Psychedelic Drugs Could Be the Future of Mental Health Care | 22 Words

Beneath the surface of mainstream American culture during the 1960s was a counterculture movement designed to roil the hegemony. The youth (yes, "the youth”) were adopting eastern philosophy, donning a free-love attitude, revolting against the draft, and experimenting with psychedelics, a word that translates to "mind manifesting" from ancient Greek. LSD may the most familiar psychedelic, but by no means is it the only – psilocybin mushrooms, ayahuasca, mescaline, DMT, and even 5-MeO DMT, which is derived from the venom of the Bufo Alvarius toad, are included in this class substances.

Although psychedelics surged in popularity amongst clinicians and researchers due to their undeniable therapeutic potential, all legal manufacture and research came to an abrupt end by 1970. But there's been a renaissance. From psilocybin based interventions for terminally-ill patients to MDMA guided therapy sessions for those who suffer from post-traumatic stress disorder (PTSD), psychedelics may be redeemed. In fact, the FDA has granted psilocybin and MDMA “breakthrough therapy” status, permitting their expedited review.

Though lest we forget, psychedelics have endured a troubled past in America and in order to shed its old skin, supporters must tread carefully. Ready to expand your consciousness with me? Let's explore the history, neuroscience, and the real-life contexts these substances are being used for today.

Psychedelics in Ancient Mesoamerica

Although psychedelics may be seen as the flavor du jour, humans have been using them for millennia. Temples dedicated to mushroom deities can be found in Mesoamerica and proof that various plants and decoctions were used to achieve a higher state of consciousness date back to the Olmec period, from 1200 to 400 BCE.

Psychedelics in Ancient Greece

In Ancient Greece, the Eleusinian mysteries were conducted using kykeon, a drink of barley, mint, and likely ergot fungus, the same psychoactive substance from which LSD is derived. This ritual honored Demeter, the goddess of agriculture, and sought to honor the cyclical nature of life. Although those who participated in the Eleusinian ceremonies were sworn to secrecy, it’s clear from some accounts that people emerged from their experience no longer fearing death.

Psychedelics in the Amazon

The psychedelic brew ayahuasca has caught on as a tourist attraction to those seeking shamanic healing (though, its commoditization has led to some grave consequences). Historically, ayahuasca was used by indigenous peoples near the upper basin of the Amazon river, namely the Shipibo tribe. Shipibo shamans who administer ayahuasca, known as curanderos, use the plant to realign an individual’s physical, mental, and spiritual state.

A New Kind of Psychedelic

Fast forward to the 20th century and place yourself in Basel Switzerland. Albert Hofmann was a chemist who worked in Sandoz Laboratory studying derivatives of the ergot fungus. Although Hofmann created lysergic acid diethylamide (LSD) in 1938, it failed to meet its intended use as a circulatory stimulant and was shelved until 1943.

Taking the First LSD Trip

After incidentally absorbing some LSD while working with it in the lab, Hofmann described his consciousness shifting into an imaginative and pleasant one. Looking to replicate the effects, he dosed himself with 250 mcg of LSD, a very large quantity by today's standards. Hofmann soon dismissed himself from work, experiencing a rapid onset of symptoms on his bike ride home. Thus, April 19th, 1943 marks the first purposeful LSD trip and is remembered as "Bicycle Day" in the psychedelic culture.

LSD Leaves the Lab

Soon, Sandoz patented the substance and distributed it by its trade-name, Delysid. Studies used LSD to understand psychosis, treat alcoholism, and even attempt mind-control. This exciting and foreign new compound had already fomented a revolution, just no one knew it yet.

The Dark Side of LSD Research

Although the American government came to strongly oppose LSD, this wasn't always the case. During the 1950s and '60s, the CIA attempted to use LSD to enhance interrogation tactics in a clandestine experiment deemed "MK-Ultra."  The studies were completed on volunteers who, often unwittingly, ingested the substance and were subjected to various forms of manipulation. MK Ultra was eventually abandoned, as LSD did not produce consistent effects and was labeled as unfit for use in the field.

Evangelists of Psychedelics

Amidst the psychedelic researchers and practitioners of the 1950s, a Harvard psychology professor by the name of Timothy Leary stood apart. After experiencing his own transformative psychedelic journey, he became convinced that entheogens should be democratized. Leary and his colleague, Richard Alpert (later renamed Ram Dass), established the Harvard Psilocybin Project in 1960.

