FDA Law and the Psychedelic Renaissance

By Edgar J. Asebey & James T. O’Reilly*

Update Magazine, Food & Drug Law Institute (Spring 2024)

On December 11, 2023, the U.S. Food and Drug Administration (FDA) received the first ever New Drug Application (NDA)^[1]for a psychedelic-assisted therapy.^[2] The application was filed by the Multidisciplinary Association for Psychedelic Studies (MAPS) Public Benefit Corporation (PBC) for MDMA-assisted therapy for Post-Traumatic Stress Disorder (PTSD) and represents the culmination of over a decade of clinical trials by the organization. On February 9, 2024, MAPS-PBC, now known as Lykos Therapeutics, announced that FDA had accepted its NDA, granted the application priority review, and assigned a PDUFA^[3]target date of August 11, 2024. If approved, this would be the first ever FDA-approved psychedelic therapy.

In light of a potential impending FDA approval as well as a proliferation of clinical studies using psychedelic substances, in 2024 it is essential to understand the history of what some indigenous cultures consider “sacred medicines”^[4] and what FDA has, in two cases,^[5]recently classified as “breakthrough therapies”^[6] for certain mental health diseases. In this article we briefly review the history of psychedelics’ discovery and traditional use, psychedelics as breakthrough therapies, the policy debate of decriminalization vs. FDA approval of psychedelic therapeutics, as well as the regulatory and policy challenges that lie ahead.

I. A Brief History

In 1943, Albert Hofmann, a Swiss chemist working at Sandoz, discovered the psychedelic properties of lysergic acid diethylamide (LSD), but it was not until the late 1950s that LSD started to be investigated for use in psychiatry, alcohol addiction, and other mental afflictions in North American clinics and academic institutions.^[7]

Similarly, the psychedelic properties of the Psilocybe mexicana mushroom from Oaxaca, Mexico, known as teonanacatl, were described by a priest, Father Sahagún, as early as 1577. But it was not until 1958 that Hofmann isolated two constituents of that mushroom, psilocybin^[8]and psilocin.^[9]Throughout the 1960s, Sandoz, Hofmann’s employer, sold pure psilocybin under the brand name Indocybin for basic psychopharmacological and therapeutic clinical research throughout the world.^[10]

When the Controlled Substances Act (CSA) was signed into law by President Nixon in 1970, psychedelic drugs that are now being researched for treatments of medical conditions, such as psilocybin, LSD, and methylenedioxymethamphetamine (MDMA), were classified as Schedule I drugs, defined as drugs with “a high potential for abuse” and “no currently accepted medical use in treatment in the United States.”^[11] The coca leaf, a sacred medicinal plant of Andean indigenous cultures containing over a dozen alkaloids, was classified as a Schedule II drug, defined as a drug with “a high potential for abuse” and “a currently accepted medical use in treatment in the United States,” the abuse of which “may lead to severe psychological or physical dependence.”^[12]Two purified alkaloids found in the coca plant were also classified as Schedule II drugs: cocaine and ecgonine, a precursor of cocaine. The original purpose of the CSA was to implement the requirements of two international treaties the United States had joined: the Single Convention on Narcotic Drugs (1961) and the U.N. Convention on Psychotropic Substances (1971). In practical terms, the CSA became the basis for federal enforcement of controlled substances laws.

Scientific inquiry into the natural products we now call “psychedelics” has involved anthropology, ethnobotany, natural products chemistry, phytopharmacology, neuropharmacology, psychopharmacology, and clinical pharmacology. This research began over 450 years ago with the first scientific observations made by Father Sahagún in Mexico, as memorialized in his 1577 publication.^[13]While scheduling of these natural products and the substances contained therein made it very difficult to obtain funding or academic support for research, we are now, it appears, on the doorstep of a psychedelic renaissance.

II. Psychedelics as “Breakthrough Therapies”

An unfortunate consequence of placing psychedelic plants and substances on Schedule I or II of the CSA was not only the stigmatization of such substances, but also the stifling of scientific research into those chemically fascinating natural products for the better part of the next 50 years.

The U.S. National Institutes of Health (NIH) remains the world’s single largest funder of biomedical research, with a budget of $45 billion in 2022.^[14] Between 2000 and 2018, NIH granted approximately $1.49 billion to researchers investigating marijuana and its cannabinoids. Notably, 98.6% of that funding (or $1.47 billion) went to studies focused on drug abuse and adverse mental health effects of marijuana and cannabinoids,^[15] leaving 1.4% of that budget to the study of the endocannabinoid system and the therapeutic potential of cannabis.

