PTSD has a physiological dimension. CAD Therapeutics is developing an investigational approach designed to study it there.

Who is CAD Therapeutics?

CAD Therapeutics is a privately held, U.S.-based clinical-stage (Phase III candidate) biotechnology company developing a novel investigational approach 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.

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 for other uses. The specific combination and its use for PTSD are investigational and are what CAD is developing; CAD intends to seek FDA approval following its planned Phase III clinical trial, subject to FDA IND clearance and IRB approval.

Is Clonicaine™ FDA-approved?

No. Clonicaine™ is an investigational drug. It is not approved by the FDA for PTSD or any other indication; safety and efficacy have not been established. Clonicaine™ is not commercially available. Any future access would occur only through an authorized clinical investigation, subject to IND clearance, IRB approval, site activation, eligibility criteria, and informed consent.

Why clonidine — and what makes injectable clonidine distinctive as an adjuvant?

Clonidine is an alpha-2 adrenergic agonist. In the published anesthesiology literature, when clonidine is added to a local anesthetic for peripheral nerve and plexus blocks, it has been reported to hasten the onset of the block, increase its intensity, and prolong the duration of both sensory analgesia and motor block relative to local anesthetic alone — with the prolongation of duration being the most consistently documented effect. In a meta-analysis of 20 randomized trials (1,054 patients), adding clonidine prolonged postoperative analgesia by roughly two hours (about 122 minutes), extended sensory block by about 74 minutes, and extended motor block by about 141 minutes.

Clonidine is also mechanistically distinct from the adjuvants it would replace. Epinephrine, a traditional local-anesthetic adjuvant, stimulates the sympathetic nervous system that is already overactive in PTSD, whereas clonidine's alpha-2 action is sympatho-inhibitory — aligned with the goal of a cervical sympathetic block — and, unlike opioid adjuvants, it carries no opioid-related respiratory risk.

Important: These findings come from the published literature on clonidine as an adjuvant in surgical and regional anesthesia. They are not findings about Clonicaine™ or about SGB for PTSD, and they do not establish that Clonicaine™ is safe or effective. Whether these reported benefits — and in particular the magnitude and durability of the effect when clonidine is delivered by stellate ganglion block for PTSD — carry over to Clonicaine™ is precisely what CAD's planned Phase III program is designed to test. The literature is not uniform: at least one controlled volunteer study found that perineural clonidine did not prolong sensory block once systemic effects were accounted for, which is why durability in particular remains a hypothesis to be proven rather than an established fact.

Source: Reported prolongation of analgesia, sensory, and motor block (with dose-limiting hypotension, bradycardia, and sedation) — Pöpping DM et al., meta-analysis of 20 randomized trials, Anesthesiology (2009); alpha-2 adjuvant mechanism and block prolongation — Kirksey MA et al., systematic review, PLOS One (2015); contrasting result on durability — “Clonidine… does not prolong the duration of sensory block when controlling for systemic effects,” randomized volunteer trial, PLOS One (2017).

How does injected clonidine differ from an oral clonidine tablet?

Clonidine's vascular effects depend on how — and how much — it is delivered. Taken systemically, as with the oral tablets long used for high blood pressure, clonidine acts mainly in the brainstem as a central alpha-2 agonist that reduces sympathetic outflow; the dominant, whole-body result is lowered vascular resistance and blood pressure — a systemic vasodilatory, blood-pressure-lowering action.

Delivered locally by injection next to the nerve, clonidine additionally engages peripheral alpha-2 receptors on vascular smooth muscle, which can cause vasoconstriction at the injection site. That local vasoconstriction is one of several mechanisms proposed to slow the washout of the co-injected local anesthetic and thereby help prolong the block — a site-directed action fundamentally different from a systemically absorbed tablet. In short, the same molecule can lower blood pressure through its central effect when swallowed while producing local vasoconstriction at the point of a perineural injection; the two routes are not interchangeable.

