Summary

Clonidine is an alpha-2 adrenergic agonist that is primarily used to treat high blood pressure, but it is also relatively widely used to treat attention deficit hyperactivity disorder (ADHD).

Clonidine also has sedative effects, making it useful in the treatment of sleep problems, especially those related to ADHD and dysautonomia, including POTS.

It is also a mast cell inhibitor, meaning it reduces mast cell activation and helps with MCAS. This means it can have a knock-on effect on related conditions, including POTS (postural orthostatic tachycardia syndrome), dysautonomia, and pain in Ehlers Danlos Syndromes (EDS).

In patients with Ehlers Danlos Syndromes (EDS), clonidine has been used to manage the symptoms of joint hypermobility and chronic pain.

Known effects

In short, it calms mast cells and blocks adrenaline rushes – which is great for the typical sleep issues experienced by many with chronic illnesses.

The mast cell inhibition effect makes it especially useful in Mast Cell Activation Syndrome (MCAS) and its related conditions, especially HyperPOTS, but also seemingly standard POTS where ADHD or MCAS is present – maybe others. But caution must be taken in patients with low to normal blood pressure.

It may have positive effects on the vascular system, lungs, and endothelial issues – see studies.

Daytime use in POTS can cause excessive fatigue – better viewed more as a sleep aid.

Rose takes this like this

I recently started taking clonidine as recommended for POTS, especially hyperadrenergic POTS (HyperPOTS, which I don’t actually have, though I do have ADHD and MCAS). POTS UK also suggests using clonidine where both POTS and MCAS are present, and I do have this combination.

I was having trouble with not really getting sleepy at night – rather, I would feel more awake, and often get quite warm (even hot). This gets worse when I am going through a healing phase and experiencing overall better energy levels – so I end up paradoxically improving overall, while being permanently exhausted and suffering worse dysautonomia from a lack of sleep.

I started taking 75 mcg (less than the 0.1 mg in studies) a couple of hours before I go to bed. It works amazingly well – I feel calm and sleepy. I will need to watch my blood pressure as I’m naturally on the low side – especially as I am already on low-dose beta blockers for POTS.

I’ve noticed a reduction in brain fog and increase in energy. The fact it helps with mast cells is especially good. I’m sleeping the best I’ve slept in a very long time.

Research

Clonidine for Sleep Disturbances Associated with Attention-Deficit Hyperactivity Disorder: A Systematic Chart Review of 62 Cases
https://www.sciencedirect.com/science/article/abs/pii/S0890856709634316
Brief summary – in short, clonidine is promising in sleep disorders with ADHD.

Central catecholaminergic blockade with clonidine prevent SARS-CoV-2 complication: A case series (2019)
https://www.sciencedirect.com/science/article/pii/S221425092100175X
This case series suggests it helps treat acute covid-19 in some cases.

Ways to Address Perinatal Mast Cell Activation and Focal Brain Inflammation, including Response to SARS-CoV-2, in Autism Spectrum Disorder (2021)
https://www.mdpi.com/2075-4426/11/9/860
This wide-ranging article addresses MCAS and Covid-19 in relation to mast cells. It proposes nighttime use of clonidine to combat MCAS and hyperactivity in autism. While largely written as an expert opinion, this paper has a lot of information well supported elsewhere and by patient expetience.

Clonidine restores vascular endothelial growth factor expression and improves tissue repair following severe trauma (2017)
https://pubmed.ncbi.nlm.nih.gov/28666582/
In the authors’ words: “Clonidine increased VEGF and VEGF-receptor expression, decreased HMGB1 expression, decreased lung inflammation, and improved lung tissue repair.” – this could be useful given vascular and lung damage and inflammation, and endothelial issues, in long covid.

Autonomic dysfunction in ‘long COVID’: rationale, physiology and management strategies (2021)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850225/
Clonidine is proposed here as a potential treatment for the hyperadrenergic symptoms caused by the catecholamine surge on standing in long covid (and POTS, by association).

Long-COVID Syndrome and the Cardiovascular System: A Review of Neurocardiologic Effects on Multiple Systems (2022)
https://link.springer.com/article/10.1007/s11886-022-01786-2
Similar conclusions to the above, but with explicit mention of POTS.

Dysautonomia in COVID-19 Patients: A Narrative Review on Clinical Course, Diagnostic and Therapeutic Strategies (2022)
https://www.frontiersin.org/articles/10.3389/fneur.2022.886609/full#B69
Clonidine is mentioned under POTS treatment options. It’s claimed clonidine is poorly tolerated, but it seems they mean daytime use from the studies referenced – the first reference gives no information, and the second, added below, reveals they were talking about daytime rather than nightly use. (Well, duh?)

Pharmacotherapy for postural tachycardia syndrome (2018)
https://www.autonomicneuroscience.com/article/S1566-0702(18)30025-0/fulltext
This study explains the exact issue. In short, it makes you sleepy, which is a problem when using it throughout the day. The problem with the approach here, IMHO, is that they focus solely on using it as the main therapy for POTS, where the side effect of fatigue will be intolerable. They only propose using it 2-3x a day, rather than just at night.

Other sources

Clonidine as a Medication Choice for ADHD
https://www.verywellmind.com/clonidine-for-adhd-symptoms-4125406
A good summary of clonidine in ADHD. Note that clonidine is often given in much higher doses in ADHD, and twice a day rather than at night, before going to sleep.

POTS UK: Mast Cell Activation Syndrome – an overview
https://www.potsuk.org/wp-content/uploads/2021/10/MCAS_v_1_sept_2017_formatted.pdf
Clonidine is suggested where POTS is found in combination with MCAS.

OHSU Long-Covid-19 Clinical Guidelines
https://www.ohsu.edu/sites/default/files/2021-04/Long-COVID-19-Clinical-Guidelines-English-April-21-2021.pdf
These guidelines recommend clonidine to decrease sympathetic activity (0.3 mg twice daily – much higher than the dose used in sleep disorders, would be risky in low blood pressure).