NIH has also funded some research into the medicinal use of psychedelics. For example, in 2021, Professor Matthew Johnson, PhD, of Johns Hopkins University School of Medicine was awarded a $4 million NIH grant to investigate the potential effects of psilocybin on tobacco addiction.^[16]This marked the first time NIH had funded any psychedelics research. Professor Johnson had been studying psilocybin for tobacco addiction for 13 years with the support of private funding and had, in 2014, published the results of a pilot study reporting impressive rates of abstinence from tobacco use.

In 2017, FDA granted the Multidisciplinary Association of Psychedelic Studies (MAPS), a non-profit research organization dedicated to the development of psychedelic medicines, Breakthrough Therapy designation for its MDMA treatment for post-traumatic stress disorder (PTSD).^[17] FDA designates a drug as a Breakthrough Therapy if preliminary clinical evidence shows that it may demonstrate substantial improvement over available therapies on a clinically significant endpoint. In January 2023, MAPS announced positive results from its Phase 3 clinical trials using MDMA-assisted therapy for PTSD.^[18] On February 9, 2024, MAPS-PBC, now known as Lykos Therapeutics, announced that FDA had accepted its NDA, granted the application priority review, and assigned a PDUFA^[19]target date of August 11, 2024. If approved, this would be the first ever FDA-approved psychedelic therapy.

In another instance in 2018, FDA granted COMPASS Pathways, a life science company focused on mental health indications, Breakthrough Therapy designation for its psilocybin therapy for treatment-resistant depression.^[20]Since the designation, COMPASS has been studying psilocybin in patients with PTSD. In December of 2023, COMPASS reported the initial results from a Phase II clinical trial, announcing that the initial data indicated that their psilocybin product known as COMP360 was well-tolerated and that patients had experienced no adverse results.^[21]Efficacy results are expected in the spring of 2024 and the multi-center study is being conducted in two cites in the United States and one in England.^[22]

The impact of NIH funding for what Johns Hopkins has claimed was the first clinical study using a psychedelic substance in 50 years^[23] combined with the Breakthrough Therapy designations for two psychedelic substances currently on Schedule I cannot be overstated. First, it removes the stigma associated with funding human clinical research using psychedelic substances. Second, it clearly signals to the biomedical and life sciences communities that, despite the Drug Enforcement Administration’s (DEA) Schedule I classification, two critically important U.S. government entities, FDA and NIH, consider at least two psychedelics substances promising potential human therapeutics.

The investor and venture capital communities have also taken note of these new opportunities in psychedelic drug development. Between July 2021 and July 2022, psychedelics-related start-ups raised over $236 million.^[24]New venture capital (VC) funds focused on supporting psychedelic drug development start-ups have proliferated. These include Iter Investments,^[25]Palo Santo,^[26]Noetic Fund,^[27] JLS Fund,^[28]Empath Ventures,^[29] and PsyMed Ventures,^[30] to name a few. These new VC funds have provided start-up capital to scientific ventures such as: Psilera,^[31]Psygen,^[32] Awakn Life Sciences,^[33]atai Life Sciences,^[34] Beckley Psytech,^[35] MindMed,^[36]Reset Pharma,^[37] Usona Institute,^[38]Cybin,^[39] Freedom Biosciences,^[40]and Sensorium Therapeutics, to name a few.

These innovative psychedelics biotech ventures are spending the capital they have raised on pursuing preclinical and clinical studies using either traditional psychedelic natural products or patentable structural analogues of those traditional psychedelic compounds. Indications targeted by these companies include:

• Psilocybin for treatment-resistant depression
• Psilocybin for anxiety in advanced-stage cancer patients
• N,N-dimethyltryptamine (DMT) for alcohol use disorder (AUD)
• LSD D-Tartrate for general anxiety disorder (GAD)
• MDMA-assisted therapy for severe PTSD
• 5-MeO-DMT for anxiety and depression

NIH’s clinicaltrials.gov^[41]currently lists 156 registered clinical trials involving psilocybin, 172 involving DMT, 142 involving MDMA, 117 involving LSD, and 13 involving 5-MeO-DMT. Human clinical trials utilizing psychedelics have become so common that, in June 2023, FDA published a draft Guidance for Industry entitled, “Psychedelic Drugs: Considerations for Clinical Investigations.”^[42]

The coming years may see a boom in scientific publications substantiating the clinical efficacy of certain psychedelic or psychedelic-inspired drug products and potentially more than one FDA approval of psychedelic drugs for medical conditions.