Because a portion of injected clonidine is still absorbed into the circulation, the central effects — lowered blood pressure, a slowed heart rate, and sedation — can still occur and are the principal dose-limiting considerations. This is a central reason the specific dose, concentration, and route are being defined under CAD's controlled Phase III protocol rather than assumed, and nothing here should be read as a claim that Clonicaine™ is safe or effective. (Injectable clonidine is FDA-approved for epidural analgesia; its use as a perineural adjuvant and in stellate ganglion block is not FDA-approved.)

Source: Central alpha-2 sympatholysis producing vasodilation and lowered blood pressure, and peripheral alpha-2-mediated vasoconstriction (early/transient hypertension with rapid or high-dose exposure) — Patel P & Saadabadi A, “Clonidine,” StatPearls (2026); dose-dependent peripheral vasoconstriction partly offsetting the central blood-pressure-lowering effect — Kawada T et al., Journal of Physiological Sciences (2021); local vasoconstriction among the proposed mechanisms of block prolongation — Kirksey MA et al., PLOS One (2015); systemic hypotension, bradycardia, and sedation reported with perineural clonidine — Pöpping DM et al., Anesthesiology (2009); FDA-approved (epidural) status of injectable clonidine — Duraclon (clonidine HCl injection), Drugs@FDA.

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 about 5% of U.S. adults — roughly 13 million — in a given year, with particularly high prevalence among military veterans and first responders.

Source: PTSD definition, symptoms, and prevalence (about 5% of U.S. adults — ~13 million — in a given year; higher among veterans) — National Center for PTSD, U.S. Dept. of Veterans Affairs (adults, veterans). Proposed nerve-growth-factor / norepinephrine / sympathetic mechanism — Lipov EG et al., Medical Hypotheses (2009); Lynch JH et al., Brain & Behavior (2020).

What treatments are currently approved for PTSD, and what are their limitations?

As of 2026, only two drugs remain 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. No new PTSD medication has been approved in more than two decades — recent attempts were declined by the FDA, including MDMA-assisted therapy (Lykos) in August 2024 and the brexpiprazole-plus-sertraline combination (Otsuka/Lundbeck) in September 2025 — underscoring how difficult the prevailing pharmacologic approach has been to improve upon.

Source: U.S. FDA prescribing information for Zoloft (sertraline) and Paxil (paroxetine), the only two agents FDA-approved specifically for PTSD; Otsuka/Lundbeck, FDA Complete Response Letter for brexpiprazole + sertraline in PTSD (Sept 20, 2025; advisory committee voted 10–1 against on July 18, 2025); FDA Complete Response Letter for MDMA-assisted therapy (Aug 2024).

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.

Source: SGB’s sympathetic-nervous-system mechanism — Lipov EG et al., Medical Hypotheses (2009); Lynch JH et al., Brain & Behavior (2020). CPT/CBT as first-line psychotherapies — VA/DoD Clinical Practice Guideline for PTSD. SGB combined with cognitive processing therapy — open-label randomized trial, Psychotherapy and Psychosomatics (2024).

What about complex PTSD (C-PTSD)?

C-PTSD develops from prolonged or repeated trauma and includes core PTSD symptoms plus difficulties in emotion regulation, self-concept, and relationships. SGB targets the sympathetic hyperarousal common to both PTSD and C-PTSD, and in published clinical experience has been used as one component of broader care that includes psychotherapy — not as a standalone treatment for the full range of C-PTSD features. Any benefit for C-PTSD specifically remains to be studied.

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 is a well-characterized procedure used in pain medicine for decades.

Source: Stellate-ganglion anatomy (C6–C7, base of the neck), ultrasound-guided technique, and use in pain medicine — StatPearls, “Stellate Ganglion Blocks” (NCBI). SGB has been in clinical use since about 1925 — Summers & Nevin, Current Psychiatry Reports (2015).

What is the history of SGB in medicine?

SGB was first developed in the early 20th century — in clinical use since the 1920s — 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.

