Two Models of Legalization of Psychedelic Substances: Reasons for Concern

In 1973 psychedelics were classified as schedule I substances at the federal level, which effectively made possession illegal and restricted research except under tightly regulated circumstances. Although these constraints limited clinical investigation for decades, a recent revival of research has generated renewed interest in therapeutic applications. Parallel to this scientific resurgence, several states and localities have pursued measures to legalise possession and use of psychedelic substances, prompting debate about regulatory approaches and public-health implications. This Viewpoint examines two prominent policy paths to legalisation: Oregon's approach to broad clinical psilocybin services and California's proposed bill to legalise personal possession and noncommercial sharing of psychedelics. Smith and colleagues frame the analysis by comparing these models and drawing lessons from prior experiences with the legalisation and commercialisation of other controlled substances, with the aim of identifying potential risks that policymakers and the public should consider.

Smith and colleagues describe two distinct models that have emerged in US jurisdictions. Oregon enacted the Oregon Psilocybin Services Act by ballot in November 2020, instructing the Oregon Health Authority to implement regulation and licensure for clinical psilocybin treatment by the end of 2022 and creating an advisory board with members from psychology, medicine, public health and related fields. The authors note that Oregon appears to anticipate federal non-enforcement for state-legal use, analogous to state-level marijuana policies. By contrast, California Senate Bill 519, which passed the state Senate in June 2021 and was pending in the Assembly as of July 12, 2021, would legalise adult possession, personal use and noncommercial sharing of psychedelics; similar local ordinances already exist in several cities. The bill also mandates a Department of Public Health study on approaches to promote safe and equitable access, and a 2022 ballot initiative is being prepared should legislative action fail. The paper summarises the current evidence base for therapeutic benefits and the uncertainties that remain. While some studies show promising effects on depression, suicidality, substance use disorders and PTSD, much of the literature is preliminary: many trials are small, blinding is difficult because of the subjective effects of psychedelics, and study samples commonly exclude people with comorbidities, prior drug use or personal or family histories of psychotic disorders. The authors highlight two illustrative trials reported in the extracted text: a Phase II trial of 59 selected patients in which psilocybin did not differ significantly from escitalopram for depressive symptoms, and a Phase III trial of 91 patients in which MDMA produced a large effect versus placebo for PTSD (d = 0.91). They emphasise the need to distinguish serotonergic psychedelics (for example, psilocybin) from entactogens such as MDMA: mechanisms likely differ, investigators often characterise the therapeutic mechanism for serotonergic agents in terms of “mystical experiences” and for MDMA in terms of empathogenic effects, and the safety profiles are not the same. Regarding risks, the authors note that the epidemiology and acute toxic effects of MDMA are relatively well studied and include hyperthermia, hypertension, seizure, arrhythmia and psychosis. In contrast, the risks of serotonergic psychedelics outside controlled trials are less well understood. Case reports have raised concern about psychedelics precipitating psychotic episodes in susceptible individuals, and population surveys provide conflicting signals. One survey of 1,993 psilocybin users who experienced “bad trips” found that 62% described them among the 10 most challenging experiences of their lives, 10.7% reported placing themselves or others at physical risk, 2.6% reported becoming physically violent, and 10% had symptoms lasting more than one year, with a small number exhibiting features consistent with enduring psychosis. Other studies, however, suggest associations between lifetime psychedelic use and decreased suicidality or no link with current psychotic symptoms; overall, the incidence of transient psychedelic-induced psychosis remains uncertain. The authors identify four converging forces driving advocacy for legalisation: favourable media coverage generating public enthusiasm, concerns about harms from criminalisation and disproportionate incarceration of marginalised groups, philanthropic funding from wealthy proponents, and commercial and fiscal incentives such as investment opportunities and potential tax revenue. They warn that these drivers may underplay countervailing concerns; commercial expansion could increase access among vulnerable populations, and the extent to which psychedelic enforcement contributes to racialised criminalisation is unclear and likely far smaller than for substances such as cocaine and cannabis. To illustrate potential downstream effects, the paper draws lessons from cannabis legalisation and from the rapid expansion of for-profit ketamine clinics. Cannabis legalisation has delivered clear benefits related to decriminalisation, but the broader outcomes have been mixed: in states that legalised marijuana, cannabis use disorder rose by 25% among 12- to 17-year-olds from 2008 to 2016 and by 36% in people older than 26 years, and increases in self-medication, functional impairment, impaired driving and psychiatric comorbidity have been reported. The authors also cite reports correlating legalisation with rising prevalence of psychosis and hospitalisation, providing Portugal as an example where public-hospital admissions for psychotic disorders rose substantially after decriminalisation and the proportion of patients with concomitant cannabis use disorder increased from 0.87% to 10.60%. For strictly clinical models, such as Oregon’s, Smith and colleagues caution that non-evidence-based marketing and clinic proliferation—paralleling problems seen in many ketamine clinics—could supplant rigorous, evidence-based practice. Investigative accounts suggest that some ketamine providers have failed to screen appropriately, have offered unsupported indications or dosing, lacked mental-health professionals on staff and have promoted exaggerated claims. The authors contrast this unregulated off-label ketamine landscape with the more stringent US Food and Drug Administration Risk Evaluation and Mitigation Strategy applicable to esketamine. In their concluding discussion the authors argue for prudence: rapid legalisation and commercialisation may short-circuit careful policy development and obscure potential harms that are not yet well characterised. They recommend alternatives that could achieve some goals of reform while limiting risks, for example deprioritising enforcement of possession laws. Ultimately, Smith and colleagues urge slowing the push to legalise psychedelic substances to allow clarification of the evidence base, better information for policymakers and the public, and the development of careful regulatory frameworks to govern therapeutic and non-clinical use.