III. FDA-Approved or Decriminalized?

The Psychedelic Renaissance currently taking place in the scientific research/biotechnology sectors is only half the story. The other half is comprised of the decriminalization efforts that have been taking place at the state and municipal level since 2019.

These two movements are arguably related. Research into psychedelics continues to grow at prestigious research institutions such as Johns Hopkins University,^[43]Imperial College London,^[44]and Yale School of Medicine.^[45] Utilizing traditional psychedelics like psilocybin (a constituent of “magic mushrooms”), DMT (the hallucinogenic chemical in ayahuasca),^[46]and LSD, researchers at the universities have examined the therapeutic potential of these once-maligned psychedelics, including their dosing and administration. These academic studies, many of which have led to publication in peer-reviewed journals, have given ammunition to advocacy groups seeking decriminalization of psychedelics.

Not surprisingly, the first psychedelic that was the subject of a decriminalization campaign was psilocybin, when Denver, Colorado became the first city to decriminalize the psychedelic in May 2019.^[47]The California cities of Oakland (June 2019)^[48]and Santa Cruz (January 2020)^[49] also decriminalized psilocybin. Washington, D.C. passed Initiative 81,^[50]the Entheogenic Plant and Fungus Policy Act of 2020, which went into effect on March 15, 2021, and which made arrests for adult possession of “magic mushrooms” among the lowest law enforcement priority. Somerville, Massachusetts decriminalized psilocybin in January 2021 and was followed by Cambridge (February 2021) and Northampton (March 2021). Next to decriminalize psilocybin were Seattle, Washington (October 2021) and Detroit, Michigan (November 2021).

In November 2020, Oregon became the first state to legalize a psychedelic.^[51] The passage of Measure 109 and implementing regulations^[52]overseen by the Oregon Health Authority address the administration of psilocybin to individuals over age 21 for therapeutic purposes through licensed psilocybin service center operators and psilocybin service facilitators.

Following Oregon’s lead, Colorado became the second U.S. state to legalize facilitated psilocybin services when voters passed Proposition 122, the Natural Medicine Health Act, in November 2022. The legislation opens the door to treatment with other psychedelics and decriminalizes the personal use and possession—within some limits—of most entheogens. Psilocybin treatment services are expected to begin in Colorado by late 2024, although the measure could be expanded in 2026 to include facilitated sessions with ibogaine, mescaline (not derived from peyote), and natural DMT (such as the type contained in ayahuasca)—all of which have psychoactive effect and therapeutic potential.^[53]

Licensed “healing centers” will be permitted by the Colorado law to utilize psilocybin mushrooms. The law^[54] permits cultivating for personal use by individuals over 21, with some limits. The holder of the healing center state license need not apply to also be granted a treatment center license, and any violations may result in suspension of the license.^[55]

Between 2019 and 2022, a study by Siegel in JAMA Psychiatry described that psychedelic bills have been introduced at the state level with steady and increased frequency: five initiatives in 2019, six in 2020, 27 in 2021, and 36 by the end of 2022. This study also found that of the 74 bills considered across 25 states, ten have been enacted and 32 remained active in 2022—the majority focusing on psilocybin, a substantial number including MDMA, and a significant portion advocating for decriminalization, albeit with limited regulatory guidance, signaling a move towards bipartisan support for psychedelic reform.^[56]

In 2023, the biggest news was the decriminalization movement in the state of California. Senate Bill 58 passed the legislature and sought to decriminalize naturally occurring substances, including psilocybin, psilocyn, DMT, and mescaline, allowing for the possession and personal use of the psychedelics for those 21 and older with various restrictions. In early October 2023, Governor Newsom vetoed the bill, stating that “California should immediately begin work to set up regulated treatment guidelines—replete with dosing information, therapeutic guidelines, rules to prevent against exploitation during guided treatments, and medical clearance of no underlying psychoses.”^[57]

IV. Regulatory and Other Challenges Ahead

An overly eager decriminalization movement, however, may endanger the progress made by dedicated research scientists in the United States and abroad.

