Humanity’s interest in a different way of life and a better existence is growing. Mushrooming. Our timing on this couldn’t be better or more urgent as we are currently slogging through an ongoing pandemic and a nationally divided political landscape with the “scandal of our times” looming ahead, if there’s even a 2020 election.
War, famine, poverty, homeless, racism, greed. Words like these are already ugly enough without becoming or remaining our daily reality. Add in presidential tweets, necrocracies, aristocracies, a threat around every corner, or warnings to “Save Lives, Stay Home”, and it’s not really shocking that so many of us around the globe are confused, anxious, depressed, hopeless.
The search for substances that can rapidly help bring about a paradigm shift in our mental health is not only paramount, it’s actively evolving as we speak. The molecular portfolio is broadening to include drugs that have either been previously labeled as devoid of medicinal value (Schedule I drugs like lysergic acid diethylamide (LSD), cannabis, or psilocybin) or so-called “club drugs” that have been recognized as breakthrough drugs (i.e. ketamine).
Amazingly, there are now companies that are based around the development of novel psychedelics for mental health applications. Recently, I spoke with Ian McDonald, Founder of Bright Minds Biosciences, a group of veteran drug hunters that are looking to change the template for the treatment of depression.
“In 2015, I began to appreciate the potential for psychedelics as a class of drugs to transform mental health treatment,” McDonald said. “The further down the rabbit hole I went, it became clear that these medicines could be improved upon and targeted for specific diseases by removing side effects and maximizing the therapeutic benefit.”
“I was lucky enough to speak with the top researchers in the field,” he continued. “Through those relationships, we formed an all-star team of psychedelic drug designers and developers who are creating novel psychedelics every day!”
The standard methodology for treating depression includes a daily dose of medication, an onset measured in weeks, required daily dose to feel the effects of the medication, long-term treatment with the risk of relapsing should the medication be discontinued, and the risk of withdrawal.
Bright Minds wants to accomplish an alternative way of treatment such that patients get better, faster, and where the positive effects of the drug are felt long after it’s been taken, without withdrawal.
“Today, the first drug a doctor will prescribe you for a mental health disorder is a SSRI [selective serotonin reuptake inhibitor] like Prozac®,” McDonald replied. “The issue is that about one-third of patients don’t get better and the ones that do are often burdened with undesirable side effects like loss of personality, sexual dysfunction, and/or weight gain.”
Despite these potential issues, McDonald says that there’s been little to no innovation in the last 30 years for these disorders. “Psychedelics offer a new treatment paradigm: instead of pill a day, you undergo a psychedelic therapy session and we’ll have a remission in symptoms for some time. Think of it as an electrochemical reset of your brain. In a depressed brain, the wiring is off. Psychedelics fix that almost immediately.”
In addition to treating depression, McDonald and Bright Minds are also looking to take on cluster headaches, a disease with a tremendous unmet medical need. Roughly one in a thousand people experience cluster headaches, and the pain these people experience is agonizing and often unbearable.
“It’s the worst pain known to humankind,” McDonald added. “So bad that if you have cluster headache, you are 10 to 20 times more likely to commit suicide. We believe that we are well on our way to developing a novel preventative treatment for these sufferers.”
Phantom Nerve Pain, Inflammation, and Beyond
McDonald says another application of psychedelic pain treatment that’s shown promise is for phantom nerve pain, where amputees experience ongoing painful sensations that seem to come from the part of the limb that’s no longer there. Traditional medications used for treating phantom pain include antidepressants, anticonvulsants like gabapentin, and opioids like morphine. Interestingly, ketamine has proven to be beneficial.
“Recently, we’ve entered into a partnership with the National Institutes of Health to develop drugs for pain management,” Ian added. “We’re are also in discussion with them to evaluate our novel compounds for other areas such as seizures.”
The possibilities don’t end with depression, cluster headaches, phantom nerve pain, or seizures. “The anti-inflammatory effects of psychedelics are real,” McDonald continued. “A company called Eleusis is working on LSD to treat Alzheimer’s disease.”
Interestingly, to experience the effects of LSD (and psilocin or mescaline), a specific receptor called 5-HT2A must be activated. This receptor is also involved in immune function, and agonists of this receptor, such as LSD, suppress inflammation.
The Safety of Synthetics
Naturally, many people wonder about the safety of molecules created in labs, especially given the stories regarding synthetic cannabinoids in products like Spice. Unfortunately, an internet search of the most common synthetic drugs litters the screen with discussions on illegal substances like ecstasy or LSD, but the term “synthetic” refers to anything created from man-made ingredients – a chemical synthesis. And chemical synthesis innovates modern pharmaceutical drug design, hence the term, design. The nomenclature can be misleading (synthetic drug versus drug synthesis; designer drugs versus drug design).
“The safety of a synthetic molecule really depends on the molecule you are synthesizing,” McDonald added. “As an example, psilocybin has cardiotoxic effects associated with its activation of the 5-HT2b receptor. [1,2] Our improved versions are designed to eliminate this risk, thus making the novel compounds safer.”
The Future is Now
How will this soaring interest in psychedelics turn out? Will more people have access to these types of molecules such that they, too, can evolve to a more harmonious life with less pain, less mental unrest, and perhaps more focus?
“This question is all about the regulatory State of Affairs,” McDonald answered, “and as it stands today and for the foreseeable future, legal access will be granted to drugs that make it through the FDA [US Food & Drug Administration] pathway and into prescription medications which anyone will be able to receive through their doctor. If you are investing in the sector, place your bets on innovative R&D focused biotechnology companies developing second generation psychedelics.”
“There are some grassroots campaigns today like TheraPsil in Canada but expect progress to be slow,” McDonald concluded. “What we saw with medical cannabis is a long way off for psychedelics. Someday, psychedelics will be legal, but not soon enough…”
- Elangbam CS, Job LE, Zadrozny LM, et al. 5-hydroxytryptamine (5HT)-induced valvulopathy: compositional valvular alterations are associated with 5HT2B receptor and 5HT transporter transcript changes in Sprague-Dawley rats. Exp Toxicol Pathol. 2008;60(4-5):253-262. [journal impact factor = 2.023; times cited = 73 (Semantic Scholar)]
- Hutcheson JD, Setola V, Roth BL, Merryman WD. Serotonin receptors and heart valve disease–it was meant 2B. Pharmacol Ther. 2011;132(2):146-157. [journal impact factor = 10.557; times cited = 129 (Semantic Scholar)]