Advocacy for Medicinal Use of Controlled Substances

Many of your patients are using illegal drugs. More than half of American adults have tried marijuana and 14% consume marijuana once or more per month.¹ Over 30 million Americans have tried a psychedelic during their lifetimes ², and use rates are increasing with more than 5.5 million Americans using a hallucinogenic in the past year.³ To best serve and care for your patients, you have an obligation to be knowledgeable about controlled substances. You should know how they can be used and are being used for the conditions and comorbidities you treat. You need to know how controlled substances interact with the medicines you are prescribing. You should be asking your patients about substances they may be using and advise them on how to use them safely in conjunction with the other medicines you are prescribing them. Furthermore, to improve the quality and range of medicines available to your patients, you should be an advocate for research, rescheduling, and access to psychedelic substances that are not yet approved for medicinal use by the Food and Drug Administration (FDA).

The Story of Clusterbusters

Cluster headache is one of the most painful experiences a human being can endure.⁴ The typical patient is diagnosed in their mid-20s and experiences debilitating attacks that can last anywhere from 1 to 3 hours and occur 4 to 8 times per day, often for decades. These clusters tend to occur in 6-week to 3-month stints, 1 to 2 times a year, often during a change of seasons.⁵

In 1998, the online cluster headache community at clusterheadaches.com began sharing patient reports that usage of lysergic acid diethylamide (LSD) and psychedelics in general might be effective in treating cluster headaches. Psychedelics were observed to help patients avoid the onset of a cycle or end one early.

Because of the illegal status of psychedelics, which were not being studied by the medical community, the cluster patient community performed their own research to explore the effectiveness of these molecules. The online community (ClusterHeadaches.com and Clusterbusters Forum) systematically captured patient reports and began to build a treatment protocol for using psychedelics for cluster headache. Because LSD was very difficult to procure, some patients grew or foraged psilocybin-containing mushrooms. Over the past 24 years, the community has refined the treatment protocol and has collected thousands of patient-reported success stories of ending cluster cycles early, preventing attacks during cycles, and prolonging remission periods.

In 2006, researchers published the first reports on the efficacy of psychedelics to treat cluster headache.⁶ This research was funded by patients and Clusterbusters (clusterbusters.org), a nonprofit organization that grew out of the online cluster community. Not long after, Clusterbusters-supported research revealed that BOL-148, a non-hallucinogenic LSD analog, showed promise in treating cluster headaches in a clinical setting.⁷ Since 2006, Clusterbusters has collaborated with researchers and headache specialists to study the effects of psilocybin, LSD, and BOL-148, and patients have worked with their doctors to determine how to treat their cluster headaches safely and effectively.

Based on internet forum discussions, it is estimated that thousands of individuals with headache worldwide are using psychedelics to treat their cluster headaches and other headache disorders. There are few FDA-approved treatments for cluster headache and psychedelics are an exciting area of treatment to explore.

Psychedelics—Past, Present, and Future

For thousands of years, indigenous cultures have used a variety of natural psychedelics to facilitate spiritual journeys and healing. In the 1930s, Dr. Albert Hoffman, while working for Sandoz, was researching ergotamines as treatments for vascular diseases. He developed LSD and put it on his shelf for a few years. When he revisited the substance, he personally discovered the hallucinogenic effects of LSD.

During the 1950s, 1960s, and into the 1970s, research evaluating the effectiveness of a wide range of psychedelics to treat a range of conditions was ongoing. This research came to a halt with the passage of the Controlled Substances Act of 1970. This act created the drug scheduling system and many substances, including marijuana and most known psychedelics, were assigned as Schedule I and labeled as having no known medical value.⁸

The labeling of marijuana and psychedelics as not having any medical value was not based on science and was contradictory to the studies showing a wide range of patient benefits. The scheduling was the result of Nixon adminstration policies. The Controlled Substances Act stopped the robust research that had been occurring with psychedelics and led to decades of no progress in research.

Over the past 15 years, rigorous research on psychedelics as medicines has been increasing, and the latest predictions are that 3,4-methyl-enedioxy-methamphetamine (MDMA), also known as ecstasy, and psilocybin will be approved by the FDA as psychedelic-assisted therapy in the next few years.⁹ A broad range of other psychedelics (eg, LSD, ibogaine, 5-methoxy-N,N-dimethyltryptamine [5-meO-DMT]) are also being studied and likely will be approved for a diverse range of conditions over the coming decade.

During the long FDA review process, some states and localities have taken the lead in passing legislation to decriminalize psychedelics or create therapeutic access programs for psychedelics. In 2020, Oregon voters passed Measure 109, a ballot initiative that will create clinics throughout the state where patients can access psychedelic-assisted therapy with psilocybin for an unrestricted range of conditions. These clinics are expected to start providing services in mid-2023. About 15 cities across the country, including Denver; Washington, DC; San Francisco; Detroit; and Cambridge, MA, have passed laws decriminalizing the possession, use, and sharing of psychedelics or deprioritizing psychedelics for local law enforcement.

The United States is battling massive challenges in worsened mental health, increased substance use disorders, and pain that is ineffectively treated. At the same time, psychedelics are garnering more favorable media coverage, earning more positive study results, and becoming more widely available. The result is dramatically increasing rates of psychedelic usage by all sectors of society. Some of your patients are almost certainly already using controlled psychedelic substances.

