like MDMA, psilocybin (“magic mushrooms”), LSD, and DMT are substances that have psychoactive properties. Their widespread use during the counterculture movement of the 1960s invoked harsh criticism and, ultimately, backlash from the government, earning these substances Schedule I designation as drugs that have “no currently accepted medical use.” Increased societal focus on the importance of mental health and wellbeing in recent years has led to a renaissance of scientific and commercial interest in psychedelics and their potential as valuable and effective therapies.
Efforts are advancing across the United States to reschedule (from Schedule I to less-restrictive schedules), decriminalize, and (in some instances) legalize the use of psychedelics in a therapeutic setting. This article provides a brief overview of the regulatory framework restricting the production, sale, and use of psychedelics; discusses psychedelic drugs which have been approved for limited use; and addresses recent legislative developments in the movement to decriminalize and/or legalize the use of psychedelics.
The Regulatory Framework for Psychedelics: A Brief Introduction
They are illegal to produce, possess, distribute, or consume. This does not mean that progress toward legitimization is not occurring.
The U.S. Drug Enforcement Administration’s (DEA) Diversion Control Division manages the registration of applicants seeking to study or otherwise handle Schedule I controlled substances for medical and scientific purposes, clinical research, and religious/indigenous use.The DEA also regulates and enforces the importation of controlled substances, their precursors and analogues. In addition to DEA registration, most states have their own controlled substances laws that require pre-review and authorization or licensure for proposed research projects involving any Schedule I substances.
On May 19, 2021, Wake Network, Inc. announced the completion of the first legal psilocybin mushroom import into the United States. Wake had successfully applied for and received all required permits from the DEA to import psilocybin from its production facility in Jamaica to its laboratory in California for research purposes. The fact that the DEA has permitted the import of psilocybin signals a marked departure from its previously strict stance.Since that time, other entities have also been licensed by the DEA to allow the importation of psilocybin. In late 2021 the DEA approved Mycrodose Therapeutics for a Schedule I Import & Distribution license that allows the company to import and sell Schedule I compounds.
The Federal Analogue Act allows any chemical that is “substantially similar” to a listed controlled substance in the CSA to be treated as if it were a Schedule I substance. Psilocybin, DMT, and psilocin are tryptamines, which are a group of alkaloids derived from tryptophan. Because the five tryptamine analogues at issue are chemically similar to these classic psychedelics, the DEA seeks to classify them as Schedule I substances. The research community is challenging this proposed scheduling and Administrative Law Judge Teresa Wallbaum ordered that parties requesting a hearing to file statements and granted a prehearing conference on the matter for May 4, 2022. The DEA is not bound by the judge’s recommendation; however, is it unusual for a hearing to be granted before the agency’s rulemaking is finalized.
Psychedelic Drug Development and FDA Review
The FDA has numerous programs to facilitate and expedite the development and review of new drugs and address unmet medical need in the treatment of serious or life-threatening conditions.
Breakthrough Therapy Designation, Other Expedited Programs, and Clinical Trials Granted to Psychedelic Drugs
Breakthrough therapy designation confers a number of benefits, including eligibility for all fast track designation features and guidance from senior managers at the FDA. Johnson & Johnson obtained the designation for esketamine (a Schedule III substance, now commercialized as Spravato®) in 2013 (for treatment-resistant depression) and 2016 (for major depressive disorder). Of all the drugs colloquially known as “psychedelics,” MDMA is the furthest along on the path to FDA approval, as it received breakthrough therapy designation from the FDA in August 2017.
Psilocybin for the treatment of resistant depression is entering Phase 3 clinical trials. It is also being investigated for behavioral disorders such as smoking cessation, binge eating discovers, clinician depression and burnout, cocaine use, and obsessive-compulsive disorder. cluster headaches, fibromyalgia, and distress in palliative care are also underway.
The FDA has not yet granted breakthrough therapy status for other psychedelics that are currently undergoing research, including LSD, Ibogaine, and DMT.It will be interesting to see whether research results eventually support these substances’ inclusion for breakthrough therapy designation.
In addition to breakthrough therapy designation, the FDA has other forms of expedited review processes to streamline the development of pharmaceuticals and treatments.
In certain situations, the FDA allows companies to provide their investigational medical products, including drugs, biologics, or medical devices, to people outside of clinical trials. This is referred to as compassionate use or expanded access. Getting access to not-yet-approved drugs through a compassionate use request is a complex process.
State and Federal Right to Try Legislation
Eligible investigational drugs under the Right to Try Act must meet certain criteria defined by the FDA, and patients must meet certain criteria to seek Right to Try use; Since reporting requirements have yet to be standardized, the FDA currently does not report, and it is unknown what drugs or how many patients have applied for and received approval under this statute.
In this case, a group of physicians in Washington State seeking to administer palliative psilocybin therapy to their terminally ill patients to treat end-of-life anxiety approached the DEA for a determination as to whether this was allowable. The DEA stated that there could be no access to this Schedule I substance other than for research, and thus the therapeutic use by the physicians would not be allowed. The physicians petitioned the 9th Circuit via a direct review provision. Amicus briefs filed in support of the petitioners include a bipartisan group of attorneys general from eight U.S. states, the American Civil Liberties Union, and leading policy and advocacy groups on both sides of the political spectrum. Ultimately the panel dismissed the petition for lack of jurisdiction, finding that the DEA’s response letter was informational and did not constitute a final agency action. In February 2022, the petitioners submitted to the DEA a Petition to Reschedule Psilocybin from Schedule I to Schedule II, and a Request for Waiver to enable access to psilocybin pursuant to state and federal Right to Try laws, seeking an agency action sufficiently “final” to enable judicial review.
