Ibogaine, an alkaloid derived from the Tabernanthe iboga shrub found in Africa, has received attention as a potential treatment for addiction, particularly opioid use disorder.
While small studies have hinted at effectiveness, a new clinical study shows ibogaine comes with concerning safety risks that may limit its therapeutic potential.
Key facts:
- Ibogaine resulted in significant QT prolongation, indicating risk of fatal heart arrhythmia
- All patients developed transient but severe ataxia (loss of motor coordination)
- Mild reductions in heart rate and blood pressure were seen
- Patients reported vivid dreaming but minimal withdrawal symptoms or delirium
- The cardiac risks likely outweigh the potential benefits of ibogaine
Source: Addiction 2022
What is Ibogaine and How Could it Help with Opioid Addiction?
Ibogaine is one of the primary active compounds found in the Tabernanthe iboga plant, which has been used for centuries in coming-of-age rituals by the Bwiti tribe in Africa.
More recently, ibogaine has been used in non-medical settings as an experimental treatment for substance use disorders, particularly opioids and stimulants.
Animal studies and small human case series have suggested ibogaine may reduce drug cravings, drug-seeking behavior, and withdrawal symptoms.
It is thought to work via effects on multiple neurotransmitter systems involved in addiction, including glutamate, opioid, and dopamine signaling.
Ibogaine is also metabolized into noribogaine, which has a much longer half-life and may contribute to prolonged therapeutic effects.
The potential of ibogaine to treat addiction with a single dose resulting in long-lasting effects has generated enthusiasm. However, safety concerns have tempered this enthusiasm.
Past Concerns About Ibogaine’s Safety
Even before the recent clinical study, there were concerns about ibogaine’s safety profile, especially regarding the cardiovascular system.
Case reports have associated ibogaine use with sudden death due to heart arrhythmias.
Studies suggest the deaths were likely caused by a dangerous prolongation of the QT interval on electrocardiograms (ECGs).
A prolonged QT interval indicates abnormal heart electrical activity and elevated risk of life-threatening ventricular arrhythmias like torsades de pointes.
Additionally, ibogaine appears to reduce heart rate, which could compound the risk of arrhythmias when combined with QT prolongation.
There have also been isolated reports of seizures and long-lasting visual disturbances.
However, these past concerning cases lacked controlled study conditions to definitively determine causation or carefully quantify the risks.
New Clinical Study Assesses Safety of Ibogaine for Opioid Withdrawal
To better understand ibogaine’s safety profile, researchers conducted a prospective open-label observational study in 14 patients with opioid use disorder.
All patients were stable on opioid maintenance therapy like methadone but wished to detox.
After converting patients to short-acting morphine for stabilization, researchers administered a single 10 mg/kg oral dose of ibogaine hydrochloride.
This dose is on the lower end of doses typically used in addiction treatment settings.
Patients were monitored closely before and for 24 hours after ibogaine administration.
Outcomes included ECG measurements, heart rate, blood pressure, neurological exams to assess ataxia, scales to assess withdrawal and psychotic symptoms, and adverse events.
Ibogaine Resulted in Prolonged QT Interval
The most concerning finding was that ibogaine administration led to substantial QT interval prolongation in virtually all patients.
- The median maximum QT interval prolongation was 95 ms above baseline
- 7 out of 14 patients had a QT interval exceeding 500 ms at some point – a level associated with high risk of arrhythmias
- Around 30% still had markedly prolonged QT interval after 24 hours
While no actual arrhythmias occurred, likely due to close monitoring, the researchers concluded that ibogaine carries a clinically important risk of QT prolongation even at lower doses.
This risk seems to arise from ibogaine’s inhibition of potassium channels involved in cardiac electrical conduction.
Transient Ataxia Was Also Consistently Observed
In addition to QT prolongation, all patients developed acute ataxia, or lack of muscle coordination, after ibogaine administration.
The ataxia peaked within 2-6 hours and fully resolved within 24 hours.
Patients had difficulty with balance and gait but did not have broader cognitive impairment.
Researchers hypothesized the ataxia may result from mild, reversible effects on the vermis region of the cerebellum.
This indicates ibogaine likely crosses the blood-brain barrier.
Alternatively, it could reflect ibogaine’s psychotropic effects on motor control rather than direct cerebellar toxicity.
Mild Decreases in Heart Rate and Blood Pressure
On average, patients exhibited a mild 9 bpm decrease in heart rate and 22 mmHg drop in systolic blood pressure over the first 12 hours.
This adds to ibogaine’s concerning cardiovascular profile, as lowered heart rate can further increase QT-related arrhythmia risk.
Minimal Withdrawal Symptoms But Vivid Psychotropic Effects
Despite acute opioid withdrawal, patients exhibited surprisingly minimal objective withdrawal symptoms, with low scores on the clinical opioid withdrawal scale.
This suggests potential beneficial effects of ibogaine on withdrawal.
Subjectively, patients reported vivid dream-like visions and emotional experiences lasting 3-7 hours, consistent with ibogaine’s described oneirogenic and psychotropic properties.
However, observers saw minimal signs of ibogaine-induced delirium or psychosis.
Overall, the psychotropic and mildly withdrawal-suppressing effects were well-tolerated, suggesting ibogaine may have some benefits if the cardiovascular risks can be managed.
Researchers Caution Ibogaine’s Risks Likely Outweigh Benefits
The researchers concluded that ibogaine carries substantial cardiac risks that likely outweigh its potential benefits for treating opioid use disorder.
They emphasized that if ibogaine is to be used, it should only be administered under careful clinical monitoring capable of detecting QT prolongation and arrhythmias.
However, the efficacy evidence is still lacking compared to standard treatments like buprenorphine or methadone.
It remains unclear if lower but more frequent ibogaine dosing could provide a safer toxicity profile while retaining benefits.
Future studies could assess individual dose adjustment based on metabolism gene testing.
But for now, the researchers do not recommend ibogaine use outside controlled medical settings due to toxicity concerns.
The Path Forward for Ibogaine Research in Addiction
While concerning, this study should not yet close the door on ibogaine research.
But it highlights that we must proceed cautiously and focus on safety first.
Ibogaine’s apparent ability to temporarily reduce opioid withdrawal severity and cravings via a single dose is unique, and could be valuable if proven safe.
Opioid use disorder remains an escalating public health crisis with devastating consequences and limited effective treatments.
Further research should continue to characterize ibogaine’s complex pharmacology and effects on neuronal signaling related to addiction.
Identifying the key active metabolites and evaluating less toxic synthetic analogues may uncover safer therapeutic approaches.
Human studies will need to closely monitor cardiac function and exclude high-risk patients.
Lower doses and dose regimens minimizing noribogaine accumulation may also be warranted.
And above all else, patient safety must remain the top priority.
With prudence, science may yet uncover if ibogaine or related compounds could fill a vital unmet need in battling the opioid epidemic.
But for now, non-medical use poses unjustifiable dangers, and evidence supporting therapeutic potential over proven treatments remains lacking.
The risks identified in this study serve as an important reminder that all medications, even those with natural origins, demand rigorous scientific vetting.
References
- Study: Safety of ibogaine administration in detoxification of opioid-dependent individuals: a descriptive open-label observational study
- Authors: Thomas Knuijver et al. (2022)