“Turn On, Tune In, and Drop Out"

The Harvard Psilocybin Project aimed to establish data for the healing properties of psychedelics, but its methods swiftly came under scrutiny. First, Leary and Alpert failed to randomly assign their intervention. Then evidence surfaced that they were dosing themselves while in session with their subjects and even encouraging the recreational use of psychedelics. The final straw proved to be Alpert’s sale of psilocybin to an undergraduate student, which ended both his academic career and the project.

An End of an Era

Research on psychedelics came to a grinding halt when, believing that their use represented the insidious destruction of society, the American government outlawed their manufacture in 1965. The public also seemed to foster resentments. As the hippies' beloved substance-of-choice, psychedelics had come to represent the unlawful counterculture. Soon they were lost to the social milieu, only resurfacing during the next century.

Moving Into the Present

Many advocates of the movement believe that the Americans during the 1950s and '60s simply weren’t ready for psychedelics, having no precedent on how to use them safely or interpret their effects. But now the culture has updated and we’ve embraced a few of its contemporaries such as yoga, meditation, and mindfulness-based therapy. The time seems ripe to give them a second chance, let's start by examining the science.

How Psychedelics Work

During the first era of psychedelic research, we didn’t know how they worked, leaving the public to fill in the gaps. Beliefs that psychedelics melted holes in the brain and caused permanent psychosis permeated popular culture and until brain imaging was developed, there was no way to prove otherwise. Today, the brain is still the most difficult human organ to unlock (many compare its nuance to the solar system!) but it’s possible to set a more realistic perception on how they work.

Stimulating Serotonin

All classic psychedelics such as psilocybin, LSD, and DMT stimulate a particular neurotransmitter receptor subtype, called the serotonin 2A receptor. Serotonin is one of the primary neurotransmitters in our brain, contributing to our mood, sexual function, sleep, and memory. By latching onto this receptor, psychedelic drugs mimic serotonin in the brain. Why do the effects of some psychedelic trips last longer than others? Different compounds are “stickier" on the receptor, meaning that they take longer to dissipate.

Traveling Deeper Into the Brain

Alright hold on tight, it’s about to get a little neuro-nerdy and technical. Serotonin 2A receptors are particularly present on excitatory pyramidal neurons, whose hallmark trait is its long axons, capable of connecting distant regions of the brain. The serotonin 2A receptors that are contained on these excitatory pyramidal neurons are most dense in layer 5 of the cortex. The brain is organized into 6 layers of cell types and layer 5 neurons connect the outer cortex to the inner brain structures, such as the basal ganglia.

Disrupting How the Brain Communicates

Interestingly, despite being labeled as “excitatory", pyramidal neurons project an inhibitory effect when stimulated (an action that is largely governed by the serotonin 2A receptor). Thus when we take psychedelics the deeper structures of our brain, associated with emotion, habit, and fear, are less communicative to our cortex, which regulates reason, language, and planning. 

Dyssynchrony Can be Beautiful, Too

Although the overall break in communication between deep and outer cortical structures is a revelatory discovery, it’s not the only one. Under normal conditions, the brain fires electrical impulses in a synchronized and orderly fashion. But psychedelics interrupt this frequency, rendering the usual cerebral structures of control and governance ineffective.

Real Life Contexts for the Serotonin 2A Phenomenon

Though neuroscience is fascinating, what does it mean for people? First, it’s well established that many common mental disorders like depression, anxiety, and addiction are characterized by rumination, negative self-perception, and repetitive behavior. By occupying serotonin 2A receptors on pyramidal neurons, psychedelics manage to decouple the emotional and cognitive regions of the brain. This offers the individual a chance to avoid their well-worn electrical pathways and blaze a new trail, one that can possibly lead to a more positive perspective.

Real Life Contexts for the Dyssynchrony Phenomenon

The overall electrical disarray, or entropy, that psychedelics cause in the brain may serve to increase its flexibility. It’s quite possible that when individuals have such an entrenched negative view of themselves and the world, “shaking up" their cognitive state offers them additional insights they otherwise wouldn’t have access to.

