Defying the “War on Drugs”: The Rebirth of Psychedelic Medicine & Research

Nick Beebe

Illustrations by: Cherrie Chang

Widely recognized by U.S. historians as igniting the “Summer of Love” (1967), San Francisco’s “Human Be-In” gathering made for anything but a typical day; more than 30,000 hippies flooded the Golden Gate Park in what ultimately became a defining moment for America’s counterculture movement. United by support of nonviolence and primary disdain for the U.S.’ role in the Vietnam War, hippies resulted during the 1960s as predominantly young Whites (ages 15–25) fully ‘dropping out’ of their everyday lives. One participant of the demonstration himself, Dr. Timothy Leary, psychologist and prominent LSD advocate, first vocalized the phrase "tune in, turn on, drop out." In his signature soft-yet-monotone voice, this simple saying would soon blossom into an iconic saying amongst psychedelics users and the collective counterculture movement [1]. 

To the delight of its everyday supporters alongside hopeful scientists, including the late Dr. Leary, psychedelics are experiencing an enthusiastic rebirth across various healthcare systems. In the past, psychedelics (also known as hallucinogens) had stood as a promising "North Star'' within U.S. medicine; however, the eclectic array of wavy chemicals saw its luster vanish just as the Nixon administration (1969–1974) anchored itself to a fervent anti-drug attitude. With the government’s “War on Drugs” surging ahead, the Nixon administration illegalized drugs to thwart the anti-establishment mentality sweeping the country [2,3]. 

As evidenced, the inexplicable allure of psychedelics is enough to instigate its use amongst humanity—from recreational use to scientific investigation. Most notably, their current return results from an entirely new psychedelic-based practice: microdosing. Even in just partial dosage (a microdose), their ‘rebirth’-seeking clientele spreads far—from the innovative architects of Silicon Valley to the ceremonial yogis leading spiritual retreats [4–6]. Until recently, few researchers were permitted to revisit the past studies that had halted following psychedelic criminalization. Of the few psychedelic trials allowed to occur from the early 1970s until the late 2000s, most centered on rodent test subjects in preclinical contexts [3,7,8]. 

In stark contrast, studies of psychedelics — including psilocybin (the key compound of magic mushrooms, or “shrooms”), MDMA, and LSD — have finally entered into the clinical stages. Emerging evidence continues to highlight the drug class as game-changing for the treatment of various conditions, many of which are neuropsychological [9,10]. Despite the legal suppression psychedelics have faced, they continue to mesmerize and modify users’ minds. Recent studies of psychedelics have even helped researchers pinpoint some cognitive processes to specific brain regions [11]. Ultimately, current psychedelics research aims to alter and expand the scope of emerging medicine [12]. But is the world really ready for psychedelic-infused healthcare? 

Psychedelics: Beyond Woodstock & Tame Impala

As is the case with most drugs, psychedelics have a complex history shaped by numerous sociocultural pressures. In regards to their origin(s), lies persisting across mainstream society still allow some to deem the emergence of psychedelics as a spontaneous “flower child” of the counterculture age. In reality, however, the first humans to interact with psychedelics were Indigenous populations, who have incorporated entheogens (plant-based psychedelics) into religious and ceremonial practices for centuries (and counting) [4,5]. Additionally, in the medical sector, psychedelics were incorrectly classified as “psychotomimetic,” implying that their use would invoke psychosis, or the alteration of the brain’s connection to reality. Naturally, this was able to overwhelmingly instill fear, panic, and consequent objection throughout the American public. However, as recent research refutes, any continuing association between psychedelics and psychosis stems from baseless assumptions [13,14]. In other words, psychedelics pose nearly none of their once-expected threat — provided that they are used under appropriate professional supervision. 

Continued research has demonstrated that the toxicity of psychedelics is relatively low, meaning that these drugs may not be associated with once-feared adverse health conditions (e.g., organ damage, overdose fatality, and cancer instigation) [15]. The success behind psychedelic administration also lies in the compiled testimonials that confirm these drugs promote unmatched changes in brain function and personality. In particular, improvements have best been demonstrated amongst individuals with major depressive disorder and post-traumatic stress disorder (PTSD) [2]. Regardless of the success of short-term clinical studies, much still remains uncertain about the long-term effects of psychedelics. As such, the gap spanning between possible and known information has been deeply perpetuated by widespread restrictions on access to psychedelics for the purpose of performing knowledge-expanding research.

