A BRIGHT SOLUTION FOR OPIOID ADDICTION

BY LARS ZEANA-SCHLIEP

A lack of feasible opioid addiction treatments in the United States leaves a vast majority of addicts untreated, imprisoned, or left to die. A partnership between Knoa Pharmaceuticals and researchers at Massachusetts General Hospital could lead to the development of a vitamin D-based solution.

Telisha Lockwood was a varsity cheerleader at her high school in Fairmount, West Virginia when she first tried drugs at age 14. Beginning with marijuana and alcohol in high school, Telisha moved onto harder and more dangerous substances – first trying heroin after a stint in a rehabilitation facility post-high school. Eventually going to jail for assorted petty crimes needed to fund her addiction, she lost custody of her two baby daughters and continued injecting heroin for years. Throughout this time, she attempted, unsuccessfully, to get treatment multiple times in a center, and finally got sober on her own. She became a functioning member of society, taking on a full-time job, getting married, and finding a permanent home. However, after two years, she relapsed again and continued using heroin for a year before her third pregnancy forced her to go clean. She remains in recovery to this day.

Telisha is among the minority of heroin users who manage to beat their addiction. Even so, it took her over a decade of attempts to reach long-term sobriety. Her life was destroyed; she lost all of her personal and familial connections for a decade.

The Problem

Hundreds of thousands of Americans, and millions around the world, are not so lucky. Opiates, particularly heroin and fentanyl, are among the most addictive and deadly drugs in the world, taking the lives of over 75,000 Americans in 2021. Broadly, this data point reveals the alarming uptick in opiate overdoses taking place around the world, likely due to the increasing illicit fentanyl production in Mexico and China.1 For users, the drugs create intense withdrawal symptoms; severe muscle pain, spasms, diarrhea, insomnia, and cold flashes are just some of the effects that plague those trying to get clean.2

No Way Out

Despite the far-reaching societal and personal implications of opioid addiction, and the all-too-tangible fiscal and human cost of this epidemic, the scientists, governments, and social workers of the world have failed to come up with a treatment that works. Currently, efforts to treat opioid addiction are sporadic –ranging from harsh war-on-drugs type legal initiatives to holistic rehabilitation programs.

Opioid agonists – molecules that block opioid receptors in the brain – have been most effective in opioid addiction treatment, but remain far from perfect. Methadone, the most common agonist, binds to similar opioid receptors in the brain as heroin. These receptors include the Mu, Delta, and Kappa receptors, which cause feelings of euphoria, analgesia, and dysphoria, respectively. Methadone is a full opioid agonist, binding to all three receptors. It produces a very similar response in users to heroin, albeit a muted euphoric response and a heightened dysphoric response.3 As a treatment, Methadone blocks users from experiencing the terrible physical withdrawal symptoms associated with heroin.

Methadone remains dangerous, however. Its power and similar chemical structure to heroin can make users susceptible to overdose, and in 2019, 30 percent of overdose deaths linked to prescription painkillers were from methadone.4 Additionally, as per the National Institutes of Health, methadone is only dispensed at specialized drug treatment clinics and cannot be prescribed by normal physicians.5

In addition to medical treatment, holistic rehabilitation programs also exist, both government-subsidized and private. These programs typically provide therapy, incentives for maintaining sobriety, and sometimes medical supplements. Governmentsubsidized programs are oftentimes severely underfunded and typically have long wait times for access to a bed. Yet, looking at alternatives, these public programs are often the only choice for addicts who want to get clean.

Private rehabilitation programs are oftentimes expensive and have been criticized as for-profit business models with shady practices that affect people while at their lowest moments. A 2021 article from NPR mentions a 2017 case where parents sent their daughter to Florida for addiction rehabilitation. After seven months, the daughter died of an overdose and the family was billed $600,000. While it presents only one anecdotal case, the situation underscores poor regulation within an addiction treatment industry that feeds on the fear of families who need help immediately.6

If solely financially motivated, rehabilitation centers may not be incentivized to cure their patients. Long-term treatment increases revenue and may encourage proposals for additional treatment. Further, despite the fact that opioid agonists like methadone are scientifically proven to help addicts, less than a third of private rehabilitation centers incorporate these

agonists in their programs.7

The Future Of Opioid Addiction Treatment

On June 11, 2021, researchers and doctors at the Massachusetts General Hospital published a groundbreaking paper detailing their discoveries on the interaction between vitamin D deficiency and opioid addiction. Ultraviolet light exposure has been known to cause the release of beta-endorphins, an endogenous (or naturally produced) opiate in humans.8 However, the opiate relationship to vitamin D has not yet been fully explored.

In the paper, the researchers discovered a pathway where low vitamin D levels exacerbate cravings for the opiate response but are diminished in bodies producing vitamin D through sunlight exposure. The study found that high vitamin D levels reduced cravings for opiates in mice. This pathway makes sense, as a sort of evolutionary incentive for humans to maintain vitamin D levels through sun exposure. Unlike the opioids naturally released by the body after sun exposure, synthetic opioids do not affect vitamin D levels. In short, a lack of vitamin D may play a part in the cycle of cravings and addiction observed in heroin addicts. Importantly, the researchers’ findings were not just limited to mice.

