by Gabriel Iván Vega Bellido
This is the second post in our series on the consequences of outside influences on the performance and communication of science.
1. Introduction
Medical research has a history going back to when the Egyptians started documenting the medicinal properties of plants, but it has drastically changed in the context of the industrial revolution and capitalism. Though these changes have undoubtedly contributed to medical advancements and an increase in longevity, the interests of industry can often be in tension with optimal human health. Some notable examples of this include the enormous fast and processed food industries' contributions to the current obesity epidemic, and the continued promotion of fossil fuels by large oil companies despite having knowledge of their environmental impact for at least 50 years. Given the multibillion dollar size of the medical research industry, there is ample room for such conflicts of interest. This blog will examine how the external interests of industry and politics have recently shaped medicine of the pharmaceutical and psychedelic kind.
2. Overprescription of pharmaceuticals
In the modern era of drug regulation, the main issues are not related to a lack of proper testing but rather the oversupply and overprescription of potentially addictive drugs. Two types of drugs stand out in this regard: opioid painkillers and benzodiazepine depressants. The most pernicious of these are the opioid painkillers used for treating chronic pain, in particular Oxycontin. After receiving FDA approval in the mid 1990s and a marketing campaign by Purdue Pharma that falsely claimed a “less than one percent” risk of addiction, annual sales rocketed to almost $1.1 billion in 2001. The rampant overprescription of Oxycontin went on to spark the first wave of opioid overdose deaths and facilitated the two that followed, which have resulted in more than 645,000 deaths in the US and continue to plague the country to this day.
It is possible to attribute Purdue Pharma’s “success” with Oxycontin to the drug’s only significant advantage over conventional opioid painkillers, a sustained-release formulation which substantially decreased the frequency of dosing. Another potential reason is the large influence Purdue wielded over three key players in the pharmaceutical industry: doctors, regulators, and policy makers. Doctors routinely receive in-person office visits, large and small gifts, and direct financial payments in exchange for endorsement of industry products. In 2001, Oxycontin sales representatives who managed to increase sales in their territories by convincing doctors to write more prescriptions could receive bonuses which quadrupled their annual salary. In a turn of events suspiciously akin to regulatory capture, the FDA official which gave Purdue approval for selling Oxycontin soon after resigned and three years later was hired as Purdue’s director of medical research. Purdue also provided funding for regulatory organizations such as the Joint Commission, whose job it is to accredit hospitals and other health-care organizations. This partnership is thought to have subsequently facilitated the promotion of Oxycontin at accredited hospitals. In terms of political influence, in comparison with activists advocating for stricter limits on opioid prescriptions, the pharmaceutical industry spent over 200 times as much in lobbying for their business interests from 2006 to 2015. Pharmaceutical companies have also engaged in “astroturfing”, in which they covertly fund seemingly grassroots organizations or infiltrate legitimate ones to promote their own messages. A clear example of this was the American Pain Foundation, a group which depicted itself as an advocate for people with pain while echoing opioid manufacturers' messages about the many benefits and minimal risks of opioids; it later shut down when it was revealed that almost 90% of its funding came from the pharmaceutical industry. For the crime of misbranding OxyContin, Purdue Pharma was forced to pay $600 million in fines in 2007. Later, after declaring bankruptcy in 2019, they tried settling more than 2000 lawsuits by agreeing to a $10 billion settlement plan with 8 states and the District of Columbia in 2022. The money is intended to be used for victim compensation, opioid crisis abatement, and overdose rescue medicines. As of 2023, the Supreme Court has halted the settlement given that it grants legal immunity to the owners of Purdue Pharma, the Sackler family, in exchange for contributing $6 billion to the plan.
