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Playing Well Together

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    Every doctor, every pharmacist, will warn about drug interactions…some chemicals simply do not play well with others in the body. Sometimes, one drug will block the actions of another. Sometimes, one drug will strengthen or change the actions of another, or the two together will cause something else entirely to happen.

    The bad news for clusterheads: many medications commonly used to treat clusters will block the effectiveness of tryptamines. In fact, when the clusterbuster treatment doesn’t work, most of the time it is because these drugs are interfering.

    There are other drugs and substances that make the tryptamines work too well…that is, they enhance the psychedelic side effects of tryptamines, and make for some unwanted surprises.

    Based on the reports of clusterheads and expectations based on research and theory, a list of drugs likely to interfere with the treatment. There are other drugs we are not sure will interact with tryptamines, and drugs that might enhance the psychoactive effect of tryptamines. And of course there are drugs and treatment that do play well with cluster-busting tryptamines.

    Experience has shown the clusterbuster treatment works best when drugs that interfere are avoided for long enough to be cleared from the body. We call this period “detox,” short for “detoxification,” though technically, this is not the proper term. Many clusterheads use some of these drugs for other conditions, and should talk with their doctors before stopping or changing any medications; some cluster medications must be withdrawn from slowly with a prescribed schedule so, again, see your doctor first.

    Any medication change should only be done under the direct supervision of your Medical Doctor.
    See Warnings
    See Legal

    Dropping cluster meds can be difficult while the attacks keep coming, but there are ways to help you survive during detox.



    Perhaps the most common culprits for ClusterBuster failure are the triptans, since they unfortunately are the most popular abortive treatments for cluster attacks. Sumatriptan (Imitrex) can stop an attack quickly, and it’s possible it foils the clusterbuster treatment more often than any other blocker. Other triptans are used less often, and there are fewer experiences, but for the sake of caution, these should also be avoided.

    Sumatriptan (Imitrex®)
    Zolmatriptan (Zomig®)
    Rizatriptan (Maxalt®)
    Naratriptan (Amerge®)
    Frovatriptan (Frova®)
    Almotriptan (Axert®)
    Eletriptan (Relpax®)


    Steroids, the corticosteroids Prednisone and Prednisolone particularly, can be very effective at completely stopping cluster attacks while they are being used. They are also very effective at causing some nasty side effects, and most doctors prescribe them only for short periods in decreasing dosages.

    There are many reports that prednisone will block the clusterbuster treatment.

    Verapamil and other calcium channel blockers

    Verapamil is a blood-pressure drug often prescribed for the long-term, preventive treatment of clusters. Most reports seem to indicate verapamil and other calcium channel blockers will interfere with the clusterbuster treatment, though a few say they successfully used tryptamines while on verapamil, and some reports seem to indicate that it impeded but didn’t completely block the treatment. Verapamil is known by the brand names Isoptin, Verelan, Verelan PM, Calan, Bosoptin and Covera-HS.


    Topamax (topiramate) is another of those drugs developed for some other disease that clusterheads have found useful. Many find its side effects objectionable. There are indications it will block the effectiveness of tryptamines, as will other anti-seizure medications such as Depakote and Tegretol.


    Opiates usually have little to no effect on clusters for most, but a few say the stuff works for them, and it is too-often prescribed by doctors in desperation or under the faulty assumption that such powerful pain killers must automatically work for painful “headaches.” There are many tales of emergency room doctors who are surprised and aghast when a shot of morphine has no effect on a cluster attack.

    Other drawbacks

    – the infamous addiction potential, while sometimes overstated, is real. It results in such medications becoming a target for theft. In any case the opiate and opioid pain killers seem to interfere with the cluster treatment. There are many in use; here is an incomplete list:

    •Demerol (pethidine)
    •Percoset (oxycodone)
    •Oxycontin (oxycodone)
    •Vicodin (hydrocodone)
    •Dilaudid (hydromorphone)
    •Actiq (fentanyl)
    •Duragesic (fentanyl)
    •Suboxone (buprenorphine)
    •Ultram (tramadol)
    •Ultracet (tramadol)


    Including but not limited to:
    •Dihydroergotamine (DHE) (nasal sprays [migranal] and injections)

    The molecules of these substances are very similar in shape to the tryptamines. This means they fill the same neuroreceptors as tryptamines, and interfere with the clusterbuster method. They can have some very serious side effects as well. They are powerful vasoconstrictors, and can cause bad circulation problems, particularly in the fingers and toes.


    SSRIs, or selective serotonin re-uptake inhibitors, widely used to treat mood and other psychological disorders may be blockers, as they are involved with serotonin. The SSRIs include Prozac, Celexa, Lexapro, Paxil and Zoloft.
    Other similar serotonin-affecting drugs include Effexor, Pristiq and Cymbalta. Drugs known as tricyclics, including Elevil and Tofranil. may also interfere with tryptamine treatment.



    People taking lithium, whether it is for preventing cluster headaches or for some other reason (it is often prescribed for people with bipolar affective disorder – see below for more on bipolar disorder). Anecdotal reports suggest that lithium can greatly potentiate the effects of LSD or mushrooms, and that it can produce very unpleasant feelings. An examination of a number of reports suggested that lithium can either increase or decrease effects.

    The combination of lithium and tryptamines may even produce episodes that seem like, and that perhaps are, epileptic seizures. If people are taking lithium for treating cluster headaches and it is not working, they may want to talk with their doctor about not taking it any more before trying mushrooms or LSD. If people are taking lithium for bipolar affective disorder, they probably should continue taking lithium, and they should avoid taking tryptamines for cluster headaches.


    Monoamine oxidase inhibitors (MAOIs) such as Nardil or Parnate are prescribed for depression and sometimes other conditions. They can block the action of enzymes that can break down some tryptamines, and as such may act to intensify the action of a given dose of tryptamine, especially when first taking tryptamines. However, after continued use (as perhaps after a month or more), MAOIs will tend to reduce the psychedelic effects of mushrooms and LSD. It is not known if long term use of MAOIs will interfere with tryptamine treatment of cluster headache, but it is possible.


    There are substances which will probably not interfere with the actions of psilocybin:
    • antibiotics
    • NSAIDs (non-steroidal anti-inflammatory drugs) such as Tylenol (acetaminophen), aspirin (ASA), ibuprofen, Vioxx (rofecoxib), etc.
    • antacids and anti-ulcer medications
    • asthma medications
    • insulin
    • caffeine
    • caffeine/taurine energy drinks
    • Tylenol
    • aspirin
    • B-Complex and multi vitamins
    • Diovan (blood pressure)
    • protonix (for acid reflux)
    • Indomethacin
    • meclizine and dimenhydramine (The antinausea agents)
    • Lipitor

    in Treatment Options

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