Decriminalization and Legalization
Decriminalization is the decision of a governing authority to not enforce criminal laws relating to the use and possession of drugs such as psychedelics. Legalization would allow for regulation and taxation of drugs, and permission for personal use within parameters set by the government.
Movements to decriminalize psychedelics and other drugs in the United States have been underway for decades, but the last three years have seen significant movement in the passing of legislation. In May 2019, Denver, Colorado, became the first city in the United States to decriminalize psilocybin. Similar legislation has passed, both for psilocybin and other entheogenic substances, in Oregon (statewide); Arcata, Oakland, and Santa Cruz, California; Port Townsend and Seattle, Washington; Ann Arbor, Detroit, and Hazel Park, Michigan; Somerville, Cambridge, Easthampton, and Northampton, Massachusetts; and Washington DC.
Oregon’s Measure 110 passed in 2020 with a 58 percent vote of the state population and decriminalized the personal possession of all drugs.and
On a statewide level, legislation is currently being proposed to decriminalize, investigate, or otherwise ease restrictions on some psychedelics in a growing list of states. Bills are currently active in Colorado, Florida, Georgia, Hawaii, Iowa, Kansas, Maryland, Massachusetts, Missouri, New Jersey, New York, Oklahoma, Rhode Island, Vermont, Virginia, and Washington, and more states no doubt will follow.
Oregon was the first state to legalize psilocybin therapy in 2020.passed with a 56 percent vote of the state population and will establish a regulated psilocybin therapy system in Oregon to provide people therapeutic access to psilocybin. Oregon Psilocybin Services (OPS) will be housed within the Oregon Health Authority (OHA) Public Health Division’s Center for Health Protection. Measure 109 created the Oregon Psilocybin Advisory Board (OPAB) to make recommendations to the OHA on the requirements, specifications, and guidelines for providing psilocybin services in Oregon. OPS is developing the first regulatory framework for psilocybin services in the United States including regulations regarding the manufacture, standards for testing, transportation, delivery, sale, and purchase of psilocybin products and the provision of psilocybin services. Several subcommittees have been formed to advise the OPAB: equity, licensing, products, research, and training. Each subcommittee has been tasked to evaluate and recommend regulations pertaining to different aspects of this new sector, including equity and access to psilocybin treatment, manufacturer standards, facilitator licensing, service center licensing, consumer protection, informed consent, social equity in licensing and laboratory requirements, permissible products, requirements to obtain/renew manufacturing permits, testing protocols, tracking systems, packaging, taxes, safety, efficacy, and production aspects of psilocybin, psilocybin facilitator training, and curriculum development.
Unlike the legislation surrounding the decriminalization and legalization of cannabis, the proposed laws on psychedelics do not require individual patients/users to register with a provider or obtain a license (as in the case of medical marijuana licenses). Instead, the burden and responsibility for obtaining the proper licenses and registering with the state falls on providers of psychedelic therapies, such as physicians or clinics seeking to provide the substances for patients. The focus on regulating the providers, not the users, makes enforcement and tracking easier for authorities and reflects the clinical and therapeutic-based approach taken by proponents of psychedelics.
Potency and reality-altering properties of some psychedelic substances may be why the current proposed legislation has largely avoided seeking legalization on a recreational level. Microdosing is an increasingly popular practice in the use of psychedelics like psilocybin and LSD —It remains to be seen whether legislators will eventually push for the legalization of microdoses in a less-regulated setting or without the need for a licensed provider.
Legalization of psychedelics is, as of now, a state-level effort in conflict with federal law. Thus, legislative changes that have taken place at the state level do not change the fact that these substances remain federally illegal. The interplay between states’ movements to legalize psychedelics for certain uses and the federal government’s control over the same drugs will eventually come to a head. Some policymakers have suggested that the federal government adopt the equivalent of the Cole Memorandum for psychedelics.The purpose was to not waste already scarce federal resources on enforcing laws where states had determined marijuana would be allowed and where the states had established strong regulatory and enforcement mechanisms to enforce those laws.
Equity, Inclusion, and Preservation of Indigenous Tradition
Legislative efforts to decriminalize and legalize psychedelic therapeutics have rightly taken into account the traditional use of these substances by indigenous communities. Ayahuasca, mescaline, peyote, and psilocybin, to name a few, have been used for hundreds of years in indigenous ceremonies, and there is growing awareness of the possible effects of legalization.The American Indian Religious Freedom Act of 1978 (amended in 1994), codified at 42 U.S.C. 1996-1996a, protects American Indians from penalty, prosecution, or discrimination in public assistance programs for the sacramental use, possession, or transportation of peyote. Ongoing legislative and policy efforts to decriminalize and legalize psychedelics will likely continue to protect their sacramental use by indigenous populations.
The landscape is changing fast around psychedelic drug development, legislation, and research. Phase 3b clinical trials of MDMA-mediated therapy for the treatment of PTSD are anticipated to conclude in 2022, which points to a possible approval of this new modality of treatment in 2023. There are a dizzying number of moving parts to the puzzle, and what holds true today may change tomorrow. As the movement to legitimize psychedelic therapy progresses, one thing is certain: we are entering uncharted waters, and what a trip it will be.