CHICAGO — Findings from the first study to assess treatment for tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) showed significantly improved outcomes after cannabidiol (CBD; Epidiolex) was added to standard care.

The 6-month interim results from the ongoing phase 3b/4 EpiCom trial, involving nearly 80 pediatric and adult participants, showed that adjunctive CBD was associated with improvements in aberrant behaviors, the severity of behavioral problems, and irritability at 26 weeks.

“I’m excited because this is the first trial looking at TAND, which is so impactful for people,” study investigator Elizabeth A. Thiele, MD, PhD, director of the Carol and James Herscot Center for Tuberous Sclerosis Complex at Massachusetts General Hospital, Boston, told Medscape Medical News.

The study was presented on April 20 at the American Academy of Neurology (AAN) 2026 Annual Meeting.

From Anecdotal Observation to Clinical Trial

TSC is a rare genetic disorder that affects approximately 1 in 6000 individuals. It can cause benign tumors in the brain, eyes, heart, and other parts of the body, resulting in a combination of symptoms, including seizures. 

In 2020, the FDA approved CBD for the treatment of seizures in patients with TSC who were at least 1 year of age.

TAND encompasses a range of severe behavioral, psychiatric, intellectual, and psychosocial difficulties affecting up to 90% of individuals with TSC. An international consensus statement published in 2023 recommends screening for TAND at least annually.

Although TAND substantially reduces quality of life for most individuals with TSC, treatment options remain limited, the researchers noted.

“A big focus of my career has been taking care of people with tuberous sclerosis,” Thiele said. She also said she has been researching cannabidiols for more than 10 years.

“When we were doing epilepsy clinical trials with Epidiolex, anecdotally we saw significant improvements in anxiety and some cognitive improvement, and that’s what led to this trial, which is the first to look at these symptoms of TSC,” Thiele reported.

The ongoing open-label EpiCom trial (epilepsy comorbidities) is designed to assess TAND outcomes following adjunctive initiation of CBD oral solution in patients aged 1-65 years with TSC-associated seizures. 

All 79 participants enrolled at 6 months (79% pediatric patients; mean age, 18.5 years; 58% male) had moderate/severe behavioral challenges, such as aggression, temper tantrums, and self-injury. They received up to 25 mg/kg/d of CBD plus standard of care for 26 weeks.

Outcome measures included the most problematic behavior numerical rating scale, the TAND Self-Report Quantified Checklist (TAND-SQ), the Aberrant Behavioral Checklist (ABC), and the Caregiver- and Clinician-reported Global Impression of Severity scales. All were administered at baseline and weeks 13 and 26.

Significant Improvement

Results from the prespecified 6-month analysis showed a mean change of -2.0 (95% CI, -3.0 to -1.0) on the most problematic behavior scale from baseline to week 26 after CBD initiation.

On the TAND-SQ, the greatest baseline-to-week 26 changes occurred in the areas of eat/sleep problems (-2.0) and overactive/impulsive behaviors (-1.3). There were also significant changes for ABC irritability (-8.0) and hyperactive noncompliance (-7.0) scores.

Fewer clinicians rated behavioral problems as severe at weeks 13 and 26 (10% and 0%, respectively) compared with baseline (47%), and none rated them as very severe at the same timepoints (0% and 0% vs 10% at baseline). These findings were similar to ratings from caregivers, with 14% and 13% vs 38% reporting severe and 4% and 13% vs 18% reporting very severe behavioral problems.

In further analysis, 60% of the participants who experienced seizures at baseline achieved a ≥ 50% reduction in total seizure count at week 13, and 36% achieved it at week 26. In addition, 67% and 55% of the participants achieved at least a 25% reduction in seizure count at those timepoints.

Treatment-emergent adverse events affected 62% of the participants, with the most common being diarrhea (n = 19), infections (n = 18), and psychiatric disorders (n = 13). Among the infections, the most common were influenza and upper respiratory tract infections; the most common psychiatric disorder was abnormal behavior and aggression.

There were six serious adverse events, with four deemed to be treatment-related, and they were resolved.

“The safety profile was consistent with previous CBD studies,” Thiele told meeting attendees. She added that the study will continue treating the participants through 52 weeks and that final results are expected to be released by the end of this year.

A ‘Double Win’

David C. Spencer, MD, professor of neurology and director of the Comprehensive Epilepsy Center at Oregon Health & Science University in Portland, Oregon, said the study addresses an important and often underrecognized aspect of care.

In the epilepsy field, “we sometimes get a bit narrowly focused on seizures, but what also needs to be addressed are the comorbidities that go along with that,” Spencer told Medscape Medical News.

“These neuropsychiatric behavioral issues that accompany some forms of epilepsy can really affect quality of life for patients and their families. So I’m glad [the researchers] were addressing this — it’s an area that needs more attention,” he added.

Spencer noted that because CBD is already an approved treatment for seizures, additional benefit for TAND represents a “double win” for patients with TSC.

However, he said he would like to see more detailed data, including whether reductions in seizures contributed to improvements in TAND or whether behavioral gains were observed even in patients with no seizure improvement.

“Did they move in parallel with each other, or was this completely unrelated? Seizures can disrupt the same brain networks involved with mood and behavior, so it wouldn’t be surprising if they’re linked here,” Spencer said.

He added that future research should include larger patient populations.

The study was funded by Jazz Pharmaceuticals. Thiele reported having consulted for, conducted studies funded by, and/or received honoraria for services provided by Jazz Pharmaceuticals. Spencer reported involvement in an upcoming study of CBD for adult patients with focal epilepsy.