Two Models of Legalization of Psychedelic Substances : Reasons for Concern

Psilocybin may have antidepressant properties, but direct comparisons between psilocybin and established treatments for depression are lacking.

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants ( n  = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo ( P  < 0.0001, d  = 0.91) and to significantly decrease the SDS total score ( P  = 0.0116, d  = 0.43). The mean change in CAPS-5 scores in participants completing treatment was −24.4 (s.d. 11.6) in the MDMA group and −13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation. Results from a phase 3, double-blind, randomized, placebo-controlled trial demonstrate that MDMA-assisted therapy is safe and effective in treating severe post-traumatic stress disorder. Show more

This study uses repeated cross-sectional survey data from the National Survey on Drug Use and Health (2008-2016) to investigate the association between recreational marijuana legalization and changes in marijuana use and cannabis use disorder in the United States. How did marijuana use and cannabis use disorder change during 2008 to 2016 after the legalization of recreational marijuana in the United States? In this multilevel, difference-in-difference survey study with 505 796 respondents comparing marijuana use before and after the legalization of recreational marijuana in the United States, the proportion of respondents aged 12 to 17 years reporting cannabis use disorder increased from 2.18% to 2.72%, while the proportion of respondents 26 years or older reporting frequent marijuana use increased from 2.13% to 2.62% and those with cannabis use disorder, from 0.90% to 1.23%. This study’s findings suggest that possible increases in the risk for cannabis use disorder among adolescent users and increases in frequent use and cannabis use disorder among adults after legalization of recreational marijuana use may raise public health concerns and warrant ongoing study. Little is known about changes in marijuana use and cannabis use disorder (CUD) after recreational marijuana legalization (RML). To examine the associations between RML enactment and changes in marijuana use, frequent use, and CUD in the United States from 2008 to 2016. This survey study used repeated cross-sectional survey data from the National Survey on Drug Use and Health (2008-2016) conducted in the United States among participants in the age groups of 12 to 17, 18 to 25, and 26 years or older. Multilevel logistic regression models were fit to obtain estimates of before-vs-after changes in marijuana use among respondents in states enacting RML compared to changes in other states. Self-reported past-month marijuana use, past-month frequent marijuana use, past-month frequent use among past-month users, past-year CUD, and past-year CUD among past-year users. The study included 505 796 respondents consisting of 51.51% females and 77.24% participants 26 years or older. Among the total, 65.43% were white, 11.90% black, 15.36% Hispanic, and 7.31% of other race/ethnicity. Among respondents aged 12 to 17 years, past-year CUD increased from 2.18% to 2.72% after RML enactment, a 25% higher increase than that for the same age group in states that did not enact RML (odds ratio [OR], 1.25; 95% CI, 1.01-1.55). Among past-year marijuana users in this age group, CUD increased from 22.80% to 27.20% (OR, 1.27; 95% CI, 1.01-1.59). Unmeasured confounders would need to be more prevalent in RML states and increase the risk of cannabis use by 1.08 to 1.11 times to explain observed results, indicating results that are sensitive to omitted variables. No associations were found among the respondents aged 18 to 25 years. Among respondents 26 years or older, past-month marijuana use after RML enactment increased from 5.65% to 7.10% (OR, 1.28; 95% CI, 1.16-1.40), past-month frequent use from 2.13% to 2.62% (OR, 1.24; 95% CI, 1.08-1.41), and past-year CUD from 0.90% to 1.23% (OR, 1.36; 95% CI, 1.08-1.71); these results were more robust to unmeasured confounding. Among marijuana users in this age group, past-month frequent marijuana use and past-year CUD did not increase after RML enactment. This study’s findings suggest that although marijuana legalization advanced social justice goals, the small post-RML increase in risk for CUD among respondents aged 12 to 17 years and increased frequent use and CUD among adults 26 years or older in this study are a potential public health concern. To undertake prevention efforts, further studies are warranted to assess how these increases occur and to identify subpopulations that may be especially vulnerable. Show more