Background: Hypophosphatasia (HPP) is a rare congenital disease caused by a mutation affecting tissue nonspecific alkaline phosphatase, an enzyme involved in phosphate metabolism. The clinical manifestation usually includes bone mineralization disorders, neurological symptoms, and persistent muscle pain. Case Report: This case involves a woman in her sixties of Central European descent who suffers from lifelong chronic pain and muscle weakness due to HPP and concomitant degenerative changes of the lumbar spine. The patient is physically impaired and limited in her ability to walk as a result. HPP-specific and guideline-based multimodal pain management including enzyme replacement therapy with asfotase alfa, opioids, invasive orthopedic and neurosurgical procedures, long-term physiotherapy, and psychotherapy did not yield sufficient treatment results. The average pain was given as 8.5 on a numerical rating scale (NRS, 0–10) for the last 3 years. Treatment with a cannabidiol-predominant, full-spectrum, prescription cannabis extract led to a clinically meaningful pain reduction to 2.5/10 NRS, a discontinuation of opioids, and a recent resumption of employment as a physician. Conclusion: A more widespread consideration of medical cannabinoids in the treatment of complex chronic pain is proposed. Cannabinoids may pose a particularly potent treatment option for HPP-related symptoms and inflammation due to their known anti-inflammatory properties.