Source: SGB’s clinical history and its first reported use for PTSD (Lipov, 2008) — Summers & Nevin, Current Psychiatry Reports (2015); Lipov EG et al., “Cervical Sympathetic Blockade in a Patient with PTSD: A Case Report,” Annals of Clinical Psychiatry (2008).

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. Functional neuroimaging has been used to examine changes in amygdala activity following SGB.

Source: Proposed nerve-growth-factor / norepinephrine / sympathetic-“reset” mechanism — Lipov EG et al., “A unifying theory…,” Medical Hypotheses (2009); reviewed in Lynch JH et al., Brain & Behavior (2020).

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.

Source: Clonidine (an alpha-2 agonist) as a local-anesthetic adjuvant that prolongs the block — Kirksey MA et al., systematic review, PLOS One (2015); drug approvals via U.S. FDA Drugs@FDA — bupivacaine (Marcaine) and clonidine injection (Duraclon).

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.

Source: Controlled efficacy — Rae Olmsted KL et al., randomized clinical trial, JAMA Psychiatry (2020); symptom improvement in a large case series — Mulvaney SW et al., 166-patient case series, Military Medicine (2014).

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.

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.

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.

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 independent third-party results on stellate ganglion block, including retrospective and non-CAD-sponsored cohorts; they are hypothesis-generating and are not completed CAD-sponsored trials, and should not be interpreted as evidence that Clonicaine™ is safe or effective. 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.

Who has SGB been studied in?

Published SGB research spans combat veterans, first responders, sexual-assault survivors, motor-vehicle-accident and disaster survivors, and others. These are third-party studies of the procedure; whether any individual is an appropriate candidate for SGB is a medical decision for a qualified clinician, and Clonicaine™ itself remains investigational.

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.

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 received FDA feedback that informs the planned clinical trial design, 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.

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.

How will Clonicaine™ be manufactured?

CAD intends to manufacture Clonicaine™ through an established U.S.-based contract development and manufacturing organization (CDMO) using pharmaceutical-grade (cGMP) processes, rather than through compounding pharmacies. Manufacturing under the 505(b)(2)/NDA framework involves rigorous FDA review of processes, quality control, and stability data, and generally supports broader distribution and reimbursement than compounded preparations. Manufacturing plans are subject to change and to FDA review.

Is the treatment protected by intellectual property?

Clonicaine™ and its use in stellate ganglion block for PTSD are the subject of issued U.S. patents and pending applications owned by or licensed to CAD. As with any early-stage intellectual property, applications may be pending and unpublished, may not issue, and, if issued, may be challenged, narrowed, or invalidated. Nothing here is a representation regarding the scope, validity, or enforceability of any intellectual property.

What is CAD's Planned Phase III Clinical 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, with a four-arm factorial design — a placebo control, the active combination (Clonicaine™), clonidine alone, and bupivacaine alone — and a crossover after 90 days that allows participants in the comparison arms to subsequently receive the active combination. As currently designed it is expected to enroll on the order of ~250 participants across six U.S. sites; the final target sample size (N) is being determined by the study's biostatistician through formal statistical power analysis and may be larger — potentially up to roughly 400. The primary endpoint (change in CAPS-5 Total Symptom Severity) is assessed at 90 days, with secondary endpoints at 24 weeks and 52 weeks. Neither the planned Phase III trial nor Clonicaine™ is currently approved by the FDA, and both are subject to FDA IND submission and IRB approval.

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.

Is it a paid study?

Yes. Participants are expected to be compensated for their time and study-related travel in accordance with the IRB-approved protocol. Participation is voluntary, and enrollment does not guarantee assignment to the active treatment arm.

How can I receive treatment or learn more?

Clonicaine™ is not commercially available. Any future access would occur only through an authorized clinical investigation, subject to IND clearance, IRB approval, site activation, eligibility criteria, and informed consent. For general, investor, or media inquiries, please reach us through the Contact section.