CBD and guanfacine (e.g. Intuniv)
David ReichUpdated:Key points at a glance:
CBD may inhibit the enzyme CYP3A4, which can potentially increase guanfacine levels in the body. This has been associated with effects such as tiredness, dizziness, low blood pressure, slower heart rate and difficulties concentrating. Particular care is advisable when starting treatment or adjusting the dose, including with higher CBD intakes and prolonged‑release formulations. It is often recommended to avoid grapefruit and pomegranate, as well as alcohol, which can enhance sedative effects. In children, use should only take place following medical advice. During the first few weeks, blood pressure and pulse should be monitored.
CBD and guanfacine (e.g. Intuniv) can interact in ways that may increase side effects for some people. Both can cause tiredness and lower blood pressure, and CBD may affect how guanfacine is broken down in the body. Careful medical supervision is advisable if you are considering using CBD alongside guanfacine.
How do CBD and guanfacine work? (clarified)
CBD: receptors, enzymes, relevance for interactions
CBD, also known as cannabidiol, is a natural compound from the cannabis plant and is commonly used as an oil, in capsule form or as a cream. CBD has only low affinity for CB1 and CB2 receptors and mainly modulates the endocannabinoid system indirectly (e.g. via FAAH). It also influences other targets such as 5‑HT1A and TRPV1 receptors. For CBD–medicine interactions, it is relevant that in vitro CBD can inhibit drug‑metabolising liver enzymes, particularly CYP3A4 and CYP2C19. These enzymes are involved in the metabolism of many prescription medicines.
Read our article on how CBD interacts with the body here.
CBD has complex effects in the body and can inhibit liver enzymes such as CYP3A4 and CYP2C19 in vitro. This is one reason why CBD drug interactions with prescription medicines, including guanfacine, are considered possible.
Guanfacine: α2A agonist, metabolism, key aspects
Guanfacine is a selective α2A adrenoceptor agonist. It dampens central sympathetic tone, supports prefrontal networks (in ADHD) and lowers blood pressure. Guanfacine is mainly metabolised via CYP3A4; extended‑release formulations (e.g. Intuniv ER) release the active substance slowly over time. Sudden discontinuation can lead to rebound hypertension. Alcohol can enhance sedative effects.
Guanfacine is used in the management of attention deficit hyperactivity disorder (ADHD) and sometimes of high blood pressure.
Guanfacine acts on α2A receptors in the central nervous system and is broken down primarily via the CYP3A4 enzyme. Because CBD can affect CYP3A4, combining CBD and guanfacine may influence guanfacine levels and effects.
Interactions between CBD and guanfacine
- CYP3A4 inhibition by CBD → potentially higher guanfacine levels
- Additive effects: tiredness, dizziness, low blood pressure, bradycardia
- Avoid grapefruit/pomegranate (additional CYP3A4 inhibition)
- Avoid alcohol (enhanced sedation)
- Children/adolescents: CBD only after medical advice
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There is limited direct research on CBD and guanfacine together, but their mechanisms of action suggest plausible CBD–guanfacine interaction pathways. CBD may enhance the effects of centrally acting medicines and influence the metabolism of other medicines via CYP3A4. These are theoretical and mechanism‑based considerations rather than firmly established clinical outcomes, so individual medical assessment is important. Read our article on interactions between CBD and medicines here.
CYP3A4: why guanfacine levels may increase with CBD
Guanfacine is mainly metabolised by the liver enzyme CYP3A4. CBD can inhibit CYP3A4 in vitro. When this enzyme is inhibited, guanfacine may be broken down more slowly, which can result in higher blood levels. This may be associated with more pronounced effects and side effects – particularly with extended‑release formulations, high CBD doses, concurrent intake of grapefruit/pomegranate (also CYP3A4 inhibitors) or in people with sensitive cardiovascular regulation.
Because both CBD and guanfacine are linked to the CYP3A4 enzyme, CBD may slow guanfacine metabolism. This can allow more guanfacine to remain in the bloodstream and may increase the risk of side effects in some people.