"Biohacking" by Microdosing

 In recent years, there has been a significant uptick in "biohacking," or the process of developing one's optimal self through the use of particular drugs, vitamins, and exercises [6]. One of the various "biohacking" practices gaining traction is the act of microdosing. Microdosers take psychedelic drugs, often several times a week, in small amounts to prevent a "trip." Typically, this dosage level falls between 10–20% of any particular drug's "normal" dose [16]. Similarities between user reports collectively suggest that microdosing can elevate cognitive performance, creativity, and productivity [16]. However, more clinical research is needed to explore these claims empirically. 

One recent survey-based study with over 2,400 microdosing participants determined that those identifying as male were nearly twice as likely to microdose than females—and that tech industry workers and retired people were most likely to partake [17]. With the bounds of technology rapidly expanding, employment within this sector might overwhelm one’s creative abilities and cause them to microdose—though it is not entirely certain why retirees also prominently microdose. Furthermore, of 393 microdosers, nearly half reported using LSD, followed by psilocybin (~25%) and MDMA (~12%). Many in this pool also reported improvements to depression (~72%), sociability (~67%), increased focus (~59%), and decreased anxiety (~57%) following microdosing [17]. However, these rates are self-reported, meaning they only represent participants' perceptions of their own experiences. Aside from these initial reports, very little is known about microdosing — particularly its effects, both during and after the duration of dosage [18,4]. 

One recent source shares that a participant’s optimism regarding microdosing treatment may impact its outcome, demonstrating one of the many variables relevant to developing effective psychedelic treatments [18]. Nevertheless, it has proven exceedingly difficult to decode the neurobiological mechanisms responsible for psychedelics’ beneficial impact on cognition with certainty. Due to the abundant ambiguity, some argue that these drugs are veering towards gaining the status of a panacea — a hypothetical remedy for all diseases and difficulties — despite the lack of scientific support for this position [19]. However, due to legal constraints, research into psychedelic drugs remains far from comprehensive. Researchers can rarely investigate beyond the most common drugs and have visibly failed to study the newest psychedelics of all: new psychoactive substances (NPS) [20,21]. Regardless of one's stance, further research must be conducted on the use of psychedelics and NPS, particularly through microdosing, in order to assess their medicinal properties. To develop a consistent understanding of the potential benefit held within these drugs, additional supporting research is needed to decode them — most urgently being the substances most commonly used by microdosers: LSD, psilocybin, and MDMA (sometimes incorrectly referred to as "ecstasy").

LSD

In an attempt to mirror the positive effects of plant-based ergotamine—once widely used to treat migraines—practicing drug manufacturers of the early 1900s began searching for synthetic molecules to act as superior medicines [22]. Swiss chemist Albert Hofmann was able to extract one portion of ergotamine's dense structure: lysergic acid [1,8]. Years later, Hofmann sought to mix the lysergic acid he had produced with other organic molecules to create new drugs. During his twenty-fifth trial, Hofmann was able to fuse lysergic acid with nikethamide—known commercially as Coramine, a circulatory stimulant. However, this produced an array of unexpected behaviors in test rats and was subsequently ignored [8,1]. Years later, still captivated by his creation, Hofmann unknowingly consumed an indefinite amount of LSD while handling it in the lab [9,1]. When he first realized something was abnormal, Hofmann reported "a remarkable restlessness combined with a slight dizziness" in his notebook. Shortly after, he found himself exposed to "fantastic pictures, extraordinary shapes, with intense kaleidoscopic plays of color" [1]. Much later, Hofmann was unable to even handle pen and paper to record his experienced sensations.

We now know that LSD has the potential to decrease brain connectivity in ways that can last for years, potentially even impacting one’s personality ("sense of self" network, formally named the default mode network) [23,24]. This network is responsible for one's capacity for mental time travel (the ability to think in past or future tense), self-reflection, and autobiographical memory. When these functions are disturbed, it becomes difficult for an individual to maintain their personal identity and connection with the physical world. So, should LSD temporarily skew the framework of the default mode network, a user may struggle to process the world around them, leading to the experience of ego dissolution (disintegration from one's self-identity) [24,25]. This comes as no surprise, given that immediately after consumption, LSD is known to distort one’s perception of time, identity, depth, size, and shape [26]. 