After decades of research, FDA may approve MAPS’s MDMA-assisted therapy for severe PTSD sometime in 2024, as the non-profit announced positive results of a second Phase 3 clinical trial in September of 2023.^[58]If this occurs, this historic drug approval will, no doubt, provide additional impetus to the movement that seeks to decriminalize MDMA and other psychedelics. Activists will likely argue that MDMA has been proven an efficacious treatment for PTSD and, therefore, it should be widely available to all that need it.

This is a dangerous argument because any FDA-approved drug must be manufactured in an FDA-registered facility under strict good manufacturing practice (GMP) controls. Any FDA-approved labeling may include restrictions with respect to the patient population and how the drug may be administered to patients that meet certain criteria and will be necessarily coupled with integration therapy.^[59] Even MAPS, arguably the staunchest proponent of MDMA’s therapeutic value, states on its PTSD web page: “The safety and efficacy of MDMA-assisted therapy is currently under investigation. It is not yet approved by FDA, does not work for everyone, and carries risks even in therapeutic settings.”^[60]Consequently, any FDA approval of MDMA for a particular indication does not justify making MDMA of dubious origin (i.e., illegally manufactured, likely not under GMP and possibly adulterated) freely available to individuals who may or may not benefit from using the drug and with likely no medical professional involved either at the moment of administration or during what is referred to as a critical “integration” period, discussed below.

Thoughtful proponents of decriminalization will likely seek to create a state statutory framework to address these pitfalls. This could include access to clinics; laboratory testing services to determine the purity of a patient’s MDMA; verified, safe sources of MDMA; and access to integration therapy. This same model could potentially be used with psilocybin, DMT, ibogaine, and LSD.

Beyond the quality of the psychedelic substance, another challenge lies in the actual clinical administration. Anthropologists and ethnobotanists, such as Richard Evan Schultes, PhD, and Wade Davis, PhD, who have observed and written extensively about traditional indigenous use of sacred medicines such as ayahuasca (containing DMT) or Psilocybe mexicana (containing psilocybin) have maintained that the “set and setting,” referring to the one’s mindset (set) and physical and social environment (setting), are factors that can greatly influence the effects of the psychedelic experience. It is for this reason that sacred indigenous ceremonies typically surround the use of these powerful substances with shamans greatly influencing the set and setting in order to facilitate spiritual and physical healing.

When translating use of these traditional indigenous medicines into Western clinical settings, researchers have recognized the critical role of set and setting.^[61]Accordingly, researchers have developed protocols that include “integration” and behavioral cognitive therapy as a way to provide support and guidance to the subject receiving the psychedelic therapy and potentially improve any therapeutic outcome.^[62]Today, integration or therapy is recommended when administering not only psychedelics that come from traditional indigenous cultures, but also other controlled substances, such as ketamine, MDMA, and LSD. This will necessitate the creation of practitioner certification standards for health professionals providing psychedelic integration services.

Companies like MAPS/Lykos have designed their psychedelic therapeutics in close association with integration therapy. It is anticipated that, if FDA approves MAPS’s MDMA, the approval may address MDMA-assisted therapy.^[63]FDA has previously approved products that, while efficacious, have a higher risk profile and require some type of monitoring or preparation through its Risk Evaluation and Mitigation Strategies (REMS), which specify conditions for safe use. FDA has previously used the REMS program to mitigate serious safety concerns but not to increase the effectiveness of a drug.^[64] Like therapists, doctors, and other health care practitioners, FDA will need to make some necessary adjustments when regulating psychedelic-based medicines.

Another regulatory challenge will emerge when psychedelics become more widely available through state legalization efforts: the drugs are still illegal under the CSA. State-approved medical marijuana programs typically require at least a yearly visit to a prescribing physician and give medical marijuana cardholders access to marijuana products that have been cultivated under a specific set of controls and which have been subject to testing for adulterants, such as microbes, residual solvents, heavy metals, pesticides, herbicides, and fungicides. Few, if any, of these safeguards are present with regard to the psychedelic substances that are the object of decriminalization efforts, potentially endangering the health of unsuspecting users. If more states “legalize” psychedelics at the state level, as was recently attempted in California, these issues will need to be adequately addressed though state legislation.

