Perillyl Alcohol (POH) for brain tumors via nasal spray


Cherries and POHA less known but very effective natural anti cancer element, Perillyl alcohol is isolated from the essential oils of several plants including citrus, cherries, lavender, peppermint, spearmint, celery seeds, sage, cranberries, lemongrass, ginger grass, etc.

Accessible at Medicor (see below) or it can be ordered from chemical suppliers under the CAS 18457-55-1.

Oral administration has lead to gastrointestinal toxicity, the side effects being dose limiting. However, in clinical trials, it has been shown that POH can be administrated via nasal spray without side effects (Ref) and in this case it will specifically address brain tumors. The clinical trials results are promising indicating >50% response (including stable disease).

In lab studies, it has been shown to have anticancer effects by killing cancer cells and blocking the growth of new blood vessels in tumors. In animal studies, it has been shown to shrink pancreatic, breast and liver tumors. Unfortunately, the gastro-intestinal side effects of these compounds have retarded their clinical development. When given as a nasal spray, perillyl alcohol has been shown to shrink brain tumours in humans without any serious side effects. A phase 1 study was conducted of 67 patients with anaplastic oligodendroglioma. Perillyl alcohol treatment of 440mg per day resulted in marked tumour reduction and improvement in overall survival in over 50% of patients.

Case Reports and Clinical Trials

  1. “A case has been published of a 37 year old glioblastoma patient who has been taking perillylalcohol for over 5 years and has tumour shrinkage demonstrated on her MRI scans: “The efficacy of any anti-cancer drug greatly depends that therapeutic concentrations reaches the tumor site, a situation that is difficult to overcome concerning brain tumors due to the presence of the blood-brain barrier that restrains free drug access into the central nervous system [18]. However, the intranasal route provides a practical, noninvasive method for transportation of lipophilic and apolar drugs straight to the central nervous system [19]. In this context, we have been conducting a Phase I/II clinical trial to assess the efficacy of the monoterpene POH administered by intranasal route in patients with recurrent GBM [20,21]. This report aimed to document a case of recurrent GBM successfully treated with intranasal perillyl alcohol administration as single chemotherapeutic agent without any evidence of adverse effects for more than 5 years.”
  2.  “After six months of treatment, PR was observed in 3.4% (n=1) of the patients with GBM and 33.3% (n=1) with AO; stable disease in 44.8% (n=13) with GBM, 60% (n=3) with AA, and 33.3% (n=1) with AO; and PC in 51.7% (n=15) with GBM, 40% (n=2), with AA and 33.3% (n=1) AO. PFS (sum of PRs and stable disease) was 48.2% for GBM, 60% for AA, and 66.6% for AO patients.”
  3. Perillyl alcohol inhalation concomitant with oral temozolomide halts progression of recurrent inoperable glioblastoma: a case report
  4. Anaplastic oligodendroglioma responding favorably to intranasal delivery of perillyl alcohol: a case report and literature review. Intranasal delivery of 0.3% concentration of POH 4 times daily was performed. A follow-up MRI scan after 5 months of treatment revealed reduction in size of the enhancing lesion.

See more in the Reference section.


It works by blocking a type of protein in the cell called €œRas€ which is involved in signaling the cellto grow. (Ref.)

Iterestingly, it has been suggested recently that”The anticancer drug perillyl alcohol is a Na/K-ATPase inhibitor” (Ref.). If this is true, we can see POH in the same way as other Na/K-ATPase inhibitors, i.e. cardiac glycosides such as oleandrin/oleander, bufalin, ouabain, etc. which are also known as strong anti cancer elements.

Intranasal Administration of Perillyl Alcohol Activates Peripheral and Bronchus-Associated Immune System In Vivo


The gastro-intestinal side effects of these compounds have retarded their clinical development.

The side effects of POH treatment, when administrated as a nasal spray, were almost nonexistent, even in patients treated for over 4 years.€J Cancer Res Clin Oncol. 2011 Feb;137(2):287-9

As a nasal spray (discomfort and irritation of the nose) – it causes temporary burning discomfort. However, anesthetic nasal spray is typically used to reduce or prevent the discomfort. No toxicity or serious side effects were noted.

