Is Tetrahydrocannabinol (THC) known to elevate Periodic Limb Movement Index (PLMI) during sleep?

THC and Periodic Limb Movement Index During Sleep

THC appears to increase periodic limb movements during sleep, as evidenced by research showing that during marijuana withdrawal, periodic limb movements increase significantly. 1

Relationship Between THC and Periodic Limb Movements

Periodic limb movements in sleep (PLMS) are characterized by repetitive, highly stereotyped movements involving dorsiflexion of the ankle and extension of the big toe, sometimes with flexion of the knee and hip. Each movement typically lasts 2-4 seconds and occurs roughly every 20-40 seconds 2.

The evidence regarding THC's impact on PLMS shows:

• A study of heavy marijuana users undergoing abstinence demonstrated that Periodic Limb Movements (PLM) increased across the abstinence period 1
• Importantly, the quantity (joints/week) and duration (years) of marijuana use were positively associated with more PLMs, suggesting a dose-dependent relationship 1
• This indicates that THC may suppress PLMs during active use, with a rebound increase in PLMs during withdrawal

Mechanisms and Clinical Implications

The relationship between THC and PLMS may be explained by THC's effects on:

1. Sleep architecture: THC is known to reduce REM sleep and increase Stage 4 sleep during acute administration 3
2. Dopaminergic system: Both PLMS and substance use disorders involve dopaminergic pathways, which may explain the interaction 4

Clinical Considerations:

• PLMS are diagnosed when the PLMS Index exceeds 15 per hour in adults, as determined by polysomnography 2
• PLMS are more common with aging and are associated with disturbed sleep 5
• PLMS can cause brief awakenings or arousals from sleep, contributing to poor sleep quality 2
• The presence of PLMS may support but is not sufficient for the diagnosis of Restless Legs Syndrome (RLS) 2

Assessment and Management

For patients using THC who report sleep disturbances that might be related to PLMS:

• Diagnostic assessment: Polysomnography with EMG is required for accurate PLM detection 2
• Consider withdrawal effects: Sleep disturbances, including increased PLMS, may worsen during THC withdrawal 1, 3
• Evaluate iron status: Check serum ferritin levels, as iron supplementation may help manage PLMS even when blood levels are not low 5

Treatment options for PLMS (if clinically significant):

• Alpha-2-delta ligands (gabapentin, pregabalin) are suggested as first-line treatment for PLMD 2
• Iron supplementation for patients with ferritin ≤75 ng/mL or transferrin saturation <20% 2
• Dopamine agonists like ropinirole and pramipexole (FDA-approved for RLS) may be considered, though they have side effects including nausea, orthostatic hypotension, and sleepiness 5

Pitfalls and Caveats

• PLMS should not be confused with Periodic Limb Movement Disorder (PLMD), which requires clinical sleep disturbance or daytime fatigue in addition to elevated PLMS Index 2
• Actigraphy should not be used in place of EMG for the diagnosis of PLMD, as it produces unreliable estimates 2
• The effects of cannabis on sleep depend on multiple factors including metabolomic composition, dosage, and route of administration 6
• Different cannabis strains (indica vs. sativa) and cannabinoid concentrations (THC vs. CBD) may have varying effects on sleep parameters 7

Understanding the relationship between THC use and PLMS is important for clinicians managing patients who use cannabis and report sleep disturbances, as these movements may contribute to poor sleep quality and daytime impairment.