsberg Depression Rating Scale (MADRS). Results showed a significant reduction in depression scores, with the 25 mg group experiencing an average drop of 12 points, compared to 7.9 points for the 10 mg group and 5.4 points for the control group.
Dr. Levine emphasized that the 25 mg dose induced a psilocybin psychedelic experience and highlighted the importance of administering psilocybin in a supervised medical setting conducive to therapy. Sessions lasted six to eight hours, during which patients wore an eyeshade and listened to curated music playlists. Additionally, a therapist provided support throughout and engaged with patients post-session.
Remarkably, the study demonstrated that a single dose of psilocybin could yield therapeutic effects, unlike conventional antidepressants that require daily intake
However, while initial remission was observed in the 25 mg group at three weeks, this effect did not persist at the 12-week mark.
Furthermore, adverse effects were reported by a significant number of participants, including headaches, nausea, and dizziness. Notably, suicidal ideation or behavior occurred across all dosage groups, underscoring the severity of treatment-resistant depression.
Bertha Madras, a professor at Harvard Medical School, penned an editorial accompanying the study, expressing both interest and caution regarding the findings. Despite acknowledging the short-term benefits of psilocybin in select populations, Madras raised concerns about its potential risks.
Currently, the psilocybin study is advancing to phase 3, focusing on further evaluating the efficacy of the 25 mg dosage. Dr. Levine suggested that if psilocybin were to become a regulated medication, it would likely be administered in a similar manner—under specialized supervision in medical settings.
In a separate context, states like Oregon and Colorado are exploring legislative measures concerning the decriminalization and regulated use of psilocybin, indicating a growing interest in psychedelic-assisted therapy as a potential avenue for mental health treatment.
The trend of using "magic" mushrooms, which contain the psychedelic compound psilocybin, is on the rise in North America, evidenced by the emergence of mushroom dispensaries and the legalization of psychedelic therapy in several states. Despite this modern fascination, the use of these fungi dates back thousands, if not millions, of years, with ancient humans likely turning to them for their potential to enhance creativity, spiritual connection, and to combat mental health issues such as depression and anxiety.
Recognizing psilocybin's therapeutic potential, the U.S. Food and Drug Administration (FDA) has granted it "Breakthrough Therapy" status twice, accelerating its path through the drug approval process. Although it's projected to receive FDA approval by 2026, its current legal status at the federal level remains illegal.
Future psilocybin therapies might not involve natural mushrooms but could rely on synthetically produced psilocybin.
This raises questions about the differences between the natural and synthetic forms, especially as some believe that the natural mushrooms' complex chemical makeup might offer a more profound experience, known as the "entourage effect." This concept suggests that the combination of compounds in magic mushrooms works together to produce a more significant effect than psilocybin alone.
Despite the challenges posed by federal laws, some companies are investing heavily in researching the entourage effect, believing that natural mushrooms might offer a unique therapeutic potential. Over 180 species of psilocybin-producing mushrooms exist, each developed not for human use but possibly as a defense mechanism against pests. The similarity between psilocybin and the neurotransmitter serotonin is what allows these mushrooms to affect human brains.
Interest in the entourage effect extends beyond psilocybin, with research into other psychedelics like ayahuasca showing potential benefits from a combination of compounds. However, the pursuit of these natural compound formulations raises concerns about the motives behind pharmaceutical companies' interests, with some fearing that profit rather than patient benefit drives the research.
As the debate between natural and synthetic psychedelics continues, what remains clear is the ancient and ongoing human interest in these substances for their mind-altering and potentially therapeutic effects. The future might see a blend of natural and synthetic approaches to psychedelic therapy, as researchers work to uncover the full potential of these complex compounds.