SSRN Electronic Journal
Vincent Joralemon
The Drug Enforcement Administration (DEA) classifies MDMA as a Schedule I controlled substance, the most restrictive category under the Controlled Substances Act. However, Lykos Therapeutics (formerly MAPS PBC) has submitted a New Drug Application for MDMA-assisted therapy for PTSD. If the FDA approves this drug, it would provide the 'accepted medical use' that Schedule I drugs are statutorily denied, triggering a rescheduling process. Based on precedents like XYWAV and cannabis-derived medications, the DEA would likely reschedule only the specific FDA-approved drug product—likely to be marketed as RENSANSE—to Schedule II or III, while raw MDMA remains on Schedule I. This mechanism offers a model for incrementally relaxing federal restrictions on psychedelic substances and expanding research access.
Julia Etkin, Vincent Joralemon
Psilocybin, currently a Schedule I controlled substance with no accepted medical use and high abuse potential, is actually among the safest psychoactive compounds by comparative-harm metrics—far safer than alcohol and tobacco, which are exempt from the Controlled Substances Act and regulated as adult-use commodities. This essay argues that psilocybin should be regulated under food law, specifically the dietary-supplement framework of the Dietary Supplement Health and Education Act of 1994, rather than drug law.
Brazilian Journal of Psychiatry
June 16, 2026
Daniel B.a. Prado, Matheus T. Rossignoli, Rafael N. Ruggiero et al.
In a rat model of schizophrenia-like symptoms induced by ketamine, the combination of cannabidiol and sodium nitroprusside given during brain development prevented hyperactivity and memory problems in both sexes, while each drug alone had limited effects. The model produced different symptoms in males and females: females showed greater hyperactivity and long-term memory deficits, whereas males showed reduced pleasure-seeking and short-term memory impairments. The combined treatment was more effective in females, and distinct behavioral patterns were seen between sexes. This suggests that a combination of these two compounds may offer a sex-specific preventive strategy for schizophrenia symptoms.
Psychoactives
June 8, 2026
Fizza Mitter, Anton Sheptooha, Janni Leung et al.
Post-traumatic stress disorder (PTSD) is often not well treated by current medications or talk therapies, leading to interest in psychedelic-assisted psychotherapy. A systematic review and meta-analysis of 11 randomized controlled trials with 358 participants examined MDMA, ketamine, and cannabidiol. MDMA-assisted psychotherapy produced a moderate-to-large reduction in PTSD symptoms, with more participants achieving clinical response and loss of PTSD diagnosis. Ketamine showed a small, non-significant effect, and one trial of cannabidiol found no clear benefit. All agents were generally well tolerated. The evidence is dominated by MDMA trials, and safety data remain insufficient for strong comparisons. More studies with standardized outcomes and direct comparisons are needed.
Physiological research
May 12, 2026
M Bochin, Č Vejmola, V Koudelka et al.
Acute oral administration of THC (10 mg/kg), CBD (10 mg/kg), or their combination in freely moving rats alters resting-state EEG dynamics. THC and THC+CBD produced the strongest and most spatially extensive increases in low-frequency spectral power, with significant delta-beta clusters in prefrontal, cingulate, hippocampal, and striatal regions. CBD yielded fewer and smaller clusters. Connectivity analyses revealed altered functional coupling within overlapping CB1 receptor-rich regions. The combination treatment closely resembled THC alone, suggesting a dominant THC-driven contribution. These findings identify a cannabinoid-specific EEG signature of enhanced low-frequency oscillatory activity and altered large-scale network organization.
American Journal of Preventive Medicine
May 4, 2026
Kevin H. Yang, Nora Satybaldiyeva, Wayne Kepner et al.
1 citation
Cannabis is the most commonly microdosed substance among U.S. adults, with 9.4% (24.1 million) reporting lifetime use, followed by psilocybin (5.3%, 13.7 million), LSD (4.8%, 12.4 million), and MDMA (2.2%, 5.7 million). Cannabis is primarily microdosed for medical reasons such as pain management, whereas psilocybin, LSD, and MDMA are more often used recreationally. Lifetime microdosing is more prevalent among people with poorer mental health and those living in jurisdictions with fewer restrictions on cannabis and psychedelics. As policies continue to evolve, the prevalence of microdosing may increase, highlighting the need for ongoing surveillance.
Neuropharmacology
May 1, 2026
Jairo S Acosta-Vargas, Natalia De Las Heras-Martínez, Alberto Marcos et al.
Adolescent rats exposed to vaporized THC, alone or with CBD, showed no significant changes in behavioral traits or alcohol self-administration compared to controls. However, females exhibited a more vulnerable pattern of alcohol consumption and seeking. In THC-exposed males, a negative correlation appeared between sucrose preference and compulsive alcohol seeking; in females, THC disrupted the link between novelty preference and alcohol intake and was associated with a negative correlation between goal-tracking and compulsive seeking. Naltrexone reduced alcohol intake most effectively in THC-exposed rats versus those given a high-CBD/low-THC mixture. Adolescent cannabinoid exposure has limited effects on overall alcohol risk but may alter psychological underpinnings of alcohol-related behaviors and increase naltrexone potency, with sex differences highlighting the need for personalized interventions.
Biological psychiatry
March 16, 2026
Xianglian Wang, Jing Xia, Heyi Luo et al.
Ketamine produces rapid antidepressant effects but also causes hyperlocomotion, a side effect linked to increased dopamine activity in the ventral tegmental area (VTA). Cannabidiol (CBD) blocked ketamine-induced hyperlocomotion in mice when given systemically (30 mg/kg) or directly into the VTA (10 μg per mouse). Whole-brain imaging showed that ketamine increased neuronal activity in the VTA, prefrontal cortex, and nucleus accumbens, which CBD reduced. Electrophysiology revealed that ketamine suppressed glycine receptor (GlyR) function, while CBD reversed this dysfunction by antagonizing ketamine-driven delays in GlyR activation. In GlyRα1S296A mice, CBD's effect on hyperlocomotion was abolished, indicating that VTA GlyRα1 signaling, particularly the S296 residue, is essential for CBD's dissociation of ketamine's therapeutic and adverse effects.
Journal of psychopharmacology (Oxford, England)
March 1, 2026
Eilidh Macnicol, Michelle Kokkinou, Maria Elisa Serrano Navacerrada et al.
2 citations
THC increases brain functional connectivity and blood flow in rats, while CBD decreases connectivity without affecting blood flow. When combined, CBD moderates THC's effects. Adult male rats received THC, CBD, a combination, or a placebo. Brain scans two hours later showed THC raised whole-brain connectivity and blood flow in cortical and subcortical regions. CBD lowered connectivity metrics. The combination produced moderate increases in both measures. THC specifically strengthened connections between the cortex and hippocampus and between the cortex and striatum, an effect reduced when CBD was present. These distinct neurophysiological profiles suggest cannabinoids induce different brain states, supporting the use of functional neuroimaging in developing cannabinoid-based therapies.
Psychoactives
February 3, 2026
Eliana Rodrigues
Interest in psychoactive substances like psychedelics is growing in medicine and academia, but misclassifications of certain plants, animals, fungi, and their substances persist in media and scholarly circles. This opinion piece argues whether cannabidiol (CBD) is a non-psychoactive phytocannabinoid, noting that hundreds of robust studies support its clinical use for seizures, anxiety, psychosis, schizophrenia, post-traumatic stress disorder, and addiction. The text reviews historical classifications of psychoactive substances, reflects on terminology, and proposes a new classification for psychedelics.