Generalized Anxiety Disorder
Conditions
Keywords
Cannabidiol, CBD, Cannabigerol, CBG, Cannabinol, CBN, Generalized Anxiety Disorder, GAD-7, Sleep Quality, Psychological Well-Being
Brief summary
This open-label, single-group, non-randomized interventional study will evaluate longitudinal changes in anxiety symptoms, sleep quality, psychological well-being, treatment adherence, tolerability, and safety in adults with clinician-confirmed generalized anxiety disorder. Participants will receive CannaRiver CBD Calm, an oral/sublingual broad-spectrum cannabinoid tincture containing cannabidiol (CBD), cannabinol (CBN), and cannabigerol (CBG), at a protocol dose of 0.5 mL approximately every 12 hours for 8 weeks. Follow-up will continue through Week 12. The study has no placebo or concurrent comparator group. The primary outcome is change in the Generalized Anxiety Disorder 7-item scale (GAD-7) total score from baseline to Week 8. Findings will be descriptive and hypothesis-generating; the design cannot establish that any observed change was caused by the product.
Detailed description
Generalized anxiety disorder is a chronic condition characterized by excessive and difficult-to-control worry and associated symptoms that may include restlessness, fatigue, impaired concentration, irritability, muscle tension, and sleep disturbance. Evidence for cannabidiol in anxiety is heterogeneous and formulation-specific. Acute experimental studies involving CBD, including studies associated with the Crippa and Zuardi research programs, provide a rationale for further investigation but do not establish efficacy for generalized anxiety disorder or for the CannaRiver formulation. Evidence for the combined use of CBD, CBN, and CBG in this formulation and schedule is limited. The study will enroll approximately 60 adults with clinician-confirmed generalized anxiety disorder and a GAD-7 score of at least 10 at screening and baseline, subject to the final ethics-approved age range. Participants will receive CannaRiver CBD Calm at 0.5 mL approximately every 12 hours for 8 weeks, followed by assessment through Week 12. The nominal product composition is 5,000 mg CBD, 1,250 mg CBN, and 1,250 mg CBG per 60 mL bottle; actual exposure will be based on the lot-specific Certificate of Analysis. The product will not be titrated routinely. The study is open-label, non-randomized, and single-group. It has no placebo or concurrent control group. The primary outcome is change in GAD-7 total score from baseline to Week 8. Secondary outcomes include trajectories of anxiety symptoms, selected measures of sleep quality and psychological well-being, adherence, retention, and safety. Optional instruments will be included only if their final versions, permissions, language validation, and electronic implementation are confirmed before registration. Scheduled serum AST/TGO and ALT/TGP testing will be performed at baseline/Day 0 before first dose, Week 4 and Week 8/end of treatment. These tests provide transaminase surveillance but are not a complete hepatic panel. Routine urine, toxicology and pregnancy testing is not planned. If results or symptoms suggest liver injury, or if another serious adverse event or urgent condition occurs, the study product will be interrupted when appropriate and the participant will be referred for clinical evaluation and additional diagnostic testing. The protocol remains limited by the possibility of changes between scheduled sampling time points. Data will be collected through the Lidera Health ePRO/eCRF environment, subject to documented validation, role-based access, audit trails, data-processing agreements, privacy-impact assessment, contingency procedures, and human review of safety alerts. The platform will not independently diagnose, determine eligibility, change the dose, assign causality, or replace clinical judgment or emergency services. The protocol will be submitted to the Research Ethics Committee (CEP) via Plataforma Brasil, following CNS Resolutions 466⁄2012 and 510⁄2016. Results will be reportedfollowing STROBE guidelines for observational studies.
Interventions
DRUGCannabidiol (CBD) With Cannabinol (CBN) and Cannabigerol (CBG) Oral Tincture (CannaRiver CBD Calm)
CannaRiver CBD Calm Tincture, broad-spectrum oral/sublingual cannabinoid formulation. The current nominal label states 5,000 mg CBD, 1,250 mg CBN, and 1,250 mg CBG per 60 mL bottle. At the protocol dose of 0.5 mL approximately every 12 hours, the nominal daily exposure is approximately 83.33 mg CBD, 20.83 mg CBN, and 20.83 mg CBG. The final record will use the lot-specific Certificate of Analysis and final product manual to describe the exact formulation, excipients, flavor, storage, dosing device, and validated administration instructions.
Sponsors
Associação Pan-Americana Multidisciplinar de Endocanabinologia
Lidera Health Tecnologia LTDA.
Canna River LLC DBA River Botanicals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All enrolled participants receive the same CannaRiver CBD Calm intervention. There is no placebo or concurrent comparator group.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adult within the final protocol-approved age range of 18-65 years years at the time of informed consent. * Capacity to understand the study and provide written informed consent before research procedures. * Clinician-confirmed generalized anxiety disorder using the prespecified structured diagnostic interview or another approved validated diagnostic method. * Clinically significant generalized anxiety disorder symptoms for at least 6 months. * GAD-7 total score of at least 10 at screening and again at baseline, within the prespecified interval. * Stable permitted psychiatric medication regimen for at least 6 weeks before baseline, if applicable, with no elective dose change planned during the 8-week treatment period. * Stable psychotherapy modality and frequency for at least 8 weeks before baseline, if applicable, with no elective intensification planned during treatment. * Willingness to administer the study product at 0.5 mL approximately every 12 hours for 8 weeks, complete electronic assessments, attend scheduled contacts, return unused product, and report medications, supplements, alcohol, cannabis, and adverse events. * Access to a compatible smartphone or web-enabled device and sufficient Portuguese literacy for the approved participant-reported instruments. * For participants with reproductive potential, no known or suspected pregnancy, agreement to the approved contraception requirements, and no plan for pregnancy through the end of the safety follow-up.
