About CAD Therapeutics & Clonicaine™
1. What is CAD Therapeutics?
CAD Therapeutics is a privately held, U.S.-based clinical-stage (Phase III candidate) biotechnology company developing a novel treatment method and drug formulation for PTSD. "CAD" stands for Ctrl-Alt-Del — the guiding idea is to help reset the nervous system's overactive stress response, rather than manage symptoms with daily psychiatric medication. Both the drug, Clonicaine™, and its use in combination with the Stellate Ganglion Block procedure are covered under issued U.S. patents owned by CAD.
2. What is Clonicaine™?
Clonicaine™ is a proprietary, patent-protected fixed-dose formulation combining bupivacaine (a long-acting local anesthetic) and clonidine (an alpha-2 adrenergic agonist), delivered via a right-sided Stellate Ganglion Block. Both components are individually FDA-approved drugs with decades of established safety data. The specific combination and its use for PTSD are what CAD is developing.
3. Is Clonicaine™ FDA-approved?
No. Clonicaine™ is an investigational drug. It is not approved by the FDA for PTSD or any other indication and is not available commercially. It is currently accessible only to patients enrolled in CAD's clinical trials.
Understanding PTSD & today's options
1. What is PTSD, and what causes it?
PTSD is a condition that can develop after exposure to traumatic events such as combat, assault, serious accidents, or disaster. It is characterized by intrusive memories, nightmares, hypervigilance, avoidance, and disrupted mood and sleep. The prevailing neurobiological model links these symptoms to sympathetic ("fight-or-flight") nervous-system hyperactivity — including elevated nerve growth factor (NGF), sympathetic nerve sprouting in the amygdala, and norepinephrine dysregulation. PTSD is estimated to affect roughly 8 million U.S. adults each year, with particularly high prevalence among military veterans and first responders.
2. What treatments are currently approved for PTSD, and what are their limitations?
Only two drugs are FDA-approved specifically for PTSD — sertraline (Zoloft, 1999) and paroxetine (Paxil, 2001), both SSRIs. They typically take 6–8 weeks to show effect, benefit an estimated 40–60% of patients, and are commonly associated with sexual dysfunction, weight gain, and emotional blunting. They generally require ongoing daily use, with relapse common on discontinuation, and they modulate neurotransmitter levels rather than targeting the underlying physiology of PTSD.
3. How does this approach differ from SSRIs, ketamine, or talk therapy?
SGB is designed to act on the sympathetic nervous system directly, at the point believed to drive PTSD's underlying physiology, rather than adjusting neurotransmitters over weeks. Emerging psychotropic options such as ketamine and MDMA carry their own adverse-effect and administration profiles, and behavioral therapies like CPT and CBT — while effective for many — require sustained engagement over months. SGB can also be used alongside psychotherapy, potentially by reducing physiological hyperarousal that can interfere with therapeutic work.
The SGB procedure & how it works
1. What is a Stellate Ganglion Block (SGB)?
SGB is a minimally invasive, image-guided injection of local anesthetic near the stellate ganglion — a cluster of sympathetic nerves at the base of the neck (around the C6–C7 level). The procedure typically takes 10–15 minutes under ultrasound guidance and has been used safely in pain medicine for over 80 years.
2. What is the history of SGB in medicine?
SGB was first developed in the 1940s for chronic pain conditions such as complex regional pain syndrome, hyperhidrosis, and vascular disorders of the upper body, with millions of procedures performed worldwide. Its application to PTSD began with a 2008 case report by Dr. Eugene Lipov, which launched a new field of investigation. More than 15 years of independent research has since studied SGB for trauma-related disorders.
3. How is SGB thought to work for PTSD?
The mechanistic rationale, supported by external published literature, describes a neurobiological cascade: after trauma, excessive NGF production drives sympathetic nerve sprouting in the amygdala and sustained norepinephrine release, producing chronic hyperarousal. A block near the stellate ganglion temporarily interrupts sympathetic signaling; the bupivacaine component creates the initial nerve block, while the clonidine component provides extended alpha-2 adrenergic modulation. The intent is to allow the system to "reset" toward baseline. Imaging studies (e.g., PET) have been used to examine changes in amygdala activity following SGB.
4. Why combine bupivacaine and clonidine?
Bupivacaine is a long-acting local anesthetic that blocks nerve signal transmission for several hours. Clonidine, an alpha-2 adrenergic agonist used safely for decades in other indications, is added as an adjuvant to deepen and prolong the sympathetic blockade and to reduce norepinephrine release beyond the anesthetic's duration. Unlike epinephrine — a traditional adjuvant that stimulates the sympathetic system already overactive in PTSD — clonidine's effect is aligned with the treatment goal.
