Targeting Underlying Biology: Novel Combination Therapies For Chronic Disease

By Joel Latham, president and chief executive officer, Incannex

Chronic diseases, such as obstructive sleep apnea (OSA), rheumatoid arthritis (RA), and generalized anxiety disorder (GAD), affect millions worldwide yet remain inadequately treated for many patients. We have seen that conventional therapies often focus on symptom management, which leaves substantial gaps in efficacy, patient adherence, and overall quality of life. Increasingly, researchers are exploring combination therapies that target underlying biological pathways rather than simply alleviating symptoms. Among emerging approaches, the integration of cannabinoids or psychedelics with well-characterized pharmacological agents is gaining attention, offering potential for more meaningful and durable patient outcomes. Developing these next-generation therapies requires a commitment to scientific rigor, regulatory compliance, and patient-centered design — all principles that are guiding both academic and industry efforts in this space.

The Rationale For Combination Therapies

Combination therapies are built on a straightforward idea: using two or more treatments that work in different but complementary ways can produce better results than relying on a single drug alone. When it comes to cannabinoids, synthetic compounds that act on CB1 and CB2 receptors can help regulate inflammation and immune activity in ways that conventional therapies may not fully capture. Likewise, psychedelic-assisted approaches, such as synthetic psilocybin combined with structured psychological support, may help patients break out of rigid thought patterns and become more receptive to therapy by temporarily increasing brain flexibility. Early laboratory and clinical studies have shown these approaches to be both safe and promising, supporting the use of multimodal strategies to address complex chronic conditions. For drug developers, this reinforces the value of moving beyond one-size-fits-all treatments toward therapies designed to influence multiple biological pathways and deliver more meaningful patient outcomes.

Obstructive Sleep Apnea

OSA affects more than 1 billion people globally, yet adherence to standard therapies, such as continuous positive airway pressure (CPAP) devices, remains low. While CPAP remains the standard of care for OSA, long-term adherence is often poor, stressing the need for alternative approaches that patients can realistically maintain. Incannex’s preclinical work has focused on models that assess respiratory drive and airway stability, supporting combination strategies that target complementary physiological mechanisms underlying the disorder.

Recent research illustrates how combination therapy can address mechanistically distinct aspects of disease. For instance, the combination of dronabinol, a synthetic cannabinoid, with acetazolamide demonstrates complementary effects: dronabinol stimulates airway dilation, while acetazolamide induces mild metabolic acidosis, which increases respiratory drive. The takeaway for drug developers is that targeting multiple complementary pathways simultaneously may enhance efficacy and improve patient adherence compared to monotherapy approaches.

Rheumatoid Arthritis

RA is another condition where combination therapies may offer meaningful benefits. The disease is driven by ongoing inflammation and an immune system that is too active, and many patients do not respond adequately to current treatment options. Although disease-modifying antirheumatic drugs (DMARDs) and biologics form the backbone of RA treatment, many patients experience incomplete disease control or tolerability challenges. In preclinical inflammatory arthritis models, Incannex’s combination approach demonstrated greater reductions in arthritis-related measures than either component alone, providing a rationale for advancing this strategy into clinical testing.

Pairing hydroxychloroquine, which helps regulate immune activity, with synthetic cannabidiol, which can reduce inflammation through the body’s endocannabinoid system, is one way to address both drivers of the disease at the same time. Early laboratory results from Incannex showed that this combination was safe and well tolerated, with early signs of potential benefit. The incidence of treatment-related adverse events was comparable to cannabidiol alone, supporting the feasibility of combining these therapies in a single regimen. Together with preclinical data suggesting enhanced anti-inflammatory effects versus either component alone, these findings reinforce an important lesson for drug development: in complex diseases such as RA, targeting multiple biological pathways simultaneously may offer advantages over single-agent approaches.

Generalized Anxiety Disorder

GAD affects an estimated 6.8 million adults in the United States, yet many people do not experience sufficient relief from commonly prescribed medications, such as antidepressants. These treatments can take weeks to work and are often associated with unwanted side effects. Incannex’s preclinical and translational research using neurobehavioral models has helped support the hypothesis that combining pharmacological intervention with structured psychological support may address these limitations more effectively than medication alone. 

Synthetic psilocybin, taken orally and paired with structured psychological support, represents a much different approach. Researchers believe psilocybin may help patients become more open and flexible in their thinking, allowing therapy to be more effective. Together, these findings point to the potential value of combining medication and psychological support to move beyond managing symptoms and toward more comprehensive improvement for patients.

Lessons For Drug Development And Clinical Practice

Taken together, these examples point to several practical lessons for researchers and drug developers. Combination therapies work best when they are built around a clear understanding of how each component contributes to treating different parts of a disease. Just as important, clinical trials should be designed with patients in mind, focusing on tolerability, ease of use, and outcomes that matter in everyday life, not only what looks good on paper. From a regulatory standpoint, early and ongoing dialogue with agencies is essential, particularly to align on trial design, appropriate endpoints, and how to evaluate the safety and contribution of each component within a combination therapy. For therapies involving novel mechanisms or controlled substances, regulators may also require additional clarity around manufacturing consistency, dosing strategies, and risk management plans. In most cases, progress can be achieved within existing regulatory frameworks, provided developers engage early, generate high-quality data, and clearly articulate the rationale for combining agents. Finally, closer collaboration among scientists, regulators, and patient groups can help speed progress while keeping patient benefit at the center of innovation.

Ongoing preclinical work with cannabinoid- and psychedelic-based combinations suggests these approaches are beginning to move beyond early experimentation and toward more established treatment strategies. When developed within structured programs that prioritize biological understanding and patient experience, combination therapies have the potential to improve effectiveness, reduce side effects, and address persistent gaps in care across conditions, such as OSA, RA, and GAD.

Conclusion

Combination therapies that incorporate cannabinoids and psychedelics signal an important shift in how complex chronic diseases are being approached. Rather than focusing only on managing symptoms, these treatments aim to address the biological drivers of disease, with the goal of delivering longer lasting and more meaningful improvements for patients. Turning this promise into real-world impact requires careful preclinical research, clinical testing, early and ongoing engagement with regulators, and study designs that reflect what patients actually experience in daily life.

 These multimodal approaches have the potential to change how conditions, such as OSA, RA, and GAD, are treated. More broadly, this work reflects a growing recognition across drug development that meaningful progress in chronic disease will come not from incremental tweaks to existing therapies but from a deeper understanding of disease biology and a willingness to design treatments that work across multiple pathways to better meet patient needs.

About The Author

Joel Latham has served as the chief executive officer, president, and director of Incannex Healthcare Inc. since July 2023. He brings more than 20 years of senior management and operations experience in both public and private sectors. Previously, he was the CEO and managing director of Incannex Australia, where he played a key role in the company’s growth and its successful transition to Nasdaq. Joel has also held senior leadership roles in corporate strategy and global market development at Mars Foods, Tabcorp, and Philip Morris International.