Exclusion criteria
* Current psychotic disorder, bipolar I disorder, current mania or hypomania, severe and unstable major depressive episode, severe dissociation, or another psychiatric condition that compromises safety or interpretability. * Current suicidal intent or plan, preparatory behavior, recent suicide attempt within the protocol-defined interval, inability to collaborate with a safety plan, or investigator judgment that outpatient participation is unsafe. * Moderate or severe substance use disorder within the previous 12 months, other than nicotine or caffeine, or current recreational drug use likely to affect safety or outcomes. * Use of CBD, CBN, CBG, THC, cannabis-derived products, or another systemically absorbed cannabinoid product within 30 days before baseline, or inability to abstain through Week 12. * Pregnancy, breastfeeding, attempting to become pregnant, intention to become pregnant during the study, or refusal to comply with pregnancy-prevention requirements. * Active liver disease; clinically important previous drug-induced liver injury; known clinically significant hepatic dysfunction; current jaundice, dark urine, pale stools, persistent unexplained right-upper-quadrant pain, or another finding judged by the investigator to create unacceptable hepatic risk. * Clinically significant renal, cardiovascular, neurologic, respiratory, endocrine, or gastrointestinal disease that may increase risk or confound outcomes. * Severe untreated obstructive sleep apnea, severe uncontrolled daytime sleepiness, recurrent unexplained syncope, or an occupation that cannot accommodate temporary driving or safety-sensitive-work restrictions. * Known hypersensitivity to cannabinoids, MCT oil, or a confirmed product component. * Current clobazam, valproate, or stiripentol use. Other sedatives, opioids, sedating antihistamines, muscle relaxants, sedating antipsychotics, strong CYP3A4/CYP2C19 modulators, narrow-therapeutic-index medicines, or selected antiepileptic medicines require protocol-approved investigator and pharmacist review. * Unstable medication or psychotherapy regimen, planned elective medication change during treatment, or another interventional study within 30 days or five half-lives, whichever is longer. * Inability to comply with study visits, electronic assessments, clinical safety monitoring, product accountability, or emergency procedures. * Any other condition judged by the investigator to be incompatible with safe participation or scientifically interpretable follow-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Generalized Anxiety Disorder 7-Item Scale (GAD-7) Total Score From Baseline to Week 8 | Baseline to Week 8 (Day 56 ±5 days) | The GAD-7 is a 7-item participant-reported measure scored from 0 to 21, with higher scores indicating greater anxiety symptom severity. Change will be calculated as the Week 8 score minus the baseline score. The primary analysis will estimate the mean within-participant change with a two-sided 95% confidence interval using the prespecified repeated-measures model. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trajectory of GAD-7 Total Score From Baseline Through Week 12 | Baseline, Weeks 2, 4, 6, 8, and 12 | GAD-7 total scores will be collected at baseline and scheduled follow-up visits to describe the longitudinal pattern of anxiety symptoms during treatment and after treatment. The study is uncontrolled; the trajectory will be interpreted as an observed within-participant pattern rather than a causal treatment effect. |
| Participants With a Decrease of at Least 4 Points in GAD-7 Total Score at Week 8 | Baseline to Week 8 (Day 56 ±5 days) | The number and percentage of participants with a decrease of at least 4 points from baseline to Week 8 will be summarized. The threshold is a prespecified descriptive benchmark and does not establish that the intervention caused the change. |
| Change in World Health Organization 5-Item Well-Being Index (WHO-5) Score From Baseline to Week | Baseline to Week 8 (Day 56 ±5 days) | The WHO-5 is a participant-reported measure of positive psychological well-being. Scores will be transformed according to the prespecified scoring method, with higher scores indicating greater well-being. The analysis will estimate within-participant change from baseline to Week 8. |
| Change in Pittsburgh Sleep Quality Index (PSQI) Global Score From Baseline to Week 8 | Baseline to Week 8 (Day 56 ±5 days) | The PSQI global score is a participant-reported measure of global sleep quality over the preceding month. Change from baseline to Week 8 will be summarized using the prespecified analysis. Higher PSQI global scores indicate poorer sleep quality. |
| Adherence to the CannaRiver CBD Calm Dosing Schedule Through Week 8 | From first dose through Week 8 (Day 56) | Adherence will be assessed using electronic dose diaries, participant reports, returned-product reconciliation, and documented dose interruptions. The percentage of expected doses taken during the applicable exposure period will be summarized. |
| Treatment-Emergent Adverse Events and Serious Adverse Events Through Week 12 | From first dose through Week 12 | Treatment-emergent adverse events, serious adverse events, events leading to product interruption or discontinuation, clinically suspected liver injury, serum AST and ALT values at baseline/Day 0, Week 4 and Week 8/end of treatment, sedation or psychomotor symptoms, gastrointestinal symptoms, psychiatric deterioration, suicidality, pregnancy, and suspected medication interactions will be collected and summarized. Routine urine, toxicology and pregnancy testing is not planned; additional testing will be clinically indicated when needed. |
Contacts
CONTACTJosé Wilson N V Andrade, MD
CONTACTAlethéia B Pablos, DDS
PRINCIPAL_INVESTIGATORJosé Wilson N V Andrade, MD
Associação Pan Amerivana Multidisciplinar de Endocanabinologia
Outcome results
None listed