From the Guidelines
Cannabis or opiate withdrawal does not typically cause hypercalcemia. The common symptoms of cannabis withdrawal include irritability, anxiety, sleep disturbances, decreased appetite, and sometimes physical symptoms like headaches or stomach pain, as noted in a study on cannabis use in adults with cancer 1. Opiate withdrawal typically presents with flu-like symptoms including muscle aches, restlessness, anxiety, lacrimation, runny nose, sweating, diarrhea, nausea, and vomiting, as described in a clinical policy on opioids in adult patients presenting to the emergency department 1. The physiological mechanisms of both cannabis and opiate withdrawal primarily involve changes in neurotransmitter systems rather than calcium metabolism. Hypercalcemia is more commonly associated with conditions such as hyperparathyroidism, certain cancers, excessive vitamin D intake, or specific medications. If a patient experiencing withdrawal from cannabis or opiates shows signs of hypercalcemia, clinicians should investigate other potential causes rather than attributing it to the withdrawal process itself. Key considerations in managing withdrawal symptoms include the use of symptomatic treatments for opioid withdrawal, such as α2-adrenergic agonists, and addressing the underlying causes of hypercalcemia if it occurs. In the context of cannabis use, understanding the potential for long-term side effects, including psychiatric risks and the risk of cannabis use disorder, is crucial for comprehensive patient care 1.
From the Research
Hypercalcemia Causes
- Primary hyperparathyroidism and malignancy are responsible for greater than 90% of all cases of hypercalcemia 2
- Other causes of hypercalcemia include granulomatous disease, endocrinopathies, immobilization, genetic disorders, and medications such as thiazide diuretics and supplements like calcium, vitamin D, or vitamin A 3
- Hypercalcemia has been associated with sodium-glucose cotransporter 2 protein inhibitors, immune checkpoint inhibitors, denosumab discontinuation, SARS-CoV-2, ketogenic diets, and extreme exercise, but these account for less than 1% of causes 3
Opiate Withdrawal and Hypercalcemia
- Opioid therapy can cause clinically significant secondary adrenal insufficiency, which may present as hypercalcemia 4
- Adrenal insufficiency is a rare cause of hypercalcemia and should be considered when more common causes are excluded 4
- Treatment with hydration and glucocorticoid replacement is effective in promptly resolving the hypercalcemia due to hypoadrenalism 4
Cannabis Withdrawal and Hypercalcemia
- There is no direct evidence in the provided studies to suggest that cannabis withdrawal causes hypercalcemia 5, 2, 3, 6, 4
- The provided studies do not mention cannabis withdrawal as a cause of hypercalcemia, and the current evidence does not support a link between cannabis withdrawal and hypercalcemia
Hypercalcemia Treatment
- Treatment of hypercalcemia should be started with hydration 2, 3, 4
- Loop diuretics may be required in individuals with renal insufficiency or heart failure to prevent fluid overload 2
- Calcitonin is administered for the immediate short-term management of severe symptomatic hypercalcemia 2
- For long-term control of severe or symptomatic hypercalcemia, the addition of bisphosphonate is typically required 2, 3