Is America Tripping?

How psychedelics may gain FDA approval

Earlier this year, Donald Trump signed his 475th executive order. This one, unlike many others from the start of his term, is not a hyperpartisan example of executive overreach.  Instead, it genuinely supports an emerging area of pharmaceutical research. The order directs the Food and Drug Administration (FDA) to establish more concrete guidelines for testing psychedelic drugs as treatments for select mental health conditions.

Psychedelics have come to the forefront of the pharmaceutical industry due to breakthrough treatments but have encountered hurdles on the path to approval. While visiting St Andrews, Professor Marco Scarselli, a psychedelics researcher at the University of Pisa, answered some emerging questions about the field. The main treatment approach, Scarselli explained, is to give a calm patient a controlled dose of a drug like psilocybin (the active compound in magic mushrooms) large enough to noticeably alter perception. This has two main effects that aid treatment: increased neuroplasticity and psychedelic effects.

Neuroplasticity, or the brain’s ability to rewire itself, is much higher in children, who quickly pick up languages, motor skills, and reasoning. Psychedelics can temporarily boost this effect even in adults, helping people break entrenched rumination patterns and adopt healthier thinking patterns.

Psychedelic effects are the altered perceptions and thoughts people often associate with these drugs. Though researchers control the dose to avoid full hallucinations, the aim is still to change patients’ perceptions. Scarselli explained that psychedelics do this by decreasing activity in the thalamus, the part of the brain that filters information. Just as a tap on your shoulder can go unnoticed if your focus is elsewhere, changes in how the brain processes information can affect what we notice and how we interpret it. This, combined with lower prefrontal cortex activity (the part of the brain that judges, plans, and makes decisions), allows people to discover the roots of their biases, thoughts, and feelings.

Importantly, Scarselli said these drugs can have lasting impacts for weeks or even months, unlike current antidepressants, which are taken daily. Pairing this shift with psychotherapy shows promise for lasting change in patient behaviour.

Unfortunately, these drugs struggle in the current pharmaceutical system. Many psychedelics, such as peyote, LSD, and MDMA, are designated Schedule I, the most heavily restricted class, intended for highly addictive drugs with no medical use.

Scarselli attributed some of this restriction to stigma, believing many people see these trials as only for irresponsible addicts seeking to escape. He stressed that many things that produce no chemical dependence, such as gambling, can still be extremely addictive. Still, he said, we should be careful, warning, “people can sometimes have panic attacks, increased anxiety, distorted thought, […] increased heartbeat, and increased  blood pressure. So this is why you need to be monitored.” Getting the regulation right is down to, as he framed it, a “balance between cautious optimism and constructive skepticism,” and is what the FDA strives for with their new guidelines.

Another difficulty is the standard placebo trial required for approval, as the effects on perception are so pronounced that patients accurately guess whether they are taking drugs or not. One solution possible for the FDA is comparing a psychedelic with another drug, such as ketamine, that noticeably affects perception but lacks psychedelics’ possible therapeutic properties. This gives a baseline against which researchers can determine the true improvement created by psychedelics.

For a long time, patients have lacked sufficient treatment options, stuck in a cycle of persistent medication. New administrative support promises more rigorous research for novel solutions to a mental health crisis growing annually. These treatments still carry risks, but the challenge is now balancing hope with moderation.

Image from Wikimedia Commons