As with cannabis, any state-sanctioned access to psychedelics will not change the fact that these substances are Schedule I drugs, and it will remain federally unlawful to buy, possess, or sell these substances. Today, state-sanctioned medical marijuana programs exist in 38 states, three territories, and the District of Columbia (D.C.), with 24 states, alongside two territories and D.C., also legalizing it for recreational use.^[65]

Each state that permits the lawful use of marijuana has implemented state regulatory frameworks that dictate requirements with respect to the production, storage, processing, and sale of cannabis products. The DEA and the Department of Justice have, to date, generally exercised enforcement discretion with regard to cannabis producers and purchasers who comply with state cannabis laws. While there has been no systematic enforcement of the CSA or the Federal Food, Drug, and Cosmetic Act (FDCA) against producers or purchasers of psychedelics in states or municipalities that have decriminalized such substances, there is no guarantee that federal agencies will remain on the sidelines, especially if states decriminalize psychedelics with no accompanying framework for the safe production and sale of such products.

New state or federal regulations regarding use of psychedelics will also need take into consideration existing religious use protections for some psychedelic natural products.

There is much work yet to be done—not only in scientifically substantiating the therapeutic efficacy of psychedelic medicines, but also with regard to state and federal regulations under which those psychedelic medicines will become available to patients. Today, we know that psilocybin facilitates neuroplasticity of the brain by activating the serotonin 2A receptors,^[66] allowing the brain to reorganize neural networks,^[67]underlining a biological mechanism through which psilocybin could be used as basis to treat a spectrum of neurological and psychiatric disorders. We also know that MDMA, in combination with psychotherapy, may be a potential treatment for PTSD.^[68] Psychedelics have also shown promise in treatment-resistant depression^[69]and various types of addiction.^[70]There remain scientific, clinical, legal, and regulatory challenges with regard to psychedelics, but there is no doubt that the Psychedelic Renaissance has arrived.

* The authors would like to thank Guilherme Ferrari Faviero, Esq., M.S., MPH for his invaluable assistance in researching and editing this article.

[1] See New Drug Application (NDA), U.S. Food & Drug Admin. (Jan. 21, 2022), https://www.fda.gov/drugs/types-applications/new-drug-application-nda (last visited Feb. 9, 2024).

[2] Max Bayer, First-Ever Drug Application for MDMA Finally Reaches FDA After Near 40-Year Journey, Fierce Biotech (Dec. 13, 2023), https://www.fiercebiotech.com/biotech/maps-pbc-files-seminal-new-drug-application-mdma (last visited Feb. 9, 2023).

[3] See Priority Review, U.S. Food & Drug Admin. (Jan. 4, 2018), https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review.

[4] Yuria Celidwen, Nicole Redvers, Cicilia Githaiga, Janeth Calambás, Karen Añaños, Miguel Evanjuanoy Chindoy, Riccardo Vitale, Juan Nelson Rojas, Delores Mondragón, Yuniur Vázquez Rosalío & Angelina Sacbajál, Ethical Principles of Traditional Indigenous Medicine to Guide Western Psychedelic Research and Practice, Lancet Regional Health – Americas, vol. 18 100410. 16 Dec. 2022, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9950658/ (last visited Feb. 9, 2024).

[5] Sean J. Belouin, Lynnette A. Averill, Jack E. Henningfield, Stephen N. Xenakis, Ingrid Donato, Charles S. Grob, Ann Berger, Veronica Magar, Alicia L. Danforth & Brian T. Anderson, Policy Considerations that Support Equitable Access to Responsible, Accountable, Safe, and Ethical Uses of Psychedelic Medicines, Neuropharmacology (Nov. 15, 2023), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536012/pdf/nihms-1833588.pdf; Megan Brooks, FDA Grants Psilocybin Second Breakthrough Therapy Designation for Resistant Depression, Medscape Medical News (Nov. 25, 2019), https://www.medscape.com/viewarticle/921789?form=fpf.

[6] See Breakthrough Therapy, U.S. Food & Drug Admin. (Jan. 4, 2018), https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy (last visited Feb. 9, 2024).

[7] Erika Dyck, In Review Flashback: Psychiatric Experimentation With LSD in Historical Perspective, 50 Can. J. Psychiatry 7 (2005), https://journals.sagepub.com/doi/pdf/10.1177/070674370505000703 (last visited Feb. 9, 2024).

[8] Gerard Sanacora, Brandon M. Kitay & Samuel T. Wilkinson, The Search for Rapid Acting Antidepressants: Research Synthesis and Perspectives, in Neurobiology of Depression: Road to Novel Therapeutics 401–13 (2019), https://www.sciencedirect.com/topics/neuroscience/psilocybin (last visited Feb. 9, 2024).

[9] John T. Cody, Psilocin, in Handbook of Analytical Separations (2008), https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/psilocin (last visited Feb. 9, 2024).