Human data from NHANES, a national health database consisting of 18,000 members from the United States, showed that people with severe vitamin D deficiency were 90 percent more likely to develop an opioid addiction. Those with moderate vitamin D deficiency were 50 percent more likely.9 Today, approximately 75 percent of American teenagers and adults are vitamin D deficient.10 The implications of this study are huge: not only is there a possible explanation for the severity of the opioid epidemic in the US but there is also a potential path forward. The primary investigator of this study, Dr. David Fisher, went so far as to say: “We may have an opportunity in the public health arena to influence the opioid epidemic.”11

Unfortunately, public laboratories move slowly and are reliant on limited funding from government grants. Thus, the timeline for Massachusetts General Hospital to explore the potential for creating treatment for opioid addiction based on these findings is long. But, with the support of a pharmaceutical company, the MGH researchers could combine their knowledge and expertise with the resources to explore, develop, and market a treatment for opioid addiction.

Big Pharma On Notice

After Purdue Pharmaceuticals’ legal backlash, which has been unfolding for the past two years, the company went through Chapter 11 bankruptcy. It restructured Purdue Pharma into Knoa Pharma, a company owned by the National Opioid Abatement Trust, and legally obligated to operate for the public good. Purdue announced that Knoa Pharma would continue producing opiates in a controlled manner, but would donate profits to anti-addiction efforts and attempt to bring other opiate-related life-saving medications to fruition through its drug development pipeline.12 The main benefit of this approach is that many of Purdue Pharma’s top-tier researchers will continue working for Knoa Pharma, putting them in a unique position. The company is replete with strong resources, both in terms of funding and human capital, and a court-mandated mission to serve the public good.

With both Knoa Pharma and Massachusetts General Hospital in partnership, the production of a novel opioid addiction treatment can begin. Further studies will be conducted to identify what exactly in the chemical structure of vitamin D might contribute to the amelioration of opioid cravings.

The partnership shows promise. Noting both chemical and natural vitamin processes, researchers from the hospital and pharmaceutical companies may be able to engineer a derivative of vitamin D that maximizes the uptake of this chemical by the human body while limiting the risk of hypercalcification which occurs with high levels of vitamin D.

A History Of Possibility

A similar approach to isolating a less dangerous and more effective derivative of a vitamin was successful in the 1950s in experiments conducted by scientists at Hoffman-LaRoche, with the creation of the massively successful acne drug isotretinoin.13 Isotretinoin is a derivative of one of the most dangerous vitamins, vitamin A, where its overconsumption may cause liver failure. However, isotretinoin’s unique chemical structure allows the body to reach much higher concentrations of the chemical without experiencing the extreme side effects associated with high blood concentrations of vitamin A. Similarly successful vitamin D derivatives might be marketed in pill form, similar to isotrentinoin.

Theoretically, to reduce withdrawal symptoms, the partnership might investigate the potential benefits and risks of exposing recovering addicts to high levels of ultraviolet light. Ultraviolet light exposure booths, similar to those used in tanning salons, could be researched as a possible source of vitamin D therapy. Incorporating a combination of UV light exposure and a vitamin D derivative into addiction treatment may enable addicts to reach sobriety more easily than through any prior treatment.

Should a vitamin D drug be successfully developed, Knoa Pharma might establish their patent rights and obtain initial exclusivity as the medication is introduced to the market. As an alternative, and noting their mandated mission to maximize the public good, the derivative could be made available for everyone through a prescription from any licensed physician. Further, with success and broad acceptance, it is also crucial that health insurance companies and the government be willing to subsidize such opioid addiction treatment for people that would not be able to afford it.

A DOCTOR'S PERSPECTIVE

As the chief of the infectious disease department at BronxCare hospital, Dr. Zeana has been struggling with opioid-addicted patients for her whole career. She knows the struggle of treating patients for other diseases while they are addicted to opiates and has had patients die from overdoses while she treats them for various bacterial and viral infections that come from sharing dirty needles. She is “amazed that no one has come up with anything to help these people.”14 After reading the Massachusetts General Hospital article, she agreed with Dr. David Fisher, saying “this really could make a difference… they will need to perform further studies to confirm this relationship in humans, but if it holds strong, this is a big breakthrough for treatment.”15

Potential Shortfalls

The solution proposed does have some risks, but the potential good that stems from the development of an effective treatment for opioid addiction far outweighs them.

One major risk is that the treatment cannot be developed by the combined resources of Knoa Pharma and the researchers at MGH. While this outcome is a possibility, preliminary research suggests that the relationship between vitamin D, ultraviolet light, and opioid response is strong and present. When asked about the time necessary to create such a vitamin D derivative treatment, Dr. Zeana said, “Theoretically, it makes sense. It is just that in science we need to make sure every little risk and step is extensively analyzed before releasing something to humans.” 16

Potentially the largest shortcoming of this treatment is that one treatment may not be enough to solve the overwhelming size of the opioid epidemic. The opioid epidemic is as much a societal problem as it is a medical one. The current system to deal with drugs and addiction in the United States is flawed, with the government taking a legal and