Accessibility Is Key for the Psychedelic Revolution

Psychedelics are being touted as a revolutionary mental health treatment, because of their broad efficacy, fast onset, and long-duration benefits.¹

However, psychedelics cannot be revolutionary therapeutics if patients cannot easily access them. Indeed, the use of psychedelic drugs as medications, albeit promising, may be restricted for various reasons to a select few.

Globally, millions, or by some accounts even billions, of individuals suffer from mental health disorders, including more than 20% of Americans.² Despite the pervasiveness, treatments have long been insufficient for many patients struggling with disorders, such as anxiety, depression, and substance use disorder, a disconnect further exacerbated by the COVID-19 pandemic. Long a pariah to the medical establishment and society, psychedelic-assisted therapies are now hailed at drug discovery conferences and by mainstream media outlets as potentially miraculous cures for patients suffering from a wide variety of illnesses. Compounds such as DMT (“the spirit molecule”), LSD (acid), or psilocybin (magic mushrooms) through both anecdotal reporting and increasingly formal study, have been shown to achieve remarkable efficacy for diseases as disparate as cluster headaches and treatment-resistant depression and cluster headaches.³ Additionally, psychedelic-assisted therapies seem to help many patients previously unresponsive to medications, and some can do so within 24 hours after a single dose with long-lasting effects that can endure for weeks. These data herald an exciting era of putative fast-acting relief to the many patients suffering from mental health disorders.

Unfortunately, by their nature, psychedelics may be limited in terms of the number of patients they can help. The profound affective and sensory changes eponymous with their name inherently restricts the number of patients who are able, or willing, to take them. For patients with symptoms of psychosis, like those with bipolar disorder and schizophrenia, or even patients with a family history of a psychotic disorder, psychedelics may be contraindicated, because of the risk that their symptoms may be exacerbated or initiated by these experiential medicines. Further, strong feelings of anxiety can emerge during a hallucinogenic experience. Psychedelics have been shown to induce strong feelings of fear in more than 30% of healthy volunteers.⁴ Thus, patients who have a history of panic attacks or other types of anxiety disorders will likely be advised to avoid these treatments. In addition, patients with dementia have diminished cognitive capacity, which can prevent the establishment of the rapport needed between patients and therapists that is often required to accompany the taking of psychedelics. These patients may exhibit strong negative reactions to hallucinations and may be deemed ineligible for this class of therapeutics, despite the clear need and potential benefits they could otherwise gain. Sadly, in addition to Alzheimer disease, dementia can be a part of many disorders, including Lewy body dementia, Parkinson disease, traumatic brain injury, and vascular dementia, and mild forms may exist for years before a formal diagnosis. Thus, taking these medications could be problematic for patients with even mild, potentially undiagnosed dementia.

In addition, psychedelic therapies present cardiovascular risks to many patients. Most psychedelic compounds are agonists at 5-HT2B receptors. Repeated administration of 5-HT2B agonists can cause cardiac valvulopathy.⁵ Although infrequent administration of psychedelics may mitigate these issues, their use may be contraindicated in patients with certain cardiac conditions.

Thus, because of a variety of symptoms, many patients who could potentially benefit most from this class of therapeutics will necessarily be excluded, based on long-standing guidance in the medical community, from having them prescribed by a licensed medical professional.

Beyond the medical limitations, financial and personal reasons will further restrict the number of patients who can benefit from psychedelic therapies.

Some, especially those who grew up in the era of the “war on drugs,” may simply not be comfortable experiencing hallucinogenic effects under any circumstance.

Other patients may object to psychedelics for moral or religious reasons, while others may be wary of the heightened state of personal and physical vulnerability induced by psychedelics.

Even for the able and willing, there will be significant financial barriers to access. Because of safety considerations, psychedelics must be administered in a clinic under the supervision of multiple health care professionals, with several visits needed for full efficacy. Multiple visits with multiple therapists greatly increase the cost of treatment, further restricting accessibility to those who can afford it, much in the same way that expensive rehabilitation centers are only accessible to those most fortunate to afford them. This leads us to a particularly plausible scenario where treatment with psychedelic medications is limited to the few who want to take them, can be medically cleared, and can afford them.

Yet there is great hope for treatments with the transformative nature of hallucinogenic psychedelics but without the financial and physical limitations. Recently, scientists have deepened our understanding of the remarkable therapeutic effects of psychedelics and can dissociate their benefits from their baggage. Psychedelics alter the structure of key neurons in the brain, and these morphological changes occur independently of their hallucinogenic activity. Indeed, it has been discovered that psychedelics belong to a more general class of compounds called psychoplastogens, which are small molecules that rapidly promote robust functional and structural neural plasticity in key circuits relevant to brain health with an enduring benefit over weeks or even months without chronic administration. In an exciting recent development, multiple scientists have identified psychoplastogens that are unlikely to produce hallucinations.^6,7 Further, some of these novel psychoplastogens do not carry the same cardiovascular risk as first-generation psychedelic drugs. Thus, this new class of non-hallucinogenic psychoplastogens would not have the same restricted access as classic psychedelic drugs and could possibly be safe enough to keep in the medicine cabinet. This represents an evolution of the psychedelic revolution that would bridge the gap between the pitfalls and power of psychedelics, bringing accessibility to the world of psychoplastogens and democratizing access to transformative therapeutics.

More treatment options are needed for the massive number of patients suffering from mental health disorders across the world. Psychedelic-assisted therapies, as the many companies working on them are proving each day, will offer new options for some of these patients.However, it is vital that more accessible, non-hallucinogenic, neuroplasticity-promoting medications are also available to ensure the remaining patients in need can also benefit.

References

1. Vargas MV, Meyer R, Avanes AA, Rus M, Olson DE. Psychedelics and other psychoplastogens for treating mental illness. Front Psychiatry. 2021;12:727117. doi: doi:10.3389/fpsyt.2021.72711

2. Mental health by the numbers. National Alliance on Mental Illness. Updated June 2022, Accessed July 15, 2022. https://www.nami.org/mhstats

3. Dos Santos RG, Hallak JEC. Therapeutic use of serotoninergic hallucinogens: a review of the evidence and of the biological and psychological mechanisms. Neurosci Biobehav Rev. 2020;108:423-434. doi:10.1016/j.neubiorev.2019.12.00

4. Griffiths RR, Richards WA, McCann U, Jesse R. Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance.Psychopharmacology. 2006;187(3):268-283. doi:10.1007/s00213-006-0457-5

5. 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 Pathology. 2008;60(4-5):253-262. doi:10.1016/j.etp.2008.03.005

6. Olson DE. Psychoplastogens: a promising class of plasticity-promoting neurotherapeutics. J Exper Neurosci. 2018;12:1179069518800508. doi:10.1177/1179069518800508

7. Cao D, Yu J, Wang H. Structure-based discovery of nonhallucinogenic psychedelic analogs. Science. 2022;375(6579):403-411. doi:10.1126/science.abl8615