“All the patients were submitted to the toxicity tests required by National Cancer Institute Common Toxicity Criteria version 3 for this kind of clinical trial. Laboratory exams and images of the thorax, brain, and abdominal cavity were normal. Indeed, we now have 6 patients with more than one year of POH. None of them presents any signs of toxicity. POH intranasal delivery was well tolerated in all patients. No dose reduction or drug discontinuation was required for any of the study participants.”

Preparation & Administration

Some patent background:

Nebulizer: The monoterpenes (or sesquiterpenes) can be formulated for use in a nebulizer device as an aqueous solution or as a liquid suspension. Ref

Topical: Because of their ability to easily penetrate the dermis, monoterpenes may also be used alone or in combination with other chemotherapeutic agents via topical application for the treatment of localized cancers such as breast cancer or melanomas. Ref

Some articles statements:

After our in vitro and in vivo studies we determined the administration of POH 23 drops diluted in 3ml of mineral water with pH above 7 to alkalinize the acidity of peritumoral edema (PTBE), in a common nebulizer. The POH was administered by inhalation four times daily in an interrupted administration schedule in patients with recurrent malignant gliomas after standard therapy. In this study, all patients received  the  starting  dose  of  23  drops  (66.7mg)  four  times  totaling  266,  8mg/daily, with dose escalation up to 46 drops (133, 4mg) four times daily totaling 533, 6mg/daily. The cohort included 198 patients (117 men and 81 women) with mea-surable contrast-enhancing tumor image, Karnofsky index ‰¥70%, mean age 53.4 years (range 19€“83) with primary GBM n=154), grade III astrocytoma (AA; n=26) and anaplastic oligodendroglioma (AO; n=15). POH inhalation schedule four times daily started with 66.7mg/dose totaling 266mg/day with escalation to 133.4mg/dose totaling 533.6mg/day. Clinical toxicity and overall survival following treat-ment were compared with tumor size, topography, extent of peritumoral edema, and histological classification. (Reference)

Based on the above info and various other sources I conclude the following: Intra nazal administration is the primary way for POH preparation and administration:

  • There are two major formulations that have been used previously on humans:
    • Formulation as used in the Brazilian clinical trials that may contain a few percent POH in water (e.g. 67 to 110mg POH in 3ml to 4.5ml water) and administrated via a nebulizer such as this one (which may need to be addapted at home for nazal administration since it is in general for administration by mouth) – in case the link to nebulizer will not work in the future, its name is “Pari Boy SX inhaler”. The nice point about this nebulizer is that the administration can be easily stopped when pause is required during the treatment, to avoid drug wastage.  (Ref) And here is a nasal nebulizer that may be an even better option for administration.
    • Formulation as used by Medicore containing 20% POH (relatively high concentration) and administrated via nazal spray. This option may be suitable when travelling or during the night when we would not want to spend time with the nebulizer. However, whenever possible, nebulizer is preferred since the produced particles are smaller and will go deeper in to the nose. (Ref)
      Note: nazal spray can be bought from pharmacy or supermarket. It may already contain a drug inside that should be discard and replaced by POH solution. The only thing that needs to be calculated is how many times you have to push the nazal spray to deliver the desired dose.
  • Each of the formulation above may need some Ethanol >96% to help the solubility of POH in water and even Glycerol based on the following patent
  • The daily dose is 440mg POH divided in 4 administrations every day –  four times daily at intervals of 6 h – this max dose was chosen to avoid or limit nasal discomfort
  • The side effects reported in the human trials of perillyl alcohol were mainly related to administration as a nasal spray (discomfort and irritation of the nose). No toxicity or seriousside effects were noted. These side effects can be overcome with Lidocaine 2% used after POH administration when needed (can be bought from pharmacy on prescription e.g. Lidocaine 2% Nasal Spray, 30ml)
  • administrate for at least 3 months to evaluate the response
  • if response the therapy may continue indefinitely

More thoughts on formulation of solution for intranasal administration

Based on experiments I conclude the following:

  • as it is well known POH in water is not soluble. While the above clinical trial indicates using POH drops in water I am not sure if I would use this formulation
  • POH mixed with Ethanol will also not lead to a clear solution as desired
  • POH + Ethanol + Kolliphor ELP (instead of Glycerol) can be combine so that leads to clear solution

Here is the formulation of POH using Ethanol and Kolliphor ELP:

  • add in a glass vial 140mg POH (i.e. 19%of total)
  • add 0.3ml Ethanol and mix with POH (i.e. 41% of total)
  • in the above solution add 300mg Kolliphor ELP and mix (i.e. 41% of total)
  • this solution can be added to e.g. 3ml water and nebulized according to the administration protocol above
  • the 19%/41%/41% ratio can be extrapolated to any other weights, other than indicated above

Note: the disadvantage is that we add more substances as it is always good to stay as simple as possible. about Kolliphor what you should know is that it is used to formulate IV substances so its safety profile is relatively good. Next to that, I see there are patents using it for nasal formulations as well, e.g. . Some people may be allergic to Kollifor. So i think the dose should be increased step by step (but anyway that has to be done regardless of the composition).

The above formulation seems to be very irritant for the nose as well so here is another option for the formulation which is much more simple (as used in the clinical study):

  • add 3ml (alcaline) water in the nebulizer
  • add 23 drops of POH
    • however I just weighted 23 drops of POH (measured with a syringe needle Sterican 1,20 x 50 mm – 18Gx2) and they contain about 150mg POH which is much higher compared to what was indicated in clinical trial. i.e. 23 drops were containing 67mg POH. It is possible that their solution was actually including Ethanol as well at about 50% of the total. Alternatively, we can use only 10-11 drops (measured with the Sterican needle mentioned above) that would represent about 67mg pure POH. Based on this, we can chose to use pure POH (at 10-11 drops) or POH 50% + Ethanol (purity>96%) 50% (at 23 drops)
    • I decided to exclude Kolliphor in this option since some users of POH from Brazil are suggesting that the POH they use as received in the clinical study it looks like oil in water, which is how POH or POH+Ethanol looks like when Kolliphor is not added to the solution

Note: these are just some experiments I did for fun out of curiosity – nothing more than that as we do not need it

Update July 8th 2019: According to the Facebook page of NeOnc Technologies, 

“Inc.’s phase one clinical trial is fully subscribed and is progressing with encouraging results. NTI is preparing to begin recruiting for Phase 2 which should begin in July 2019. The phase 1 study was a dose escalation study.

Cohort 1: 96 mg/dose 4 times a day (384 mg/day total)
• Brazilian dose 440 mg/day.
Cohort 2: 144 mg/dose 4 times a day (576 mg/day total)
Cohort 3: 192 mg/dose 4 times a day (768 mg/day total)
Cohort 4: 288 mg/dose 4 times a day (1152 mg/day total)

Key results
• 1. NEO100 has induced a radiographic reduction in size in recurrent GBM in a dose-dependent manner in several patients
• 2. NEO100: very well tolerated – no significant adverse effects
• 3. Patients tolerate treatment regimen very well (compliance by patient log and self-reporting) {Regimen is a 4x/day for 28 days}
• 4. Higher doses of NEO100 result in a higher response in patients over six months

• Cohort 1 – no response (0/3)
• Cohort 2 – 33% response (1/3)
• Cohort 3 – 67% response (2/3) – one has a complete radiographic response
• Cohort 4 – underway

Individual Cohort Results – note results between cohorts vary because dose escalated from cohort to cohort for toxicity assessment and improved therapeutic outcome evidenced with higher dose cohorts.

Cohort 1, Phase I
1. No significant adverse effects
2. All patients had a progression of tumor size after two months.
3. MRI scans from two of the patients demonstrated a change from solid to cystic tumor
4. 0 % response rate
• Two of the patients had repeat surgery; A change in characteristics of the tumor; A decrease in Ki-67 for both tumors

Cohort 2, Phase 1
1. First patient-progressed after two months
2. Second patient-2 years of treatment
• still alive, no seizures (prior to treatment 2-3 seizures per week, mostly partial but some generalized), tumor smaller on MRI,  the patient is continuing on therapy
3. Third patient-progressed after four months
4. 33% response rate after six months

Cohort 3, Phase 1
1. Cleveland Clinic-1 patient-one year out
• complete response
2. USC-1 patient –one year out
• no progression
• reduction in tumor size
3. USC 1 patient-3 months out-stable
4. 67% response rate over six months

Results-Cohort 4, Phase 1
• Three patients recruited
• Two at one month of treatment
• One just started treatment”


Conclusion: According to the above, the daily dose of  768 mg (given 192 mg/dose 4 times a day) leads to a 67% response (2/3). 2/3 is a small number but the results are very promising.