Following its accidental creation by Hofmann, LSD would soon be used to combat addiction, anxiety, and depression in over 40,000 patients up until the mid-1960s [1]. LSD has also demonstrated success in the treatment of alcoholism and other substance addictions [15,25]. The performed studies of LSD (on participants) have ultimately permitted researchers to further understand brain systems previously regarded as entirely unrelated to each other—one example being the brain's visual processing component; LSD increases activity in brain regions tagged responsible for creating intense and dreamlike visions [24]. Ultimately, since LSD research was restricted during the War on Drugs, we have much more to learn about the fascinating compound. The resurrection of LSD, like other psychedelics undergoing clinical trials, has been astonishing — though it is clear that future trials and literature must weigh its potential negative effects with efficacy in changing the mind for the better [24,25]. 

PSILOCYBIN

In 1958, psilocybin was initially identified by Albert Hofmann, following its extraction from mushrooms [27]; in comparison to Hofmann’s other psychedelic ‘child’ (LSD), psilocybin is roughly 100x less potent [28]. However, the first clinical study involving psilocybin only concluded six years ago, resulting in 10 participants’ complete recovery from alcohol use disorder [9]. Today, the FDA has remarkably referred to psilocybin as a “breakthrough therapy” for the treatment of major depressive disorder, including treatment-resistant depression [29]. Most of the 30 registered trials currently studying psychedelic drugs center around psilocybin, examining its uses for treating anorexia, obsessive-compulsive disorder (OCD), addiction and substance use disorders, and depression [30,10,31]. As of 2018, similar trials also conducted with psilocybin were seeking to demonstrate its efficacy in alleviating alcoholism, tobacco addiction, and cocaine addiction [7]. In terms of tobacco addiction, two-thirds of 15 participants in a 2014–2016 study reported sustained abstinence from tobacco use in the year following initial treatment of psilocybin-aided psychotherapy [32,33]. While the U.S. has prioritized substance abuse and depression treatment in regards to psilocybin, there are several other conditions that psilocybin may treat—including Alzheimer's and OCD [34–36]. For example, a recent case study found that a 38-year-old male subject with OCD reported a significant decrease in intrusive thoughts following psilocybin administration, despite initially finding the drug's immediate effects unpleasant [36]. Though this source represents just one individual's experience, it highlights one of the many circumstances where psilocybin can assist in healing [37]. Nevertheless, many newer studies have begun to further explore the role of psilocybin for individuals facing OCD [38].

Furthermore, psilocybin has been praised for its ability to improve the quality of life of patients facing advanced or terminal cancer [39,9]. A recent study exploring this type of psilocybin use confirmed that even years following initial treatments, over 80% of participants maintained improved spirituality, positive behavior, and satisfaction. However, since most of these participants were White cancer patients, these findings cannot be generalized to individuals outside of these categories. While psilocybin shows promise in treating numerous conditions such as addiction and depression, additional studies are needed to determine how the drug could affect larger populations [39]. 

MDMA

MDMA, alongside LSD and psilocybin, is another example of a psychedelic with gleaming value for medicine [40]. Initially designed by pharmaceutical company Merck to control bleeding, MDMA improves one's overall mood by decreasing anxiety, while enhancing relaxation and sociality [41,42]. However, MDMA's legacy is tainted by its association with ecstasy. While many people believe these drugs to be synonymous, ecstasy can actually contain several other substances apart from MDMA — though this fact remains widely unknown due to the prevailing public uncertainty surrounding most things psychedelic-related [42]. Early research in MDMA’s effect of PTSD found that over half of participants experienced relief so significant that they no longer matched the criteria for a definitive PTSD diagnosis [4]. However, the study's participant pool contained very little diversity, especially biogeographic ancestry — a common issue within clinical research. As briefly noted above, while some forms of psychedelic therapy might work for a White person, the same methods might not work for someone of differing biogeographic ancestry [4].

MDMA actively stimulates the release of neurotransmitters and hormones known to enhance prosocial behaviors, such as serotonin, oxytocin, and vasopressin. Psychiatrists have found numerous positive effects linked to MDMA-aided psychotherapy for patients with PTSD, including sensory intensification, increased emotional awareness, slight ego dissolution, and changes in interpersonal relationships [43]. Traumatic events are often followed by a critical period, a brief time span where the brain is more plastic (or subject to potential change[s]). Irreversible neuronal changes can occur during this period, however, meaning MDMA’s therapeutic success (for PTSD) may decrease with the passage of time. However, study participants receiving MDMA during the critical period reported elevated feelings of closeness and trust [41]. This means that MDMA, even when administered during one’s critical period, can still assist PTSD treatment. Closeness and trust, particularly, can prove vital to treatment success as they enhance patient-therapist bonding [41]. 

