Watery eyes from PARGY-LAD

Watery eyes (epiphora or excessive lacrimation) during psychoactive substance use refers to the overproduction of tears by the lacrimal glands, resulting in a wet, glistening appearance of the eyes, overflow tearing down the cheeks, and potentially blurred vision from the excess fluid across the corneal surface.

Tear production is regulated by both the parasympathetic and sympathetic divisions of the autonomic nervous system, with parasympathetic stimulation (via the facial nerve and pterygopalatine ganglion) being the primary driver of reflex tearing. Any substance or physiological state that increases parasympathetic outflow or causes sympathetic rebound can produce excessive lacrimation.

Opioid withdrawal is the most clinically significant context for excessive lacrimation. Like rhinorrhea, watery eyes during opioid withdrawal result from autonomic rebound -- the sudden removal of chronic mu-opioid receptor-mediated suppression of autonomic activity. The resulting parasympathetic and sympathetic surge stimulates the lacrimal glands, often dramatically. Lacrimation is one of the earliest observable signs of opioid withdrawal and is included in standardized withdrawal assessment scales (such as the Clinical Opiate Withdrawal Scale). Its presence, along with rhinorrhea, yawning, and piloerection, helps clinicians identify and stage withdrawal severity.

Dissociatives, particularly ketamine and DXM, can produce watery eyes through NMDA receptor blockade affecting autonomic regulation and through direct irritation when insufflated (the nasiolacrimal duct connects the nasal cavity to the eye). Some psychedelics produce mild lacrimation during the come-up as part of a general autonomic activation pattern. Cannabis smoke can irritate the conjunctiva and trigger reflex tearing. Cholinergic substances directly stimulate tear production through muscarinic receptor activation.

The effect is generally benign and self-limiting. For comfort, gently blotting tears with a clean tissue and avoiding rubbing the eyes (which worsens irritation) is sufficient. Contact lens wearers should be aware that excessive tearing may dislodge lenses. In the context of opioid withdrawal, lacrimation is managed as part of the overall withdrawal treatment protocol.