[10] See Haden A. Geiger, Madeline G. Wurst & R. Nathan Daniels, DARK Classics in Chemical Neuroscience: Psilocybin, ACS Chemical Neuroscience  9(10), 2438–47 (2018), https://pubs.acs.org/doi/10.1021/acschemneuro.8b00186.

[11] 21 U.S.C. § 812(b)(1) (defining Schedule I substances).

[12] 21 U.S.C. § 812(b)(2) (defining Schedule II substances).

[13] Fray Bernardino de Sahagún, General History of the Things of New Spain by Fray Bernardino de Sahagún: The Florentine Codex, Vol. 1, Lib. of Cong. (1577), https://www.loc.gov/resource/gdcwdl.wdl_10096_001/?sp=3&st=gallery (last visited Feb. 14, 2023).

[14] See Grants & Funding, National Institutes of Health, https://www.nih.gov/grants-funding#:~:text=The%20National%20Institutes%20of%20Health,to%20reduce%20illness%20and%20disability.

[15] John M. Purcell, Tija M. Passley & Joerg R. Leheste, The Cannabidiol and Marijuana Research Expansion Act: Promotion of Scientific Knowledge to Prevent a National Health Crisis, 14 Lancet Regional Health – Americas 100325 (2022), https://doi.org/10.1016/j.lana.2022.100325 (last visited Feb. 9, 2024).

[16] Johns Hopkins Medicine Receives First Federal Grant for Psychedelic Treatment Research in 50 Years, Johns Hopkins Medicine (Oct. 18, 2021), https://www.hopkinsmedicine.org/news/newsroom/news-releases/2021/10/johns-hopkins-medicine-receives-first-federal-grant-for-psychedelic-treatment-research-in-50-years (last visited Feb. 9, 2024).

[17] FDA Grants Breakthrough Therapy Designation for MDMA-Assisted Therapy for PTSD, Agrees on Special Protocol Assessment for Phase 3 Trials, MAPS (Aug. 26, 2017), https://maps.org/news/media/press-release-fda-grants-breakthrough-therapy-designation-for-mdma-assisted-psychotherapy-for-ptsd-agrees-on-special-protocol-assessment-for-phase-3-trials/ (last visited Feb. 9, 2024).

[18] Stephanie Price, MAPS Confirms Successful Phase 3 Trial of MDMA for PTSD, Psychedelic Health (Jan. 5, 2023), https://psychedelichealth.co.uk/2023/01/05/maps-confirms-successful-phase-3-trial-of-mdma-for-ptsd/ (last visited Feb. 9, 2024).

[19] See Priority Review, U.S. Food & Drug Admin. (Jan. 4, 2018). https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review.

[20] COMPASS Pathways Receives FDA Breakthrough Therapy Designation for Psilocybin Therapy for Treatment-resistant Depression, PR Newswire (Oct. 23, 2018), https://www.prnewswire.com/news-releases/compass-pathways-receives-fda-breakthrough-therapy-designation-for-psilocybin-therapy-for-treatment-resistant-depression-834088100.html (last visited Feb. 9, 2024).

[21] James Waldron, Compass Shows Safety in First Psilocybin Trial for PTSD, but Efficacy Data Still to Come, Fierce Biotech (Dec. 20, 2023), https://www.fiercebiotech.com/biotech/compass-reads-out-safety-data-first-psilocybin-trial-ptsd-efficacy-data-come (last visited Mar. 1, 2024).

[22] Id.

[23] Johns Hopkins Medicine Receives First Federal Grant for Psychedelic Treatment Research in 50 Years, supra note 17.

[24] Keerthi Vedantam, Psychedelics Provide New Frontier For Venture Funding, But Nuances Prevail, Crunchbase News (July 19, 2022), https://news.crunchbase.com/health-wellness-biotech/psychedelics-drug-funding/ (last visited Feb. 9, 2024).

[25] Iter Investments, https://www.iterinvestments.com.

[26] Palo Santo, https://www.palosanto.vc.

[27] Noetic Fund, https://noeticfund.com.

[28] JLS Fund, https://www.jls.fund/#start.

[29] Empath Ventures, https://www.empath.vc.

[30] PsyMed Ventures, https://psymed.ventures.

[31] Psilera, https://www.psilera.com.

[32] Psygen, https://psygen.ca/.

[33] Awakn Life Sciences, https://awaknlifesciences.com.

[34] Atai Life Sciences, https://atai.life.