Source & Cost

Options 1: at Medicor is approximately $400 for a 2 week supply

Option 2: buy it from suppliers such as Sigma Aldrich under CAS 18457-55-1, and the cost is much lower than that. However, I would prefer the administration at Medicor if the the financial condition allows, as it is under a MD supervision.

Option 3: according to an image presented here I assume now (April 2017) POH is available at this clinic in Germany

Synergists & Antagonists

“Patients were not allowed to take cholesterol-lowering agents during the study.” (Ref)

Clinics Treating Patients with POH



Case of Advanced Recurrent Glioblastoma Successfully Treated with Monoterpene Perillyl Alcohol by Intranasal Administration

Perillyl alcohol inhalation concomitant with oral temozolomide halts progression of recurrent inoperable glioblastoma: a case report

Perillyl alcohol and methyl jasmonate sensitize cancer cells to cisplatin

Intranasal perillyl alcohol (POH)induces endoplasmic reticulum stress (ERS) in temozolomide sensitive and resistant malignant gliomas

The anticancer drug perillyl alcohol is a Na/K-ATPase inhibitor

Long-term outcome in patients with recurrent malignant glioma treated with Perillyl alcohol inhalation

Correlation of tumor topography and peritumoral edema of recurrent malignant gliomas with therapeutic response to intranasal administration of perillyl alcohol

Efficacy of monoterpene perillyl alcohol upon survival rate of patients with recurrent glioblastoma

Intranasal Administration of Perillyl Alcohol Activates Peripheral and Bronchus-Associated Immune System In Vivo

Monoterpene as a chemopreventive agent for regression of mammalian nervous system cell tumors, use of monoterpene for causing regression and inhibition of nervous system cell tumors, and method for administration of monoterpene perillyl alcohol

Intranasal Perillyl Alcohol for Glioma Therapy: Molecular Mechanisms and Clinical Development


This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learned on this road.

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23 thoughts on “Perillyl Alcohol (POH) for brain tumors via nasal spray

  1. Rami, all the info you need is in the text above, i.e.:
    – you can contact Medicor clinic in Canada to ask about that
    – or may want to try prepare it yourself as discussed above (while having the disclaimer in mind).

    1. Hi Daniel

      Can you please inform me on who can provide us with more information for this treatment. We are located in Vancouver and have a desperate situation with glioblastoma spread to the brain stem. I would be greatfull for any sort of advice.
      Thank you

  2. D, amazing you were ahead of this two years ago!
    I reread the recent POH 3-BP paper.

    It is simply amazing!
    If they have a way of moving 3-BP into cells without MCT-1 this would be BIG!
    It is such a disappointment that the research takes years and years.
    The POH 3-BP product from Neonc does not even appear to have advanced to mice yet.

    Perhaps I will need to look around for ways that we could fund some of this research.
    It is too important to let it drift for years and years without any forward progress.

  3. Hi J, earlier this year I was in contact with the authors. They mentioned they may soon bring it to patients as they are seeing very promising results. But as we know, typically it takes long time for small pharma to get their solutions advanced. It is however, not clear to me how the POH-3BP can be targeted to tumor cells, other then topical application …

  4. The authors want to move POH-3-BP into the clinic?
    WOW!! Very exciting. The neonc site has nothing about
    the clinic for that one.

    D, I went to the Medicor site and they are not referencing POH.
    If they no longer offer it, then that would be a shame.
    POH looks like a good one.