5. How long do the effects last?
Reported duration varies considerably by individual. Published studies and clinical experience describe symptom improvement lasting from months to years, with some patients achieving durable remission from a single session and others benefiting from periodic booster treatments. CAD's own Phase III program is designed to generate controlled durability data.
Safety & side effects
1. What are the common, temporary side effects?
The procedure has a well-characterized safety profile. The most common effects are temporary and resolve within hours as the anesthetic wears off: Horner's syndrome (drooping eyelid, constricted pupil, facial flushing on the treated side); hoarseness or voice changes; nasal congestion on the treated side; a temporary sensation of a lump in the throat; occasional arm heaviness; and mild injection-site tenderness lasting a day or two.
2. What serious complications are possible, and how rare are they?
Serious adverse events are extraordinarily rare when the procedure is performed by experienced practitioners using modern ultrasound guidance. Reported rates include pneumothorax at well under 1%, hematoma at well under 1%, and infection as rare with sterile technique. Systemic local-anesthetic toxicity is rare with appropriate dosing and monitoring. Ultrasound guidance, aspiration before injection, sterile technique, and post-procedure monitoring are standard risk-mitigation practices.
3. Who typically cannot receive SGB?
Absolute contraindications include local infection at the injection site, known allergy to the anesthetic or clonidine, recent heart attack, and severe heart block without a pacemaker. Relative contraindications — requiring individual evaluation — include anticoagulation therapy, significant arrhythmias, glaucoma, prior neck surgery or radiation, pregnancy, severe COPD, and severe hypotension. Each case is assessed individually by the treating physician.
Evidence
1. What does the published research show?
Independent, peer-reviewed studies on SGB for PTSD — including the largest published cohort to date (484 patients, Pain Physician, 2022) — have reported response rates in the 70–80%+ range across diverse populations, including combat veterans. These are independently published results on stellate ganglion block; they are not completed CAD-sponsored trials. Clonicaine™'s own efficacy and durability are what CAD's planned Phase III program is designed to study in a controlled clinical setting. See our Published Evidence section for full citations.
Regulatory status & access
1. Is SGB for PTSD FDA-approved?
No. SGB for the treatment of PTSD is not FDA-approved and is currently used off-label — meaning the procedure and the individual drugs are FDA-approved for other indications, but their specific use for PTSD has not received FDA approval. Off-label use of approved medicines is common and legal in medical practice when supported by clinical judgment. CAD's planned clinical program is studying Clonicaine™ specifically for the PTSD indication.
2. What is CAD's regulatory pathway?
CAD plans to develop Clonicaine™ under the FDA's 505(b)(2) framework, which applies to new formulations or combinations of already-approved drugs. A pre-IND meeting has been completed; following that meeting, CAD was advised it could proceed with its planned clinical trial, subject to certain modifications, and an IND is in preparation. Because both components are already FDA-approved drugs, the planned clinical work focuses on studying the specific combination for the PTSD indication. Clonicaine™ remains investigational and is not approved by the FDA.
3. Is the treatment covered by insurance?
Coverage varies by insurer and plan. Because PTSD is currently an off-label use, coverage is inconsistent and often requires prior authorization; military and veterans' systems (TRICARE and VA) have increasingly recognized SGB for PTSD. Coverage for investigational or off-label uses is limited today and may evolve over time depending on the treatment's regulatory status and the supporting evidence.
The clinical trial & eligibility
1. What is CAD's Phase III trial?
CAD's planned Phase III program is designed as a multi-site, randomized, controlled study of Clonicaine™ delivered via right-sided stellate ganglion block for PTSD. The planned factorial design compares four arms — a control group (placebo), the active combination (Clonicaine™), clonidine alone, and bupivacaine alone — with a crossover after 90 days that allows participants in the comparison arms to subsequently receive the active combination. The primary endpoint is based on change in the CAPS-5 Total Symptom Severity score. This is a planned, investigational study; Clonicaine™ is not approved by the FDA.
2. Who can enroll in the trial?
The planned study is expected to enroll adults with a confirmed clinical PTSD diagnosis (via CAPS-5 assessment, with PCL-5 screening) across several U.S. metropolitan sites. Key exclusions are expected to include prior stellate ganglion block and certain neurologic, psychiatric, or medical conditions. Specific eligibility criteria will be published upon trial registration.
3. How can I receive treatment or learn more?
Clonicaine™ is investigational and is currently available only to patients enrolled in CAD's clinical trials. For general, investor, or media inquiries, please reach us through the Contact section.
