3. Opioids

Background Information

Abuse of opioids such as heroin, morphine, and prescription pain medications has been widely recognized as a large-scale global health problem affecting all levels of society. The UN Office on Drugs and Crime World Drug Report 2015 estimates that 48.9 million people worldwide use opioids or opiates.

The most effective existing treatments for opioid use disorders are medication assisted treatments such as methadone and buprenorphine. These substances have been shown to help dramatically to reduce the severity of SUDs and to help people to significantly reclaim their mental and physical health, as well as livelihoods and family relationships. However, for those who wish to stop opioid maintenance treatments, there are few options, and withdrawal symptoms are at least as difficult and greatly prolonged compared with shorter-acting street drugs or prescriptions.

Many addiction professionals do not see a need to stop a presumably successful treatment protocol, but according to the World Health Organization, patients who are receiving treatment for substance use disorders should be helped to withdraw from opiates if it is their informed choice to do so (WHO 2009). The increasing number of patients of ibogaine therapy who have sought treatment in order to withdraw from methadone or buprenorphine is a demonstration of the difficulty that patients have in withdrawing from these medications when they wish to terminate the therapy.

Of all of ibogaine’s therapeutic benefits, one of the most impressive is in the treatment of opioid use disorders. For these patients, and for others who are properly informed and still choose not to undergo maintenance therapy, ibogaine provides a valuable treatment option.

General Considerations

In addition to ibogaine’s ability to mitigate withdrawal symptoms, it also has the potential to potentiate the analgesia of opioids if they are co-administered. The accurate calculation of half-lives and of timing in dosage in order to avoid the risk of accidental overdose, or the prolongation of residual withdrawals is critical in ensuring that the treatment is both safe and effective.

This is especially a concern for long-acting opioids, which remain in the system long after the initial onset of withdrawal symptoms.

Also, in order to prevent accidental overdose, it is very important that as part of the regular process of informed consent clients are made aware that if they use opioids during treatment they are at immediate risk for overdose. Further, it is important to reiterate at discharge that if the patient relapses and uses opioids after their treatment, they must take the same dose as an opioids naïve user, due to the fact that whatever tolerance they accumulated during the course of their previous use, has been reset.

Preparation

Patients who are using opioids by any other means of administration (smoked, insufflated, IV, IM) should be advised to switch to oral opioids under medical supervision prior to arrival. Oral morphine is preferred.

Long-Acting Opioids

If ibogaine is administered while long-acting opioids are still present in the blood there is an aforementioned risk of analgesic potentiation. However, after the ibogaine treatment, as this analgesia subsides, patients may experience residual withdrawals and PAWS. To avoid risk and ensure that detoxification can be completed successfully, patients who are attempting to withdraw from long-acting opioids should switch to shorter acting opioids, such as morphine sulfate, prior to treatment.

It is important to accurately calculate the elimination half-lives and conduct an effective switch-over. There is some controversy about the best way to calculation this timeline, but a general guide is to ensure that there is a residual dose of no more than .125mg of buprenorphine, or 2mg of methadone, prior to treating with ibogaine.

Some clinicians believe that the half-lives for both of these medications be calculated at 24 hours. In this case, for example, a patient that is taking 4mg of oral buprenorphine would have a residual dose of 2mg on day 2, 1mg on day 3, .5mg on day 4, .25mg on day 5, and would be cleared for treatment by day 6.

Likewise in the case of methadone, a patient taking 100mg per day, would have a residual dose of 50mg on day 2, 25mg on day 3, 12.5mg on day 4, 6.25mg on day 5, 3.125mg on day 6, and would be cleared for treatment on day 7.

Other clinicians prefer to ensure that the elimination is calculating using a longer half-life: up to 72 hours for buprenorphine, and up to 48 hours for methadone. These considerations may be especially useful in certain situations, such as for poor metabolizers, those who have been taking these medications for many years, or simply to avoid some of the complications when the switchover cannot be completed under close supervision.

Using these calculations, a patient with a 4mg daily dose of buprenorphine, would be recommended to switch for at least 18 days. A patient taking 100mg per day of methadone would be recommended to switch for at least 14 days.

It is very important that regardless of the half-life calculations done in advance, the switch-over be conducted carefully and under medical supervision. Some of the reported instances of residual withdrawal may result because of improper calculation of the necessary dosages of short-acting opioids.

It is important to calculate the appropriate conversion dose, and to build up of this dose gradually as the long-acting opioid are eliminated. For example, a patient on 4mg per day of buprenorphine may require 100mg of oxycodone in order to stabilize. However, if the patient stops taking buprenorphine, by the end of the first half-life cycle they have a 2mg residual dose. If the patient is given 100mg of oxycodone right away, they will be over-sedated, which will result in discomfort during the switch-over process and an increased opioid tolerance prior to treatment. The switch-over must be conducted gradually, and in order to be done effectively, should be done under medical supervision and with dosages just sufficient to treat observed withdrawals. Application of the Subjective and Objective Opioid Withdrawal Scales (SOWS & OOWS) is standard.

The challenge with long switch-over times is that in many places it is very difficult to obtain the necessary short-acting medications due to legal restrictions. Under no circumstances is it preferable for a patient to switch to short-acting illicit drugs. During long unsupervised switch-over periods there is an increased risk that patients will engage in illicit activity, and that increased tolerance will develop.

As an additional safety concern, patients should not be instructed to taper their use of any other medications (including benzodiazepines) during the switchover process. Benzodiazepine use, for example, should be stabilized prior to the opioid switch. Under no circumstances should it be recommended that benzodiazepines or other potential drugs of abuse be used to counteract discomfort or withdrawal during the switch-over process.

These recommendations provide a guide for preparing a patient prior to intake, however, testing for presence in the urine can verify that the drug has been sufficiently eliminated, and it is possible that in some cases treatment may be started sooner. Note that buprenorphine and some synthetic opioids will not appear in the standard ELISA lab tests (see Ch. 11).

Other Considerations

Some clinicians have attempted to treat patients who are withdrawing off of long-acting opioids after less time by doing initial treatment 24 hours after the last dose and keeping the patient under supervision for 7 to 10 days after, using booster doses to treat residual withdrawal symptoms.

This method is not recommended for reasons previously mentioned, but especially in the case of methadone. Large doses of methadone have been shown to prolong the QT interval (Kornick 2003) by hERG channel inhibition, and there is some evidence that suggests lower doses also have this effect. In rare cases, QT prolongation from methadone alone has led to toursades de pointes (Vieweg 2013).

Intake

Ibogaine has been shown to decrease accumulated tolerance to opioids, and to increase the central nervous systems sensitivity to opioids (Parker 2001), increasing their effects when co-administered. This must be taken into consideration throughout, as well as after the treatment, when opioids are administered.

Short acting opioid, preferably morphine sulfate, should be used to stabilize the patient as long as necessary prior to ibogaine administration, or in the case that it is not possible to administer ibogaine for medical reasons. Stabilization dosage should be sufficient to manage withdrawal symptoms as identified on the SOWS and OOWS.

Extreme vigilance should be taken to ensure that the opioids dosage administered is not higher than the dose necessary to manage withdrawal symptoms.

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