Additive effects: sedation, dizziness, low blood pressure
CBD and guanfacine can both be associated with tiredness and a reduction in blood pressure. Together, these effects may be more marked: tiredness/drowsiness, dizziness (especially when standing up), low blood pressure, slow pulse (bradycardia), concentration difficulties or, in rare cases, fainting. Alcohol further enhances these sedative and circulatory effects.
CBD and guanfacine can both cause tiredness and lower blood pressure. When used together, dizziness, slow pulse and circulatory problems may be more likely, especially if alcohol or other sedating substances are added.
When is particular caution needed?
Certain situations may increase the likelihood or impact of a CBD–guanfacine interaction and warrant extra care and medical supervision:
- Starting or increasing the dose of CBD or guanfacine
- Using high CBD doses or highly concentrated CBD products
- Taking extended‑release guanfacine formulations (e.g. ER/Intuniv)
- Concurrent consumption of grapefruit or pomegranate (additional CYP3A4 inhibition)
- Use of alcohol or additional sedating substances
- Children and adolescents: CBD only after medical advice, as the safety profile of CBD in minors is not yet fully established
Warning signs – when to seek medical advice?
Seek prompt medical advice if you notice any of the following while using CBD with guanfacine:
- Fainting or near‑fainting, severe dizziness
- Persistent drowsiness, confusion or marked tiredness
- Very slow pulse, palpitations, chest pain
- Noticeable drop in blood pressure (if measurable at home)
Side effects compared
CBD – commonly reported effects
CBD (cannabidiol) is generally considered to have a favourable tolerability profile. Possible side effects include tiredness, dry mouth, dizziness, changes in appetite and, occasionally, gastrointestinal issues such as nausea or diarrhoea. Product quality and purity are important; follow the recommended dosage and choose tested products, such as oils, capsules or creams. If side effects occur or persist, speak to your doctor.
Guanfacine – typical effects and warning signs
Common side effects of guanfacine include drowsiness, dizziness, dry mouth and tiredness; nausea or constipation may occur in some cases. In some people, guanfacine can lower blood pressure noticeably, which may be associated with circulatory symptoms. Sudden discontinuation can lead to rebound hypertension. Alcohol enhances sedation. Take guanfacine exactly as prescribed and report side effects promptly.
| Side effect | CBD | Guanfacine | Additive risk together? |
|---|---|---|---|
| Tiredness/drowsiness | Possible | Common | Yes |
| Dizziness | Possible | Common | Yes |
| Dry mouth | Occasional | Common | Moderate risk |
| Low blood pressure | Possible | Related to mechanism of action | Yes (particularly at the start/with dose changes) |
| Gastrointestinal (nausea/diarrhoea) | Occasional | Occasional | Possible |
| Heart rate (bradycardia) | Rare | Known | Yes (medical monitoring advised) |
Practical checklist before combining CBD and guanfacine
- Inform your doctor or pharmacist that you wish to use CBD, and mention all prescription medicines, including guanfacine.
- Avoid grapefruit and pomegranate products, as well as alcohol, while using CBD with guanfacine because of interaction and sedation risks.
- Start low with CBD and change one thing at a time (do not adjust both CBD and guanfacine doses simultaneously); always follow your doctor’s instructions.
- If you have a home device, check blood pressure and pulse more frequently during the first 1–2 weeks after starting or changing CBD.
- If sedation is a problem, discuss dosing time with your doctor; do not change timing or dose on your own.
- Seek urgent medical attention in case of fainting, severe dizziness, persistent drowsiness, chest pain or very slow heart rate.
- In children and adolescents, use CBD only after medical advice; potential benefits and risks should be assessed individually.
Conclusion
CBD is used for a variety of reasons and is generally regarded as having a favourable tolerability profile, but CBD–guanfacine interactions are possible. These may involve CYP3A4‑related changes in guanfacine metabolism and additive effects on blood pressure, heart rate and sedation. Always discuss planned CBD use with your doctor, monitor for warning signs and avoid additional risk factors such as grapefruit, pomegranate and alcohol.
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Disclaimer: This article is for information purposes only and does not replace medical advice. Do not change medicines or dosages without consulting your doctor. No claims are made regarding the treatment or cure of illnesses.