    I reread the POH 3-BP article.
    It looks like POH gives selective entry to cancer cells as a result of plasma cell interaction.
    POH caused no side effects for the people who were taking it intranasally for years.
    They do not need MCT-1 to enter cells.
    This is big news! 3-BP without MCT-1 should be extremely effective.

    I feel so bad for people with brain mets.
    Established medicine simply gives up on them after a while.
    I wish that POH, isoPOH, TMZ-POH, and POH-3-BP can help them soon.

    1. Interesting J. Thank you. I missed that one regarding the mechanism. I will look into it. And it makes sense we can then look into the prep method. At least I checked and 3BP is soluble in POH.

      I think another clinic in Germany, Koln – a large one focused on immunotherapy – is using POH for their patients.

  5. The Neonc drug NEO218 is a conjugation of POH and 3-BP.
    POH gets the 3-BP into the cell.

    It is super exciting!
    The question though is whether NEO218 could be used in the rest of the body?
    Intranasal worked fine for POH, though oral dosing did not work out.

  6. Hi Daniel – As always you have provided immense amount of info on this page along with actionable protocol. I would also like to add the below protocol that I found on a different forum (as advised by original Lead Researcher on POH, Dr. Da Fonseca).

    Dissolve 450ml glicerin in 450ml 96% alcohol and mix thoroughly
    Add 100ml perillyl alcohol to solution and mix thoroughly
    Store in refrigerator in amber bottle not longer than 3 months
    Shake well before use
    Administer 1.5ml solution 4x per day with nebuliser

    Ideally you need a magentic stirrer to do the mixing. You can read the original post here:

    I am planning to start with this protocol for my Mother who has Triple Negative Breast Cancer with recently diagnosed brain lesion along with other known lesions. If Glycerin does not work well enough to enable mixing of POH with Ethanol, then may be we will consider adding a small amount ok Kollipher which is mostly a surfactant and should allow mixing of the two.

    1. kapil, I was not clear about this point. Is there evidence that suggests that POH is a universal brain cancer treatment (i.e., mets from breast or elsewhere)? The Brazilian results seemed to be exclusively focused on GBM other primary brain cancers. Considering the seriousness and lack of other treatment options for other brain cancers, one might have thought they would have quickly moved POH to a broaad brain cancer treatment.

      1. I agree with your point Jcancom. I am yet to come across a clinical study on POH for anything apart from Primary brain cancers. Though, given its good safety profile and lack of side effects, we are planning to consider it for my Mother. My sense is there are some pre-clinical studies by Chen carried out in mice with TMZ-POH conjugate (you might be aware of) for brain lesions from breast cancer. Since, brain metastases is such a serious condition and apparently more common than primary brain cancers, one finds it very unfortunate that not much efforts and time has been dedicated to handle the same.

        I am yet to come across any clinical study or even a case report on POH use for metastatic lesions though. Another point worth highlighting in the GBM studies is that, investigators clearly highlighted that once started POH, it’s sudden discontinuation led to disease recurrence in some patients. This needs attention and is also one of the reasons, we are debating before starting it yet.

        Separately, I read Daniel’s article on Artemisia Annua (AA) where it was mentioned that it crosses Blood Brain Barrrier. It might be a worthwhile strategy to tackle brain lesions as well. If you have any other thoughts, I look forward to hear from you.

    2. Hi Kapil,
      I am Stage IV lung cancer with metastasis to the brain. Do you mind if I communicate (e-mail) with you directly w.r.t. the protocol?.
      Thank you

      1. Absolutely Westie. Feel free to reach out directly. I will try to help as much as I can. Just FYI, we are exploring adding it for my Mother but we are not there yet given that once started it cannot be discontinued all at once.

          1. Salut Sergiu! Some years ago, I’ve got for my wife from a chemical supplier such as Sigma Or Santa Cruz Biotech or others, where it was found under CAS 18457-55-1. Regarding Glioblastoma, please check the comments of Manuel on this website (use search function) – he is helping his mom fighting glioblastoma and you will learn a lot from his comments and discussions around that.

            Kind regards,

  7. buna Daniel, am reusit sa gaseesc perillyl alcohol , ma poti ajuta te rog mult cum ar trebui sa il prepar pt nebulizator, sau cine ma poate ajuta!? ms mult

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