The 19+ Benefits Of Cyproheptadine (Periactin) With Side Effects And Mechanisms

The 19+ Benefits Of Cyproheptadine (Periactin) With Side Effects And Mechanisms

Cyproheptadine appetitie.jpg

In this post, we will discuss therapeutic and off-label effects of Cyproheptadine (Periactin), as well as side effects and mechanisms of this drug.


  1. Basics Of Cyproheptadine

  2. Benefits Of Cyproheptadine

  3. Alternatives To Cyproheptadine

  4. Caveats, Side Effects, And Overdose

  5. Mechanism Of Action

  6. More Research

Basics Of Cyproheptadine

Cyproheptadine (Periactin) is a first generation antihistamine traditionally used for allergic rhinitis, hives, and appetite stimulation.

Cyproheptadine acts on diverse pathways (more described below) and anticholinergic, antiserotonergic, and local anesthetic.

Benefits Of Cyproheptadine

1. Stimulates Appetite And Reduces Muscle Wasting


Cyproheptadine has been used to increase appetite and weight gain, which may be beneficial for certain diseases such as cystic fibrosis, HIV, and sarcopenia. R

Cyproheptadine has been also used in young children with feeding difficulties and poor growth. R

2. Helps Allergies

Cyproheptadine is used to treat allergies (specifically hay fever). R

3. Combats Migraines And Headaches

Although weak, cyproheptadine has been used as a preventive measure against migraines in children and adolescents. R R

4. May Treat Excessive Vomiting

Cyproheptadine has been used in treatment of cyclical vomiting syndrome in infants and children. R R

5. May Reduce Side Effects Of Some Antipsychotics

Cyproheptadine has been used to improve restlessness from patients using antipsychotic medications. R

6. Can Improve Certain Skin Conditions

Cyproheptadine has been used to reduce drug induced excess sweating. R

It can also reduce itchiness as a result of anxiety. R

It has been used to reduce blistering in those with Epidermolysis Bullosa Simplex (EBS). R

7. Can Prevent And Treat Serotonin Syndrome

Cyproheptadine has been used in moderate to severe cases of serotonin syndrome (usually from use of SSRI’s, MAOI’s, or serotonin secreting tumors). R

8. May Improve Attention And Verbal Fluency

In a small trial with Schizophrenic patients, Cyproheptadine was able to improve attention and verbal fluency. R

Although, other another trial (~50 patients) failed to reproduce these effects. R

9. May Improve PTSD

Cyproheptadine has been used to treat nightmares associated with Post-Traumatic Stress Disorder (PTSD). R

10. Has Antiandrogenic Properties

Cyproheptadine has weak antiandrogenic activity, which may be useful for men (prostate cancer, enlarged prostate, scalp hair loss, overly high sex drive, problematic sexual urges, and early puberty) and women (acne, seborrhea, excessive hair growth, scalp hair loss, and high androgen levels, such as those that occur in polycystic ovary syndrome (PCOS)). R

11. May Help With Withdrawal

Cyproheptadine may be a useful withdrawal from baclofen and benzodiazepines. R

12. May Help With Cancer

Cyproheptadine cancer.jpg

In breast cancer, cyproheptadine can decrease the expression and transcriptional activity of Estrogen Receptor Alpha (ERα), thereby inhibiting estrogen-dependent cell growth. R

In liver cancer, cyproheptadine has shown to reduce tumor growth by blocking p38 MAPK function. R

In urothelial carcinoma cells, cyproheptadine is able to target GSK3β and suppress mTOR and β-catenin signaling pathways. R

Cyproheptadine may also improve survival outcomes of patients treated with sorafenib for advanced liver cancer patients. R

13. May Improve Digestion

By acting as a serotonin (5-HT) antagonist on the gut-brain axis, cyprohetadine may be useful for management of functional gastrointestinal disorders (FGIDs), such as functional abdominal pain (FAP), functional dyspepsia (FD), irritable bowel syndrome (IBS), abdominal migraine (AM), and cyclic vomiting syndrome (CVS). R