[35] Beckley Psytech, https://www.beckleypsytech.com/.

[36] MindMed, https://mindmed.co.

[37] Reset Pharma, https://www.resetpharma.com.

[38] Usona Institute, https://www.usonainstitute.org.

[39] Cybin, https://cybin.com.

[40] Freedom Biosciences, https://www.freedombio.co.

[41] ClinicalTrials,gov, National Library of Medicine, https://clinicaltrials.gov.

[42] Draft Guidance: Psychedelic Drugs: Considerations for Clinical Investigations—Guidance for Industry, U.S. Food & Drug Admin. (June 2023), https://www.fda.gov/media/169694/download (last visited Feb. 9, 2024).

[43] Research, Johns Hopkins Center for Psychedelic & Consciousness Research, https://hopkinspsychedelic.org/index/#research.

[44] Centre for Psychedelic Research, Imperial College London, https://www.imperial.ac.uk/psychedelic-research-centre/.

[45] Ongoing Research, Yale School of Medicine, https://medicine.yale.edu/psychiatry/research/programs/clinical_people/psychedelic/research/.

[46] Daniel F. Jiménez-Garrido, María Gómez-Sousa, Genís Ona, Rafael G. Dos Santos, Jaime E. C. Hallak, Miguel Ángel Alcázar-Córcoles & José Carlos Bouso, Effects of Ayahuasca on Mental Health and Quality of Life in Naïve Users: A Longitudinal and Cross-Sectional Study Combination, Nature Sci. Reps. 10, 4075 (2020), https://www.nature.com/articles/s41598-020-61169-x#citeas.

[47] Denver Becomes First US City to Decriminalize ‘Magic Mushrooms,’ The Guardian (May 9, 2019), https://www.theguardian.com/us-news/2019/may/08/denver-votes-against-initiative-to-decriminalize-psilocybin-magic-mushrooms (last visited Feb. 9, 2024).

[48] Resolution Supporting Entheogenic Plant Practices and Declaring that the Investigation and Arrest of Individuals Involved with the Adult Use of Entheogenic Plants on the Federal Schedule 1 List Be Amongst the Lowest Priority for the City of Oakland (May 15, 2019), https://oakland.legistar.com/LegislationDetail.aspx?ID=3950933&GUID=5E53E7F6-F79F-433D-B669-0D687786590F&Options=&Search=.

[49] Marina Pitofsky, Santa Cruz Votes to Decriminalize Hallucinogenic Mushrooms, The Hill (Jan. 29, 2020), https://thehill.com/blogs/blog-briefing-room/news/480577-santa-cruz-votes-to-decriminalize-hallucinogenic-mushrooms/ (last visited Feb. 9, 2024).

[50] D.C. Law 23-268, Entheogenic Plant and Fungus Policy Act of 2020, D.C. Act 23-572 (Dec. 2, 2020).

[51] Andrew Jacobs, Legal Use of Hallucinogenic Mushrooms Begins in Oregon, The N.Y. Times (Jan. 3, 2023), https://www.nytimes.com/2023/01/03/well/mind/oregon-psilocybin-mushrooms.html (last visited Feb. 9, 2024).

[52] See Oregon Psilocybin Services, Oregon.gov, https://www.oregon.gov/omb/topics-of-interest/pages/oregon-psilocybin-services.aspx#:~:text=OPS%20will%20implement%20Ballot%20Measure,for%20licensure%20in%20early%202023.

[53] Kenneth W. Tupper, Evan Wood, Richard Yensen & Matthew W. Johnson, Psychedelic Medicine: A Re-emerging Therapeutic Paradigm, 187 CMAJ 1054 (2015), https://doi.org/10.1503/cmaj.141124 (last visited Feb. 9, 2024).

[55] See Joshua S. Siegel, James E. Daily, Demetrius A. Perry & Ginger E. Nicol, Psychedelics Drug Legislative Reform and Legalization in the US, 80 JAMA Psychiatry 77 (2023), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069558/ (last visited Feb. 9, 2024).

[56] See Joshua S. Siegel, James E. Daily, Demetrius A. Perry & Ginger E. Nicol, Psychedelic Drug Legislative Reform and Legalization in the US, 80 JAMA Psychiatry 77 (2023), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069558/.

[57] Governor Gavin Newsom, Veto Message on Senate Bill 58 (Oct. 7, 2023), https://www.gov.ca.gov/wp-content/uploads/2023/10/SB-58-Veto-1.pdf (last visited Feb. 9, 2024).