Another class of often prescribed medications with potentially dangerous addictive properties are the depressants known as benzodiazepines. Benzodiazepines work by magnifying the calming effect that gamma amino butyric acid (GABA) has on the brain and the central nervous system. As such, they are commonly used to treat anxiety, insomnia, seizures, alcohol withdrawal, and muscle spasms. The amount of adults filing a benzodiazepine subscription increased by 67% from 8.1 million in 1996 to 13.5 million in 2013. In this time, the total quantity of benzodiazepines prescribed more than tripled, and the global benzodiazepine market is expected to continue to grow from its current $2.35 to $3.1 billion by 2032. Overdose deaths linked to benzodiazepines have also multiplied from 1,135 in 1999 to 8,791 in 2015, with three quarters of those deaths involving an opioid, leading the FDA to issue drug labeling changes warning of the dangers of co-prescribing these drugs. These trends have been linked to an increasing number of mental health diagnoses amongst young adults who were treated by primary care doctors that weren’t properly trained in the prescription of benzodiazepines and lacked a proper understanding of their potential dangers. The main dangers of benzodiazepines are the speed with which users build up tolerance and develop a physical dependence, possibly within a few weeks of use. Upon developing a dependence, stopping use can be excruciatingly difficult due to extreme withdrawal symptoms including debilitating panic, psychosis, sleep disturbance, severe depression, weakness, and fatigue. The rapidly growing rates of prescriptions and overdoses have led to many comparisons with the opioid crisis, but doctors hope that the infrastructure developed to address the opioid epidemic can also be used to respond to benzodiazepine overuse, misuse, and addiction.
3. Re-emergent Therapies: Psychedelics
Meanwhile in 1938, a Swiss chemist named Albert Hoffman first discovered and synthesized lysergic acid diethylamide (LSD) while testing the stimulant properties of ergot derivatives, ergot being a type of fungus which affected rye. He didn’t learn of its effects until 1943, when he had a very strange bike ride home after having accidently absorbed 250 micrograms of the substance. After purposely ingesting it several more times, he concluded that it could have significant use in psychiatric treatment. In 1958 he also synthesized psilocybin and psilocin, the hallucinogenic compounds in the mushroom Psilocybe mexicana, after receiving samples from the mycologist Roger Heim who knew of his work with LSD. These discoveries kicked off a period of exciting research into the potential uses of “psychedelics” as breakthrough therapies for treatment-resistant mental disorders such as alcoholism and anxiety. We now know these compounds exert their effects by mimicking the neurotransmitter serotonin (5-hydroxytryptamine), acting as agonists for the 5-HT2A (5-hydroxytryptamine 2A) receptor. This receptor, widespread in the central nervous system, has been implicated in processes like learning, mood, anxiety, and appetite; and its abnormal activity has been linked with depression, schizophrenia, and drug addiction. Unfortunately, the illicit production and distribution of these compounds resulted in their widespread use in uncontrolled environments, leading to many reports of “bad trips” marked by hallucinations, panic, aggression, and significant psychological distress; putting the safety of these substances into question. Coupled with their strong associations to the counterculture movement of the 60s, this made them clear targets for President Richard Nixon’s “War on Drugs''. Consequently, they were labeled as Schedule 1 in the 1970s Controlled Substances Act, a category reserved for drugs thought to have a high abuse potential and no currently accepted medical use. This caused most research on psychedelics to come to a screeching halt as it became practically impossible to secure government funding for new projects, even for secret government projects bent on developing mind control. However, after several decades of softening drug laws and continued advocacy by a variety of groups, a “psychedelic renaissance” is now unfolding as research into the treatment possibilities of these substances has regained momentum in recent years.
Non-profit organizations such as the Multidisciplinary Association for Psychedelic Studies (MAPS), founded in 1986 by Rick Doblin, have long championed the healing potential of psychedelic therapies. MAPS has pioneered research into the use of the entactogen MDMA (3, 4-methylenedioxymethamphetamine, commonly known as “Molly” or “ecstasy”) for assisting psychotherapy of treatment-resistant Post Traumatic Stress Disorder (PTSD). In 2022, they completed a second Phase 3 trial for MDMA-assisted therapy of PTSD where 67% of patients no longer met the diagnostic criteria 18 weeks after baseline. MDMA acts as a serotonin-releasing agent, but it also interacts with the dopamine and noradrenaline systems, setting it apart from “classic psychedelics”. Its effects include facilitating introspection, reducing fear response to perceived emotional threats, and encouraging friendliness with others while lacking the perceptual alterations generally attributed to 5-HT2A agonists. While no serious adverse effects from use of MDMA in a controlled setting have been reported, misuse in an uncontrolled setting remains a concern. Given the large cost associated with the extensive monitoring protocols established by these studies, MDMA-assisted therapy is unlikely to become a first-line treatment for PTSD, but it shows great promise in helping those for whom other treatments have been unsuccessful.
Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine), the psychoactive component found in Psylocybe cubensis or “magic” mushrooms, has also attracted a lot of research interest. Known for its effects on perception and mood, current research has focused on psylocybin’s effectiveness in treating mental illnesses for which other treatments have failed. A study on treatment-resistant depression (TRD) had promising results, with seven patients (58%) from the 12 person open-label non-controlled study remaining in remission at a 3-month checkup after just two treatment sessions. This small number of sessions is particularly significant considering the substantial burden of direct and indirect costs incurred by TRD patients. Obsessive-Compulsive Disorder (OCD) is a chronic condition characterized by obsessive thoughts and compulsive behavior, from which it is unlikely to achieve full recovery without treatment. Though limited in number of patients, studies into the use of psilocybin for combatting treatment-resistant OCD have found both short and long-term reduction in symptoms. Psilocybin has also been explored as a treatment for smoking addiction, a major contributor to premature death worldwide. Although based on a self-selected population that was motivated to quit, a fifteen person trial for smoking cessation including three sessions of psilocybin treatment over 15 weeks found that ten participants (66.7%) remained abstinent at a 12-month checkup. Impressively, none of these studies reported serious adverse effects as a result of using psilocybin, and long-term analyses of 110 patients have found no evidence of drug abuse or long-term impairment. This growing body of research points to the potential of psychedelics as safe and effective treatment options for several challenging mental health conditions.
Although possibly perplexing to many, the utility of these compounds in treating mental illnesses would probably be unsurprising to shamans of Native American cultures, who have used analogues of them in healing rituals and religious ceremonies for millenia. One such shaman was the poet María Sabina Magdalena García, a Mazatec “sabia” (wise woman) that lived in Huatla de Jimenez in the Sierra Mazateca area of Oaxaca, Mexico for 101 years (1894-1985). María dedicated several decades of her life to healing others through a ritual called the velada, which involved the ingestion of psilocybin mushrooms, or holy children as she called them. In 1955 she introduced the ethnomycologist and banker R. Gordon Wasson to psilocybin, after he deceived her by saying he was concerned about the whereabouts and wellbeing of his son, since he knew that the velada was commonly used to heal the sick or find lost objects. Wasson made multiple return trips to Oaxaca to witness additional veladas, on one of which he was accompanied by Roger Heim, the mycologist who supplied Albert Hofmann the mushroom samples from which he first synthesized psilocybin. In 1957 Wasson turned his story into the article “Seeking the Magic Mushroom'' in Life Magazine, where he detailed the enlightening vision the mushroom gave him. The resulting influx of foreigners seeking enlightenment proved disastrous for María, as it led the Mazatec community to charge her with bringing misfortune to the village and defiling the velada. Her house was burned down, and police frequently raided her home, accusing her of drug trafficking. She later lamented: “from the moment the foreigners arrived to search for God, the holy children lost their purity. They lost their force…From now on they won’t be any good.” Maria Sabina’s story can remind us that the true value of these compounds can only be harnessed when they are approached with the appropriate respect and understanding.
4. Summary
The overprescription of drugs like opioids and benzodiazepines by the profit-driven pharmaceutical industry, often overlooking their addictive nature and the dire outcomes of misuse, highlights a need for more accountable drug development and prescribing practices. In stark contrast, psychedelic therapies, historically sidelined by political agendas and championed primarily by non-profit organizations, present a different paradigm with their lower abuse potential and generally favorable safety profiles. While compounds like MDMA and psilocybin show promise in treating various mental health conditions, their use also demands wisdom. The history of psychedelics, as seen through figures like María Sabina, shows us that these substances are not merely tools for healing but they also hold profound cultural and spiritual significance. Going forward, it is imperative to critically evaluate the addictive potential of pharmaceuticals and approach psychedelic therapies with the reverence and caution they deserve. Perhaps then advancements in medical science will be better aligned with the goal of improving human health.