What are the side effects of psoralen?

October 12, 2025 •

4 min read

Did you know that the use of psoralen combined with ultraviolet (UV) light therapy has declined over the years partly due to growing concerns over its long-term safety? For those considering or currently undergoing this treatment, a clear understanding of what are the side effects of psoralen is crucial for managing health and mitigating potential risks.

Quick Summary

Psoralen side effects vary from common issues like nausea and increased photosensitivity to more serious concerns, including long-term risks of skin cancer and cataracts, particularly when used in combination with UVA phototherapy.

Key Points

Enhanced Photosensitivity: Psoralen dramatically increases skin sensitivity to UV light, necessitating strict sun protection for at least 24 hours post-treatment to avoid severe burns.
Increased Skin Cancer Risk: Long-term, cumulative PUVA therapy is associated with an increased risk of developing skin cancers, including squamous cell carcinoma, basal cell carcinoma, and potentially melanoma.
Ocular Damage: If proper eye protection is not used, psoralen significantly increases the risk of cataracts and keratitis due to heightened sensitivity to UVA radiation.
Gastrointestinal Issues: Nausea is a common side effect of oral psoralen, but can often be mitigated by taking the medication with food.
Potential Liver Complications: In rare cases, psoralen can cause liver injury (hepatotoxicity), especially with long-term use or in individuals with pre-existing liver disease.
Premature Skin Aging: Chronic PUVA therapy can lead to premature aging of the skin, with increased dryness, wrinkles, and pigmentation.

Psoralen is a light-sensitive compound, or photosensitizer, used primarily in phototherapy treatments, most notably Psoralen + Ultraviolet A (PUVA) therapy. In this treatment, psoralen is administered either orally or topically to the skin, followed by controlled exposure to UVA light. The activation of psoralen by UVA light helps to treat skin conditions like psoriasis and vitiligo by slowing the growth of excess skin cells. However, this powerful mechanism also carries a range of potential side effects, from common, manageable reactions to more serious, long-term health risks. Understanding these effects is vital for anyone considering or undergoing PUVA treatment.

Common Short-Term Side Effects

Many patients experience immediate, temporary side effects during or shortly after PUVA treatment. The severity can vary depending on the dosage, skin type, and duration of exposure.

Gastrointestinal Upset

Nausea is one of the most frequently reported side effects of oral psoralen, sometimes leading patients to discontinue treatment. This can often be managed by taking the medication with food, milk, or ginger. Other potential gastrointestinal issues include vomiting.

Skin Reactions

Photosensitivity and Sunburn: Psoralen makes the skin highly sensitive to all UV light, not just the therapeutic UVA. This can lead to exaggerated sunburn-like reactions, including redness (erythema), blistering, and pain, if proper sun protection is not used for at least 24 hours after treatment.
Itching and Stinging: A sensation of itching (pruritus) or stinging is a common reaction.
Tanning: Tanning or darkening of the skin is a universal side effect, occurring in nearly all patients undergoing PUVA. This tanning is a phototoxic effect and should not be mistaken for a normal sun tan.

Other Systemic Effects

Some individuals may experience other side effects that are not localized to the skin:

Headache: Mild headaches can occur during treatment.
Dizziness and Fatigue: Feeling lightheaded or unusually tired is a less common but reported side effect.
Depression: In some instances, patients have reported feelings of depression.

Serious Long-Term Side Effects

The long-term risks are a major reason why PUVA therapy is used less frequently today than in the past, especially for chronic conditions.

Increased Risk of Skin Cancer

Multiple studies have shown that long-term PUVA therapy, especially in individuals receiving a high number of treatments, increases the risk of developing certain skin cancers.

Squamous Cell Carcinoma (SCC): The risk of SCC is significantly elevated in patients receiving numerous PUVA treatments, particularly in fair-skinned individuals.
Basal Cell Carcinoma (BCC): The risk of BCC is also moderately increased.
Melanoma: While less common, some reports suggest a potential link between long-term, high-dose PUVA and an increased risk of melanoma. This risk is higher for those receiving 250 or more treatments.

Ocular Risks

Proper eye protection is critical during and after psoralen administration, as psoralen can cause serious eye damage.