[58] Drug Discovery and Development: MAPS Predicts FDA Approval for MDMA-assisted Therapy in 2024, MAPS (Jan. 27, 2023), https://maps.org/news/media/drug-discovery-and-development-maps-predicts-fda-approval-for-mdma-assisted-therapy-in-2024/ (last visited Feb. 9, 2024).

[59] See News Release, Lykos Therapeutics Announces FDA Acceptance and Priority Review of New Drug Application for MDMA-Assisted Therapy for PTSD (Feb. 9, 2024), https://news.lykospbc.com/2024-02-09-Lykos-Therapeutics-Announces-FDA-Acceptance-and-Priority-Review-of-New-Drug-Application-for-MDMA-Assisted-Therapy-for-PTSD#:~:text=The%20FDA%20has%20granted%20the,therapy%20and%20psychedelic%2Dassisted%20therapy.

[60] MDMA-Assisted Therapy for PTSD, MAPS, https://maps.org/mdma/ptsd/ (last visited Feb. 9, 2024).

[61] Geoff J. Bathje, Eric Majeski & Mesphina Kudowor, Psychedelic Integration: An Analysis of the Concept and Its Practice, 13 Frontiers in Psychology (Aug. 3, 2022), https://doi.org/10.3389/fpsyg.2022.824077 (last visited Feb. 9, 2024).

[62] Ingmar Gorman, Elizabeth M. Nielson, Aja Molinar, Ksenia Cassidy & Jonathan Sabbagh, Psychedelic Harm Reduction and Integration: A Transtheoretical Model for Clinical Practice, 12 Frontiers in Psychology (Mar. 15, 2021), https://www.frontiersin.org/journals/psychology/articles/10.3389/fpsyg.2021.645246/full(last visited Feb. 9, 2024).

[63] MDMA-Assisted Therapy for PTSD, MAPS, https://maps.org/mdma/ptsd/ (last visited Feb. 9, 2024).

[64] Risk Evaluation and Mitigation Strategies (REMS), U.S. Food & Drug Admin. (May 25, 2023), https://www.fda.gov/drugs/our-perspective/risk-evaluation-and-mitigation-strategies-rems#:~:text=Risk%20evaluation%20and%20mitigation%20strategy,particular%20adverse%20event(s).

[65] State Medical Cannabis Laws, National Conference of State Legislatures, (June 22, 2023), https://www.ncsl.org/health/state-medical-cannabis-laws (last visited Feb. 9, 2024).

[66] Maxemiliano V. Vargas, Lee E. Dunlap, Chunyang Dong, Samuel J. Carter, Robert J. Tombari, Shekib A. Jami, Linday P. Cameron, Seona D. Patel, Joseph J. Hennessey, Hannah N. Saeger, John D. McCorvy, John A. Gray, Lin Tian & David E. Olson, Psychedelics Promote Neuroplasticity Through the Activation of Intracellular 5-HT2A Receptors, 379 Science 700 (2023), https://doi.org/10.1126/science.adf0435 (last visited Feb. 9, 2024).

[67] Ling-Xiao Shao, Clara Liao, Ian Gregg, Pasha A. Davoudian, Neil K. Savalia, Kristina Delagarza & Alex C. Kwan, Psilocybin Induces Rapid and Persistent Growth of Dendritic Spines in Frontal Cortex In Vivo, 106 Neuron 2535 (2021), https://pubmed.ncbi.nlm.nih.gov/34228959/.

[68] Daniel Gilbert & David Ovalle, FDA to Review MDMA-Assisted Therapy, a Milestone for Psychedelics, The Washington Post (Dec. 12, 2023), https://www.washingtonpost.com/business/2023/12/12/mdma-therapy-fda-maps/.

[69] Guy M. Goodwin et al., Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression, 387 New Eng. J. Med. 1637 (Nov. 3, 2022), https://www.nejm.org/doi/full/10.1056/NEJMoa2206443 (last visited Mar. 1, 2024).

[70] Rayyan Zafar, Maxim Siegel, Rebecca Harding, Tommaso Barba, Claudio Agnorelli, Shayam Suseelan, Leor Roseman, Matthew Wall, David John Nutt & David Erritzoe, Psychedelic Therapy in the Treatment of Addiction: The Past, Present and Future, 14 Frontiers in Psychiatry (June 12, 2023), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10291338/ (last visited Mar. 1, 2024).