14. May Help With Postoperative Delirium

In a pilot study, cyproheptadine has shown to significantly decrease the incidence, but not severity of postoperative delirium. R

15. May Improve Chemical Intolerance From Organophosphates

In animal models exposed to organophosphate compounds, such as soman and sarin, cyproheptadine can effectively control seizures, improve survival, reduce seizure duration and reduce the number of dying cells in the brain following exposure. R

16. May Help Treat Cushing’s Disease

Cyproheptadine can reduce ACTH and beta-endorphin secretion from the ACTH-producing tumors. R

In a case study, 24 mg/day of cyproheptadine was able to reduce Cushing’s Disease (CD). R

17. May Help With Depression

In 6 people with major depression (dexamethasone suppression test), cyproheptadine was able to improve depression in 4 patients, but increase anxiety/irritability in the other two. R

The antidepressant/antipsychotic effect of cyproheptadine may be by its ability to increase the excitability of medial prefrontal cortex neurons. R

18. Helps With Boophone Disticha Poisoning

Ingestion of Boophone disticha (hallucinogen in Africa) may result in toxicity and death. R

Cyproheptadine (in rodent model) has a dose-dependent protective effect on mortality and toxicity produced by exposure to Boophone disticha. R

19. May Help With Hemostasis

Cyproheptadine has antiplatelet and thromboprotective effects and may help with hemostasis (reduced blood flow). R

Alternatives To Cyproheptadine

See list of 5-HT antagonists (future post).

Caveats, Side Effects, And Overdose

Cyproheptadine may inhibit insulin secretion. R

In rare cases, cyproheptadine has shown in case studies to induce acute liver failure. R

Most cases of liver failure developed after 1-6 weeks of usage. R

Cyproheptadine can make you overeat so weight gain is possible.

Some cases have reported choreoathetosis following cyproheptadine usage. R

Side Effects:

  • Acute labyrinthitis

  • Allergic manifestation of rash and edema

  • Anaphylactic shock

  • Anorexia

  • Anticholinergic side effects

  • Blood dyscrasias such as leukopenia, agranulocytosis and thrombocytopenia

  • Chills

  • Cholestasis

  • Confusion

  • Convulsions

  • Diarrhea

  • Diphoresis

  • Diplopia (seeing double)

  • Disturbed coordination

  • Dizziness

  • Early menses

  • Epigastric distress

  • Euphoria

  • Excitation

  • Extrasystoles

  • Faintness

  • Fatigue

  • Hallucinations

  • Headache

  • Hemolytic anemia

  • Hepatic (liver) side effects

  • Hypotension (low blood pressure)

  • Hysteria

  • Increased appetite

  • Insomnia

  • Irritability

  • Nausea

  • Nervousness

  • Neuritis

  • Palpitation

  • Paresthesias

  • Photosensitivity

  • Restlessness

  • Sedation and sleepiness (often transient)

  • Thickening of bronchial secretions

  • Tightness of chest and wheezing

  • Tinnitus

  • Tremor

  • Urinary frequency

  • Urticaria

  • Vertigo

  • Vomiting

  • Weight gain


Activated charcoal has been used to relieve symptoms of overdose (CNS depression and excess anticholinergic side effects). R

The LD50 in mice is 123 mg/kg and 295 mg/kg in rats. R

Mechanism Of Action


  • Reduces AKT R

  • Reduces Beta-catenin R

  • Reduces ER-alpha R

  • Reduces GSK3beta R

  • Reduces HMTSet7/9 R

  • Reduces Insulin R

  • Reduces mTOR R

  • Reduces PI3K R

  • Reduces P38 MAPK R

  • Reduces 5-HT2A R

More receptor binding can be seen here -> R


  • Cyproheptadine is well-absorbed following oral ingestion, with peak plasma levels occurring after 1 to 3 hours and its terminal half-life when taken orally is approximately 8 hours. R R

More Research

  • Cyproheptadine has been used in veterinary settings as well to treat pituitary pars intermedia dysfunction in horses and appetite stimulation/asthma/aggression in cats. R R