As such, MDMA-aided PTSD psychotherapy may help patients overcome the complex mental barriers that commonly already challenge PTSD treatment. Individuals with PTSD construct internal boundaries to protect themselves from experiencing the intense negative emotions that typically accompany the memory of traumatic events—and MDMA works to help unravel them. Undoubtedly, dissolving these boundaries with MDMA treatment offers an incredibly novel clinical approach to PTSD therapy [41]. Of a study devoted to MDMA-aided psychotherapy with participants of color, one participant memorably remarked that MDMA might be the best catalyst for those with PTSD to "push things along [and] enjoy their lives again" [4]. Given these positive clinical trials, approval of MDMA for medical use is likely to occur around in the next year or so, depending on the pandemic's impact on research execution [42]. 

HOW WILL WE NAVIGATE PSYCHEDELIC MEDICINE?

Supported by the results of pertinent past work, the future of psychedelic medicine appears promising, though its trajectory remains vastly uncertain. Given the resistance that cannabis legalization has faced in the past decade, pushback is almost expected [17]. Along those lines, a collaborative recentering of mainstream attitudes towards potentially drugs with potentially restorative benefits is desperately needed. As psychologist Dr. Jamilah George, of the Multidisciplinary Association for Psychedelic Studies (MAPS), admits: "I've always seen drugs as dangerous, leading to violence and incarcerations[—n]ever something… as a means [of] healing" [43]. The intensive and holistic studies of psychedelics available infer that the body's psyche wants to recover from traumatic experiences, much like how one's immune system tends to a physical wound. However, the complex nature of the human psyche does not succinctly signal where one most needs a neurobiological bandage; this is the basis for psychotherapy which, in the presence of psychedelics, displays deeper and swifter strives.

As with any drug, it is imperative to examine potential risks before choosing to experiment. Nearly one in twenty individuals (~5%) reported self-directed psychedelic use as a means of treatment reported visits to the emergency department [44]. Though not a significant portion of the population, this statistic still exhibits that a “trip” (from any psychedelic) can force a user to hail medical attention. Since the outcome of a “trip” relies on a multitude of variables (e.g. biochemical, neurocognitive), it might be impossible to weave common threads through this small subgroup of users. In this regard, researchers may opt to rely on mechanisms, like scales, to derive numeric values from qualitative, intangible elements (e.g. personality, upbringing). However, one variable to certainly account for in this context is a user’s dependency on their psychedelic(s) of choice.

The Substance Abuse and Mental Health Services Administration recently concluded that although some psychedelic addiction exists in younger users (particularly those just entering adulthood), addiction in people over 25 is very rare. Considering the near-doubled rate of psychedelic use in America’s young(est) adults (ages 18–25), it is essential to understand what factors are motivating any use of psychedelics—from sporadic microdosing to intense tripping [28]. With clinical steps being made towards FDA approval, addiction rates may vary [20,7]. Though relatively rare, a hallucinogen use disorder (HUD) arises with one’s extensive use and experienced addiction to any psychedelic(s); even if addiction does not occur, prolonged psychedelic use may pose other severe neural impacts. For example, hallucinogen persisting perception disorder (HPPD) results when someone who has used psychedelics prior experiences extended visual hallucinations, similar to the distorted visual effects brought about by one's use of psychedelics. The condition is most exaggerated for users of LSD and can be bolstered by stress, anxiety, exercise, or the use of other drugs [12,7]. With all of this in mind, it is imperative to continue clinical research to grow the understanding of psychedelics to create guidelines for all use to be safe. 

An important thing to remember is that the clinical use of psychedelics is more often than not done alongside psychotherapy. That said, findings surrounding unassisted, self-administration of psychedelics have not yet reflected positive psychological benefits [45]. Leaving the administration of psychedelics to users could easily prompt abuse. Instead, the drugs have been successfully used to enhance physiological exploration within controlled therapy settings. With the country's first legal psychedelic product coming in the form of fruity seltzers (and on sale now), it is clear that this drug class will likely remain prominent in the coming years, in various forms. Thus, the question still remains: are we ready for a psychedelic future? While we have much to learn about these distinctive drugs, the literature to-date significantly speculates an encompassed role of psychedelics within future medicine—though there is certainly no telling what that may look like.

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