The Special Case of Ketamine

Ketamine was approved by the FDA as an anesthetic in 1970 and is now categorized as a Schedule III drug. In clinical settings, it is often used for outpatient surgeries because it puts patients in a twilight state and has a very short half-life. Ketamine also does not suppress breathing, unlike opioids, making it safer than other options. Ketamine is also abused (ie, Special K). The dissociative effect of ketamine is appealing for some users. Sometimes ketamine is referred to as a horse tranquilizer because it is used in veterinary practice.

The S(+) enantiomer of ketamine, esketamine (Spravato [Janssen Pharmaceuticals; Beerse, Belgium]), was approved in 2019 for use in treatment-resistant depression. Over the past few years, there has been rapid growth of ketamine infusion clinics, where this dissociative hallucinogen is being administered for the treatment of a large array of conditions.

There is a growing body of research¹⁰ evaluating various forms of ketamine (eg, intravenous, subcutaneous, intranasal, sublingual) for the treatment of cluster headache, migraine, and other forms of headache. When used therapeutically, study results as well as patient feedback show efficacy in reducing pain and limiting the number of attacks. Ketamine should be a key tool in the neurologist’s armamentarium for the treatment of headache disorders, especially for patients whose symptoms have not responded adequately to other treatments.

Many ketamine clinics are being established throughout the United States to treat a wide range of diseases. These treatments are rarely covered by insurance. More research is needed to determine the best and safest ketamine protocols for each condition of use.

What Patients Need

Clinician knowledge about psychedelic substances and how patients are using them can be crucial in ensuring safety. Clinicians need to learn about controlled substances and their potential uses in treating neurologic diseases. Psychedelic medicines may be used primarily to treat the patient’s pain, but they are also used to treat some of the psychological issues that come with severe headache disorders. Research is evolving rapidly and it is important to stay up to date on the latest information. Patients may bring research or other documentation regarding the efficacy of psychedelics to an appointment and it is necessary for the clinician to have some informed knowledge on the subject when discussing it with the patient.

Patients should be asked about their use of controlled substances and an atmosphere created in which they feel safe discussing this topic. The clinician is entrusted to educate patients about potential contraindications with other medications they may be prescribed. In the headache field, there are many commonly prescribed medications that may interact with commonly used controlled substances. Monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), and triptans are all known to potentially block the action of psychedelic substances due to their interactions with serotonin receptors. Serotonin toxicity may also be a concern, although it is rare, and there is not much evidence that it occurs in patients using psychedelics to treat their headache disease. Nevertheless, it is wise to advise patients to discontinue use of serotonin-active medicines in the days prior to taking a controlled substance if it is safe for them to do so.

There is anecdotal evidence that suggests that some other prescription medications, such as calcium channel blockers, anticonvulsants, steroids, and opiates, may block the action of psychedelics, but less is known about the relationship between their actions in the body and the actions of psychedelic medicines. This should be discussed with patients to determine the best course of action for their individual situations to ensure treatment compliance. If patients are going to take controlled substances, their physicians must understand how these patients are managing their care at home.

Patients with cluster headache use different psychedelics in a variety of ways. They may use LSD or psilocybin to try to break or avoid their cluster cycle. They may use N,N-dimethyltryptamine (DMT) in homemade vape pens to treat individual attacks. In addition, they may be using ketamine or cannabis to treat their headache disorders.

Advocating Together

In the medical realm, doctors are considered experts because of their extensive training, knowledge, and experience, whereas patients may be perceived as medically uneducated. However, there is a growing positive trend of valuing the patient’s perspective, especially for those with chronic, debilitating diseases, such as cluster headache; these patients often are very educated about their disorder. When the patient’s voice and experience is valued alongside the clinical knowledge and experience of the health care professional, this joint knowledge and collaboration can lead to the best outcomes, especially for policy advocacy.

One of the most effective lobbying tandems is a patient who can share a powerful personal story of healing, hope, and medical need combined with the expertise and authority of a doctor. The Alliance for Headache Disorders Advocacy (AHDA) has been using this method for 15 years with great success. Founded in 2007 by headache specialist Dr. Robert Shapiro, AHDA was formed to address the policy barriers that limit research into and effective treatment of headache disorders. AHDA’s plan was to bring together doctors, scientists, researchers, and patient advocates at Capitol Hill at an annual event—“Headache on the Hill”—to meet with their members of Congress to discuss achievable policy goals for headache disorders. Similar lobbying efforts exist for other neurologic diseases.

Over the past 15 years, AHDA initiatives have successfully focused on improving specific policies of multiple federal agencies including the National Institutes of Health, FDA, Centers for Medicare & Medicaid Services, Social Security Administration, Department of Defense, and US Department of Veterans Affairs. This could not have been achieved without doctors and patients coming together to share compelling stories, provide data, and ask their representatives to sign on to a letter, change language in a bill, provide access, or allocate funding for research to support individuals with headache diseases.

Conclusion

In most cases of new therapy development, clinicians and patients must wait for FDA approval to access the new medicine. This is not the case for psychedelic medicines that can be grown, foraged, or sourced through other channels. People in pain seek relief and may be interested in trying psychedelic substances, which have a growing body of research showing their safety and efficacy for a wide range of conditions.

Clinicians who do not learn about or discuss substances until they become approved by the FDA do not best serve their patients who are already using these alternative medicines. Especially for patients with conditions that are difficult to treat with currently available medicines, learning and sharing information about lifestyle changes and alternative substances that deliver the best outcomes will be beneficial.

Beyond serving individual patients, clinicians should view policy advocacy as a key part of provision of optimal medical care. Changing and improving the health care system helps clinicians work more effectively and patients benefit from improved outcomes. Expanding access to psychedelic medicines will improve patients’ lives and their physicians should be partners in making this happen.