Cataracts: Psoralen, especially oral formulations, can increase the risk of cataract formation if the eyes are not adequately protected from UVA exposure. Patients must wear UV-absorbing, wrap-around sunglasses for 24 hours after an oral dose.
Keratitis: Inflammation of the cornea can occur from UV exposure if the eyes are unprotected.

Premature Skin Aging

Chronic or repeated PUVA treatment can lead to premature aging of the skin, characterized by dryness, fine wrinkles, and sun spots (lentigines), similar to the effects of prolonged natural sun exposure.

Potential Liver Concerns

While rare, there have been documented cases of hepatotoxicity (liver injury) associated with psoralen, particularly in oral formulations or herbal products containing psoralen derivatives.

Elevated Liver Enzymes: Some patients may experience mild-to-moderate, temporary elevations in liver enzymes (ALT, AST).
Acute Liver Injury: Rare cases of clinically apparent acute liver injury have been reported, with an insidious onset of symptoms like nausea and abdominal pain followed by jaundice. In very rare instances, fatal hepatic failure has been reported in patients with pre-existing liver disease.

Psoralen Side Effects Comparison: Oral vs. Topical


Side Effect	Oral Psoralen	Topical Psoralen (Lotion/Bath)
Nausea	Common, affecting a significant number of patients due to systemic absorption.	Rare, as the medication is not ingested.
Skin Burns	High risk if skin and eyes are not fully protected from sun exposure post-treatment.	Risk is confined to the treated areas; accidental burns are more localized.
Systemic Effects (Headache, Fatigue)	Possible, as the drug is absorbed systemically.	Generally absent, as systemic absorption is minimal.
Risk of Skin Cancer	Increased risk associated with cumulative exposure and long-term use.	The localized nature may reduce overall systemic risk, but high doses can still increase cancer risk in treated areas.
Cataract Formation	Significant risk if UV-absorbing sunglasses are not worn for 24 hours post-dose.	Risk is minimized as long as the eyes are properly shielded during the light treatment itself.
Liver Problems	Rare but documented cases of hepatotoxicity due to systemic metabolism.	Extremely rare, as systemic drug levels are negligible.

Conclusion

While psoralen, in combination with UVA phototherapy (PUVA), can be an effective treatment for certain severe skin conditions like psoriasis and vitiligo, it is essential to be aware of the associated side effects. The potential risks range from common short-term issues such as nausea, sunburn, and itching to more serious, long-term concerns, including an increased risk of skin cancer and cataracts. Due to these risks and the emergence of safer, more effective treatment options, the use of psoralen has become less common. It is imperative for patients to follow all precautions diligently, including strict UV avoidance and wearing protective eyewear, and to have regular follow-ups with a dermatologist. A thorough discussion with a healthcare provider about all potential side effects and alternatives is necessary to determine if psoralen therapy is the right choice for your specific condition.

For more in-depth medical information on psoralen and its safety, consult the National Institutes of Health (NIH) LiverTox database.

Frequently Asked Questions

PUVA therapy combines a psoralen drug with exposure to long-wave ultraviolet A (UVA) light to treat skin conditions like psoriasis, vitiligo, and eczema. The psoralen makes the skin more sensitive to the UVA light, which slows down the growth of skin cells.

To minimize nausea, it is recommended to take the oral psoralen capsules with food or a glass of milk. Some patients find relief by taking ginger supplements or splitting the dose.

When taking oral psoralen, you must wear special UV-absorbing, wrap-around sunglasses for 24 hours after each dose to protect against UVA-induced damage, which can lead to cataracts.

Yes, because psoralen significantly increases the skin's sensitivity to sunlight, excessive exposure can cause a severe sunburn-like reaction, known as phototoxic erythema.

Yes, long-term PUVA therapy is linked to an increased risk of skin cancers, including squamous cell and basal cell carcinoma. The risk is highest for those with numerous treatments.

Signs of potential liver injury, though rare, can include insidious onset of nausea, abdominal pain, and jaundice. Regular liver function tests may be required for those on long-term therapy.

Topical psoralens, like those applied via lotion or bath, have localized side effects, such as burns limited to the treated area. They cause fewer systemic effects like nausea or headaches because the drug is not widely absorbed into the bloodstream.