The Entropic Brain and the Default Mode Network

One more critical topic in psychedelic brain science includes the Default Mode Network (DMN). The DMN is a proxy for the brain’s experience while it is at rest. It involves several cortical regions that constantly relay predictions on the future and ruminates on the past, integrates self-referential and autobiographical information, and conducts social and emotional reasoning.

The DMN on Psychedelics

The DMN is often hyperactive in those with mental disorders and can contribute to an anxious and unfocused state. Psychedelics quiet the DMN – a phenomenon similar to the experience that meditators describe! This potentially explains the ego-dissolving effects or state of “oneness" that psychedelics cause.

The Latest Research

If you're not a science person, well you probably picked the wrong article. Regardless, you may be happy to know we're going to roll out the research results that are providing the bass line to this movement's melody.

Coming to Terms with End-of-Life

Two research studies with one very encouraging conclusion – when Johns Hopkins and New York University Langone Medical Center published the results from their psilocybin intervention for patients facing terminal cancer diagnoses, their success rates eclipsed all current therapies. About 80% of the group saw meaningful reductions in anxiety and depression levels while nearly 70% rated the experience as one of their most spiritually important life moments.

A Lasting Change

The most impressive conclusion, though? The effects of just a single dose of psilocybin therapy endured through the subjects’ 6-month reassessment. Compare this to conventional clinicians, whose approach is to prescribe months of therapy and potentially addictive drugs and it’s understandable why the FDA has flipped their script on psychedelics.

Solving the Opioid Crisis

Two studies from teams in Mexico and New Zealand were released in 2017, reporting the ability of Ibogaine in treating addiction, namely opioids. But before we cover the stats, let’s cover what Ibogaine is (as I'm sure it wasn't at your basement parties in high school) Ibogaine is derived from the West African shrub, Iboga. Historically, the plant was used by those who practice the Bwiti religion during healing rituals.

Ibogaine Put to the Test

Ibogaine incites strongly introspective states and in one trial, 50% of the subjects reported total abstinence from opioids during their 1-month post-treatment check-in. A second trial included patients who, on average, attempted sobriety 5 times prior. After their 12-month drug-screen tests were returned, 75% had remained opioid-free.

Fighting Post-Traumatic Stress Disorder

Those who endure a traumatic event, like sexual violence or a war crime, may be left with Post-Traumatic Stress Disorder, or PTSD. Symptoms include experiencing frightening flashbacks, a diminished sense of connectedness, and an increase in overall depression and anxiety. Research using MDMA has shown real promise and although it is not considered a psychedelic, it does produce many of the same ego-dissolving effects.

Results From MDMA Therapy

After several sessions using MDMA assisted psychotherapy, one study was able to show a mean reduction in PTSD symptoms by nearly a factor of 3. Another study reported a 23% improvement in symptoms at 3 weeks post-treatment and interestingly, both studies found that a moderate-to-high dose was more effective than a low dose. So it appears that MDMA is making a similar recovery as psychedelics – even Tim Ferris of 4-Hour Workweek fame has sponsored a documentary on their burgeoning potential.

Smoking Cessation

Nicotine addiction is one of the most difficult to break, as 85% of those who quit annually relapse. Here again, psychedelic therapy has shown potential. One pilot study enrolled 15 cigarette smokers with an average of 6 failed past attempts to quit. The therapy provided 1 moderate dose of psilocybin on the scheduled quit-date, followed by 1 high dose of psilocybin two weeks later, and an optional third high dose five weeks later. Each patient was supported by a clinician during their psychedelic experience and was enrolled in Cognitive Behavioral Therapy (CBT) as an adjunct to their treatment.

The Results

Researchers collected biological markers from the subjects, including urine samples and exhaled carbon monoxide (CO) on a weekly basis, beginning at baseline. Subjects also completed a questionnaire asking them to report how many cigarettes they smoked each day throughout treatment. At the 6-month follow up, 80% of the subjects showed complete abstinence, while the remaining 20% returned to abstinence after brief lapses. Compare this to the current smoking cessation treatments, whose success rates are often less than 35%, and you just may have your answer on how we’ll approach nicotine addiction in the future.

Carving a Middle Path

To use a reference from hippie culture, psychedelics may be best integrated using the Buddhist theme of the "middle way." Whereas America donned an overall feckless attitude during the 1950s and 60s, the other extreme denied the real utility of psychedelics. Between sound research and measured public support, we can hit the sweet-spot necessary to help countless people.